Antiretroviral drug treatment of CNS HIV-1 infection.

PubMed

Yilmaz, Aylin; Price, Richard W; Gisslén, Magnus

2012-02-01

The advent of combination antiretroviral treatment has had a profound impact on CNS HIV infection and its clinical complications, but neurological impairment still occurs in patients on systemically effective combination therapy, and in some patients it may be important to consider antiretroviral drug entry and effects within the CNS. There are now data on the CNS exposure for most antiretroviral drugs. This review focuses on the CNS pharmacokinetics and pharmacodynamics of antiretroviral drugs in humans, and also discusses controversies in this field.

Short-Term Adverse Outcomes After Deep Brain Stimulation Treatment in Patients with Parkinson Disease.

PubMed

Hu, Kejia; Moses, Ziev B; Hutter, Matthew M; Williams, Ziv

2017-02-01

Despite ongoing progress in our understanding of long-term outcomes after neuromodulation procedures, acute adverse outcomes shortly after deep brain stimulation (DBS) treatment have remained remarkably limited. To identify risk factors associated with acute 30-day outcomes after DBS treatment in patients with Parkinson disease (PD). We evaluated patients who underwent DBS treatment for PD from 2005 to 2014 through the American College of Surgeons National Surgical Quality Improvement Program database. We used bivariate analysis and multivariate logistic regression to identify short-term postoperative outcomes, including 30-day complication, discharge destination, and unplanned readmission. Overall, 650 patients with PD underwent DBS procedures and complications were identified in 32 patients (4.9%). Of 481 patients who had complete discharge data, 18 patients (3.7%) were discharged to a facility and 16 patients (3.3%) experienced an unplanned readmission. Patients with PD who were obese (P = 0.045), who had preoperative anemia (P = 0.008), and who experienced longer operative durations (P = 0.01) had increased odds of postoperative complications. Inpatient status (P = 0.001), dependent functional status (P < 0.001), and anemia (P = 0.043) were all associated with discharge to a facility other than home. Longer operative duration (P = 0.013), anemia (P = 0.036), and dependent functional status (P = 0.03) were significantly associated with unplanned readmission. As expected, complications increased the likelihood of unplanned readmission (P < 0.001). This study provides individualized estimates of the risks associated with short-term adverse outcomes based on patient demographics and comorbidities. These data can be used as an adjunct for short-term risk stratification of patients with PD being considered for DBS treatment. Copyright © 2016 Elsevier Inc. All rights reserved.

Long-Acting Antiretrovirals: Where Are We now?

PubMed

Nyaku, Amesika N; Kelly, Sean G; Taiwo, Babafemi O

2017-04-01

Current HIV treatment options require daily use of combination antiretroviral drugs. Many persons living with HIV experience treatment fatigue and suboptimal adherence as a result. Long-acting antiretroviral drugs are being developed to expand options for HIV treatment. Here, we review the agents in development, and evaluate data from recent clinical trials. In addition, we anticipate challenges to successful widespread use of long-acting antiretrovirals. Parenteral nanosuspensions of cabotegravir and rilpivirine, and dapivirine vaginal ring are the farthest in clinical development. Long-acting modalities in earlier development stages employ drug-loaded implants, microparticles, or targeted mutagenesis, among other innovations. Long-acting antiretroviral drugs promise new options for HIV prevention and treatment, and ways to address poor adherence and treatment fatigue. Further studies will identify the long-acting agents or combinations that are suitable for routine use. Creative solutions will be needed for anticipated implementation challenges.

[Dual contraception adherence among HIV-infected women].

PubMed

Brandão, Karina de Sá Adami Gonçalves; Lima, Bruno Gil de Carvalho; Travassos, Ana Gabriela Álvares; de Brito, Fabielle de Oliveira Rocha; de Souza, Eveline Xavier Pereira; Haguihara, Tatiana; da Silva, Carlos Alberto Lima

2015-10-01

To determine adherence to dual contraception using depot-medroxyprogesterone acetate (DMPA) and condom among HIV-infected women. A cross-sectional study carried out from December 2013 to September 2014 at a local reference center, with application of questionnaire elaborated after Delphi panel and content validation to 114 HIV(+) women aged 15 to 49 years, using DMPA plus condom for contraception. Mean age was 33.2 ± 7.2 years, mean time since HIV detection was 8.1 ± 5.2 years, mean time of antiretroviral use was 6.8 ± 5 years and mean CD4 cells/mm3 count was 737.6 ± 341.1. Sexual HIV acquisition was reported by 98.2% (112/114), antiretroviral use by 85.9% (98/114), and 77.7% (84/114) had a CD4>500/mm3 count. Having a single sex partner was reported by 78.9% (90/114), with HIV serodiscordance in 41.2% (47/114) of couples, 21.9% did not know the serological status of their partner and in 37.7% of cases (43/114) the partner was unaware of the HIV(+) status of the woman. The last pregnancy was unplanned in 71.9% of cases (82/114) and 14.9% of the women had become pregnant the year before, with pregnancy being unplanned in 70.5% (12/17) of cases. Current use of DMPA was reported by 64.9% (74/114), with genital bleeding in 48.2% (55/114) and weight gain in 67.5% (77/114). Use of a male condom was reported by 62.2% of the subjects (71/114). Three reported that they always used a female condom and ten that they eventually used it. Unprotected vaginal sex was reported by 37.7% (43/114) and unprotected anal intercourse was reported by 32.4% (37/114). Partner resistance to use a condom occurred in 30.7% of cases (35/114). Dual contraception using DMPA with condom was reported by 42.9% (49/114). A partner who resisted wearing a condom was associated with poor adhesion (PR=0.3; 95%CI 0.2-0.7; p<0.001). A partner who was unaware that a woman was infected with HIV favored adherence (PR=1.8; 95%CI 1.2-2.7; p=0.013). The percentage of dual contraception using DMPA plus condom was 42.9%, maintaining unplanned pregnancies and unprotected sex. Resistance of partners to use a condom increased three times the chance of a woman not adhering to dual contraception, and the partner not knowing women's HIV infection almost doubled the chance to adhere to safe contraception. to offer new hormonal contraceptives and to involve the partners in contraception and serologic detection tests.

Bictegravir, Emtricitabine, and Tenofovir

MedlinePlus

... infection in adults who have not received antiretroviral treatment in the past and in certain adults who have been stable on other antiretroviral treatment(s) for at least 3 months. Bictegravir is in ...

Prevalence of oral candidiasis in HIV/AIDS children in highly active antiretroviral therapy era. A literature analysis.

PubMed

Gaitán-Cepeda, Luis Alberto; Sánchez-Vargas, Octavio; Castillo, Nydia

2015-08-01

SummaryHighly active antiretroviral therapy has decreased the morbidity and mortality related to HIV infection, including oral opportunistic infections. This paper offers an analysis of the scientific literature on the epidemiological aspects of oral candidiasis in HIV-positive children in the combination antiretroviral therapy era. An electronic databases search was made covering the highly active antiretroviral therapy era (1998 onwards). The terms used were oral lesions, oral candidiasis and their combination with highly active antiretroviral therapy and HIV/AIDS children. The following data were collected from each paper: year and country in which the investigation was conducted, antiretroviral treatment, oral candidiasis prevalence and diagnostic parameters (clinical or microbiological). Prevalence of oral candidiasis varied from 2.9% in American HIV-positive children undergoing highly active antiretroviral therapy to 88% in Chilean HIV-positive children without antiretroviral therapy. With respect to geographical location and antiretroviral treatment, higher oral candidiasis prevalence in HIV-positive children on combination antiretroviral therapy/antiretroviral therapy was reported in African children (79.1%) followed by 45.9% reported in Hindu children. In HIV-positive Chilean children on no antiretroviral therapy, high oral candidiasis prevalence was reported (88%) followed by Nigerian children (80%). Oral candidiasis is still frequent in HIV-positive children in the highly active antiretroviral therapy era irrespective of geographical location, race and use of antiretroviral therapy. © The Author(s) 2014.

Pediatric Admissions After Dental Care Under General Anesthesia: A Retrospective Study at a Tertiary Care Center.

PubMed

Lucy, Anna L; Gandhi, Roopa P; Gross, Lilyana; McNair, Bryan

2017-05-15

The purpose of this study was to identify factors associated with planned and unplanned pediatric hospital admissions following dental treatment under general anesthesia (DGA) in a tertiary care center. Dental and medical records of 100 subjects one to 20 years of age, with a known history of admission after DGA, were reviewed retrospectively for patient-, procedure-, and anesthesia-related factors as well as adverse events following DGA. During the review period (December 3, 2011 to June 30, 2015), 10,371 subjects underwent DGA, of which 100 subjects (less than one percent) required admission. A significant association was found between postoperative (PO) recovery time and unplanned admissions following DGA (P<0.001). Adverse post-operative events significantly associated with unplanned admissions included emesis (P=0.01) and hypoxia (P<0.001). Patients who were classified as having American Anesthesiology Association (ASA) III status were more frequently admitted following DGA. Adverse events such as emesis and hypoxia were significantly associated with patients with an unplanned admission.

Increased soluble vascular cell adhesion molecule-1 plasma levels and soluble intercellular adhesion molecule-1 during antiretroviral therapy interruption and retention of elevated soluble vascular cellular adhesion molecule-1 levels following resumption of antiretroviral therapy.

PubMed

Papasavvas, Emmanouil; Azzoni, Livio; Pistilli, Maxwell; Hancock, Aidan; Reynolds, Griffin; Gallo, Cecile; Ondercin, Joe; Kostman, Jay R; Mounzer, Karam; Shull, Jane; Montaner, Luis J

2008-06-19

We investigated the effect of short viremic episodes on soluble markers associated with endothelial stress and cardiovascular disease risk in chronically HIV-1-infected patients followed during continuous antiretroviral therapy, antiretroviral therapy interruption and antiretroviral therapy resumption. We assessed changes in plasma levels of von Willebrand factor, soluble vascular cell adhesion molecule-1 and intercellular adhesion molecule-1 by enzyme-linked immunosorbent assay, as well as T-cell activation (CD8+/CD38+, CD8+/HLA-DR+ and CD3+/CD95+) by flow cytometry, in 36 chronically HIV-1-infected patients participating in a randomized study. Patients were divided into the following three groups: a, on continuous antiretroviral therapy; b, on a 6-week antiretroviral therapy interruption; or c, on antiretroviral therapy interruption extended to the achievement of viral set point. Although all measurements remained stable over a 40-week follow-up on antiretroviral therapy, plasma levels of soluble vascular cell adhesion molecule-1 (P < 0.0001) and soluble intercellular adhesion molecule-1 (P = 0.003) increased during treatment interruption in correlation with viral rebound and T-cell activation. No significant changes in von Willebrand factor were observed in any of the groups. After resuming antiretroviral therapy, soluble vascular cell adhesion molecule-1 levels remained elevated even after achievement of viral suppression to less than 50 copies/ml. The prompt rise in plasma soluble vascular cell adhesion molecule-1 and soluble intercellular adhesion molecule-1 upon viral rebound suggests an acute increase in endothelial stress upon treatment interruption, which may persists after viral resuppression of virus. Thus, viral replication during short-term treatment interruption may increase the overall cardiovascular risk during and beyond treatment interruption.

Impact of HIV-1 subtype and antiretroviral therapy on protease and reverse transcriptase genotype: results of a global collaboration.

PubMed

Kantor, Rami; Katzenstein, David A; Efron, Brad; Carvalho, Ana Patricia; Wynhoven, Brian; Cane, Patricia; Clarke, John; Sirivichayakul, Sunee; Soares, Marcelo A; Snoeck, Joke; Pillay, Candice; Rudich, Hagit; Rodrigues, Rosangela; Holguin, Africa; Ariyoshi, Koya; Bouzas, Maria Belen; Cahn, Pedro; Sugiura, Wataru; Soriano, Vincent; Brigido, Luis F; Grossman, Zehava; Morris, Lynn; Vandamme, Anne-Mieke; Tanuri, Amilcar; Phanuphak, Praphan; Weber, Jonathan N; Pillay, Deenan; Harrigan, P Richard; Camacho, Ricardo; Schapiro, Jonathan M; Shafer, Robert W

2005-04-01

The genetic differences among HIV-1 subtypes may be critical to clinical management and drug resistance surveillance as antiretroviral treatment is expanded to regions of the world where diverse non-subtype-B viruses predominate. To assess the impact of HIV-1 subtype and antiretroviral treatment on the distribution of mutations in protease and reverse transcriptase, a binomial response model using subtype and treatment as explanatory variables was used to analyze a large compiled dataset of non-subtype-B HIV-1 sequences. Non-subtype-B sequences from 3,686 persons with well characterized antiretroviral treatment histories were analyzed in comparison to subtype B sequences from 4,769 persons. The non-subtype-B sequences included 461 with subtype A, 1,185 with C, 331 with D, 245 with F, 293 with G, 513 with CRF01_AE, and 618 with CRF02_AG. Each of the 55 known subtype B drug-resistance mutations occurred in at least one non-B isolate, and 44 (80%) of these mutations were significantly associated with antiretroviral treatment in at least one non-B subtype. Conversely, of 67 mutations found to be associated with antiretroviral therapy in at least one non-B subtype, 61 were also associated with antiretroviral therapy in subtype B isolates. Global surveillance and genotypic assessment of drug resistance should focus primarily on the known subtype B drug-resistance mutations.

Cost Determinants in the 90-Day Management of Isolated Ankle Fractures at a Large Urban Academic Hospital.

PubMed

Varacallo, Matthew; Mattern, Patrick; Acosta, Jonathan; Toossi, Nader; Denehy, Kevin; Harding, Susan

2018-05-03

To determine the independent risk factors associated with increasing costs and unplanned hospital readmissions in the 90-day episode of care (EOC) for isolated operative ankle fractures at our institution. Retrospective cohort study SETTING:: Level I Trauma Center PATIENTS:: Two hundred ninety-nine patients undergoing open reduction internal fixation (ORIF) for the treatment of an acute, isolated ankle fracture between 2010 and 2015. none MAIN OUTCOME MEASUREMENTS:: Independent risk factors for increasing 90-day EOC costs and unplanned hospital readmission rates. Orthopedic (64.9%) and podiatry (35.1%) patients were included. The mean index admission cost was $14,048.65 ± $5,797.48. Outpatient cases were significantly cheaper compared to inpatient cases ($10,164.22 ± $3,899.61 versus $15,942.55 ± $5,630.85, respectively, p < 0.001).Unplanned readmission rates were 5.4% (16/299) and 6.7% (20/299) at 30- and 90-days, respectively, and were often (13/20, 65.0%) due to surgical site infections. Independent risk factors for unplanned hospital readmissions included treatment by the podiatry service (p = 0.024), and an American Society of Anesthesiologists (ASA) score of ≥ 3 (p = 0.017). Risk factors for increasing total post discharge costs included treatment by the podiatry service (p = 0.011), and male gender (p = 0.046). Isolated operative ankle fractures are a prime target for EOC cost containment strategy protocols. Our institutional cost analysis study suggests that independent financial clinical risk factors in this treatment cohort includes podiatry as the treating surgical service and patients with an ASA score ≥ 3, with the former also independently increasing total post-discharge costs in the 90-day EOC. Outpatient procedures were associated with about a one-third reduction in total costs compared to the inpatient subgroup.

“We, the AIDS people. . .”: How Antiretroviral Therapy Enables Zimbabweans Living With HIV/AIDS to Cope With Stigma

PubMed Central

Skovdal, Morten; Madanhire, Claudius; Mugurungi, Owen; Gregson, Simon; Nyamukapa, Constance

2011-01-01

We studied the impact of antiretroviral treatment availability on HIV/AIDS stigma through interviews with 118 antiretroviral treatment users, HIV/AIDS caregivers, and nurses in Zimbabwe. Treatment enables positive social and economic participation through which users can begin to reconstruct their shattered sense of social value. However, stigma remains strong, and antiretroviral treatment users remain mired in conflictual symbolic relationships between the HIV/AIDS people and the untested. To date, the restoration of users' own sense of self-worth through treatment has not reduced fear and sexual embarrassment in framing community responses to people living with HIV/AIDS. Much remains to be learned about the complex interaction of economic and psychosocial dimensions of poverty, treatment availability, and conservative sexual moralities in driving HIV/AIDS stigma in specific settings. PMID:21164081

Audiological manifestations in HIV-positive adults.

PubMed

Matas, Carla Gentile; Angrisani, Rosanna Giaffredo; Magliaro, Fernanda Cristina Leite; Segurado, Aluisio Augusto Cotrim

2014-07-01

To characterize the findings of behavioral hearing assessment in HIV-positive individuals who received and did not receive antiretroviral treatment. This research was a cross-sectional study. The participants were 45 HIV-positive individuals (18 not exposed and 27 exposed to antiretroviral treatment) and 30 control-group individuals. All subjects completed an audiological evaluation through pure-tone audiometry, speech audiometry, and high-frequency audiometry. The hearing thresholds obtained by pure-tone audiometry were different between groups. The group that had received antiretroviral treatment had higher thresholds for the frequencies ranging from 250 to 3000 Hz compared with the control group and the group not exposed to treatment. In the range of frequencies from 4000 through 8000 Hz, the HIV-positive groups presented with higher thresholds than did the control group. The hearing thresholds determined by high-frequency audiometry were different between groups, with higher thresholds in the HIV-positive groups. HIV-positive individuals presented poorer results in pure-tone and high-frequency audiometry, suggesting impairment of the peripheral auditory pathway. Individuals who received antiretroviral treatment presented poorer results on both tests compared with individuals not exposed to antiretroviral treatment.

New strategies for lowering the costs of antiretroviral treatment and care for people with HIV/AIDS in the United Kingdom

PubMed Central

Gazzard, Brian; Moecklinghoff, Christiane; Hill, Andrew

2012-01-01

In the UK, the annual cost of treatment and care for people with human immunodeficiency virus (HIV)/acquired immune deficiency virus (AIDS) rose by over 600% from £104 million in 1997 to £762 million in 2010; approximately two-thirds of the £762 million cost of treatment and care in 2010 was for the procurement of antiretrovirals and other related drugs. The number of people accessing care for HIV/AIDS rose from 22,000 in 2000 to 65,000 in 2009. Adoption of “test and treat” guidelines for treating all HIV-infected people with antiretrovirals would further increase the burden of costs. Given the current economic situation, there is now a new focus on strategies for treatment and care of people with HIV-1 infection which can maintain efficacy but at a lower cost. In this review, we propose three strategies which could potentially lower the costs of treatment and care, ie, stopping testing CD4 counts for patients with full HIV RNA suppression on antiretroviral treatment and recent CD4 counts above 350 cells/μL; more widespread use of generic antiretrovirals as replacements for patients currently taking patented versions; and use of darunavir-ritonavir monotherapy as a switch option for patients with full HIV RNA suppression on other antiretrovirals and no history of virological failure. However, it is important that high standards of clinical care are maintained despite cost-saving measures. Antiretrovirals with generic alternatives may have toxicity issues, eg, zidovudine and nevirapine. There could be ethical issues in starting patients on these drugs if they are currently tolerating other treatments. The use of darunavir-ritonavir monotherapy is not consistently recommended in international HIV treatment guidelines. PMID:22888265

Broadening the use of antiretroviral therapy: the case for feline leukemia virus

PubMed Central

Greggs, Willie M; Clouser, Christine L; Patterson, Steven E; Mansky, Louis M

2011-01-01

Antiretroviral drugs have saved and extended the lives of millions of individuals infected with HIV. The major classes of anti-HIV drugs include reverse transcriptase inhibitors, protease inhibitors, integrase inhibitors, and entry/fusion inhibitors. While antiretroviral drug regimens are not commonly used to treat other types of retroviral infections, there are instances where there is a perceived need for re-evaluation of the benefits of antiretroviral therapy. One case in point is that of feline leukemia virus (FeLV), an infection of companion felines. While vaccines exist to prevent FeLV infection and spread, they have not eliminated FeLV infection. For FeLV-infected felines and their human companions, antiretroviral therapy would be desirable and of practical importance if good options were available. Here, we discuss FeLV biology and current treatment options, and propose that there is a need for antiretroviral treatment options for FeLV infection. The comparative use and analysis of antiretroviral therapy can provide new insights into the mechanism of antiretroviral drug action. PMID:21479142

Low-abundance HIV drug-resistant viral variants in treatment-experienced persons correlate with historical antiretroviral use.

PubMed

Le, Thuy; Chiarella, Jennifer; Simen, Birgitte B; Hanczaruk, Bozena; Egholm, Michael; Landry, Marie L; Dieckhaus, Kevin; Rosen, Marc I; Kozal, Michael J

2009-06-29

It is largely unknown how frequently low-abundance HIV drug-resistant variants at levels under limit of detection of conventional genotyping (<20% of quasi-species) are present in antiretroviral-experienced persons experiencing virologic failure. Further, the clinical implications of low-abundance drug-resistant variants at time of virologic failure are unknown. Plasma samples from 22 antiretroviral-experienced subjects collected at time of virologic failure (viral load 1380 to 304,000 copies/mL) were obtained from a specimen bank (from 2004-2007). The prevalence and profile of drug-resistant mutations were determined using Sanger sequencing and ultra-deep pyrosequencing. Genotypes were interpreted using Stanford HIV database algorithm. Antiretroviral treatment histories were obtained by chart review and correlated with drug-resistant mutations. Low-abundance drug-resistant mutations were detected in all 22 subjects by deep sequencing and only in 3 subjects by Sanger sequencing. In total they accounted for 90 of 247 mutations (36%) detected by deep sequencing; the majority of these (95%) were not detected by standard genotyping. A mean of 4 additional mutations per subject were detected by deep sequencing (p<0.0001, 95%CI: 2.85-5.53). The additional low-abundance drug-resistant mutations increased a subject's genotypic resistance to one or more antiretrovirals in 17 of 22 subjects (77%). When correlated with subjects' antiretroviral treatment histories, the additional low-abundance drug-resistant mutations correlated with the failing antiretroviral drugs in 21% subjects and correlated with historical antiretroviral use in 79% subjects (OR, 13.73; 95% CI, 2.5-74.3, p = 0.0016). Low-abundance HIV drug-resistant mutations in antiretroviral-experienced subjects at time of virologic failure can increase a subject's overall burden of resistance, yet commonly go unrecognized by conventional genotyping. The majority of unrecognized resistant mutations correlate with historical antiretroviral use. Ultra-deep sequencing can provide important historical resistance information for clinicians when planning subsequent antiretroviral regimens for highly treatment-experienced patients, particularly when their prior treatment histories and longitudinal genotypes are not available.

Low-Abundance HIV Drug-Resistant Viral Variants in Treatment-Experienced Persons Correlate with Historical Antiretroviral Use

PubMed Central

Le, Thuy; Chiarella, Jennifer; Simen, Birgitte B.; Hanczaruk, Bozena; Egholm, Michael; Landry, Marie L.; Dieckhaus, Kevin; Rosen, Marc I.; Kozal, Michael J.

2009-01-01

Background It is largely unknown how frequently low-abundance HIV drug-resistant variants at levels under limit of detection of conventional genotyping (<20% of quasi-species) are present in antiretroviral-experienced persons experiencing virologic failure. Further, the clinical implications of low-abundance drug-resistant variants at time of virologic failure are unknown. Methodology/Principal Findings Plasma samples from 22 antiretroviral-experienced subjects collected at time of virologic failure (viral load 1380 to 304,000 copies/mL) were obtained from a specimen bank (from 2004–2007). The prevalence and profile of drug-resistant mutations were determined using Sanger sequencing and ultra-deep pyrosequencing. Genotypes were interpreted using Stanford HIV database algorithm. Antiretroviral treatment histories were obtained by chart review and correlated with drug-resistant mutations. Low-abundance drug-resistant mutations were detected in all 22 subjects by deep sequencing and only in 3 subjects by Sanger sequencing. In total they accounted for 90 of 247 mutations (36%) detected by deep sequencing; the majority of these (95%) were not detected by standard genotyping. A mean of 4 additional mutations per subject were detected by deep sequencing (p<0.0001, 95%CI: 2.85–5.53). The additional low-abundance drug-resistant mutations increased a subject's genotypic resistance to one or more antiretrovirals in 17 of 22 subjects (77%). When correlated with subjects' antiretroviral treatment histories, the additional low-abundance drug-resistant mutations correlated with the failing antiretroviral drugs in 21% subjects and correlated with historical antiretroviral use in 79% subjects (OR, 13.73; 95% CI, 2.5–74.3, p = 0.0016). Conclusions/Significance Low-abundance HIV drug-resistant mutations in antiretroviral-experienced subjects at time of virologic failure can increase a subject's overall burden of resistance, yet commonly go unrecognized by conventional genotyping. The majority of unrecognized resistant mutations correlate with historical antiretroviral use. Ultra-deep sequencing can provide important historical resistance information for clinicians when planning subsequent antiretroviral regimens for highly treatment-experienced patients, particularly when their prior treatment histories and longitudinal genotypes are not available. PMID:19562031

Missed Opportunities along the Prevention of Mother-to-Child Transmission Services Cascade in South Africa: Uptake, Determinants, and Attributable Risk (the SAPMTCTE)

PubMed Central

Woldesenbet, Selamawit; Jackson, Debra; Lombard, Carl; Dinh, Thu-Ha; Puren, Adrian; Sherman, Gayle; Ramokolo, Vundli; Doherty, Tanya; Mogashoa, Mary; Bhardwaj, Sanjana; Chopra, Mickey; Shaffer, Nathan; Pillay, Yogan; Goga, Ameena

2015-01-01

Objectives We examined uptake of prevention of mother-to-child HIV transmission (PMTCT) services, predictors of missed opportunities, and infant HIV transmission attributable to missed opportunities along the PMTCT cascade across South Africa. Methods A cross-sectional survey was conducted among 4–8 week old infants receiving first immunisations in 580 nationally representative public health facilities in 2010. This included maternal interviews and testing infants’ dried blood spots for HIV. A weighted analysis was performed to assess uptake of antenatal and perinatal PMTCT services along the PMTCT cascade (namely: maternal HIV testing, CD4 count test/result, and receiving maternal and infant antiretroviral treatment) and predictors of dropout. The population attributable fraction associated with dropouts at each service point are estimated. Results Of 9,803 mothers included, 31.7% were HIV-positive as identified by reactive infant antibody tests. Of these 80.4% received some form of maternal and infant antiretroviral treatment. More than a third (34.9%) of mothers dropped out from one or more steps in the PMTCT service cascade. In a multivariable analysis, the following characteristics were associated with increased dropout from the PMTCT cascade: adolescent (<20 years) mothers, low socioeconomic score, low education level, primiparous mothers, delayed first antenatal visit, homebirth, and non-disclosure of HIV status. Adolescent mothers were twice (adjusted odds ratio: 2.2, 95% confidence interval: 1.5–3.3) as likely to be unaware of their HIV-positive status and had a significantly higher rate (85.2%) of unplanned pregnancies compared to adults aged ≥20 years (55.5%, p = 0.0001). A third (33.8%) of infant HIV infections were attributable to dropout in one or more steps in the cascade. Conclusion A third of transmissions attributable to missed opportunities of PMTCT services can be prevented by optimizing the uptake of PMTCT services. Identified risk factors for low PMTCT service uptake should be addressed through health facility and community-level interventions, including raising awareness, promoting women education, adolescent focused interventions, and strengthening linkages/referral-system between communities and health facilities. PMID:26147598

Impact of HIV-1 Subtype and Antiretroviral Therapy on Protease and Reverse Transcriptase Genotype: Results of a Global Collaboration

PubMed Central

Kantor, Rami; Katzenstein, David A; Efron, Brad; Carvalho, Ana Patricia; Wynhoven, Brian; Cane, Patricia; Clarke, John; Sirivichayakul, Sunee; Soares, Marcelo A; Snoeck, Joke; Pillay, Candice; Rudich, Hagit; Rodrigues, Rosangela; Holguin, Africa; Ariyoshi, Koya; Bouzas, Maria Belen; Cahn, Pedro; Sugiura, Wataru; Soriano, Vincent; Brigido, Luis F; Grossman, Zehava; Morris, Lynn; Vandamme, Anne-Mieke; Tanuri, Amilcar; Phanuphak, Praphan; Weber, Jonathan N; Pillay, Deenan; Harrigan, P. Richard; Camacho, Ricardo; Schapiro, Jonathan M; Shafer, Robert W

2005-01-01

Background The genetic differences among HIV-1 subtypes may be critical to clinical management and drug resistance surveillance as antiretroviral treatment is expanded to regions of the world where diverse non-subtype-B viruses predominate. Methods and Findings To assess the impact of HIV-1 subtype and antiretroviral treatment on the distribution of mutations in protease and reverse transcriptase, a binomial response model using subtype and treatment as explanatory variables was used to analyze a large compiled dataset of non-subtype-B HIV-1 sequences. Non-subtype-B sequences from 3,686 persons with well characterized antiretroviral treatment histories were analyzed in comparison to subtype B sequences from 4,769 persons. The non-subtype-B sequences included 461 with subtype A, 1,185 with C, 331 with D, 245 with F, 293 with G, 513 with CRF01_AE, and 618 with CRF02_AG. Each of the 55 known subtype B drug-resistance mutations occurred in at least one non-B isolate, and 44 (80%) of these mutations were significantly associated with antiretroviral treatment in at least one non-B subtype. Conversely, of 67 mutations found to be associated with antiretroviral therapy in at least one non-B subtype, 61 were also associated with antiretroviral therapy in subtype B isolates. Conclusion Global surveillance and genotypic assessment of drug resistance should focus primarily on the known subtype B drug-resistance mutations. PMID:15839752

New Antiretroviral Therapies for Pediatric HIV Infection

PubMed Central

Morris, Jennifer L.; Kraus, Donna M.

2005-01-01

Human immunodeficiency virus (HIV) infection and acquired immunodeficiency syndrome affect millions of children worldwide. The development of antiretroviral therapy has significantly improved the morbidity and mortality of pediatric patients infected with HIV. Currently, 4 classes of antiretroviral agents exist: nucleoside / nucleotide reverse transcriptase inhibitors, non-nucleoside reverse transcriptase inhibitors, protease inhibitors, and entry inhibitors. A total of 21 single-entity antiretroviral agents and 4 co-formulated antiretroviral products hold Food and Drug Administration (FDA) approval for treatment of HIV-1 infection. However, not all of these agents are indicated for use in patients less than 18 years of age. Since the year 2000, 7 new antiretroviral agents (atazanavir, emtricitabine, enfuvirtide, fosamprenavir, lopinavir/ritonavir, tenofovir, and tipranavir) have been approved by the FDA for use in adult patients as part of combination therapy for the treatment of HIV-1 infection. Although only 3 of these newer agents (emtricitabine, enfuvirtide, and lopinavir/ritonavir) are currently FDA approved for use in pediatric patients, pediatric clinical studies of the other 4 new agents are currently underway. The purpose of this article is to review these 7 new antiretroviral agents and describe their roles in the treatment of pediatric HIV infection. For each drug, the following information will be addressed: FDA-approved indication and age groups, clinical efficacy, pharmacokinetics, adverse drug reactions, clinically relevant drug interactions, pediatric and adult dosing, dosage forms, administration, and place in the treatment of pediatric HIV infection. PMID:23118639

Access to antiretroviral therapy among HIV/AIDS patients in Chiang Mai province, Thailand.

PubMed

Himakalasa, Woraluck; Grisurapong, Siriwan; Phuangsaichai, Sasipen

2013-01-01

The objective of this study is to investigate the access to antiretroviral treatment among human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) patients in Chiang Mai province, Thailand. Access to antiretroviral treatment is defined in terms of availability, affordability, and acceptability. The data for the study were collected during the period of April 1, 2012-May 31, 2012 from a sample of 380 HIV/AIDS patients in eight hospitals who had received antiretroviral treatment for more than 6 months at the time of data collection. The results of the study show that for most patients, the average traveling time to access health care was acceptable, but the nearly half day waiting time caused them to be absent from their work. In particular, it took longer for patients in the rural and lower income groups to access the treatment than the other groups. Their travel times and food costs relating to the treatment were found to be relatively high and therefore these patients had a higher tendency to borrow or seek financial assistance from their relatives. However, due to improvements in the access to treatment, most patients were satisfied with the services they received. The results imply that policy should be implemented to raise the potential of subdistrict hospitals where access to antiretroviral treatment is available, with participating HIV/AIDS patients acting as volunteers in providing services and other forms of health promotion to new patients. Privacy issues could be reduced if the antiretroviral treatment was isolated from other health services. Additionally, efforts to educate HIV/AIDS patients and society at large should be made.

Unresolved antiretroviral treatment management issues in HIV-infected children.

PubMed

Heidari, Shirin; Mofenson, Lynne M; Hobbs, Charlotte V; Cotton, Mark F; Marlink, Richard; Katabira, Elly

2012-02-01

Antiretroviral therapy in children has expanded dramatically in low-income and middle-income countries. The World Health Organization revised its pediatric HIV guidelines to recommend initiation of antiretroviral therapy in all HIV-infected children younger than 2 years, regardless of CD4 count or clinical stage. The number of children starting life-long antiretroviral therapy should therefore expand dramatically over time. The early initiation of antiretroviral therapy has indisputable benefits for children, but there is a paucity of definitive information on the potential adverse effects. In this review, a comprehensive literature search was conducted to provide an overview of our knowledge about the complications of treating pediatric HIV. Antiretroviral therapy in children, as in adults, is associated with enhanced survival, reduction in opportunistic infections, improved growth and neurocognitive function, and better quality of life. Despite antiretroviral therapy, HIV-infected children may continue to lag behind their uninfected peers in growth and development. In addition, epidemic concurrent conditions, such as tuberculosis, malaria, and malnutrition, can combine with HIV to yield more rapid disease progression and poor treatment outcomes. Additional studies are required to evaluate the long-term effects of antiretroviral therapy in HIV-infected infants, children, and adolescents, particularly in resource-limited countries where concomitant infections and conditions may enhance the risk of adverse effects. There is an urgent need to evaluate drug-drug interactions in children to determine optimal treatment regimens for both HIV and coinfections.

Completion of Gamma Knife radiosurgery for AVM treatment after unplanned interruption-technical note.

PubMed

Raman, Hari S; Santanam, Lakshmi; Vellimana, Ananth K; Drzymala, Robert E; Tsien, Christina I; Zipfel, Gregory J

2018-02-17

Gamma Knife radiosurgery is an established technique for non-urgent treatment of various intracranial pathologies. Intra-procedural dislodgement of the stereotactic frame is an uncommon occurrence that could lead to abortion of ongoing treatment and necessitate more invasive treatment strategies. In this case report, we describe a novel method for resumption of Gamma Knife treatment after an unplanned intra-procedural interruption. The case example involves a radiosurgical treatment of a Spetzler-Martin grade I arteriovenous malformation. Our technique involves integration of scans and coordinate systems from two imaging sessions using the composite isodose line to resolve translational differences, thereby limiting delivery of remaining shots to the untreated region of the lesion. MRI follow-up at 13 months showed a reduction in the nidus size with no evidence of any radiation injury to the surrounding brain parenchyma. We believe this technique will allow care teams to effectively salvage interrupted Gamma Knife procedures and reduce progression to more invasive treatment options.

Evolving treatment implementation among HIV-infected pregnant women and their partners: results from a national surveillance study in Italy, 2001-2015.

PubMed

Floridia, Marco; Frisina, Valentina; Ravizza, Marina; Marconi, Anna Maria; Pinnetti, Carmela; Cetin, Irene; Sansone, Matilde; Molinari, Atim; Cervi, Francesca; Meloni, Alessandra; Luzi, Kety; Masuelli, Giulia; Tamburrini, Enrica

2017-06-01

The current global and national indications for antiretroviral treatment (ART, usually triple combination therapy) in adolescent and adults, including pregnant women, recommend early ART before immunologic decline, pre-exposure chemoprophylaxis (PrEP), and treatment of HIV-negative partners in serodiscordant couples. There is limited information on the implementation of these recommendations among pregnant women with HIV and their partners. The present analysis was performed in 2016, using data from clinical records of pregnant women with HIV, followed between 2001 and 2015 at hospital or university clinics within a large, nationally representative Italian cohort study. The study period was divided in three intervals of five years each (2001-2005, 2006-2010, 2011-2015), and the analysis evaluated temporal trends in rates of HIV diagnosis in pregnancy, maternal antiretroviral treatment at conception, prevalence of HIV infection among partners of pregnant women with HIV, and proportion of seronegative and seropositive male partners receiving antiretroviral treatment. The analysis included 2755 pregnancies in women with HIV. During the three time intervals considered the rate of HIV diagnosis in pregnancy (overall 23.3%), and the distribution of HIV status among male partners (overall 48.7% HIV-negative, 28.6% HIV-positive and 22.8% unknown) remained substantially unchanged. Significant increases were observed in the proportion of women with HIV diagnosed before pregnancy who were on antiretroviral treatment at conception (from 62.0% in 2001-2005 to 81.3% in 2011-2015, P  < 0.001), and in the proportion of HIV-positive partners on antiretroviral treatment (from 73.3% in 2001-2005 to 95.8% in 2011-2015, P  = 0.002). Antiretroviral treatment was administered in 99.1% of the pregnancies that did not end early because of miscarriage, termination, or intrauterine death, and in 75.3% of those not ending in a live birth. No implementation of antiretroviral treatment was introduced among male HIV-negative partners. The results suggest good implementation of antiretroviral treatment among HIV-positive women and their HIV-positive partners, but no implementation, even in recent years, of Pre-Exposure Prophylaxis (PrEP) among uninfected male partners. Further studies should assess the determinants of this occurrence and clarify the attitudes and the potential barriers to PrEP use.

Postoperative Care Fragmentation and 30-Day Unplanned Readmissions After Head and Neck Cancer Surgery

PubMed Central

Graboyes, Evan M.; Kallogjeri, Dorina; Saeed, Mohammed J.; Olsen, Margaret A.; Nussenbaum, Brian

2017-01-01

Objectives Post-discharge care fragmentation, readmission to a hospital other than the one performing the surgery, hasn’t been described in head and neck cancer patients. We sought to determine the frequency, risk factors, and outcomes for head and neck cancer patients experiencing post-discharge care fragmentation. Design Retrospective cohort study Methods We analyzed patients in the 2008–2010 California State Inpatient Database with a 30-day unplanned readmission following head and neck cancer surgery. The frequency of post-discharge care fragmentation, patient- and hospital-level risk factors for care fragmentation, readmission diagnosis, and readmission outcomes were determined. Results Of 561 patients with a 30-day unplanned readmission, 210 (37.4%) were readmitted to a hospital other than the one performing the surgery. Surgical hospitalization length of stay ≥ 15 days (OR 1.87; 95% CI 1.13–3.10) and discharge to a care facility (OR 2.85; 95% CI 1.77–4.58) were associated with care fragmentation. Overall, 39.8% of unplanned 30-day readmissions (223/561) were treatment complications and 30.9% of treatment complication readmissions (69/223) occurred at a non-index hospital. Patients with post-discharge care fragmentation had a 2.1-fold increased risk of in-hospital mortality within 30 days of readmission compared to patients readmitted to the index hospital (95% CI 1.04–4.26). Conclusions Post-discharge care fragmentation following head and neck cancer surgery is common, as 37% of readmitted patients, and 31% of patients readmitted with a treatment complication, are readmitted to a hospital other than the surgical hospital. Head and neck cancer patients experiencing care fragmentation are at increased risk of in-hospital mortality within 30 days of readmission. PMID:27740687

Postoperative care fragmentation and thirty-day unplanned readmissions after head and neck cancer surgery.

PubMed

Graboyes, Evan M; Kallogjeri, Dorina; Saeed, Mohammed J; Olsen, Margaret A; Nussenbaum, Brian

2017-04-01

Postdischarge care fragmentation, readmission to a hospital other than the one performing the surgery, has not been described in head and neck cancer patients. We sought to determine the frequency, risk factors, and outcomes for head and neck cancer patients experiencing postdischarge care fragmentation. Retrospective cohort study. We analyzed patients in the 2008 to 2010 California State Inpatient Database with a 30-day unplanned readmission following head and neck cancer surgery. The frequency of postdischarge care fragmentation, patient- and hospital-level risk factors for care fragmentation, readmission diagnosis, and readmission outcomes were determined. Of 561 patients with a 30-day unplanned readmission, 210 (37.4%) were readmitted to a hospital other than the one performing the surgery. Surgical hospitalization length of stay ≥15 days (odds ratio [OR]: 1.87, 95% confidence interval [CI]: 1.13-3.10) and discharge to a care facility (OR: 2.85, 95% CI: 1.77-4.58) were associated with care fragmentation. Overall, 39.8% of unplanned 30-day readmissions (223/561) were treatment complications, and 30.9% of treatment complication readmissions (69/223) occurred at a nonindex hospital. Patients with postdischarge care fragmentation had a 2.1-fold increased risk of in-hospital mortality within 30 days of readmission compared to patients readmitted to the index hospital (95% CI: 1.04-4.26). Postdischarge care fragmentation following head an neck cancer surgery is common, as 37% of readmitted patients and 31% of patients readmitted with a treatment complication are readmitted to a hospital other than the surgical hospital. Head and neck cancer patients experiencing care fragmentation are at increased risk of in-hospital mortality within 30 days of readmission. 4. Laryngoscope, 127:868-874, 2017. © 2016 The American Laryngological, Rhinological and Otological Society, Inc.

HIV treatment as prevention: how scientific discovery occurred and translated rapidly into policy for the global response.

PubMed

Cohen, Myron S; Holmes, Charles; Padian, Nancy; Wolf, Megan; Hirnschall, Gottfried; Lo, Ying-Ru; Goosby, Eric

2012-07-01

In 2011 interim results of HIV Prevention Trials Network study 052, a National Institutes of Health study designed to test the effectiveness of antiretroviral treatment against the spread of HIV, were reported. These results showed that in a stable relationship in which one member of the couple was infected with HIV, treatment of the infected partner with antiretroviral drugs, combined with couples counseling and condom use, resulted in a 96 percent reduction in sexual transmission of HIV-1. This finding led to the use of antiretroviral treatment as a cornerstone of HIV prevention. Independent advisory committees of the President's Emergency Plan for AIDS Relief (PEPFAR) and the World Health Organization (WHO) have since issued analyses that set the stage for broader use of antiretroviral agents in treatment and prevention. This article describes the separate PEPFAR and WHO recommendations and outlines the design of prospective new trials to test how best to maximize the benefits of early treatment for prevention.

Associations between nutritional status, weight loss, radiotherapy treatment toxicity and treatment outcomes in gastrointestinal cancer patients.

PubMed

Hill, Amanda; Kiss, Nicole; Hodgson, Belinda; Crowe, Timothy C; Walsh, Adam D

2011-02-01

Patients with gastrointestinal cancers are susceptible to nutritional deterioration which may be compounded by radiotherapy treatment toxicities. This study aimed to determine whether nutritional status at radiotherapy commencement or changes in nutritional status throughout radiotherapy were associated with treatment toxicity and outcomes in gastrointestinal cancer patients. Seventy-three gastrointestinal cancer patients receiving curative radiotherapy underwent medical record audits assessing body weight, radiotherapy toxicity, unplanned treatment breaks or hospital admissions and completion of prescribed treatment/s. Nutritional status was assessed in a subset of patients (n = 11) using the Patient-Generated Subjective Global Assessment tool. Seventy-five percent of patients lost weight throughout radiotherapy. Weight loss was significantly greater in patients experiencing unplanned radiotherapy breaks (-3.1% vs -1.6%, p < 0.05) and in patients not completing prescribed chemotherapy (-3.3% vs -1.6%, p < 0.05). Toxicity severity was strongly correlated with Patient-Generated Subjective Global Assessment score (rho = 0.839, p < 0.001) and was increased in patients experiencing unplanned admissions compared to those without admission (42.1% vs 9.3% with grade 3 toxicity respectively, p < 0.001). Deterioration in nutritional status during radiotherapy (as measured by weight loss) may be associated with poorer short-term treatment outcomes in gastrointestinal cancer patients. Patient numbers were too small to definitively determine the effect of nutritional status at radiotherapy commencement or changes in nutritional status throughout radiotherapy (defined by PG-SGA) on treatment outcomes. Further research is required to investigate this in larger, longer-term studies. Copyright © 2010. Published by Elsevier Ltd.

HIV Treatment Produces Economic Returns Through Increased Work And Education, And Warrants Continued US Support

PubMed Central

Thirumurthy, Harsha; Galárraga, Omar; Larson, Bruce; Rosen, Sydney

2013-01-01

Federal expenditures are under scrutiny in the United States, and the merits of continuing and expanding the President’s Emergency Plan for AIDS Relief (PEPFAR) to support access to antiretroviral therapy have become a topic of debate. A growing body of research on the economic benefits of treatment with antiretroviral therapy has important implications for these discussions. For example, research conducted since the inception of PEPFAR shows that HIV-infected adults who receive antiretroviral therapy often begin or resume productive work, and that children living in households with infected adults who are on treatment are more likely to attend school than those in households with untreated adults. These benefits should be considered when weighing the overall benefits of providing antiretroviral therapy against its costs, particularly in the context of discussions about the future of PEPFAR. A modest case can also be made in favor of having private companies in HIV-affected countries provide antiretroviral therapy to their employees and dependents, thus sharing some of the burden of funding HIV treatment. PMID:22778336

Factors associated with healthy and unhealthy workplace eating behaviours in individuals with overweight/obesity with and without binge eating disorder

PubMed Central

Leung, S. L.; Barber, J. A.; Burger, A.

2018-01-01

Summary Objective Most Americans spend an average of 8 hours per day in the workplace. Current understanding of eating behaviours in the workplace and their association with overweight, obesity and binge eating disorder (BED) is limited. Workplace eating behaviours and weight‐related self‐efficacy were examined in a sample of 98 individuals with overweight or obesity, with or without BED. Design Participants completed the Weight Efficacy Lifestyle Questionnaire, Work and Social Adjustment Scale, Worker's Perception of Environmental Factors, and a Workplace Questionnaire. Results Eating unplanned food occurred on average 2.43 times per week (SD = 3.37), and eating unplanned food even when meals were brought from home occurred on average 1.28 times per week (SD = 1.84). Individuals with BED purchased lunch even when they brought food from home significantly more frequently than did individuals without BED. Those with BED also reported significantly poorer work and social adjustment related to binge eating as compared with those without BED. The most significant barriers to healthy eating in the workplace were coworker influence, eating more food in general and more junk food in response to stress, eating unplanned food at work and time constraints. Conclusions These factors may be important to target in weight‐loss treatment to increase individuals' weight loss success. As individuals with BED may be the most vulnerable to eating unplanned foods, clinicians may want to focus on this potential barrier in BED treatment. PMID:29670748

Factors associated with healthy and unhealthy workplace eating behaviours in individuals with overweight/obesity with and without binge eating disorder.

PubMed

Leung, S L; Barber, J A; Burger, A; Barnes, R D

2018-04-01

Most Americans spend an average of 8 hours per day in the workplace. Current understanding of eating behaviours in the workplace and their association with overweight, obesity and binge eating disorder (BED) is limited. Workplace eating behaviours and weight-related self-efficacy were examined in a sample of 98 individuals with overweight or obesity, with or without BED. Participants completed the Weight Efficacy Lifestyle Questionnaire, Work and Social Adjustment Scale, Worker's Perception of Environmental Factors, and a Workplace Questionnaire. Eating unplanned food occurred on average 2.43 times per week (SD = 3.37), and eating unplanned food even when meals were brought from home occurred on average 1.28 times per week (SD = 1.84). Individuals with BED purchased lunch even when they brought food from home significantly more frequently than did individuals without BED. Those with BED also reported significantly poorer work and social adjustment related to binge eating as compared with those without BED. The most significant barriers to healthy eating in the workplace were coworker influence, eating more food in general and more junk food in response to stress, eating unplanned food at work and time constraints. These factors may be important to target in weight-loss treatment to increase individuals' weight loss success. As individuals with BED may be the most vulnerable to eating unplanned foods, clinicians may want to focus on this potential barrier in BED treatment.

Access to antiretroviral therapy among HIV/AIDS patients in Chiang Mai province, Thailand

PubMed Central

Himakalasa, Woraluck; Grisurapong, Siriwan; Phuangsaichai, Sasipen

2013-01-01

The objective of this study is to investigate the access to antiretroviral treatment among human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) patients in Chiang Mai province, Thailand. Access to antiretroviral treatment is defined in terms of availability, affordability, and acceptability. The data for the study were collected during the period of April 1, 2012–May 31, 2012 from a sample of 380 HIV/AIDS patients in eight hospitals who had received antiretroviral treatment for more than 6 months at the time of data collection. The results of the study show that for most patients, the average traveling time to access health care was acceptable, but the nearly half day waiting time caused them to be absent from their work. In particular, it took longer for patients in the rural and lower income groups to access the treatment than the other groups. Their travel times and food costs relating to the treatment were found to be relatively high and therefore these patients had a higher tendency to borrow or seek financial assistance from their relatives. However, due to improvements in the access to treatment, most patients were satisfied with the services they received. The results imply that policy should be implemented to raise the potential of subdistrict hospitals where access to antiretroviral treatment is available, with participating HIV/AIDS patients acting as volunteers in providing services and other forms of health promotion to new patients. Privacy issues could be reduced if the antiretroviral treatment was isolated from other health services. Additionally, efforts to educate HIV/AIDS patients and society at large should be made. PMID:23986652

HIV-1 disease progression during highly active antiretroviral therapy: an application using population-level data in British Columbia: 1996-2011.

PubMed

Nosyk, Bohdan; Min, Jeong; Lima, Viviane D; Yip, Benita; Hogg, Robert S; Montaner, Julio S G

2013-08-15

Accurately estimating rates of disease progression is of central importance in developing mathematical models used to project outcomes and guide resource allocation decisions. Our objective was to specify a multivariate regression model to estimate changes in disease progression among individuals on highly active antiretroviral treatment in British Columbia, Canada, 1996-2011. We used population-level data on disease progression and antiretroviral treatment utilization from the BC HIV Drug Treatment Program. Disease progression was captured using longitudinal CD4 and plasma viral load testing data, linked with data on antiretroviral treatment. The study outcome was categorized into (CD4 count ≥ 500, 500-350, 350-200, <200 cells/mm, and mortality). A 5-state continuous-time Markov model was used to estimate covariate-specific probabilities of CD4 progression, focusing on temporal changes during the study period. A total of 210,083 CD4 measurements among 7421 individuals with HIV/AIDS were included in the study. Results of the multivariate model suggested that current highly active antiretroviral treatment at baseline, lower baseline CD4 (<200 cells/mm), and extended durations of elevated plasma viral load were each associated with accelerated progression. Immunological improvement was accelerated significantly from 2004 onward, with 23% and 46% increases in the probability of CD4 improvement from the fourth CD4 stratum (CD4 < 200) in 2004-2008 and 2008-2011, respectively. Our results demonstrate the impact of innovations in antiretroviral treatment and treatment delivery at the population level. These results can be used to estimate a transition probability matrix flexible to changes in the observed mix of clients in different clinical stages and treatment regimens over time.

[Antiretroviral therapy for HIV-infected patients with schizophrenia. Coordinated multidisciplinary management (7 cases)].

PubMed

Leclerc, Stéphanie; Brunschwig, Olivier; Berki-Benhaddad, Zhora; Soyris, Dominique; Grataud, Christian; Breton, Guillaume; Leport, Catherine; Vildé, Jean-Louis

2005-03-26

Schizophrenia might appear to be an obstacle to the initiation of and especially compliance with antiretroviral therapy for HIV-infected patients. The aims of this study were to describe the clinical, immunologic and virologic course after initiation of antiretroviral therapy in 7 HIV patients with schizophrenia (according to DSM-IV-R criteria), and to analyse the possibilities of an adequate antiretroviral therapy for those patients. Multidisciplinary management by specialists in infectious diseases, addiction-related disorders, treatment adherence and compliance, and psychiatrists, as well as social workers, home care agencies, and patient advocacy and assistance groups, was organized with coordinated medical-psychiatric follow-up at least once a month. The patients, 6 men and 1 woman, were aged from 26 to 48 years; schizophrenia had been diagnosed in 5 patients 6 months to 20 years before the HIV infection was discovered; diagnoses of both diseases were essentially simultaneous for the other 2. All patients took long-term neuroleptics for their schizophrenia. Two were active drug addicts who received drug substitution treatment. Before antiretroviral treatment began, 6 patients had advanced infection: stage C with peak CD4 cell counts ranging from 6 to 70/mm3; they began treatment with protease inhibitors between May 1996 and August 1997. The seventh patient was first seen during primary HIV infection in July 1998, and treatment began then. Response to antiretroviral treatment with protease inhibitors was slow for all patients, but viral load became undetectable for 6 of the 7, after 5 months to 4 years; 3 had opportunistic infections. Follow-up ended in January 2002: 5 patients still had undetectable viral loads,, with CD4 cell counts ranging from 45 to 1 000/mm3. One patient died from mixed terminal cirrhosis (alcohol abuse and hepatitis C); the viral load in another was only partially controlled (10 000 copies/ml), because of poor treatment adherence. Individuals with schizophrenia can respond well to antiretroviral treatment, although response may appear slow; they can adhere to complex treatment regimens as long as they receive well coordinated and sustained multidisciplinary support.

78 FR 33848 - Draft Guidance for Industry on Human Immunodeficiency Virus-1 Infection: Developing...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-06-05

...] Draft Guidance for Industry on Human Immunodeficiency Virus-1 Infection: Developing Antiretroviral Drugs... entitled ``Human Immunodeficiency Virus-1 Infection: Developing Antiretroviral Drugs for Treatment.'' The... guidance for industry entitled ``Human Immunodeficiency Virus-1 Infection: Developing Antiretroviral Drugs...

Quality of Life Among HIV-Infected Patients in Brazil after Initiation of Treatment

PubMed Central

Campos, Lorenza Nogueira; César, Cibele Comini; Guimarães, Mark Drew Crosland

2009-01-01

INTRODUCTION Despite improvement in clinical treatment for HIV-infected patients, the impact of antiretroviral therapy on the overall quality of life has become a major concern. OBJECTIVE To identify factors associated with increased levels of self-reported quality of life among HIV-infected patients after four months of antiretroviral therapy. METHODS Patients were recruited at two public health referral centers for AIDS, Belo Horizonte, Brazil, for a prospective adherence study. Patients were interviewed before initiating treatment (baseline) and after one and four months. Quality of life was assessed using a psychometric instrument, and factors associated with good/very good quality of life four months after the initiation of antiretroviral therapy were assessed using a cross-sectional approach. Logistic regression was used for analysis. RESULTS Overall quality of life was classified as ‘very good/good’ by 66.4% of the participants four months after initiating treatment, while 33.6% classified it as ‘neither poor nor good/poor/very poor’. Logistic regression indicated that >8 years of education, none/mild symptoms of anxiety and depression, no antiretroviral switch, lower number of adverse reactions and better quality of life at baseline were independently associated with good/very good quality of life over four months of treatment. CONCLUSIONS Our results highlight the importance of modifiable factors such as psychiatric symptoms and treatment-related variables that may contribute to a better quality of life among patients initiating treatment. Considering that poor quality of life is related to non-adherence to antiretroviral therapy, careful clinical monitoring of these factors may contribute to ensuring the long-term effectiveness of antiretroviral regimens. PMID:19759880

Supervision, monitoring and evaluation of nationwide scale-up of antiretroviral therapy in Malawi.

PubMed Central

Libamba, Edwin; Makombe, Simon; Mhango, Eustice; de Ascurra Teck, Olga; Limbambala, Eddie; Schouten, Erik J.; Harries, Anthony D.

2006-01-01

OBJECTIVE: To describe the supervision, monitoring and evaluation strategies used to assess the delivery of antiretroviral therapy during nationwide scale-up of treatment in Malawi. METHODS: In the first quarter of 2005, the HIV Unit of the Ministry of Health and its partners (the Lighthouse Clinic; Médecins Sans Frontières-Belgium, Thyolo district; and WHO's Country Office) undertook structured supervision and monitoring of all public sector health facilities in Malawi delivering antiretroviral therapy. FINDINGS: Data monitoring showed that by the end of 2004, there were 13,183 patients (5274 (40%) male, 12 527 (95%) adults) who had ever started antiretroviral therapy. Of patients who had ever started, 82% (10 761/13,183) were alive and taking antiretrovirals; 8% (1026/13,183) were dead; 8% (1039/13,183) had been lost to follow up; <1% (106/13,183) had stopped treatment; and 2% (251/13,183) had transferred to another facility. Of those alive and on antiretrovirals, 98% (7098/7258) were ambulatory; 85% (6174/7258) were fit to work; 10% (456/4687) had significant side effects; and, based on pill counts, 96% (6824/7114) had taken their treatment correctly. Mistakes in the registration and monitoring of patients were identified and corrected. Drug stocks were checked, and one potential drug stock-out was averted. As a result of the supervisory visits, by the end of March 2005 recruitment of patients to facilities scheduled to start delivering antiretroviral therapy had increased. CONCLUSION: This report demonstrates the importance of early supervision for sites that are starting to deliver antiretroviral therapy, and it shows the value of combining data collection with supervision. Making regular supervisory and monitoring visits to delivery sites are essential for tracking the national scale-up of delivery of antiretrovirals. PMID:16628306

Cost-effectiveness of Newer Antiretroviral Drugs in Treatment-Experienced Patients with Multi-drug Resistant HIV Disease

PubMed Central

Bayoumi, Ahmed M.; Barnett, Paul G.; Joyce, Vilija R.; Griffin, Susan C.; Sun, Huiying; Bansback, Nick J.; Holodniy, Mark; Sanders, Gillian; Brown, Sheldon T.; Kyriakides, Tassos C.; Angus, Brian; Cameron, D. William; Anis, Aslam H.; Sculpher, Mark; Owens, Douglas K.

2014-01-01

Objective Newer antiretroviral drugs provide substantial benefits but are expensive. We determined the cost-effectiveness of using antiretroviral drugs in combination for patients with multi-drug resistant HIV disease. Design We built a cohort state-transition model representing treatment-experienced patients with low CD4 counts, high viral load levels, and multi-drug resistant virus. We estimated the effectiveness of newer drugs (those approved in 2005 or later) from published randomized trials. We estimated other parameters from a randomized trial and from the literature. The model had a lifetime time horizon and used the perspective of an ideal insurer in the United States. The interventions were combination antiretroviral therapy, consisting of two newer drugs and one conventional drug, compared to three conventional drugs. Outcome measures were life-years, quality-adjusted life-years (QALYs), costs, and incremental cost-effectiveness. Results Substituting newer antiretroviral drugs increased expected survival by 3.9 years in advanced HIV disease. The incremental cost-effectiveness ratio of newer, compared to conventional, antiretroviral drugs was $75,556/QALY gained. Sensitivity analyses showed that substituting only one newer antiretroviral drug cost $54,559 to $68,732/QALY, depending on assumptions about efficacy. Substituting three newer drugs cost $105,956 to $117,477/QALY. Cost-effectiveness ratios were higher if conventional drugs were not discontinued. Conclusions In treatment-experienced patients with advanced HIV disease, use of newer antiretroviral agents can be cost effective, given a cost-effectiveness threshold in the range of $50,000 to $75,000 per QALY gained. Newer antiretroviral agents should be used in carefully selected patients for whom less expensive options are clearly inferior. PMID:24129369

Treatment outcomes of patients on antiretrovirals after six months of treatment, Khami Clinic, Bulawayo, Zimbabwe.

PubMed

Ncube, R T; Hwalima, Z; Tshimanga, M; Chirenda, J; Mabaera, B; Apollo, T

2008-01-01

To describe treatment outcomes of patients on anti-retrovirals at six months of treatment. We conducted pre-intervention post intervention surveys using a pretest-post test design. Khami Municipal Clinic, Bulawayo. We interviewed consecutive patients eligible to receive antiretroviral drugs (ARVs). All patients had a history of TB treatment and a CD4 count less than 200 cells/mm. Mean change in CD4 count, weight, body mass index, and Karnofsky performance measured before and at six months ofantiretroviral treatment. 72 subjects were interviewed at baseline, their median age was 38 years (Q1, 32 years, Q3, 43 years). Of these, 17 (24%) died before six months of treatment. Three (4%) defaulted treatment follow up. A total of 52 respondents were alive and interviewed at six months though only 50, had repeat CD4 counts at six months. Among the 50 survivors, the mean CD4 count at six months was significantly higher than at baseline (p = 0.0003). There was a 4.2 point statistical significant increase in the mean weight from baseline (p = 0.0005). Similarly, the mean Body Mass Index (BMI) significantly increased by 1.5 kg/m2 from baseline, (p = 0.001). The mean Karnofsky performance increased from 89% at baseline to 95% at six months (p = 0004). The researchers noted that patients on TB treatment were being deferred antiretroviral therapy until they completed TB treatment. The Khami project bears testimony that even in a resource poor setting; treatment of HIV/AIDS with antiretroviral drugs is feasible. We recommend early treatment initiation for those on TB treatment in line with national guidelines.

Low levels of antiretroviral-resistant HIV infection in a routine clinic in Cameroon that uses the World Health Organization (WHO) public health approach to monitor antiretroviral treatment and adequacy with the WHO recommendation for second-line treatment.

PubMed

Kouanfack, Charles; Montavon, Celine; Laurent, Christian; Aghokeng, Avelin; Kenfack, Alain; Bourgeois, Anke; Koulla-Shiro, Sinata; Mpoudi-Ngole, Eitel; Peeters, Martine; Delaporte, Eric

2009-05-01

A cross-sectional study, performed at a routine human immunodeficiency virus (HIV)/AIDS clinic in Cameroon that uses the World Health Organization public health approach, showed low rates of virological failure and drug resistance at 12 and 24 months after initiation of antiretroviral therapy. Importantly, the cross-sectional study also showed that the World Health Organization recommendation for second-line treatment would be effective in almost all patients with HIV drug resistance mutations.

Unplanned pregnancy: does past experience influence the use of a contraceptive method?

PubMed

Matteson, Kristen A; Peipert, Jeffrey F; Allsworth, Jenifer; Phipps, Maureen G; Redding, Colleen A

2006-01-01

To investigate whether women between the ages of 14 and 25 years with a past unplanned pregnancy were more likely to use a contraceptive method compared with women without a history of unplanned pregnancy. We analyzed baseline data of 424 nonpregnant women between the ages of 14 and 25 years enrolled in a randomized trial to prevent sexually transmitted diseases and unplanned pregnancy (Project PROTECT). Women at high risk for sexually transmitted diseases or unplanned pregnancy were included. Participants completed a demographic, substance use, and reproductive health questionnaire. We compared women with and without a history of unplanned pregnancy using bivariate analysis and log binomial regression. The prevalence of past unplanned pregnancy in this sample was 43%. Women reporting an unplanned pregnancy were older, and had less education, and were more likely to be nonwhite race or ethnicity. History of an unplanned pregnancy was not associated with usage of a contraceptive method (relative risk 1.01, 95% confidence interval 0.87-1.16) in bivariate analysis or when potential confounders were accounted for in the analysis (adjusted relative risk 1.10, 95% confidence interval 0.95-1.28). Several factors were associated with both unplanned pregnancy and overall contraceptive method use in this population. However, a past unplanned pregnancy was not associated with overall contraceptive method usage. Future studies are necessary to investigate the complex relationship between unplanned pregnancy and contraceptive method use. II-2.

Impact of a supportive care service for cancer outpatients: management and reduction of hospitalizations. Preliminary results of an integrated model of care.

PubMed

Antonuzzo, A; Vasile, E; Sbrana, A; Lucchesi, M; Galli, L; Brunetti, I M; Musettini, G; Farnesi, A; Biasco, E; Virgili, N; Falcone, A; Ricci, S

2017-01-01

Supportive care in oncology is a primary need for every oncology department nowadays. In 2012, in our institution, a dedicated supportive care service (SCS) was created in order to deal with any need our on-treatment patients might have (e.g. tumour-related or treatment-related symptoms). We hypothesized that this service had a positive impact on the number of unplanned hospitalizations; to confirm our hypothesis, we decided to review admission data in 2011 and 2012. Using our internal software, we compared admission data in 2011 (that is, the year before the dedicated service was created) and 2012 (when such service began, that is April of that year). We also made an evaluation of the costs of these hospitalizations. Despite an increase of the number of patients treated in our day hospital (+6.5 %), the number of unplanned hospital admissions decreased by 3.2 % (from 17.3 to 14.1 %). The number of patients accessing to emergency room went from 66 to 61 % (a reduction of 5 %). The costs of these hospitalizations were reduced by 2.2 %. The introduction of the dedicated SCS in our oncology department caused a net reduction by 3.2 % of the number of unplanned hospitalizations of on-treatment cancer patients.

[Antiretroviral treatment for HIV infection. Where we are and where we are going?].

PubMed

Sierra-Madero, Juan G; Franco-San-Sebastián, Dennise

2004-01-01

Antiretroviral treatment for HIV infection has evolved importantly during the last few years. Eradication of HIV is currently not a realistic target of antiretroviral therapy; however, long term virologic control is possible with current antiviral combinations in the majority of patients. This has resulted in a dramatic reduction in complications and mortality associated with AIDS, even though significant challenges remain. Some of them are the limited access to antiretroviral drugs that exist in most of the affected countries because of the elevated costs of the drugs, the high level of adherence needed for efficacy and the short term and long term toxicity. It is important that antiretroviral access programs financed with public funds consider the following points in their design: specialized prescription that optimizes the use of these resources, integration of prevention to care, evaluation of costs in a global perspective, and integration of research with medical care.

The (political) economics of antiretroviral treatment in developing countries.

PubMed

Nattrass, Nicoli J

2008-12-01

Despite unprecedented international mobilisation to support universal provision of highly active antiretroviral therapy (HAART), national governments continue to play the key role in determining access to treatment. Whereas some AIDS-affected countries have performed as well as or better than expected given their level of development, institutional characteristics and demographic challenges (e.g. Thailand and Brazil), others (notably South Africa) have not. This article argues that the 'economics' of antiretroviral drug delivery is at heart a political-economy of access to treatment. It depends on commitment on the part of national governments to negotiate with pharmaceutical companies over patented antiretroviral drug prices, on their policy towards compulsory licensing, and on the approach they adopt to delivering HAART. Civil society has an important role to play in encouraging governments to become, and remain, committed to taking action to ensure sustainable and widespread access to HAART.

HIV drug resistance early warning indicators in cohorts of individuals starting antiretroviral therapy between 2004 and 2009: World Health Organization global report from 50 countries.

PubMed

Bennett, Diane E; Jordan, Michael R; Bertagnolio, Silvia; Hong, Steven Y; Ravasi, Giovanni; McMahon, James H; Saadani, Ahmed; Kelley, Karen F

2012-05-01

The World Health Organization developed a set of human immunodeficiency virus drug resistance (HIVDR) early warning indicators (EWIs) to assess antiretroviral therapy clinic and program factors associated with HIVDR. EWIs are monitored by abstracting data routinely recorded in clinical records, and the results enable clinics and program managers to identify problems that should be addressed to minimize preventable emergence of HIVDR in clinic populations. As of June 2011, 50 countries monitored EWIs, covering 131 686 patients initiating antiretroviral treatment between 2004 and 2009 at 2107 clinics. HIVDR prevention is associated with patient care (appropriate prescribing and patient monitoring), patient behavior (adherence), and clinic/program management efforts to reduce treatment interruptions (follow up, retention on first-line ART, procurement and supply management of antiretroviral drugs). EWIs measure these factors and the results have been used to optimize patient and population treatment outcomes.

[Efficacy of antiretroviral therapy and influencing factors for people living with HIV/AIDS in designated hospitals in Harbin].

PubMed

Zhao, P Y; Yu, X; Yang, K; Feng, S Y; Wang, F X; Wang, B Y

2016-05-01

To understand the efficacy of antiretroviral therapy for people living with HIV/AIDS and influencing factors; and provide evidence to improve the treatment of HIV infection and AIDS for the better life of the patients. A cross sectional study was conducted in designated AIDS hospitals in Harbin. A questionnaire was used to collect the information of the patients receiving treatment in these hospitals. The statistical analysis was done with software SAS 9.2 and Excel 2010. Univariate analysis was performed with t test and multivariate analysis was performed with ordinal logistic regression model. Wilcoxon ranks sum test was conducted to compare the CD4(+) T lymphocyte counts. The number of the patients receiving antiretroviral therapy was in increase in recent years. The HIV infection route was mainly homosexual contact. The CD4(+)T lymphocyte count of the patients increased at different levels after ≥6 months treatment(P<0.01). Household income(P<0.05), adherence to treatment plan or not(P<0.05), social relationship(P< 0.05), concern of economic cost(P<0.01)medication compliance(P<0.01)and initial level of CD4(+) T lymphocyte(P<0.01)were the influencing factors for antiretroviral therapy efficacy. In designated hospitals in Harbin, the number of the patients receiving HIV antiretroviral therapy kept to increase and the efficacy of the treatment was obvious.

Strategies for Living with the Challenges of HIV and Antiretroviral Use in Zambia

ERIC Educational Resources Information Center

Jones, Deborah; Zulu, Isaac; Mumbi, Miriam; Chitalu, Ndashi; Vamos, Szonja; Gomez, Jacqueline; Weiss, Stephen M.

2009-01-01

This study sought to identify strategies for living with the challenges of HIV and antiretroviral (ARV) use among new medication users in urban Zambia. Participants (n = 160) were recruited from urban Lusaka, Zambia. Qualitative Data was drawn from monthly ARV treatment education intervention groups addressing HIV and antiretroviral use. Themes…

Direct treatment costs of HIV/AIDS in Portugal.

PubMed

Perelman, Julian; Alves, Joana; Miranda, Ana Cláudia; Mateus, Céu; Mansinho, Kamal; Antunes, Francisco; Oliveira, Joaquim; Poças, José; Doroana, Manuela; Marques, Rui; Teófilo, Eugénio; Pereira, João

2013-10-01

To analyze the direct medical costs of HIV/AIDS in Portugal from the perspective of the National Health Service. A retrospective analysis of medical records was conducted for 150 patients from five specialized centers in Portugal in 2008. Data on utilization of medical resources during 12 months and patients' characteristics were collected. A unit cost was applied to each care component using official sources and accounting data from National Health Service hospitals. The average cost of treatment was 14,277 €/patient/year. The main cost-driver was antiretroviral treatment (€ 9,598), followed by hospitalization costs (€ 1,323). Treatment costs increased with the severity of disease from € 11,901 (> 500 CD4 cells/µl) to € 23,351 (CD4 count ≤ 50 cells/ µl). Cost progression was mainly due to the increase in hospitalization costs, while antiretroviral treatment costs remained stable over disease stages. The high burden related to antiretroviral treatment is counterbalanced by relatively low hospitalization costs, which, however, increase with severity of disease. The relatively modest progression of total costs highlights that alternative public health strategies that do not affect transmission of disease may only have a limited impact on expenditure, since treatment costs are largely dominated by constant antiretroviral treatment costs.

Five Antiretroviral Drug Class-Resistant HIV-1 in a Treatment-Naïve Patient Successfully Suppressed with Optimized Antiretroviral Drug Selection.

PubMed

Volpe, Joseph M; Ward, Douglas J; Napolitano, Laura; Phung, Pham; Toma, Jonathan; Solberg, Owen; Petropoulos, Christos J; Walworth, Charles M

2015-01-01

Transmitted HIV-1 exhibiting reduced susceptibility to protease and reverse transcriptase inhibitors is well documented but limited for integrase inhibitors and enfuvirtide. We describe here a case of transmitted 5 drug class-resistance in an antiretroviral (ARV)-naïve patient who was successfully treated based on the optimized selection of an active ARV drug regimen. The value of baseline resistance testing to determine an optimal ARV treatment regimen is highlighted in this case report. © The Author(s) 2015.

Unplanned readmission after hospital discharge in burn patients in Iran.

PubMed

Jafaryparvar, Zakiyeh; Adib, Masoomeh; Ghanbari, Atefeh; Leyli, Ehsan Kazemnezhad

2018-02-21

Burns are considered as one of the most serious health problems throughout the world. They may lead to adverse consequences and outcomes. One of these outcomes is unplanned readmission. Unplanned readmission has been commonly used as a quality indicator by hospitals and governments. This study aimed to determine the predictors of unplanned readmission in patients with burns hospitalized in a burn center in the North of Iran (Guilan province, Rasht). This retrospective analytic study has been done on the medical records of hospitalized patients with burns in Velayat Sub-Specialty Burn and Plastic Surgery Center, Rasht, Iran during 2008-2013. In general, 703 medical records have been reviewed but statistical analysis was performed on 626 medical records. All data were entered in SPSS (version 16) and analyzed by descriptive and inferential statistics. Among 626 patients with burns, the overall readmission rate was 5.1%. Predictors of readmission included total body surface area (OR 1.030, CI 1.011-1.049), hypertension (OR 2.923, CI 1.089-7.845) and skin graft (OR 7.045, CI 2.718-18.258). Considering the outcome, predictors following burn have a crucial role in the allocation of treatment cost for patients with burns and they can be used as one of the quality indicators for health care providers and governments.

Calculation of Direct Antiretroviral Treatment Costs and Potential Cost Savings by Using Generics in the German HIV ClinSurv Cohort

PubMed Central

Stoll, Matthias; Kollan, Christian; Bergmann, Frank; Bogner, Johannes; Faetkenheuer, Gerd; Fritzsche, Carlos; Hoeper, Kirsten; Horst, Heinz-August; van Lunzen, Jan; Plettenberg, Andreas; Reuter, Stefan; Rockstroh, Jürgen; Stellbrink, Hans-Jürgen; Hamouda, Osamah; Bartmeyer, Barbara

2011-01-01

Background/Aim of the Study The study aimed to determine the cost impacts of antiretroviral drugs by analysing a long-term follow-up of direct costs for combined antiretroviral therapy, cART,-regimens in the nationwide long-term observational multi-centre German HIV ClinSurv Cohort. The second aim was to develop potential cost saving strategies by modelling different treatment scenarios. Methods Antiretroviral regimens (ART) from 10,190 HIV-infected patients from 11 participating ClinSurv study centres have been investigated since 1996. Biannual data cART,-initiation, cART-changes, surrogate markers, clinical events and the Centre of Disease Control- (CDC)-stage of HIV disease are reported. Treatment duration was calculated on a daily basis via the documented dates for the beginning and end of each antiretroviral drug treatment. Prices were calculated for each individual regimen based on actual office sales prices of the branded pharmaceuticals distributed by the license holder including German taxes. Results During the 13-year follow-up period, 21,387,427 treatment days were covered. Cumulative direct costs for antiretroviral drugs of €812,877,356 were determined according to an average of €42.08 per day (€7.52 to € 217.70). Since cART is widely used in Germany, the costs for an entire regimen increased by 13.5%. Regimens are more expensive in the advanced stages of HIV disease. The potential for cost savings was calculated using non-nucleotide-reverse-transcriptase-inhibitor, NNRTI, more frequently instead of ritonavir-boosted protease inhibitor, PI/r, in first line therapy. This calculation revealed cumulative savings of 10.9% to 19.8% of daily treatment costs (50% and 90% substitution of PI/r, respectively). Substituting certain branded drugs by generic drugs showed potential cost savings of between 1.6% and 31.8%. Conclusions Analysis of the data of this nationwide study reflects disease-specific health services research and will give insights into the cost impacts of antiretroviral therapy, and might allow a more rational allocation of resources within the German health care system. PMID:21931626

Calculation of direct antiretroviral treatment costs and potential cost savings by using generics in the German HIV ClinSurv cohort.

PubMed

Stoll, Matthias; Kollan, Christian; Bergmann, Frank; Bogner, Johannes; Faetkenheuer, Gerd; Fritzsche, Carlos; Hoeper, Kirsten; Horst, Heinz-August; van Lunzen, Jan; Plettenberg, Andreas; Reuter, Stefan; Rockstroh, Jürgen; Stellbrink, Hans-Jürgen; Hamouda, Osamah; Bartmeyer, Barbara

2011-01-01

BACKGROUND/AIM OF THE STUDY: The study aimed to determine the cost impacts of antiretroviral drugs by analysing a long-term follow-up of direct costs for combined antiretroviral therapy, cART, -regimens in the nationwide long-term observational multi-centre German HIV ClinSurv Cohort. The second aim was to develop potential cost saving strategies by modelling different treatment scenarios. Antiretroviral regimens (ART) from 10,190 HIV-infected patients from 11 participating ClinSurv study centres have been investigated since 1996. Biannual data cART-initiation, cART-changes, surrogate markers, clinical events and the Centre of Disease Control- (CDC)-stage of HIV disease are reported. Treatment duration was calculated on a daily basis via the documented dates for the beginning and end of each antiretroviral drug treatment. Prices were calculated for each individual regimen based on actual office sales prices of the branded pharmaceuticals distributed by the license holder including German taxes. During the 13-year follow-up period, 21,387,427 treatment days were covered. Cumulative direct costs for antiretroviral drugs of €812,877,356 were determined according to an average of €42.08 per day (€7.52 to € 217.70). Since cART is widely used in Germany, the costs for an entire regimen increased by 13.5%. Regimens are more expensive in the advanced stages of HIV disease. The potential for cost savings was calculated using non-nucleotide-reverse-transcriptase-inhibitor, NNRTI, more frequently instead of ritonavir-boosted protease inhibitor, PI/r, in first line therapy. This calculation revealed cumulative savings of 10.9% to 19.8% of daily treatment costs (50% and 90% substitution of PI/r, respectively). Substituting certain branded drugs by generic drugs showed potential cost savings of between 1.6% and 31.8%. Analysis of the data of this nationwide study reflects disease-specific health services research and will give insights into the cost impacts of antiretroviral therapy, and might allow a more rational allocation of resources within the German health care system.

Overcoming Barriers to HIV Treatment Adherence: A Brief Cognitive Behavioral Intervention for HIV-Positive Adults on Antiretroviral Treatment

PubMed Central

Olem, David; Sharp, Kelly M.; Taylor, Jonelle M.; Johnson, Mallory O.

2014-01-01

Maximizing HIV treatment adherence is critical in efforts to optimize health outcomes and to prevent further HIV transmission. The Balance Project intervention uses cognitive behavioral approaches to improve antiretroviral medication adherence through promoting adaptive coping with medication side effect and distress related to HIV. This 5-session intervention has been documented to prevent nonadherence among persons living with HIV who experience high levels of distress associated with their antiretroviral medication side effects. We describe the theoretical underpinnings of the intervention, provide details of the training and session protocols with a case example, and discuss implications for future applications of the intervention in both research and clinical settings. PMID:24855332

Effect of Pharmacist Counseling Intervention on Health Care Utilization Following Hospital Discharge: A Randomized Control Trial.

PubMed

Bell, Susan P; Schnipper, Jeffrey L; Goggins, Kathryn; Bian, Aihua; Shintani, Ayumi; Roumie, Christianne L; Dalal, Anuj K; Jacobson, Terry A; Rask, Kimberly J; Vaccarino, Viola; Gandhi, Tejal K; Labonville, Stephanie A; Johnson, Daniel; Neal, Erin B; Kripalani, Sunil

2016-05-01

Reduction in 30-day readmission rates following hospitalization for acute coronary syndrome (ACS) and acute decompensated heart failure (ADHF) is a national goal. The aim of this study was to determine the effect of a tailored, pharmacist-delivered, health literacy intervention on unplanned health care utilization, including hospital readmission or emergency room (ER) visit, following discharge. Randomized, controlled trial with concealed allocation and blinded outcome assessors Two tertiary care academic medical centers Adults hospitalized with a diagnosis of ACS and/or ADHF. Pharmacist-assisted medication reconciliation, inpatient pharmacist counseling, low-literacy adherence aids, and individualized telephone follow-up after discharge The primary outcome was time to first unplanned health care event, defined as hospital readmission or an ER visit within 30 days of discharge. Pre-specified analyses were conducted to evaluate the effects of the intervention by academic site, health literacy status (inadequate versus adequate), and cognition (impaired versus not impaired). Adjusted hazard ratios (aHR) and 95% confidence intervals (CI) are reported. A total of 851 participants enrolled in the study at Vanderbilt University Hospital (VUH) and Brigham and Women's Hospital (BWH). The primary analysis showed no statistically significant effect on time to first unplanned hospital readmission or ER visit among patients who received interventions compared to controls (aHR = 1.04, 95% CI 0.78-1.39). There was an interaction of treatment effect by site (p = 0.04 for interaction); VUH aHR = 0.77, 95% CI 0.51-1.15; BWH aHR = 1.44 (95% CI 0.95-2.12). The intervention reduced early unplanned health care utilization among patients with inadequate health literacy (aHR 0.41, 95% CI 0.17-1.00). There was no difference in treatment effect by patient cognition. A tailored, pharmacist-delivered health literacy-sensitive intervention did not reduce post-discharge unplanned health care utilization overall. The intervention was effective among patients with inadequate health literacy, suggesting that targeted practice of pharmacist intervention in this population may be advantageous.

Use of antiretroviral therapy in households and risk of HIV acquisition in rural KwaZulu-Natal, South Africa, 2004–12: a prospective cohort study

PubMed Central

Vandormael, Alain; Newell, Marie-Louise; Bärnighausen, Till; Tanser, Frank

2014-01-01

Summary Background Studies of HIV-serodiscordant couples in stable sexual relationships have provided convincing evidence that antiretroviral therapy can prevent the transmission of HIV. We aimed to quantify the preventive effect of a public-sector HIV treatment and care programme based in a community with poor knowledge and disclosure of HIV status, frequent migration, late marriage, and multiple partnerships. Specifically, we assessed whether an individual's hazard of HIV acquisition was associated with antiretroviral therapy coverage among household members of the opposite sex. Methods In this prospective cohort study, we linked patients' records from a public-sector HIV treatment programme in rural KwaZulu-Natal, South Africa, with population-based HIV surveillance data collected between 2004 and 2012. We used information about coresidence to construct estimates of HIV prevalence and antiretroviral therapy coverage for each household. We then regressed the time to HIV seroconversion for 14 505 individuals, who were HIV-uninfected at baseline and individually followed up over time regarding their HIV status, on opposite-sex household antiretroviral therapy coverage, controlling for household HIV prevalence and a range of other potential confounders. Findings 2037 individual HIV seroconversions were recorded during 54 845 person-years of follow-up. For each increase of ten percentage points in opposite-sex household antiretroviral therapy coverage, the HIV acquisition hazard was reduced by 6% (95% CI 2–9), after controlling for other factors. This effect size translates into large reductions in HIV acquisition hazards when household antiretroviral therapy coverage is substantially increased. For example, an increase of 50 percentage points in household antiretroviral therapy coverage (eg, from 20% to 70%) reduced the hazard of HIV acquisition by 26% (95% CI 9–39). Interpretation Our findings provide further evidence that antiretroviral therapy significantly reduces the risk of onward transmission of HIV in a real-world setting in sub-Saharan Africa. Awareness that antiretroviral therapy can prevent transmission to coresident sexual partners could be a powerful motivator for HIV testing and antiretroviral treatment uptake, retention, and adherence. Funding Wellcome Trust and National Institute of Child Health and Human Development (US National Institutes of Health). PMID:24782953

Guidelines for using antiretroviral agents among HIV-infected adults and adolescents. Recommendations of the Panel on Clinical Practices for Treatment of HIV.

PubMed

Dybul, Mark; Fauci, Anthony S; Bartlett, John G; Kaplan, Jonathan E; Pau, Alice K

2002-05-17

The availability of an increasing number of antiretroviral agents and the rapid evolution of new information has introduced substantial complexity into treatment regimens for persons infected with human immunodeficiency virus (HIV). In 1996, the Department of Health and Human Services and the Henry J. Kaiser Family Foundation convened the Panel on Clinical Practices for the Treatment of HIV to develop guidelines for clinical management of HIV-infected adults and adolescents (CDC. Report of the NIH Panel To Define Principles of Therapy of HIV Infection and Guidelines for the use of antiretroviral agents in HIV-infected adults and adolescents. MMWR 1998;47[RR-5]:1-41). This report, which updates the 1998 guidelines, addresses 1) using testing for plasma HIV ribonucleic acid levels (i.e., viral load) and CD4+ T cell count; 2) using testing for antiretroviral drug resistance; 3) considerations for when to initiate therapy; 4) adherence to antiretroviral therapy; 5) considerations for therapy among patients with advanced disease; 6) therapy-related adverse events; 7) interruption of therapy; 8) considerations for changing therapy and available therapeutic options; 9) treatment for acute HIV infection; 10) considerations for antiretroviral therapy among adolescents; 11) considerations for antiretroviral therapy among pregnant women; and 12) concerns related to transmission of HIV to others. Antiretroviral regimens are complex, have serious side effects, pose difficulty with adherence, and carry serious potential consequences from the development of viral resistance because of nonadherence to the drug regimen or suboptimal levels of antiretroviral agents. Patient education and involvement in therapeutic decisions is critical. Treatment should usually be offered to all patients with symptoms ascribed to HIV infection. Recommendations for offering antiretroviral therapy among asymptomatic patients require analysis of real and potential risks and benefits. Treatment should be offered to persons who have <350 CD4+ T cells/mm3 or plasma HIV ribonucleic acid (RNA) levels of >55,000 copies/mL (by b-deoxyribonucleic acid [bDNA] or reverse transcriptase-polymerase chain reaction [RT-PCR] assays). The recommendation to treat asymptomatic patients should be based on the willingness and readiness of the person to begin therapy; the degree of existing immunodeficiency as determined by the CD4+ T cell count; the risk for disease progression as determined by the CD4+ T cell count and level of plasma HIV RNA; the potential benefits and risks of initiating therapy in an asymptomatic person; and the likelihood, after counseling and education, of adherence to the prescribed treatment regimen. Treatment goals should be maximal and durable suppression of viral load, restoration and preservation of immunologic function, improvement of quality of life, and reduction of HIV-related morbidity and mortality. Results of therapy are evaluated through plasma HIV RNA levels, which are expected to indicate a 1.0 log10 decrease at 2-8 weeks and no detectable virus (<50 copies/mL) at 4-6 months after treatment initiation. Failure of therapy at 4-6 months might be ascribed to nonadherence, inadequate potency of drugs or suboptimal levels of antiretroviral agents, viral resistance, and other factors that are poorly understood. Patients whose therapy fails in spite of a high level of adherence to the regimen should have their regimen changed; this change should be guided by a thorough drug treatment history and the results of drug-resistance testing. Because of limitations in the available alternative antiretroviral regimens that have documented efficacy, optimal changes in therapy might be difficult to achieve for patients in whom the preferred regimen has failed. These decisions are further confounded by problems with adherence, toxicity, and resistance. For certain patients, participating in a clinical trial with or without access to new drugs or using a regimen that might not achieve complete suppression of viral replication might be preferable. Because concepts regarding HIV management are evolving rapidly, readers should check regularly for additional information and updates at the HIV/AIDS Treatment Information Service website (http://www.hivatis.org).

A ‘good hospital’: Nurse and patient perceptions of good clinical care for HIV-positive people on antiretroviral treatment in rural Zimbabwe—A mixed-methods qualitative study

PubMed Central

Campbell, Catherine; Scott, Kerry; Madanhire, Claudius; Nyamukapa, Constance; Gregson, Simon

2011-01-01

Background Antiretroviral treatment for HIV is gradually being made available across sub-Saharan Africa. With antiretroviral treatment, HIV can be approached as a chronic, manageable condition rather than a shorter-term issue of palliative care. This treatment involves repeated interaction between health staff and patients for ongoing check-ups and prescription refills. Objective This study aimed to understand patient and healthcare staff perceptions of good clinical antiretroviral treatment care. Design Over 100 h of ethnographic observation at healthcare sites; interviews and focus groups with 25 healthcentre workers (mostly nurses), 53 HIV-positive adults taking ARVs and 40 carers of children on ART. The data were analyzed using thematic content analysis. Setting Three healthcare sites providing free antiretroviral drugs in rural Zimbabwe, where the adult HIV infection rate is approximately 20%. Results Contrary to reports of poor antiretroviral treatment adherence and task-oriented rather than patient-oriented nursing, our study found great patient commitment to adherence, outstanding nurse dedication and a pervasive sense of hope about coping with HIV. Within this context however there were some situations where patients and nurses had different expectations of the medical encounter, leading to stress and dissatisfaction. Patients and staff both emphasized the importance of nurse kindness, understanding, confidentiality and acceptance (i.e. treating HIV patients ‘like normal’) and patient adherence to medical directions. However, nurses at times overlooked the negative effects of long wait times and frequent hospital visits. Further, nurses sometimes conflated medical adherence with general patient obedience in all aspects of the nurse–patient relationships. Patients and staff were frustrated by the ambiguity and unpredictability surrounding key elements of hospital visits such as how much patients had to pay for service, how long it would take to be served, and whether drugs or the doctor's services would be available. PMID:20801450

Unplanned Pregnancies, Family Planning Problems, and Child Maltreatment.

ERIC Educational Resources Information Center

Zuravin, Susan J.

1987-01-01

Examined the relationship between contracepting problems, unplanned fertility, and both child abuse and neglect in 518 urban, single parent, public assistance mothers. Findings revealed that increasing numbers of unplanned conceptions increased the probability of both abuse and neglect and that the unplanned conceptions were due to both failure to…

Conspiracy Beliefs about HIV Are Related to Antiretroviral Treatment Nonadherence among African American Men with HIV

PubMed Central

Bogart, Laura M.; Wagner, Glenn; Galvan, Frank H.; Banks, Denedria

2009-01-01

Background Medical mistrust is prevalent among African Americans and may influence health care behaviors such as treatment adherence. We examined whether a specific form of medical mistrust – HIV conspiracy beliefs (e.g., HIV is genocide against African Americans) – was associated with antiretroviral treatment nonadherence among African American men with HIV. Methods On baseline surveys, 214 African American men with HIV reported their agreement with 9 conspiracy beliefs, socio-demographic characteristics, depression symptoms, substance use, disease characteristics, medical mistrust, and health care barriers. Antiretroviral medication adherence was monitored electronically for one-month post-baseline among 177 men in the baseline sample. Results Confirmatory factor analysis revealed two distinct conspiracy belief subscales: genocidal beliefs (e.g., HIV is manmade) and treatment-related beliefs (e.g., people who take antiretroviral treatments are human guinea pigs for the government). Both subscales were related to nonadherence in bivariate tests. In a multivariate logistic regression, only treatment-related conspiracies were associated with a lower likelihood of optimal adherence at one-month follow-up (Odds ratio = 0.60, 95% confidence interval = 0.37 to 0.96, p < 0.05). Conclusions HIV conspiracy beliefs, especially those related to treatment mistrust, can contribute to health disparities by discouraging appropriate treatment behavior. Adherence-promoting interventions targeting African Americans should openly address such beliefs. PMID:19952767

Antiretroviral therapy as HIV prevention: status and prospects.

PubMed

Mayer, Kenneth H; Venkatesh, Kartik K

2010-10-01

As antiretroviral treatment of HIV infection has become increasingly accessible, attention has focused on whether these drugs can used for prevention because of increased tolerability of newer medications, decreased cost, and the limitations of other approaches. We review the status of antiretroviral HIV prevention, including chemoprophylaxis, as well as the effects of treatment of infected individuals on prevention. It is possible that the life-saving agents that have transformed the natural history of AIDS can be a critical component of HIV prevention efforts, but their ultimate role in affecting HIV transmission dynamics remains to be defined.

Covariate Imbalance and Adjustment for Logistic Regression Analysis of Clinical Trial Data

PubMed Central

Ciolino, Jody D.; Martin, Reneé H.; Zhao, Wenle; Jauch, Edward C.; Hill, Michael D.; Palesch, Yuko Y.

2014-01-01

In logistic regression analysis for binary clinical trial data, adjusted treatment effect estimates are often not equivalent to unadjusted estimates in the presence of influential covariates. This paper uses simulation to quantify the benefit of covariate adjustment in logistic regression. However, International Conference on Harmonization guidelines suggest that covariate adjustment be pre-specified. Unplanned adjusted analyses should be considered secondary. Results suggest that that if adjustment is not possible or unplanned in a logistic setting, balance in continuous covariates can alleviate some (but never all) of the shortcomings of unadjusted analyses. The case of log binomial regression is also explored. PMID:24138438

Guidelines for using antiretroviral agents among HIV-infected adults and adolescents.

PubMed

Dybul, Mark; Fauci, Anthony S; Bartlett, John G; Kaplan, Jonathan E; Pau, Alice K

2002-09-03

The availability of an increasing number of antiretroviral agents and the rapid evolution of new information have introduced substantial complexity into treatment regimens for persons infected with human immunodeficiency virus (HIV). In 1996, the Department of Health and Human Services and the Henry J. Kaiser Family Foundation convened the Panel on Clinical Practices for the Treatment of HIV to develop guidelines for clinical management of HIV-infected adults and adolescents (CDC. Report of the NIH Panel To Define Principles of Therapy of HIV Infection and Guidelines for the use of antiretroviral agents in HIV-infected adults and adolescents. MMWR. 1998;47[RR-5]:1-41). This report, which updates the 1998 guidelines, addresses 1) using testing for plasma HIV ribonucleic acid levels (i.e., viral load) and CD4+ T cell count; 2) using testing for antiretroviral drug resistance; 3) considerations for when to initiate therapy; 4) adherence to antiretroviral therapy; 5) considerations for therapy among patients with advanced disease; 6) therapy-related adverse events; 7) interruption of therapy; 8) considerations for changing therapy and available therapeutic options; 9) treatment for acute HIV infection; 10) considerations for antiretroviral therapy among adolescents; 11) considerations for antiretroviral therapy among pregnant women; and 12) concerns related to transmission of HIV to others. Antiretroviral regimens are complex, have serious side effects, pose difficulty with adherence, and carry serious potential consequences from the development of viral resistance because of nonadherence to the drug regimen or suboptimal levels of antiretroviral agents. Patient education and involvement in therapeutic decisions are critical. Treatment should usually be offered to all patients with symptoms ascribed to HIV infection. Recommendations for offering antiretroviral therapy among asymptomatic patients require analysis of real and potential risks and benefits. In general, treatment should be offered to persons who have <350 CD4+ T cells/mm3 or plasma HIV ribonucleic acid (RNA) levels of >55,000 copies/mL (by b-deoxyribonucleic acid [bDNA] or reverse transcriptase-polymerase chain reaction [RT-PCR] assays). The recommendation to treat asymptomatic patients should be based on the willingness and readiness of the person to begin therapy; the degree of existing immunodeficiency as determined by the CD4+ T cell count; the risk for disease progression as determined by the CD4+ T cell count and level of plasma HIV RNA; the potential benefits and risks of initiating therapy in an asymptomatic person; and the likelihood, after counseling and education, of adherence to the prescribed treatment regimen. Treatment goals should be maximal and durable suppression of viral load, restoration and preservation of immunologic function, improvement of quality of life, and reduction of HIV-related morbidity and mortality. Results of therapy are evaluated through plasma HIV RNA levels, which are expected to indicate a 1.0 log10 decrease at 2-8 weeks and no detectable virus (<50 copies/mL) at 4-6 months after treatment initiation. Failure of therapy at 4-6 months might be ascribed to nonadherence, inadequate potency of drugs or suboptimal levels of antiretroviral agents, viral resistance, and other factors that are poorly understood. Patients whose therapy fails in spite of a high level of adherence to the regimen should have their regimen changed; this change should be guided by a thorough drug treatment history and the results of drug-resistance testing. Because of limitations in the available alternative antiretroviral regimens that have documented efficacy, optimal changes in therapy might be difficult to achieve for patients in whom the preferred regimen has failed. These decisions are further confounded by problems with adherence, toxicity, and resistance. For certain patients, participating in a clinical trial with or without access to new drugs or using a regimen that might not achieve complete suppression of viral replicatioing a regimen that might not achieve complete suppression of viral replication might be preferable. Because concepts regarding HIV management are evolving rapidly, readers should check regularly for additional information and updates at the HIV/AIDS Treatment Information Service website ( http://www.hivatis.org ).

HIV Treatment as Prevention: Natural Experiments Highlight Limits of Antiretroviral Treatment as HIV Prevention

PubMed Central

Wilson, David P.

2012-01-01

There is growing enthusiasm for increasing coverage of antiretroviral treatment among HIV-infected people for the purposes of preventing ongoing transmission. Treatment as prevention will face a number of barriers when implemented in real world populations, which will likely lead to the effectiveness of this strategy being lower than proposed by optimistic modelling scenarios or ideal clinical trial settings. Some settings, as part of their prevention and treatment strategies, have already attained rates of HIV testing and use of antiretroviral therapy—with high levels of viral suppression—that many countries would aspire to as targets for a treatment-as-prevention strategy. This review examines a number of these “natural experiments”, namely, British Columbia, San Francisco, France, and Australia, to provide commentary on whether treatment as prevention has worked in real world populations. This review suggests that the population-level impact of this strategy is likely to be considerably less than as inferred from ideal conditions. PMID:22807656

Unplanned medication discontinuation as a potential pharmacovigilance signal: a nested young person cohort study

PubMed Central

2014-01-01

Background Because of relatively small treatment numbers together with low adverse drug reaction (ADR) reporting rates the timely identification of ADRs affecting children and young people is problematic. The primary objective of this study was to assess the utility of unplanned medication discontinuation as a signal for possible ADRs in children and young people. Methods Using orlistat as an exemplar, all orlistat prescriptions issued to patients up to 18 years of age together with patient characteristics, prescription duration, co-prescribed medicines and recorded clinical (Read) codes were identified from the Primary Care Informatics Unit database between 1st Jan 2006-30th Nov 2009. Binary logistic regression was used to assess association between characteristics and discontinuation. Results During the study period, 79 patients were prescribed orlistat (81% female, median age 17 years). Unplanned medication discontinuation rates for orlistat were 52% and 77% at 1 and 3-months. Almost 20% of patients were co-prescribed an anti-depressant. One month unplanned medication discontinuation was significantly lower in the least deprived group (SIMD 1–2 compared to SIMD 9–10 OR 0.09 (95% CI0.01 – 0.83)) and those co-prescribed at least one other medication. At 3 months, discontinuation was higher in young people (≥17 yr versus, OR 3.07 (95% CI1.03 – 9.14)). Read codes were recorded for digestive, respiratory and urinary symptoms around the time of discontinuation for 24% of patients. Urinary retention was reported for 7.6% of patients. Conclusions Identification of unplanned medication discontinuation using large primary care datasets may be a useful tool for pharmacovigilance signal generation and detection of potential ADRs in children and young people. PMID:24594374

Attitudes toward antiretroviral therapy among African American women.

PubMed

Richter, Donna L; Sowell, Richard L; Pluto, Delores M

2002-01-01

To examine attitudes and beliefs of African American women of childbearing age, living with HIV, about pregnancy and antiretroviral therapy. Focus groups were conducted using an exploratory design with a convenience sample of HIV-infected women in 2 southeastern cities. Thirty-three African American women of childbearing age participated in 5 focus groups. Attitudes and beliefs about antiretroviral therapy were related to the women's willingness to comply with treatment. The challenge for health care providers is to counter women's willingness to "play the odds" of having a noninfected baby without taking antiretrovirals.

[Unplanned extubation in ICU, and the relevance of non-dependent patient variables the quality of care].

PubMed

González-Castro, A; Peñasco, Y; Blanco, C; González-Fernández, C; Domínguez, M J; Rodríguez-Borregán, J C

2014-01-01

To evaluate, for a consecutive year, the magnitude of unplanned extubation, looking for non-dependent patient variables. Prospective, observational study of cases and controls in a mixed intensive care unit within in a tertiary hospital. Patients were considered cases with more than 24 hours who had an episode of unplanned extubation. Prospective collection of variables case as time of unplanned extubation (collection time), identification of the box where the patient was admitted, presence and type of physical restraint, development of ventilator-associated pneumonia (VAP) and death. There were 17 unplanned extubation in 15 patients, 1.21 unplanned extubation per 100 days of MV. The unplanned extubation had an inhomogeneous spatial distribution (number of boxes). The time distribution of cases compared with controls showed significant differences in time distribution (P=.02). The comparative analysis between cases and controls, showed increased mortality, increased length of ICU stay, longer hospital stay and increased risk for VAP when patients suffer an episode of unplanned extubation. Unplanned extubation occurs most frequently in a given time slot of the day, may play a role in the spatial location of the patient; occurs most often in patients who are in the process of weaning from mechanical ventilation, and develop greater VAP. Copyright © 2014 SECA. Published by Elsevier Espana. All rights reserved.

Unplanned Drinking and Alcohol-Related Problems: A Preliminary Test of the Model of Unplanned Drinking Behavior

PubMed Central

Pearson, Matthew R.; Henson, James M.

2013-01-01

Much research links impulsivity with alcohol use and problems. In two studies, unplanned (or impulsive) drinking is assessed directly to determine whether it has direct effects on alcohol use and alcohol-related problems. In study 1, we examined whether unplanned drinking serves as a proximal mediator of the effects of impulsivity-like traits on alcohol-related outcomes. With a sample of 211 college student drinkers, we found that the Unplanned Drinking Scale was significantly related to alcohol use, and perhaps more importantly, had a direct effect on alcohol-related problems even after controlling for frequency and quantity of alcohol use. Further, unplanned drinking partially mediated the effects of negative urgency on alcohol-related problems. In study 2, we examined whether unplanned drinking accounts for unique variance in alcohol-related outcomes when controlling for use of protective behavioral strategies. With a sample of 170 college students, we replicated the findings of Study 1 in that the Unplanned Drinking Scale had a significant direct effect on alcohol-related problems even after controlling for alcohol use; further, this effect was maintained when controlling for use of protective behavioral strategies. Limitations include the modest sample sizes and the cross-sectional design. Future directions for testing the Model of Unplanned Drinking Behavior are proposed. PMID:23276312

Psychosocial factors in maternal phenylketonuria: women's adherence to medical recommendations.

PubMed Central

Waisbren, S E; Hamilton, B D; St James, P J; Shiloh, S; Levy, H L

1995-01-01

OBJECTIVES. This study identified factors predicting adherence to medical recommendations in maternal phenylketonuria, which can result in severe fetal damage. METHODS. Sixty-nine women with phenylketonuria, 68 of their acquaintances, and 69 women with diabetes mellitus were interviewed annually for 5 years. A model in which each stage in the maternal phenylketonuria life cycle represented a treatment-related goal provided a means to assess adherence. RESULTS. At the stages of prevention of unplanned pregnancy, treatment initiation, and diet continuation throughout pregnancy, attitudes and social support were associated with adherence to medical recommendations. No specific variables were associated with outcome at reproductive decision making, but women with phenylketonuria were more likely to delay making a decision, resulting in unplanned and, hence, untreated or late-treated pregnancy. CONCLUSIONS. Women with phenylketonuria differed from their acquaintances and diabetic women in many respects, suggesting that special programs are needed. Greater emphasis on reproductive decision making is especially needed. Interventions that focus on improving social support networks and attitudes about treatment may increase adherence to recommendations. PMID:7503337

Potential elucidation of a novel CTL epitope in HIV-1 protease by the protease inhibitor resistance mutation L90M.

PubMed

Smidt, Werner

2013-01-01

The combination of host immune responses and use of antiretrovirals facilitate partial control of human immunodeficiency virus type 1 (HIV-1) infection and result in delayed progression to Acquired Immunodeficiency Syndrome (AIDS). Both treatment and host immunity impose selection pressures on the highly mutable HIV-1 genome resulting in antiretroviral resistance and immune escape. Researchers have shown that antiretroviral resistance mutations can shape cytotoxic T-lymphocyte immunity by altering the epitope repertoire of HIV infected cells. Here it was discovered that an important antiretroviral resistance mutation, L90M in HIV protease, occurs at lower frequencies in hosts that harbor the B*15, B*48 or A*32 human leukocyte antigen subtypes. A likely reason is the elucidation of novel epitopes by L90M. NetMHCPan predictions reveal increased affinity of the peptide spanning the HIV protease region, PR 89-97 and PR 90-99 to HLA-B*15/B*48 and HLA-A*32 respectively due to the L90M substitution. The higher affinity could increase the chance of the epitope being presented and recognized by Cytotoxic T-lymphocytes and perhaps provide additional immunological pressures in the presence of antiretroviral attenuating mutations. This evidence supports the notion that knowledge of HLA allotypes in HIV infected individuals could augment antiretroviral treatment by the elucidation of epitopes due to antiretroviral resistance mutations in HIV protease.

Neurodevelopment in children born to HIV-infected mothers by infection and treatment status.

PubMed

Le Doaré, Kirsty; Bland, Ruth; Newell, Marie-Louise

2012-11-01

We reviewed the impact of HIV, HIV exposure, and antiretroviral therapy/prophylaxis on neurodevelopmental outcomes of HIV-infected and HIV-exposed-uninfected infants and children. A literature search of Medline, Embase, PsychINFO, Web of Science, PubMed, and conference Web sites (1990-March 2011) using the search terms, infant, child, HIV, neurodevelopment, cognition, language, and antiretroviral therapy, identified 31 studies of HIV/antiretroviral exposure using standardized tools to evaluate infant/child development as the main outcome. Articles were included if results were reported in children <16 years of age who were exposed to HIV and antiretrovirals in fetal/early life, and excluded if children did not acquire HIV from their mothers or were not exposed to antiretrovirals in fetal/early life. Infants who acquired HIV during fetal and early life tended to display poorer mean developmental scores than HIV-unexposed children. Mean motor and cognitive scores were consistently 1 to 2 SDs below the population mean. Mean scores improved if the infant received treatment before 12 weeks and/or a more complex antiretroviral regimen. Older HIV-infected children treated with highly active antiretroviral therapy demonstrated near normal global mean neurocognitive scores; subtle differences in language, memory, and behavior remained. HIV-exposed-uninfected children treated with antiretrovirals demonstrated subtle speech and language delay, although not universally. In comparison with resource-rich settings, HIV-infected and HIV-exposed-uninfected infants/children in resource-poor settings demonstrated greater neurodevelopmental delay compared with HIV-unexposed infants. The effects on neurodevelopment in older HIV-infected children commenced on antiretroviral therapy from an early age and HIV-exposed-uninfected children particularly in resource-poor settings remain unclear.

AIDS in Brazilian children: history, surveillance, antiretroviral therapy, and epidemiologic transition, 1984-2008.

PubMed

Ramos, Alberto Novaes; Matida, Luiza Harunari; Hearst, Norman; Heukelbach, Jorg

2011-04-01

We present a systematic review of historical, political, and epidemiologic aspects of AIDS in Brazilian children. Over 25 years, Brazil has developed different strategies to control AIDS in children. Three revisions of criteria for defining AIDS cases in children and nine national guidelines on antiretroviral therapy administration for management of HIV infection were published. These guidelines represent important progress, including aspects of HIV/AIDS surveillance, antiretroviral treatment, opportunistic conditions, prophylaxis, and laboratory testing. Brazil has significantly expanded access to free therapy with different classes of antiretroviral drugs. Initially focusing on treatment for HIV and opportunistic conditions, the scope of treatment guidelines gradually expanded to comprehensive health care for children and adolescents. From 1996 to 2008, the number of AIDS cases and deaths in children has been reduced by 67% and 65%, respectively, as a result of different strategies to prevent mother-to-child transmission of HIV and highly active antiretroviral therapy administration to infected children. Improved morbidity, mortality, and survival of Brazilian children with AIDS demonstrate clear benefits of adopting a policy of free and universal access to antiretroviral drugs associated with comprehensive care. However, important issues remain to be resolved, mainly concerning social, operational, and regional inequalities in coverage and quality of care, and epidemiological surveillance in different regions of the country. This broad review shows that the overall situation of pediatric AIDS in Brazil represents an incomplete process of epidemiologic and demographic transition, with the coexistence of old and new clinical and epidemiologic challenges.

Sexual risk behavior among people living with HIV and AIDS on antiretroviral therapy at the regional hospital of Sokodé, Togo

PubMed Central

2014-01-01

Background Several studies on the sexual risk behaviors in sub-Saharan Africa have reported that the initiation of antiretroviral therapy leads to safer sexual behaviors. There is however a persistence of risky sexual behavior which is evidenced by a high prevalence of sexually transmitted infections among people living with HIV and AIDS (PLWHA). We sought to determine the factors associated with risky sex among PLWHA on antiretroviral therapy in Togo. Methods An analytical cross-sectional survey was conducted from May to July 2013 at regional hospital of Sokodé, Togo, and targeted 291 PLWHA on antiretroviral therapy for at least three months. Results From May to July 2013, 291 PLWHA on antiretroviral treatment were surveyed. The mean age of PLWHA was 37.3 years and the sex ratio (male/female) was 0.4. Overall, 217 (74.6%) PLWHA were sexually active since initiation of antiretroviral treatment, of which, 74 (34.6%) had risky sexual relations. In multivariate analysis, the factors associated with risky sex were: the duration of antiretroviral treatment (1 to 3 years: aOR = 27.08; p = 0.003; more than 3 years: aOR = 10.87; p = 0.028), adherence of antiretroviral therapy (aOR = 2.56; p = 0.014), alcohol consumption before sex (aOR = 3.59; p = 0.013) and level of education (primary school: aOR = 0.34 p = 0.011; secondary school: aOR = 0.23 p = 0.003; high school: aOR = 0.10; p = 0.006). Conclusion There was a high prevalence of unsafe sex among PLWHA receiving ART at the hospital of Sokodé. Factors associated with sexual risk behaviors were: low education level, non-adherence to ART, alcohol consumption before sex and the duration of ART. It is important to strengthen the implementation of secondary prevention strategies among this population group. PMID:24952380

Risk factors for unplanned and crash dialysis starts: a protocol for a systematic review and meta-analysis.

PubMed

Molnar, Amber O; Hiremath, Swapnil; Brown, Pierre A; Akbari, Ayub

2016-07-19

Many patients with kidney failure "crash" onto dialysis or initiate dialysis in an unplanned fashion. There are varying definitions, but essentially, a patient is labeled as having a crash dialysis start if he or she has little to no care by a nephrologist prior to starting dialysis. A patient is labeled as having an unplanned dialysis start when he or she starts dialysis with a catheter or during a hospitalization. Given the high prevalence and poor outcomes associated with crash and unplanned dialysis starts, it is important to establish a better understanding of patient risk factors. We will conduct a systematic review and meta-analysis with a focus on both crash and unplanned dialysis starts. The first objective will be to determine patient risk factors for crash and unplanned dialysis starts. Secondary objectives will be to determine the most common criteria used to define both crash and unplanned dialysis starts and to determine outcomes associated with crash and unplanned dialysis starts. We will search MEDLINE, EMBASE and Cochrane Library from inception to the present date for all studies that report the characteristics and outcomes of patients who have crash vs. non-crash dialysis starts or unplanned vs. planned dialysis starts. We will also extract from included studies the criteria used to define crash and unplanned dialysis starts. If there are any eligible randomized controlled trials, quality assessment will be performed using the Cochrane Risk of Bias Assessment Tool. Observational studies will be evaluated using the Newcastle-Ottawa Scale. Data will be pooled in meta-analysis if deemed appropriate. The results of this review will inform the design of strategies to help reduce the incidence of crash and unplanned dialysis starts. Prospero CRD42016032916.

The Assessment of the Risk of Unplanned Extubation in an Adult Intensive Care Unit.

PubMed

Aydoğan, Semine; Kaya, Nurten

In order to plan and implement nursing intervention to reduce the incidence rate of unplanned extubation problem in the intensive care unit (ICU), it is necessary to determine the risk factors of unplanned extubation and the patients under risk. This study was undertaken with the aim of evaluating the risk of unplanned extubation of endotracheal tube in adult ICU. This was a case-control study. The population constituted patients hospitalized in the adult ICU during 1-year period in a university hospital. The sample from this population was composed of patients whose extubation was unplanned (30 patients) and the randomly selected patients (60 patients) who were intubated at the same time in the ICU for each patient whose extubation was unplanned. In data collection, the Richmond Agitation-Sedation Scale, Glasgow Coma Scale, Acute Physiology and Chronic Health Evaluation II were utilized. According to the findings, the variables such as sex, age, mechanical ventilation period, and Acute Physiology and Chronic Health Evaluation II and Glasgow Coma Scale scores did not have any effect on the unplanned extubation, but variables such as internal medicine diseases and Richmond Agitation-Sedation Scale did have an effect. It was also revealed that there was no extubation plan in most of the unplanned extubation group, the nurse was anticipating the unplanned extubation, the patient was intubated again, and a complication occurred. The patients who are provided inadequate sedation and analgesia and who have problems in their respiratory system are under risk of unplanned extubation. In order to prevent unplanned extubation, an adequate amount of sedation and private nursing care should be provided to patients in the ICU.

Characteristics and outcome of unplanned out-of-institution births in Norway from 1999 to 2013: a cross-sectional study.

PubMed

Gunnarsson, Björn; Smárason, Alexander K; Skogvoll, Eirik; Fasting, Sigurd

2014-10-01

To study the incidence, maternal characteristics and outcome of unplanned out-of-institution births (= unplanned births) in Norway. Register-based cross-sectional study. All births in Norway (n = 892 137) from 1999 to 2013 with gestational age ≥22 weeks. Analysis of data from the Medical Birth Registry of Norway from 1999 to 2013. Unplanned births (n = 6062) were compared with all other births (reference group). The annual incidence rate of unplanned births was 6.8/1000 births and remained stable during the period of study. Young multiparous women residing in remote municipalities were at the highest risk of experiencing unplanned births. The unplanned birth group had higher perinatal mortality rate for the period, 11.4/1000 compared with 4.9/1000 for the reference group (incidence rate ratio 2.31, 95% confidence interval 1.82-2.93, p < 0.001). Annual perinatal mortality rate for unplanned births did not change significantly (p = 0.80) but declined on average by 3% per year in the reference group (p < 0.001). The unplanned birth group had a lower proportion of live births in all birthweight categories. Live born neonates with a birthweight of 750-999 g in the unplanned birth group had a more than five times higher mortality rate during the first week of life, compared with reference births in the same birthweight category. Unplanned births are associated with adverse outcome. Excessive mortality is possibly caused by reduced availability of necessary medical interventions for vulnerable newborns out-of-hospital. © 2014 The Authors. Acta Obstetricia et Gynecologica Scandinavica published by John Wiley & Sons Ltd on behalf of Nordic Federation of Societies of Obstetrics and Gynecology (NFOG).

Analysis of Unplanned Intensive Care Unit Admissions in Postoperative Pediatric Patients.

PubMed

Landry, Elizabeth K; Gabriel, Rodney A; Beutler, Sascha; Dutton, Richard P; Urman, Richard D

2017-03-01

Currently, there are only a few retrospective, single-institution studies that have addressed the prevalence and risk factors associated with unplanned admissions to the pediatric intensive care unit (ICU) after surgery. Based on the limited amount of studies, it appears that airway and respiratory complications put a child at increased risk for unplanned ICU admission. A more extensive and diverse analysis of unplanned postoperative admissions to the ICU is needed to address risk factors that have yet to be revealed by the current literature. To establish a rate of unplanned postoperative ICU admissions in pediatric patients using a large, multi-institution data set and to further characterize the associated risk factors. Data from the National Anesthesia Clinical Outcomes Registry were analyzed. We recorded the overall risk of unplanned postoperative ICU admission in patients younger than 18 years and performed univariate and multivariate logistic regression analysis to identify the associated patient, surgical, and anesthetic-related characteristics. Of the 324 818 cases analyzed, 211 reported an unexpected ICU admission. There was an increased likelihood of unplanned postoperative ICU in infants (age <1 year) and children who were classified as American Society of Anesthesiologists physical status classification of III or IV. Likewise, longer case duration and cases requiring general anesthesia were also associated with unplanned ICU admissions. This study establishes a rate of unplanned ICU admission following surgery in the heterogeneous pediatric population. This is the first study to utilize such a large data set encompassing a wide range of practice environments to identify risk factors leading to unplanned postoperative ICU admissions. Our study revealed that patient, surgical, and anesthetic complexity each contributed to an increased number of unplanned ICU admissions in the pediatric population.

Incidence and etiology of unplanned cast changes for fractures in the pediatric population.

PubMed

DiPaola, Matthew J; Abzug, Joshua M; Pizzutillo, Peter D; Herman, Martin J

2014-09-01

The majority of pediatric fractures are treated in casts due to the child's ability to heal rapidly and remodel. Unplanned cast changes are a time and economic burden with potentially adverse effects on fracture management. The purpose of this study is to document the incidence, etiology, and complications related to unplanned cast changes. A prospective study was conducted over a 6-month period to determine the incidence of unplanned cast changes. All casts applied were nonwaterproof. Data collected include the reason for cast placement, type of cast placed, duration of wear before the unplanned change, reason for the unplanned change, experience level of the original cast applicator, and cast-related complications. A total of 1135 casts were placed with 58% placed by a resident, 38% by a cast technician, 2% by a physician's assistant, and 2% by an attending physician. Sixty casts (5.3%) required an unplanned change including 19 short-arm casts, 18 short-leg casts, 17 long-arm casts, 4 thumb spica casts, and 2 long-leg casts. The average duration from cast application until the unplanned change was 13 days. Twenty-eight (47%) were changed for wetness, 20 (33%) for wear/breakage, 2 (3%) for skin irritation, and 10 (17%) for other reasons including objects in the cast and patient self-removal. Two patients had superficial skin infections requiring oral antibiotics. No fracture reductions were lost secondary to an unplanned cast change. The need for an unplanned cast change did not correlate with the level of experience of the applicator. Most unplanned cast changes were the result of patient nonadherence to instructions and not related to cast application technique. Improved patient and family education regarding cast care may reduce the frequency of unplanned cast changes, thus reducing an economic and time burden on the health care system. Level II--prognostic study.

Rapid HIV RNA rebound after antiretroviral treatment interruption in persons durably suppressed in Fiebig I acute HIV infection.

PubMed

Colby, Donn J; Trautmann, Lydie; Pinyakorn, Suteeraporn; Leyre, Louise; Pagliuzza, Amélie; Kroon, Eugène; Rolland, Morgane; Takata, Hiroshi; Buranapraditkun, Supranee; Intasan, Jintana; Chomchey, Nitiya; Muir, Roshell; Haddad, Elias K; Tovanabutra, Sodsai; Ubolyam, Sasiwimol; Bolton, Diane L; Fullmer, Brandie A; Gorelick, Robert J; Fox, Lawrence; Crowell, Trevor A; Trichavaroj, Rapee; O'Connell, Robert; Chomont, Nicolas; Kim, Jerome H; Michael, Nelson L; Robb, Merlin L; Phanuphak, Nittaya; Ananworanich, Jintanat

2018-06-11

Antiretroviral therapy during the earliest stage of acute HIV infection (Fiebig I) might minimize establishment of a latent HIV reservoir and thereby facilitate viremic control after analytical treatment interruption. We show that 8 participants, who initiated treatment during Fiebig I and were treated for a median of 2.8 years, all experienced rapid viral load rebound following analytical treatment interruption, indicating that additional strategies are required to control or eradicate HIV.

In a study of a population cohort in South Africa, HIV patients on antiretrovirals had nearly full recovery of employment.

PubMed

Bor, Jacob; Tanser, Frank; Newell, Marie-Louise; Bärnighausen, Till

2012-07-01

Antiretroviral therapy for HIV may have important economic benefits for patients and their households. We quantified the impact of HIV treatment on employment status among HIV patients in rural South Africa who were enrolled in a public-sector HIV treatment program supported by the President's Emergency Plan for AIDS Relief. We linked clinical data from more than 2,000 patients in the treatment program with ten years of longitudinal socioeconomic data from a complete community-based population cohort of more than 30,000 adults residing in the clinical catchment area. We estimated the employment effects of HIV treatment in fixed-effects regressions. Four years after the initiation of antiretroviral therapy, employment among HIV patients had recovered to about 90 percent of baseline rates observed in the same patients three to five years before they started treatment. Many patients initiated treatment early enough that they were able to avoid any loss of employment due to HIV. These results represent the first estimates of employment recovery among HIV patients in a general population, relative to the employment levels that these patients had prior to job-threatening HIV illness and the decision to seek care. There are large economic benefits to HIV treatment. For some patients, further gains could be obtained from initiating antiretroviral therapy earlier, prior to HIV-related job loss.

Nearly Full Employment Recovery Among South African HIV Patients On Antiretroviral Therapy: Evidence From A Large Population Cohort

PubMed Central

Bor, Jacob; Tanser, Frank; Newell, Marie-Louise; Bärnighausen, Till

2013-01-01

Antiretroviral therapy for HIV may have important economic benefits for patients and their households. We quantified the impact of HIV treatment on employment status among HIV patients in rural South Africa who were enrolled in a public-sector HIV treatment program supported by the U.S. President’s Emergency Plan for AIDS Relief. We linked clinical data from more than 2000 patients in the treatment program with ten years of longitudinal socioeconomic data from a complete community-based population cohort of over 30,000 adults residing in the clinical catchment area. We estimated the employment effects of HIV treatment in fixed effects regressions. Four years after the initiation of antiretroviral therapy, employment among HIV patients had recovered to about 90 percent of baseline rates observed in the same patients three to five years before they started treatment. Many patients initiated treatment early enough that they were able to avoid any loss of employment due to HIV. These results represent the first estimates of employment recovery among HIV patients in a general population, relative to the employment levels that these patients had prior to job-threatening illness and the decision to seek care. We find large economic benefits to HIV treatment. For some patients, further gains could be obtained from initiating antiretroviral therapy earlier, prior to HIV-related job loss. PMID:22778335

Effect of a redesigned fracture management pathway and 'virtual' fracture clinic on ED performance.

PubMed

Vardy, J; Jenkins, P J; Clark, K; Chekroud, M; Begbie, K; Anthony, I; Rymaszewski, L A; Ireland, A J

2014-06-13

Collaboration between the orthopaedic and emergency medicine (ED) services has resulted in standardised treatment pathways, leaflet supported discharge and a virtual fracture clinic review. Patients with minor, stable fractures are discharged with no further follow-up arranged. We aimed to examine the time taken to assess and treat these patients in the ED along with the rate of unplanned reattendance. A retrospective study was undertaken that covered 1 year before the change and 1 year after. Prospectively collected administrative data from the electronic patient record system were analysed and compared before and after the change. An ED and orthopaedic unit, serving a population of 300 000, in a publicly funded health system. 2840 patients treated with referral to a traditional fracture clinic and 3374 patients managed according to the newly redesigned protocol. Time for assessment and treatment of patients with orthopaedic injuries not requiring immediate operative management, and 7-day unplanned reattendance. Where plaster backslabs were replaced with removable splints, the consultation time was reduced. There was no change in treatment time for other injuries treated by the new discharge protocol. There was no increase in unplanned ED attendance, related to the injury, within 7 days (p=0.149). There was a decrease in patients reattending the ED due to a missed fracture clinic appointment. This process did not require any new time resources from the ED staff. This process brought significant benefits to the ED as treatment pathways were agreed. The pathway reduced unnecessary reattendance of patients at face-to-face fracture clinics for a review of stable, self-limiting injuries. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

HIV-1 genetic diversity and antiretroviral drug resistance among individuals from Roraima state, northern Brazil

PubMed Central

Leão, Renato Augusto Carvalho; Granja, Fabiana; Naveca, Felipe Gomes

2017-01-01

The HIV-1 epidemic in Brazil has spread towards the Northern country region, but little is known about HIV-1 subtypes and prevalence of HIV strains with resistance mutations to antiretrovirals in some of the Northern states. HIV-1 protease (PR) and reverse transcriptase (RT) sequences were obtained from 73 treatment-naive and -experienced subjects followed between 2013 and 2014 at a public health reference unit from Roraima, the northernmost Brazilian state. The most prevalent HIV-1 clade observed in the study population was the subtype B (91%), followed by subtype C (9%). Among 12 HIV-1 strains from treatment-naïve patients, only one had a transmitted drug resistance mutation for NNRTI. Among 59 treatment-experienced patients, 12 (20%) harbored HIV-1 strains with acquired drug resistance mutations (ADRM) that reduce the susceptibility to two classes of antiretroviral drugs (NRTI and NNRTI or NRTI and PI), and five (8%) harbored HIV-1 strains with ADRM that reduced susceptibility to only one class of antiretroviral drugs (NNRTI or PI). No patients harboring HIV strains with reduced susceptibility to all three classes of antiretroviral drugs were detected. A substantial fraction of treatment-experienced patients with (63%) and without (70%) ADRM had undetectable plasma viral loads (<40 copies/ml) at the time of sampling. Among treatment-experienced with plasma viral loads above 2,000 copies/ml, 44% displayed no ADRM. This data showed that the HIV-1 epidemic in Roraima displayed a much lower level of genetic diversity and a lower prevalence of ADRM than that described in other Brazilian states. PMID:28301548

Risk factors for treatment-limiting toxicities in patients starting nevirapine-containing antiretroviral therapy.

PubMed

Kesselring, Anouk M; Wit, Ferdinand W; Sabin, Caroline A; Lundgren, Jens D; Gill, M John; Gatell, Jose M; Rauch, Andri; Montaner, Julio S; de Wolf, Frank; Reiss, Peter; Mocroft, Amanda

2009-08-24

This collaboration of seven observational clinical cohorts investigated risk factors for treatment-limiting toxicities in both antiretroviral-naive and experienced patients starting nevirapine-based combination antiretroviral therapy (NVPc). Patients starting NVPc after 1 January 1998 were included. CD4 cell count at starting NVPc was classified as high (>400/microl/>250/microl for men/women, respectively) or low. Cox models were used to investigate risk factors for discontinuations due to hypersensitivity reactions (HSR, n = 6547) and discontinuation of NVPc due to treatment-limiting toxicities and/or patient/physician choice (TOXPC, n = 10,186). Patients were classified according to prior antiretroviral treatment experience and CD4 cell count/viral load at start NVPc. Models were stratified by cohort and adjusted for age, sex, nadir CD4 cell count, calendar year of starting NVPc and mode of transmission. Median time from starting NVPc to TOXPC and HSR were 162 days [interquartile range (IQR) 31-737] and 30 days (IQR 17-60), respectively. In adjusted Cox analyses, compared to naive patients with a low CD4 cell count, treatment-experienced patients with high CD4 cell count and viral load more than 400 had a significantly increased risk for HSR [hazard ratio 1.45, confidence interval (CI) 1.03-2.03] and TOXPC within 18 weeks (hazard ratio 1.34, CI 1.08-1.67). In contrast, treatment-experienced patients with high CD4 cell count and viral load less than 400 had no increased risk for HSR 1.10 (0.82-1.46) or TOXPC within 18 weeks (hazard ratio 0.94, CI 0.78-1.13). Our results suggest it may be relatively well tolerated to initiate NVPc in antiretroviral-experienced patients with high CD4 cell counts provided there is no detectable viremia.

Fosamprenavir calcium plus ritonavir for HIV infection.

PubMed

Torres, Harrys A; Arduino, Roberto C

2007-06-01

Fosamprenavir is a protease inhibitor (PI) approved for the treatment of HIV-1 infection. Fosamprenavir is a prodrug of amprenavir developed to reduce the pill burden yet maintain the unique resistance pattern and efficacy associated with amprenavir. In a head-to-head, noninferiority trial in antiretroviral treatment-naive HIV-infected patients, the antiviral efficacy and tolerability of ritonavir-boosted fosamprenavir was not inferior to ritonavir-boosted lopinavir, when the PIs were combined with two other nucleoside reverse transcriptase inhibitors. There are fewer studies published about fosamprenavir use in antiretroviral treatment-experienced HIV-infected patients. The high genetic barrier to the development of resistance to fosamprenavir and the low level of cross-resistance between ritonavir-boosted fosamprenavir and other PI regimens are notable. As with amprenavir, gastrointestinal disturbance and rash are the most frequent short-term treatment-limiting events with fosamprenavir. Treatment with ritonavir-boosted fosamprenavir can produce a durable response. To date, fosamprenavir is one of the recommended preferred PI components for the treatment of antiretroviral-naive HIV-infected patients.

Health benefits, costs, and cost-effectiveness of earlier eligibility for adult antiretroviral therapy and expanded treatment coverage: a combined analysis of 12 mathematical models.

PubMed

Eaton, Jeffrey W; Menzies, Nicolas A; Stover, John; Cambiano, Valentina; Chindelevitch, Leonid; Cori, Anne; Hontelez, Jan A C; Humair, Salal; Kerr, Cliff C; Klein, Daniel J; Mishra, Sharmistha; Mitchell, Kate M; Nichols, Brooke E; Vickerman, Peter; Bakker, Roel; Bärnighausen, Till; Bershteyn, Anna; Bloom, David E; Boily, Marie-Claude; Chang, Stewart T; Cohen, Ted; Dodd, Peter J; Fraser, Christophe; Gopalappa, Chaitra; Lundgren, Jens; Martin, Natasha K; Mikkelsen, Evelinn; Mountain, Elisa; Pham, Quang D; Pickles, Michael; Phillips, Andrew; Platt, Lucy; Pretorius, Carel; Prudden, Holly J; Salomon, Joshua A; van de Vijver, David A M C; de Vlas, Sake J; Wagner, Bradley G; White, Richard G; Wilson, David P; Zhang, Lei; Blandford, John; Meyer-Rath, Gesine; Remme, Michelle; Revill, Paul; Sangrujee, Nalinee; Terris-Prestholt, Fern; Doherty, Meg; Shaffer, Nathan; Easterbrook, Philippa J; Hirnschall, Gottfried; Hallett, Timothy B

2014-01-01

New WHO guidelines recommend initiation of antiretroviral therapy for HIV-positive adults with CD4 counts of 500 cells per μL or less, a higher threshold than was previously recommended. Country decision makers have to decide whether to further expand eligibility for antiretroviral therapy accordingly. We aimed to assess the potential health benefits, costs, and cost-effectiveness of various eligibility criteria for adult antiretroviral therapy and expanded treatment coverage. We used several independent mathematical models in four settings-South Africa (generalised epidemic, moderate antiretroviral therapy coverage), Zambia (generalised epidemic, high antiretroviral therapy coverage), India (concentrated epidemic, moderate antiretroviral therapy coverage), and Vietnam (concentrated epidemic, low antiretroviral therapy coverage)-to assess the potential health benefits, costs, and cost-effectiveness of various eligibility criteria for adult antiretroviral therapy under scenarios of existing and expanded treatment coverage, with results projected over 20 years. Analyses assessed the extension of eligibility to include individuals with CD4 counts of 500 cells per μL or less, or all HIV-positive adults, compared with the previous (2010) recommendation of initiation with CD4 counts of 350 cells per μL or less. We assessed costs from a health-system perspective, and calculated the incremental cost (in US$) per disability-adjusted life-year (DALY) averted to compare competing strategies. Strategies were regarded very cost effective if the cost per DALY averted was less than the country's 2012 per-head gross domestic product (GDP; South Africa: $8040; Zambia: $1425; India: $1489; Vietnam: $1407) and cost effective if the cost per DALY averted was less than three times the per-head GDP. In South Africa, the cost per DALY averted of extending eligibility for antiretroviral therapy to adult patients with CD4 counts of 500 cells per μL or less ranged from $237 to $1691 per DALY averted compared with 2010 guidelines. In Zambia, expansion of eligibility to adults with a CD4 count threshold of 500 cells per μL ranged from improving health outcomes while reducing costs (ie, dominating the previous guidelines) to $749 per DALY averted. In both countries results were similar for expansion of eligibility to all HIV-positive adults, and when substantially expanded treatment coverage was assumed. Expansion of treatment coverage in the general population was also cost effective. In India, the cost for extending eligibility to all HIV-positive adults ranged from $131 to $241 per DALY averted, and in Vietnam extending eligibility to patients with CD4 counts of 500 cells per μL or less cost $290 per DALY averted. In concentrated epidemics, expanded access for key populations was also cost effective. Our estimates suggest that earlier eligibility for antiretroviral therapy is very cost effective in low-income and middle-income settings, although these estimates should be revisited when more data become available. Scaling up antiretroviral therapy through earlier eligibility and expanded coverage should be considered alongside other high-priority health interventions competing for health budgets. Bill & Melinda Gates Foundation, WHO. Copyright © 2014 Eaton et al. Open Access article distributed under the terms of CC BY-NC-ND. Published by .. All rights reserved.

Blockade of the spinal BDNF-activated JNK pathway prevents the development of antiretroviral-induced neuropathic pain.

PubMed

Sanna, Maria Domenica; Ghelardini, Carla; Galeotti, Nicoletta

2016-06-01

Although antiretroviral agents have been used successfully in suppressing viral production, they have also been associated with a number of side effects. The antiretroviral toxic neuropathy induces debilitating and extremely difficult to treat pain syndromes that often lead to discontinuation of antiretroviral therapy. Due to the critical need for the identification of novel therapeutic targets to improve antiretroviral neuropathic pain management, we investigated the role of the JNK signalling pathway in the mechanism of antiretroviral painful neuropathy. Mice were exposed to zalcitabine (2',3'-dideoxycytidine, ddC) and stavudine (2',3'-didehydro-3'-deoxythymidine, d4T) that induced a persistent mechanical allodynia and a transient cold allodynia. Treatment with the JNK blocker SP600125 before antiretroviral administration abolished mechanical hypersensitivity with no effect on thermal response. A robust spinal JNK overphosphorylation was observed on post-injection day 1 and 3, along with a JNK-dependent increase in p-c-Jun and ATF3 protein levels. Co-immunoprecipitation experiments showed the presence of a heterodimeric complex between ATF3 and c-Jun indicating that these transcription factors can act together to regulate transcription through heterodimerization. A rise in BDNF and caspase-3 protein levels was detected on day 1 and BDNF sequestration prevented both caspase-3 and p-JNK increase. These data suggest that BDNF plays a role in the early stages of ddC-induced allodynia by promoting apoptotic events and the activation of a hypernociceptive JNK-mediated pathway. We illustrated the activation of a BDNF-mediated JNK pathway involved in the early events responsible for the promotion of neuropathic pain, leading to a better knowledge of the mechanisms involved in the antiretroviral neuropathy. JNK blockade prevents antiretroviral-induced pain hypersensitivity. This may represent a potential prophylactic treatment of neuropathic pain to improve antiretroviral tolerability. Copyright © 2016 Elsevier Ltd. All rights reserved.

Immunologic status and virologic outcomes in repeat pregnancies to HIV-positive women not on antiretroviral therapy at conception: a case for lifelong antiretroviral therapy?

PubMed Central

French, Clare E.; Thorne, Claire; Tariq, Shema; Cortina-Borja, Mario; Tookey, Pat A.

2014-01-01

During their second pregnancy with diagnosed HIV (n = 1177), two-fifths of women in the UK/Ireland not on antiretroviral therapy (ART) at conception had an immunological indication for treatment (CD4+ <350 cells/μl), of whom nearly half had CD4+ at least 350 cells/μl in their previous pregnancy. Those initiating ART during pregnancy had a 4.3-fold increased odds of detectable viral load at delivery compared with those conceiving on treatment, suggesting that continuation of ART after pregnancy may be beneficial for many women. PMID:24685820

Pharmacotherapy of Pediatric HIV Infection

PubMed Central

Rakhmanina, Natella; Phelps, Ryan

2012-01-01

SYNOPSIS With the ongoing epidemic of human immune deficiency virus (HIV) infections in the pediatric age group, the delivery of safe and effective antiretroviral therapy to children and adolescents is crucial to save the lives of millions of children worldwide. Antiretroviral drugs have been demonstrated to significantly decrease HIV-associated morbidity and mortality, assure normal growth and development, and improve survival and quality of life in children and adolescents. The immunologic response to HIV infection is closely related to the child’s development and creates age specific parameters for the evaluation of therapeutic response to antiretroviral therapy in pediatric HIV disease. In addition to the changes in immunological response to HIV infection, the development and maturation of organ systems involved in drug absorption, distribution, metabolism, and elimination determines significant changes in the pharmacokinetics of antiretroviral drugs throughout the childhood. Multiple factors including age-specific adherence barriers, changes in social and economical surroundings, and psychological and sexual maturation affect the choices and outcomes of the treatment of pediatric HIV disease. In this chapter we will review the evolution of antiretroviral treatment from early infancy through adolescence. PMID:23036246

Treatment and prevention of HIV infection with long-acting antiretrovirals.

PubMed

Benítez-Gutiérrez, Laura; Soriano, Vicente; Requena, Silvia; Arias, Ana; Barreiro, Pablo; de Mendoza, Carmen

2018-05-01

Current antiretroviral therapy allows to achieve and sustain maximal suppression of HIV replication in most treated patients. As result, the life expectancy of HIV-infected persons has improved dramatically and is nowadays similar to that of the HIV-negative population. However, oral antiretrovirals have to be taken daily and indefinitely to avoid resumption of HIV replication and selection of drug resistance. Unfortunately, drug adherence is often suboptimal and tends to decline over time. Areas covered: New drugs, formulations and delivery systems are being developed for extended-release of antiretrovirals. At this time, intramuscular cabotegravir and rilpivirine, dapivirine vaginal rings and tenofovir alafenamide subdermal implants are the products in more advanced stages of clinical development. Their pharmacokinetics/dynamics and safety/efficacy are reviewed. Expert commentary: In the absence of eradicative therapy for individuals with HIV infection and protective vaccines for persons at risk, long-term antiretroviral therapy is the best approach for preventing disease progression in patients and halting transmissions, either as result of 'treatment as prevention' for HIV carriers or 'pre-exposure prophylaxis' for uninfected individuals at risk. In all these scenarios, the advent of long-acting antiretrovirals will expand options for overcoming the challenge of suboptimal drug adherence and reduce the burden of HIV infection.

What to Start: Selecting a First HIV Regimen

MedlinePlus

... to treat HIV infection is called antiretroviral therapy (ART). People on ART take a combination of HIV medicines (called an ... infection. HIV treatment (also called antiretroviral therapy or ART) begins with choosing an HIV regimen. People on ...

A structured bowel management program for patients with severe functional constipation can help decrease emergency department visits, hospital admissions, and healthcare costs.

PubMed

Reck-Burneo, Carlos A; Vilanova-Sanchez, Alejandra; Gasior, Alessandra C; Dingemans, Alexander J M; Lane, Victoria A; Dyckes, Robert; Nash, Onnalisa; Weaver, Laura; Maloof, Tassiana; Wood, Richard J; Zobell, Sarah; Rollins, Michael D; Levitt, Marc A

2018-03-24

Published health-care costs related to constipation in children in the USA are estimated at $3.9 billion/year. We sought to assess the effect of a bowel management program (BMP) on health-care utilization and costs. At two collaborating centers, BMP involves an outpatient week during which a treatment plan is implemented and objective assessment of stool burden is performed with daily radiography. We reviewed all patients with severe functional constipation who participated in the program from March 2011 to June 2015 in center 1 and from April 2014 to April 2016 in center 2. ED visits, hospital admissions, and constipation-related morbidities (abdominal pain, fecal impaction, urinary retention, urinary tract infections) 12 months before and 12 months after completion of the BMP were recorded. One hundred eighty-four patients were included (center 1 = 96, center 2 = 88). Sixty-three (34.2%) patients had at least one unplanned visit to the ED before treatment. ED visits decreased to 23 (12.5%) or by 64% (p < 0.0005). Unplanned hospital admissions decreased from 65 to 28, i.e., a 56.9% reduction (p < 0.0005). In children with severe functional constipation, a structured BMP decreases unplanned visits to the ED, hospital admissions, and costs for constipation-related health care. 3. Copyright © 2018. Published by Elsevier Inc.

Prices paid for adult and paediatric antiretroviral treatment by low- and middle-income countries in 2012: high, low or just right?

PubMed

Perriëns, Joseph H; Habiyambere, Vincent; Dongmo-Nguimfack, Boniface; Hirnschall, Gottfried

2014-01-01

A viable market for antiretroviral drugs in low- and middle-income countries is key to the continued scale-up of antiretroviral treatment. We describe the price paid by low- and middle-income countries for 10 first- and 7 second-line adult and paediatric treatment regimens from 2003 to 2012, and compare the price of their finished formulations with the price of their active pharmaceutical ingredients in 2005, 2007, 2010 and 2012. Between 2003 and 2012 the median price of adult first-line treatment regimens per treatment-year decreased from USD499 to USD122, and that of second-line regimens from USD2,934 to USD497. In 2005 adult formulations were sold for a price 170% higher than the cost of their active pharmaceutical ingredients. This margin had decreased to 28% in 2012. Between 2004 and 2013, the price of paediatric treatment per treatment-year decreased from USD585 to USD147 for first-line and from USD763 to USD288 for second-line treatment. In 2005, paediatric treatment regimens were sold at a price 231% higher than the cost of their active pharmaceutical ingredients. This margin remained high and was 195% in 2012. The prices paid for antiretroviral drugs by low- and middle-income countries decreased between 2003 and 2012. Although the margins on their sale decreased, there is likely still space for price reduction, especially for the more recent World Health Organization recommended adult first-line regimens and for paediatric treatment.

'We will eat when I get the grant': negotiating AIDS, poverty and antiretroviral treatment in South Africa.

PubMed

Leclerc-Madlala, Suzanne

2006-11-01

The maturing HIV epidemic has led to a decline in the health status of many South Africans. One result is an increasing number of AIDS-affected poor who qualify for a government disability grant. Recent research has drawn attention to the unintended conflict that this may present for poor people who might be faced with choosing between maintaining health through antiretroviral treatment and obtaining money through the state grant. While some evidence suggests that most AIDS-affected people would choose antiretroviral treatment over access to a disability grant, other evidence suggests that some would rather die than lose the grant. This paper is a qualitative exploration of ways that AIDS treatment policies and practices and grants for people disabled by AIDS are currently being negotiated by people caught in the double-bind of managing their own health and income. As South Africa continues to broaden its delivery of antiretroviral treatment and AIDS support services, it is important that planners incorporate an understanding of how an HIV or AIDS diagnosis in the context of entrenched poverty may represent both a threat and a means to financial survival. There is a need to consider the 'disinhibiting' effects on HIV prevention and treatment that may result when AIDS support services are aimed at addressing the needs of individuals as opposed to the needs of highly affected communities.

Given Resource Constraints, It Would Be Unethical To Divert Antiretroviral Drugs From Treatment To Prevention

PubMed Central

Macklin, Ruth; Cowan, Ethan

2013-01-01

Striking advances in HIV prevention have set the stage for renewed debate on setting priorities in the fight against HIV/AIDS. Two new prevention strategies preexposure prophylaxis and treatment as prevention—use antiretroviral drugs for prevention of HIV/AIDS in addition to treating patients. The potential for success of these new prevention strategies sets up an ethical dilemma: where resources are limited and supplies of lifesaving antiretroviral medications are insufficient to treat those currently living with HIV, how should these resources be divided between treatment and prevention? This article explores several ethical principles used in formulating public health policy. Assuming that limited resources are available for spending on drugs, we conclude that it would be unethical to watch patients with treatable AIDS worsen and die, even with supportive care, so that medications for treatment can be diverted for prevention. PMID:22778343

Current Perspectives on HIV-1 Antiretroviral Drug Resistance

PubMed Central

Iyidogan, Pinar; Anderson, Karen S.

2014-01-01

Current advancements in antiretroviral therapy (ART) have turned HIV-1 infection into a chronic and manageable disease. However, treatment is only effective until HIV-1 develops resistance against the administered drugs. The most recent antiretroviral drugs have become superior at delaying the evolution of acquired drug resistance. In this review, the viral fitness and its correlation to HIV-1 mutation rates and drug resistance are discussed while emphasizing the concept of lethal mutagenesis as an alternative therapy. The development of resistance to the different classes of approved drugs and the importance of monitoring antiretroviral drug resistance are also summarized briefly. PMID:25341668

Transitions of Care Model Inclusive of Unplanned Care Improves the Patient Experience

PubMed Central

Cox, Jon; Teague, Stephanie; Beck, Eric

2016-01-01

A major emphasis in health care is creating an experience whereby patients receive the right care at the right time from the right provider in the right setting at the right cost. Over the past several decades, there has been considerable effort in the area of medical management, with prior authorization, gatekeeper utilization management regimens, and other techniques designed to guide patients and caregivers into desired treatment pathways. Alternatively, the concept of demand management may be employed to achieve these desired outcomes by giving patients meaningful, expanded choices beyond traditional acute-care settings. The implementation of a novel, patient-centered, unplanned care delivery model is described along with illustrative case studies. PMID:28725828

Dealing with large-scale supply lines when introducing new regimens.

PubMed

Malati, Christine; Rosenfeld, Joshua; Mowafy, Sherif; Rittmiller, Trevor; Kuritsky, Joel; Crowley, John

2017-07-01

As programs plan the introduction of a new antiretroviral as part of a regimen for HIV treatment, supply chain considerations need to be taken into account. The key to success is balancing the introduction of a new regimen with the phasing out of an old regimen in a manner that does not result in either a shortage or an excess supply of either product while ensuring that patients continue receiving their medications. This necessitates that country programs, donors, and procurement entities possess an appreciation of the global antiretroviral market and understand the dynamics that the manufacturing of new antiretrovirals will have on the transition. Supply, demand, and financial considerations affect the capacity of the supply chain to facilitate a successful antiretroviral transition. Although this commentary draws on United States Agency for International Development experiences under the President's Emergency Plan for AIDS Relief from earlier antiretroviral treatment shifts, the approaches are applicable to other institutions and to future transitions. Three approaches were employed: ensuring the engagement of all key stakeholders in transition planning and execution, including clinicians, advocacy groups, supply chain professionals, ministry, and donors; conducting and updating regularly the national quantification and supply plans for all regimens; and introducing antiretroviral products into programs from regional warehouses based on firm orders. Extensive planning and accounting for supply chain factors is essential to ensuring a smooth transition to a new regimen and to enable the global antiretroviral market to respond adequately.

Evaluation of bone mineral density in Iranian HIV/AIDS patients.

PubMed

Badie, Banafsheh Moradmand; Soori, Tahereh; Kheirandish, Parastoo; Izadyar, Saeed; SeyedAlinagh, SeyedAhmad; Foroughi, Maryam; Rostamian, Alireza; Mohraz, Minoo

2011-01-01

Bone disorders have emerged as a worrisome complication in HIV-infected patients in recent years. It is not clear that HIV infection itself or antiretroviral treatment or both are causes of bone loss. However, most studies have found a high prevalence of osteopenia and osteoporosis in HIV/AIDS patients. The objectives of this study were to determine the prevalence of osteopenia and osteoporosis in HIV-infected patients either untreated or receiving Highly Active Antiretroviral Therapy as compared with HIV negative persons. We also assessed the factors associated with these conditions. Bone Mineral Density was assessed by Dual Energy X-Ray Absorptiometry scans at the hip and lumbar spine in 36 AIDS patients receiving antiretroviral therapy and 44 HIV infected patients not receiving antiretroviral therapy (naïve patients) and 40 HIV negative individuals as control. Factors that affect BMD were also determined. Prevalence of osteopenia or osteoporosis in different regions was significantly higher in HIV/AIDS patients compared with HIV negative subjects (77.3% in HIV positive naïve patients, 86.1% in HAART-treated patients and 60% in the control group, P=0.002). Mean serum alkaline phosphatase was higher in HIV/AIDS patients than the control group (P=0.003). Osteopenia and osteoporosis in HIV-infected patients were associated with duration of HIV infection (P<0.0001) and antiretroviral treatment (P=0.012). Prevalence of osteopenia and osteoporosis in HIV/AIDS patients was higher than HIV negative individuals. Osteopenia and osteoporosis in HIV/AIDS patients was associated with duration of HIV infection and antiretroviral treatment.

A Comparison of Adverse Drug Reaction Profiles in Patients on Antiretroviral and Antitubercular Treatment in Zimbabwe.

PubMed

Masuka, Josiah T; Chipangura, Precious; Nyambayo, Priscilla P; Stergachis, Andy; Khoza, Star

2018-01-01

Few studies describe the adverse drug event profiles in patients simultaneously receiving antiretroviral and anti-tubercular medicines in resource-limited countries. To describe and compare the adverse drug reaction profiles in patients on highly active antiretroviral therapy only (HAART), HAART and isoniazid preventive therapy (HHART), and HAART and antitubercular treatment (ATTHAART). We analysed individual case safety reports (ICSRs) for patients on antiretroviral therapy and antitubercular treatment submitted to the national pharmacovigilance centre during the targeted spontaneous reporting (TSR) programme from 1 September 2012 through 31 August 2016. All reports considered certain, probable or possible were included in the analysis. A total of 1076 ICSRs were included in the analysis. Most of the reports were from the HAART only group (n = 882; 82.0%), followed by patients on HHART (n = 132; 12.3%), and ATTHAART (n = 62; 5.7%). The ATTHAART (35.5%) and HHAART (34.1%) had a higher frequency of hepatic disorders than the HAART group (5.0%) (p < 0.0001). A higher frequency of rash was reported in the HHAART (35.6%) and HAART groups (29.4%) than the ATTHAART group (14.5%) (p = 0.011). Peripheral neuropathy occurred more frequently in the ATTHAART group (19.3%) than other groups (p = 0.001) while Stevens-Johnson syndrome (14.7%; p < 0.001), gynaecomastia (18.2%; p < 0.001), and lipodystrophy (4.5%; p = 0.012) occurred more frequently in the HAART group. The HHAART group was associated with a higher frequency of psychosis (4.5%; p = 0.002). Antiretroviral therapy was associated with a higher frequency of Stevens-Johnson syndrome, gynaecomastia, and lipodystrophy. Co-administration of antiretroviral and antitubercular medicines was associated with a higher frequency of drug-induced liver injury and peripheral neuropathy. Similarly, co-administration of isoniazid preventive therapy and antiretroviral drugs was associated with a higher risk for psychosis. There is a need to carefully manage TB/HIV co-infected patients, due to the higher risk of adverse drug reactions which may lead to poor treatment adherence and outcomes.

HIV/AIDS and Infertility: Emerging Problems in the Era of Highly Active Antiretrovirals

PubMed Central

Kushnir, Vitaly A.; Lewis, William

2011-01-01

Objective To review the effects of HIV/AIDS, associated co-morbid conditions, and side effects of antiretroviral treatment on fertility. Design A Pubmed computer search was performed to identify relevant articles. Setting Research institution. Intervention(s) None. Result(s) Biological alterations in reproductive physiology may account for sub-fertility in patients infected with HIV. Psychosocial factors in patients with HIV infection may affect reproductive desires and outcomes. Antiretroviral medications may have direct toxicity on gametes and embryos. Available evidence indicates that fertility treatments can be a safe option for HIV-discordant couples; although, potential risk of viral transmission cannot be completely eliminated. Conclusion(s) Reproductive desires are increasingly becoming prominent in the healthcare of young HIV-infected patients. Additional data is needed to address the effect of HIV and its treatments on fertility and reproductive outcomes. PMID:21722892

First Italian consensus statement on diagnosis, prevention and treatment of cardiovascular complications in HIV-infected patients in the HAART era (2006).

PubMed

Carosi, G; Quiros-Roldan, E; Torti, C; Antinori, A; Bevilacqua, M; Bonadonna, R C; Bonfanti, P; Castagna, A; Cauda, R; d'Arminio-Monforte, A; Di Gregorio, P; Di Perri, G; Esposito, R; Fatuzzo, F; Gervasoni, C; Giannattasio, C; Guaraldi, G; Lazzarin, A; Lo Caputo, S; Maggi, P; Mazzotta, F; Moroni, M; Prestileo, T; Ranieri, R; Rizzardini, G; Russo, R; Galli, M

2007-06-01

The present document contains recommendations for assessment, prevention and treatment of cardiovascular risk for HIV-infected patients. All recommendations were graded according to the strength and quality of the evidence and were voted on by 73 members of the Italian Cardiovascular Risk Guidelines Working Group which includes both experts in HIV/AIDS care and in cardiovascular and metabolic medicine. Since antiretroviral drug exposure represents only one risk factor, continued emphasis on an integrated management is given. This should include prevention and treatment of known cardiovascular risk factors (such as dyslipidaemia, diabetes, insulin resistance, healthy diet, physical activity, avoidance of smoking), but also rational switch of antiretroviral drugs. A rational switch strategy should consider both metabolic and anthropometric disturbances and effectiveness of antiretroviral regimens.

Brainstem Auditory Evoked Potential in HIV-Positive Adults.

PubMed

Matas, Carla Gentile; Samelli, Alessandra Giannella; Angrisani, Rosanna Giaffredo; Magliaro, Fernanda Cristina Leite; Segurado, Aluísio C

2015-10-20

To characterize the findings of brainstem auditory evoked potential in HIV-positive individuals exposed and not exposed to antiretroviral treatment. This research was a cross-sectional, observational, and descriptive study. Forty-five HIV-positive individuals (18 not exposed and 27 exposed to the antiretroviral treatment - research groups I and II, respectively - and 30 control group individuals) were assessed through brainstem auditory evoked potential. There were no significant between-group differences regarding wave latencies. A higher percentage of altered brainstem auditory evoked potential was observed in the HIV-positive groups when compared to the control group. The most common alteration was in the low brainstem. HIV-positive individuals have a higher percentage of altered brainstem auditory evoked potential that suggests central auditory pathway impairment when compared to HIV-negative individuals. There was no significant difference between individuals exposed and not exposed to antiretroviral treatment.

Global trends in antiretroviral resistance in treatment-naive individuals with HIV after rollout of antiretroviral treatment in resource-limited settings: a global collaborative study and meta-regression analysis.

PubMed

Gupta, Ravindra K; Jordan, Michael R; Sultan, Binta J; Hill, Andrew; Davis, Daniel H J; Gregson, John; Sawyer, Anthony W; Hamers, Raph L; Ndembi, Nicaise; Pillay, Deenan; Bertagnolio, Silvia

2012-10-06

The emergence and spread of high levels of HIV-1 drug resistance in resource-limited settings where combination antiretroviral treatment has been scaled up could compromise the effectiveness of national HIV treatment programmes. We aimed to estimate changes in the prevalence of HIV-1 drug resistance in treatment-naive individuals with HIV since initiation of rollout in resource-limited settings. We did a systematic search for studies and conference abstracts published between January, 2001, and July, 2011, and included additional data from the WHO HIV drug resistance surveillance programme. We assessed the prevalence of drug-resistance mutations in untreated individuals with respect to time since rollout in a series of random-effects meta-regression models. Study-level data were available for 26,102 patients from sub-Saharan Africa, Asia, and Latin America. We recorded no difference between chronic and recent infection on the prevalence of one or more drug-resistance mutations for any region. East Africa had the highest estimated rate of increase at 29% per year (95% CI 15 to 45; p=0·0001) since rollout, with an estimated prevalence of HIV-1 drug resistance at 8 years after rollout of 7·4% (4·3 to 12·7). We recorded an annual increase of 14% (0% to 29%; p=0·054) in southern Africa and a non-significant increase of 3% (-0·9 to 16; p=0·618) in west and central Africa. There was no change in resistance over time in Latin America, and because of much country-level heterogeneity the meta-regression analysis was not appropriate for Asia. With respect to class of antiretroviral, there were substantial increases in resistance to non-nucleoside reverse transcriptase inhibitors (NNRTI) in east Africa (36% per year [21 to 52]; p<0·0001) and southern Africa (23% per year [7 to 42]; p=0·0049). No increase was noted for the other drug classes in any region. Our findings suggest a significant increase in prevalence of drug resistance over time since antiretroviral rollout in regions of sub-Saharan Africa; this rise is driven by NNRTI resistance in studies from east and southern Africa. The findings are of concern and draw attention to the need for enhanced surveillance and drug-resistance prevention efforts by national HIV treatment programmes. Nevertheless, estimated levels, although increasing, are not unexpected in view of the large expansion of antiretroviral treatment coverage seen in low-income and middle-income countries--no changes in antiretroviral treatment guidelines are warranted at the moment. Bill & Melinda Gates Foundation and the European Community's Seventh Framework Programme. Copyright © 2012 Elsevier Ltd. All rights reserved.

The prevalence of antiretroviral multidrug resistance in highly active antiretroviral therapy-treated patients with HIV/AIDS between 2004 and 2009 in South Korea.

PubMed

Choi, Ju-yeon; Kwon, Oh-Kyung; Choi, Byeong-Sun; Kee, Mee-Kyung; Park, Mina; Kim, Sung Soon

2014-06-01

Highly active antiretroviral therapy (HAART) including protease inhibitors (PIs) has been used in South Korea since 1997. Currently, more than 20 types of antiretroviral drugs are used in the treatment of human immunodeficiency virus-infected/acquired immune deficiency syndrome patients in South Korea. Despite the rapid development of various antiretroviral drugs, many drug-resistant variants have been reported after initiating HAART, and the efficiency of HAART is limited by these variants. To investigate and estimate the annual antiretroviral drug resistance and prevalence of antiretroviral multi-class drug resistance in Korean patients with experience of treatment. The amplified HIV-1 pol gene in 535 patients requested for genotypic drug resistance testing from 2004 to 2009 by the Korea Centers for Disease Control and Prevention was sequenced and analyzed annually and totally. The prevalence of antiretroviral drug resistance was estimated based on "SIR" interpretation of the Stanford sequence database. Of viruses derived from 787 specimens, 380 samples (48.3%) showed at least one drug class-related resistance. Predicted NRTI drug resistance was highest at 41.9%. NNRTI showed 27.2% resistance with 23.3% for PI. The percent of annual drug resistance showed similar pattern and slightly declined except 2004 and 2005. The prevalence of multi-class drug resistance against each drug class was: NRTI/NNRTI/PI, 9.8%; NRTI/PI, 21.9%; NNRTI/PI, 10.4%; and NRTI/NNRTI, 21.5%. About 50% and less than 10% of patients infected with HIV-1 have multidrug and multiclass resistance linked to 16 antiretroviral drugs, respectively. The significance of this study lies in its larger-scale examination of the prevalence of drug-resistant variants and multidrug resistance in HAART-experienced patients in South Korea. Copyright © 2014 Elsevier B.V. All rights reserved.

Medically Serious Suicide Attempters with or without Plan in Rural China1

PubMed Central

Sun, Long; Zhang, Jie

2015-01-01

Although previous studies have discussed the risk factors of unplanned suicide behavior in several countries, the unplanned suicide attempt in China was not explored in a large sample. We aim to look into the characteristics of unplanned suicide attempters in China, and compare them with those suicide attempters with plans. Subjects were 791 medically serious suicide attempters aged 15–54 years in rural China. The sixth item of Beck’s Suicide Intent Scale (SIS) was used to estimate the planned and unplanned suicide attempt. Logistic regression analysis was performed to examine the factors related to planned or unplanned suicide attempt. The results showed that the planned suicide attempt were associated with higher education, hopelessness and prior suicide act. The unplanned suicide attempt tend to suicide by pesticide and store pesticide at home. A ban of lethal pesticides may be a method for suicide prevention in rural China. PMID:26524517

Threshold virus dynamics with impulsive antiretroviral drug effects

PubMed Central

Lou, Jie; Lou, Yijun; Wu, Jianhong

2013-01-01

The purposes of this paper are twofold: to develop a rigorous approach to analyze the threshold behaviors of nonlinear virus dynamics models with impulsive drug effects and to examine the feasibility of virus clearance following the Manuals of National AIDS Free Antiviral Treatment in China. An impulsive system of differential equations is developed to describe the within-host virus dynamics of both wild-type and drug-resistant strains when a combination of antiretroviral drugs is used to induce instantaneous drug effects at a sequence of dosing times equally spaced while drug concentrations decay exponentially after the dosing time. Threshold parameters are derived using the basic reproduction number of periodic epidemic models, and are used to depict virus clearance/persistence scenarios using the theory of asymptotic periodic systems and the persistence theory of discrete dynamical systems. Numerical simulations using model systems parametrized in terms of the antiretroviral therapy recommended in the aforementioned Manuals illustrate the theoretical threshold virus dynamics, and examine conditions under which the impulsive antiretroviral therapy leads to treatment success. In particular, our results show that only the drug-resistant strain can dominate (the first-line treatment program guided by the Manuals) or both strains may be rapidly eliminated (the second-line treatment program), thus the work indicates the importance of implementing the second-line treatment program as soon as possible. PMID:21987085

Can the generic antiretroviral industry support access to a universal antiretroviral regimen?

PubMed

Amole, Carolyn D; Middlecote, Caroline; Prabhu, Vineet R; Kumarasamy, N

2017-07-01

The generic antiretroviral (ARV) industry played a critical role in the massive scale-up of HIV treatment in low-income and middle-income countries since 2000. As the global community looks ahead to a universal antiretroviral regimen, this article considers the industry's role in supporting universal access to affordable, simpler, more durable, and tolerable HIV treatment regimens. Generic manufacturers made treatment scale-up in low-income and middle-income countries possible through reducing prices, combining molecules from different originator companies to develop optimal fixed-dose combinations, and investing in production capacity to meet escalating demand. Achieving scale-up of a universal regimen will require continued partnership in these areas. Collaboration on the demand and supply sides of the ARV marketplace will be required to foster a healthy and sustainable marketplace for new regimens. This includes clear priority setting from the global treatment community on priority products; predictable demand; regulatory prioritization of optimal products; effective tendering and procurement practices that enable multiple suppliers to participate in the market; coordinated product introduction efforts between Ministries of Health, partners, and civil society; and transparency from both buyers and suppliers to promote and monitor supply security. New regimens will benefit people living with HIV, as well as buyers and generic suppliers, by maximizing existing production capacity and treatment budgets to reach the 90-90-90 goals.

Frequency of Antiretroviral Resistance Mutations among Infants Exposed to Single-Dose Nevirapine and Short Course Maternal Antiretroviral Regimens: ACTG A5207.

PubMed

Hitti, Jane; Halvas, Elias K; Zheng, Lu; Panousis, Constantinos G; Kabanda, Joseph; Taulo, Frank; Kumarasamy, Nagalingeswaran; Pape, Jean William; Lalloo, Umesh; Sprenger, Heather; Klingman, Karin L; Chan, Ellen S; McMahon, Deborah; Mellors, John W

2014-11-01

Intrapartum single-dose nevirapine (sdNVP) reduces HIV-1 perinatal transmission but selects NVP resistance among mothers and infants. We evaluated the frequency of antiretroviral resistance among infants with intrauterine HIV-1 infection exposed to sdNVP and maternal antenatal or breastfeeding antiretroviral therapy. This analysis included 429 infants from sub-Saharan Africa, India and Haiti whose 422 mothers received sdNVP plus maternal study treatment. At entry mothers had CD4>250/μL and were ART-naïve except for antenatal ZDV per local standard of care. Maternal study treatment started intrapartum and included ZDV/3TC, TDF/FTC or LPV/r for 7 or 21 days in a randomized factorial design. Infants received sdNVP study treatment and ZDV if local standard of care. Infant HIV RNA or DNA PCR and samples for genotype were obtained at birth and weeks 2, 4 and 12; infants who ever breast-fed were also tested at weeks 16, 24, 48 and 96. Samples from HIV-1-infected infants were tested for drug resistance by population genotype (ViroSeq). NVP or NRTI resistance mutations were assessed using the IAS-USA mutation list. Perinatal HIV-1 transmission occurred in 17 (4.0%) infants including 12 intrauterine infections. Resistance mutations were detected among 5 (42%) intrauterine-infected infants; of these, 3 had mutations conferring resistance to NVP alone, 1 had resistance to NRTI alone, and 1 had dual-class resistance mutations. Among the 2 infants with NRTI mutations, one (K70R) was likely maternally transmitted and one (K65R) occurred in the context of breastfeeding exposure to maternal antiretroviral therapy. Infants with intrauterine HIV infection are at risk of acquiring resistance mutations from exposure to maternal antiretroviral medications intrapartum and/or during breastfeeding. New approaches are needed to lower the risk of antiretroviral resistance in these infants.

Transmitted drug resistance in patients with acute/recent HIV infection in Brazil.

PubMed

Ferreira, Ana Cristina G; Coelho, Lara E; Grinsztejn, Eduarda; Jesus, Carlos S de; Guimarães, Monick L; Veloso, Valdiléa G; Grinsztejn, Beatriz; Cardoso, Sandra W

The widespread use of antiretroviral therapy increased the transmission of antiretroviral resistant HIV strains. Antiretroviral therapy initiation during acute/recent HIV infection limits HIV reservoirs and improves immune response in HIV infected individuals. Transmitted drug resistance may jeopardize the early goals of early antiretroviral treatment among acute/recent HIV infected patients. Patients with acute/recent HIV infection who underwent resistance test before antiretroviral treatment initiation were included in this analysis. HIV-1 sequences were obtained using an in house protease/reverse transcriptase genotyping assay. Transmitted drug resistance was identified according to the Stanford HIV Database for Transmitted Drug Resistance Mutations, based on WHO 2009 surveillance list, and HIV-1 subtyping according to Rega HIV-1 subtyping tool. Comparison between patients with and without transmitted drug resistance was made using Kruskal-Wallis and Chi-square tests. Forty-three patients were included, 13 with acute HIV infection and 30 with recent HIV infection. The overall transmitted drug resistance prevalence was 16.3% (95% confidence interval [CI]: 8.1-30.0%). The highest prevalence of resistance (11.6%, 95% CI: 8.1-24.5) was against non-nucleoside reverse transcriptase inhibitors, and K103N was the most frequently identified mutation. The high prevalence of nonnucleoside reverse transcriptase inhibitors resistance indicates that efavirenz-based regimen without prior resistance testing is not ideal for acutely/recently HIV-infected individuals in our setting. In this context, the recent proposal of including integrase inhibitors as a first line regimen in Brazil could be an advantage for the treatment of newly HIV infected individuals. However, it also poses a new challenge, since integrase resistance test is not routinely performed for antiretroviral naive individuals. Further studies on transmitted drug resistance among acutely/recently HIV-infected are needed to inform the predictors of transmitted resistance and the antiretroviral therapy outcomes among these population. Copyright © 2017 Sociedade Brasileira de Infectologia. Published by Elsevier Editora Ltda. All rights reserved.

"Conditional Scholarships" for HIV/AIDS Health Workers: Educating and Retaining the Workforce to Provide Antiretroviral Treatment in Sub-Saharan Africa. NBER Working Paper No. 13396

ERIC Educational Resources Information Center

Barnighausen, Till; Bloom, David E.

2007-01-01

Without large increases in the number of health workers to treat HIV/AIDS (HAHW), most developing countries will be unable to achieve universal coverage with antiretroviral treatment (ART), leading to large numbers of potentially avoidable deaths among people living with HIV/AIDS. We use Markov Monte Carlo microsimulation to estimate the expected…

CROI 2016: Advances in Antiretroviral Therapy.

PubMed

Taylor, Barbara S; Olender, Susan A; Tieu, Hong-Van; Wilkin, Timothy J

2016-01-01

The 2016 Conference on Retroviruses and Opportunistic Infections highlighted exciting advances in antiretroviral therapy, including important data on investigational antiretroviral drugs and clinical trials. Clinical trials demonstrated benefits from a long-acting injectable coformulation given as maintenance therapy, examined intravenous and subcutaneous administration of a monoclonal antibody directed at the CD4 binding site of HIV-1, and provided novel data on tenofovir alafenamide. Several studies focused on the role of HIV drug resistance, including the significance of minority variants, transmitted drug resistance, use of resistance testing, and drug class-related resistance. Novel data on the HIV care continuum in low- and middle-income settings concentrated on differentiated HIV care delivery models and outcomes. Data on progress toward reaching World Health Organization 90-90-90 targets as well as outcomes related to expedited initiation of HIV treatment and adherence strategies were presented. Results from a trial in Malawi showed reduced rates of mother-to-child transmission among HIV-infected women who initiated antiretroviral therapy prior to pregnancy, and several studies highlighted the effect of antiretroviral therapy in pediatric populations. A special session was dedicated to the findings of studies of Ebola virus disease and treatment during the outbreak in West Africa.

Antiretroviral treatment of adult HIV infection: 2008 recommendations of the International AIDS Society-USA panel.

PubMed

Hammer, Scott M; Eron, Joseph J; Reiss, Peter; Schooley, Robert T; Thompson, Melanie A; Walmsley, Sharon; Cahn, Pedro; Fischl, Margaret A; Gatell, Jose M; Hirsch, Martin S; Jacobsen, Donna M; Montaner, Julio S G; Richman, Douglas D; Yeni, Patrick G; Volberding, Paul A

2008-08-06

The availability of new antiretroviral drugs and formulations, including drugs in new classes, and recent data on treatment choices for antiretroviral-naive and -experienced patients warrant an update of the International AIDS Society-USA guidelines for the use of antiretroviral therapy in adult human immunodeficiency virus (HIV) infection. To summarize new data in the field and to provide current recommendations for the antiretroviral management and laboratory monitoring of HIV infection. This report provides guidelines in key areas of antiretroviral management: when to initiate therapy, choice of initial regimens, patient monitoring, when to change therapy, and how best to approach treatment options, including optimal use of recently approved drugs (maraviroc, raltegravir, and etravirine) in treatment-experienced patients. A 14-member panel with expertise in HIV research and clinical care was appointed. Data published or presented at selected scientific conferences since the last panel report (August 2006) through June 2008 were identified. Data that changed the previous guidelines were reviewed by the panel (according to section). Guidelines were drafted by section writing committees and were then reviewed and edited by the entire panel. Recommendations were made by panel consensus. New data and considerations support initiating therapy before CD4 cell count declines to less than 350/microL. In patients with 350 CD4 cells/microL or more, the decision to begin therapy should be individualized based on the presence of comorbidities, risk factors for progression to AIDS and non-AIDS diseases, and patient readiness for treatment. In addition to the prior recommendation that a high plasma viral load (eg, >100,000 copies/mL) and rapidly declining CD4 cell count (>100/microL per year) should prompt treatment initiation, active hepatitis B or C virus coinfection, cardiovascular disease risk, and HIV-associated nephropathy increasingly prompt earlier therapy. The initial regimen must be individualized, particularly in the presence of comorbid conditions, but usually will include efavirenz or a ritonavir-boosted protease inhibitor plus 2 nucleoside reverse transcriptase inhibitors (tenofovir/emtricitabine or abacavir/lamivudine). Treatment failure should be identified and managed promptly, with the goal of therapy, even in heavily pretreated patients, being an HIV-1 RNA level below assay detection limits.

Dietary diversity and associated factors among HIV positive adults attending antiretroviral therapy clinics at Hiwot Fana and Dilchora Hospitals, eastern Ethiopia.

PubMed

Weldegebreal, Fitsum; Digaffe, Tesfaye; Mesfin, Frehiwot; Mitiku, Habtamu

2018-01-01

Nutritional care is considered a crucial component of comprehensive care for people living with HIV/AIDS (PLWHA), particularly in resource-limited settings where malnutrition and food insecurity are endemic problems, and low quality monotonous diets are the norm. The findings of this study provide baseline information on dietary diversity and related factors for health care providers so that they will be able to improve nutritional care and support activity. Therefore, the aim of this study was to assess dietary diversity and associated factors among HIV positive adults (18-65 years old) attending antiretroviral therapy (ART) clinics at Hiwot Fana and Dilchora Hospitals, eastern Ethiopia. An institution-based cross-sectional study was conducted from November 2015 to February 2016 at the ART clinics of Hiwot Fana and Dilchora Hospitals. Using a systematic random sampling technique, a total of 303 patients were selected from all adults attending the ART clinics. The data were collected with a 95% CI used to show association between dietary diversity and independent factors. A total of 303 adult HIV positive individuals on ART participated in the study and 62.4% were females. The largest numbers of participants (49.5%) were 30-40 years of age. Eighty-seven (28.7%) participants had low dietary diversity (≤4 food groups). Duration of anti-retroviral treatment was the factor significantly associated with dietary diversity: respondents with a duration of antiretroviral treatment of more than 2 years were almost two times more likely to have high dietary diversity compared with those with less than a year of antiretroviral treatment (adjusted odds ratio =0.490; 95% CI: 0.091, 0.978). Low dietary diversity was found to be a nutritional problem among HIV positive adults. Duration of antiretroviral treatment was the predictor of low dietary diversity. Therefore, appropriate dietary management of side effects of ART is important.

Maraviroc: the evidence for its potential in the management of HIV

PubMed Central

Profit, Louise

2007-01-01

Introduction: New antiretroviral agents that are more convenient, better tolerated with fewer short- and long-term side effects, and that have novel resistance patterns are needed at all lines of therapy in patients infected with human immunodeficiency virus (HIV). Therefore, next generation products of current classes and alternative classes of antiretroviral agents are needed. The CC-chemokine receptor 5 (CCR5) antagonists are a novel class of antiretroviral agents that prevent the entry of HIV into host cells by blocking the CCR5 coreceptor. Within this class, maraviroc is the agent furthest along in development. Aims: The aim of this review is to evaluate the emerging evidence for the use of the CCR5 antagonist maraviroc in antiretroviral treatment-naïve and treatment-experienced patients with HIV-1 infection. Evidence review: Preliminary evidence from phase I/IIa short-term studies suggest that maraviroc monotherapy is effective at reducing HIV viral load, and is generally well tolerated. In-vitro evidence suggests that maraviroc will be effective in drug-naïve patients with CCR5-tropic virus, as well as in those with CCR5-tropic virus who have developed HIV resistance to existing antiretroviral regimens. However, it is not known how quickly resistance may develop to maraviroc in clinical practice. Clinical potential: Current evidence supports the continued development of maraviroc as a potentially useful, alternative treatment for the management of HIV infection. Maraviroc monotherapy has a high potency and long half-life, allowing single-pill dosing. Therefore, it is expected that maraviroc will have a beneficial effect on patient adherence and viral load in combination with other antiretroviral agents. Maraviroc is only effective against CCR5-tropic virus, which predominates throughout infection but is more common in patients at the early asymptomatic stage of infection. PMID:21221194

Tobacco and alcohol use in adolescents with unplanned pregnancies: relation with family structure, tobacco and alcohol use at home and by friends.

PubMed

Francisco, Vazquez-Nava; Carlos, Vazquez-Rodríguez; Eliza, Vazquez-Rodriguez; Octelina, Castillo-Ruiz; Maria, Iribar Ibabe

2016-03-01

Recent publications show that smoking and alcohol use among adolescents with unplanned pregnancy is increasing and the causes need to be further studied. To determine the association between living in a non-intact family household and the presence of smokers and consumers of alcoholic beverages in the adolescents' environment with smoking and consuming alcoholic beverages in adolescents with unplanned pregnancies. A cross-sectional study was carried out among 785 pregnant adolescents, aged 13-19 years. Data was collected by trained interviewers using a self-administered questionnaire. The association was determined using multivariate logistic regression analysis. In adolescents with unplanned pregnancies, the prevalence of active smoking was 21.2% and of alcohol consumption, 41.5%. The percentage of smoking at home was 57.4% and alcohol consumption, 77.5%. Approximately, 80.3% of adolescents with unplanned pregnancies had friends who smoked and 90.6% consumed alcoholic beverages. Multivariate logistic regression analysis shows that having friends who smoke or who consume alcoholic beverages is the most important risk factor for substance use in adolescents with unplanned pregnancies. Smoking and alcohol consumption at home are not associated with smoking in adolescents with unplanned pregnancies. Socializing with friends who smoke and/or consume alcoholic beverages constitutes the most important risk factor for substance use among adolescents with unplanned pregnancies.

A Biomechanical Comparison of Single-Leg Landing and Unplanned Sidestepping.

PubMed

Chinnasee, Chamnan; Weir, Gillian; Sasimontonkul, Siriporn; Alderson, Jacqueline; Donnelly, Cyril

2018-06-14

Unplanned sidestepping and single-leg landing have both been used to screen athletes for injury risk in sport. The aim of this study was to directly compare the lower limb mechanics of three single-leg landing tasks and an unplanned sidestepping task. Thirteen elite female team sport athletes completed a series of non-contact single-leg drop landings, single-leg countermovement jumps, single-leg jump landings and unplanned sidestepping in a randomized counterbalanced design. Three dimensional kinematics (250 Hz) and ground reaction force (2,000 Hz) data with a participant specific lower limb skeletal model were used to calculate and compare hip, knee and ankle joint kinematics, peak joint moments, instantaneous joint power and joint work during the weight acceptance phase of each sporting task (α=0.05). Peak knee joint moments and relevant injury risk thresholds were used to classify each athlete's anterior cruciate ligament injury risk during unplanned sidestepping and single-leg jump landing. Results showed that peak joint moments, power and work were greater during the single-leg jump landing task when compared to the single-leg drop landings and single-leg countermovement jumps tasks. Peak frontal and sagittal plane knee joint moments, knee joint power, as well as hip and knee joint work were greater during unplanned sidestepping when compared to the landing tasks. Peak ankle joint moments, power and work were greater during the landing tasks when compared to unplanned sidestepping. For 4 of the 13 athletes tested, their anterior cruciate ligament injury risk classification changed depending on whether they performed an unplanned sidestepping or single-leg jump landing testing procedure. To summarize, a single-leg jump landing testing procedure places a larger mechanical on the ankle joint when compared to single-leg drop landings, single-leg countermovement jumps and unplanned sidestepping. An unplanned sidestepping testing procedure places a larger mechanical demand on the knee joint when compared to single-leg landing tasks. Both unplanned sidestepping and single-leg jump landing testing procedures are recommended for classifying an athlete's anterior cruciate ligament injury risk in sport. © Georg Thieme Verlag KG Stuttgart · New York.

10 CFR 30.50 - Reporting requirements.

Code of Federal Regulations, 2010 CFR

2010-01-01

... requires unplanned medical treatment at a medical facility of an individual with spreadable radioactive... material or any device, container, or equipment containing licensed material when: (i) The quantity of... following: (i) A description of the event, including the probable cause and the manufacturer and model...

10 CFR 30.50 - Reporting requirements.

Code of Federal Regulations, 2011 CFR

2011-01-01

... requires unplanned medical treatment at a medical facility of an individual with spreadable radioactive... material or any device, container, or equipment containing licensed material when: (i) The quantity of... following: (i) A description of the event, including the probable cause and the manufacturer and model...

40 CFR 265.31 - Maintenance and operation of facility.

Code of Federal Regulations, 2014 CFR

2014-07-01

... WASTES (CONTINUED) INTERIM STATUS STANDARDS FOR OWNERS AND OPERATORS OF HAZARDOUS WASTE TREATMENT... any unplanned sudden or non-sudden release of hazardous waste or hazardous waste constituents to air, soil, or surface water which could threaten human health or the -environment. ...

40 CFR 265.31 - Maintenance and operation of facility.

Code of Federal Regulations, 2012 CFR

2012-07-01

... WASTES (CONTINUED) INTERIM STATUS STANDARDS FOR OWNERS AND OPERATORS OF HAZARDOUS WASTE TREATMENT... any unplanned sudden or non-sudden release of hazardous waste or hazardous waste constituents to air, soil, or surface water which could threaten human health or the -environment. ...

40 CFR 265.31 - Maintenance and operation of facility.

Code of Federal Regulations, 2013 CFR

2013-07-01

... WASTES (CONTINUED) INTERIM STATUS STANDARDS FOR OWNERS AND OPERATORS OF HAZARDOUS WASTE TREATMENT... any unplanned sudden or non-sudden release of hazardous waste or hazardous waste constituents to air, soil, or surface water which could threaten human health or the -environment. ...

40 CFR 265.31 - Maintenance and operation of facility.

Code of Federal Regulations, 2011 CFR

2011-07-01

... WASTES (CONTINUED) INTERIM STATUS STANDARDS FOR OWNERS AND OPERATORS OF HAZARDOUS WASTE TREATMENT... any unplanned sudden or non-sudden release of hazardous waste or hazardous waste constituents to air, soil, or surface water which could threaten human health or the -environment. ...

From Protocols to Publications: A Study in Selective Reporting of Outcomes in Randomized Trials in Oncology

PubMed Central

Raghav, Kanwal Pratap Singh; Mahajan, Sminil; Yao, James C.; Hobbs, Brian P.; Berry, Donald A.; Pentz, Rebecca D.; Tam, Alda; Hong, Waun K.; Ellis, Lee M.; Abbruzzese, James; Overman, Michael J.

2015-01-01

Purpose The decision by journals to append protocols to published reports of randomized trials was a landmark event in clinical trial reporting. However, limited information is available on how this initiative effected transparency and selective reporting of clinical trial data. Methods We analyzed 74 oncology-based randomized trials published in Journal of Clinical Oncology, the New England Journal of Medicine, and The Lancet in 2012. To ascertain integrity of reporting, we compared published reports with their respective appended protocols with regard to primary end points, nonprimary end points, unplanned end points, and unplanned analyses. Results A total of 86 primary end points were reported in 74 randomized trials; nine trials had greater than one primary end point. Nine trials (12.2%) had some discrepancy between their planned and published primary end points. A total of 579 nonprimary end points (median, seven per trial) were planned, of which 373 (64.4%; median, five per trial) were reported. A significant positive correlation was found between the number of planned and nonreported nonprimary end points (Spearman r = 0.66; P < .001). Twenty-eight studies (37.8%) reported a total of 65 unplanned end points; 52 (80.0%) of which were not identified as unplanned. Thirty-one (41.9%) and 19 (25.7%) of 74 trials reported a total of 52 unplanned analyses involving primary end points and 33 unplanned analyses involving nonprimary end points, respectively. Studies reported positive unplanned end points and unplanned analyses more frequently than negative outcomes in abstracts (unplanned end points odds ratio, 6.8; P = .002; unplanned analyses odd ratio, 8.4; P = .007). Conclusion Despite public and reviewer access to protocols, selective outcome reporting persists and is a major concern in the reporting of randomized clinical trials. To foster credible evidence-based medicine, additional initiatives are needed to minimize selective reporting. PMID:26304898

Antiretroviral therapy for human immunodeficiency virus infection in 1997.

PubMed Central

Katzenstein, D A

1997-01-01

It has become clear that the acquired immunodeficiency syndrome follows continuous replication of the human immunodeficiency virus (HIV) and a decrease in immune capability, most obviously a decline in the number of CD4 lymphocytes. An understanding of key elements in the infectious life cycle of HIV has led to the development of potent antiretroviral drugs selectively targeting unique reverse transcriptase and protease enzymes of the virus. Completed clinical trials have shown that antiretroviral therapy for HIV infection, begun early, reduces viral replication and reverses the decline in CD4 lymphocyte numbers. Recent studies of combination therapies have shown that decreases in plasma HIV viremia to low levels and sustained increases in CD4 cell numbers are associated with longer survival. Potent combination regimens including protease inhibitors and non-nucleoside reverse transcriptase inhibitors suppress detectable viral replication and have demonstrated clinical benefits in patients with advanced disease. Progress in antiretroviral therapy and methods to monitor responses to treatment are providing new hope in the treatment of HIV infection. PMID:9217434

Predictors of mortality among HIV infected patients taking antiretroviral treatment in Ethiopia: a retrospective cohort study

PubMed Central

2012-01-01

Background Studies indicate that there is high early mortality among patients starting antiretroviral treatment in sub-Saharan Africa. However, there is paucity of evidence on long term survival of patients on anti-retroviral treatment in the region. The objective of this study is to examine mortality and its predictors among a cohort of HIV infected patients on anti-retroviral treatment retrospectively followed for five years. Methods A retrospective cohort study was conducted among HIV infected patients on ART in eastern Ethiopia. Cox regression and Kaplan-Meier analyses were performed to investigate factors that influence time to death and survival over time. Result A total of 1540 study participants were included in the study. From the registered patients in the cohort, the outcome of patients as active, deceased, lost to follow up and transfer out was 1005 (67.2%), 86 (5.9%), 210 (14.0%) and 192 (12.8%) respectively. The overall mortality rate provides an incidence density of 2.03 deaths per 100 person years (95% CI 1.64 - 2.50). Out of a total of 86 deaths over 60 month period; 63 (73.3%) died during the first 12 months, 10 (11.6%) during the second year, and 10 (11.6%) in the third year of follow up. In multivariate analysis, the independent predictors for mortality were loss of more 10% weight loss, bedridden functional status at baseline, ≤ 200 CD4 cell count/ml, and advanced WHO stage patients. Conclusion A lower level of mortality was detected among the cohort of patients on antiretroviral treatment in eastern Ethiopia. Previous history of weight loss, bedridden functional status at baseline, low CD4 cell count and advanced WHO status patients had a higher risk of death. Early initiation of ART, provision of nutritional support and strengthening of the food by prescription initiative, and counseling of patients for early presentation to treatment is recommended. PMID:22606951

[Clinical management of acute and chronic human immunodeficiency virus infection before starting antiretroviral treatment].

PubMed

Miró, José M; Manzardo, Christian; Zamora, Laura; Pumarola, Tomas; Herreras, Zoe; Gallart, Teresa; Gatell, José M

2011-12-01

The evaluation of new cases of HIV infection is relatively common in Spain, where several thousands of patients with new infections are diagnosed each year. Eighty per cent of them have a chronic HIV infection at the first clinical evaluation, which is symptomatic (late presenters) in up to 30% of patients. The initial evaluation of HIV infection is not only directed at determining the clinical, virological (plasma HIV RNA viral load, resistance test and viral tropism) and immunological (CD4+ T-cell cell count) situation of the patients, but must also address the study of their co-infections (hepatitis, tuberculosis) and comorbidities (cardiovascular, hepatic, renal and bone) and the risk of HIV transmission. This is needed in order to decide, whether or not to start antiretroviral treatment, and with which combined antiretroviral treatment to start with, the prophylaxis of opportunistic infections, and the treatment of coinfections and comorbidities. The past and current medical history, the physical examination and laboratory tests will help us decide if the patient is to receive therapeutic intervention. The level of CD4+ T-cell lymphocytes is the best marker to suggest when to start combined antiretroviral treatment, indicating whether or not to start prophylaxis against opportunistic infections (if patients have a CD4+ T-cell count below 200 cells/mm(3)), and in advanced patients should make us suspect the presence of active opportunistic diseases in symptomatic cases. The management of patients with HIV infection must also include appropriate health education on the modes of transmission and prevention of HIV infection, and also to explain its natural history and how it can be modified with proper antiretroviral treatment, as well as to promote a healthy life. No less important is the psychological support, as these patients must learn to live with a chronic infection, which managed properly can ensure a very good long-term prognosis and quality of life. Copyright © 2011 Elsevier España, S.L. All rights reserved.

[Recommendations for initial antiretroviral treatment in HIV-infected children. Update 2003].

PubMed

2004-03-01

Highly active antiretroviral therapy in HIV-infected children has been associated with a dramatic decrease in progression to AIDS and HIV-related deaths, and infected children currently have an excellent quality of life. Antiretroviral drugs cannot eradicate the virus, although they can achieve a situation of latent infection. However, chronic use of these drugs has multiple adverse effects, the most important of which are metabolic complications. The large number of drugs required and patient characteristics such as age, tolerance to drugs, adherence, and social problems make unifying the criteria for initial therapy in HIV-infected children difficult. A balance should be sought between not delaying the start of treatment, to avoid immunologic deterioration, and minimizing the long-term adverse effects of the therapy. The present treatment recommendations are adapted from international guidelines and are based on a literature review and on our own experience. Our group previously published recommendations on the treatment of HIV-infected children and the aim of the present article is to provide an update.

Antiretroviral therapy for adults infected with HIV: Guidelines for health care professionals from the Quebec HIV care committee.

PubMed

Rouleau, Danielle; Fortin, Claude; Trottier, Benoît; Lalonde, Richard; Lapointe, Normand; Côté, Pierre; Routy, Jean-Pierre; Matte, Marie-France; Tsarevsky, Irina; Baril, Jean-Guy

2011-01-01

The appropriate use of antiretrovirals reduces morbidity and mortality caused by HIV infection. The present article provides health care professionals with a practical guide for the use of antiretrovirals. Therapy should be initiated based predominantly on clinical presentation and CD4 count, and should consist of three active drugs or at least two active drugs when this is not possible, as in cases of some treatment-experienced patients. This is the most effective way to achieve long-term suppression of viral replication. Selection of individual drugs in the regimen should consider the weight of the evidence supporting these choices, as well as their tolerability profiles and ease of use, the patients' comorbidities and treatment history. Treatment interruption is not recommended, either in aviremic patients or in those who have experienced virological failure. Instead, the therapeutic regimen should be adjusted to minimize side effects, promote adherence and suppress viral replication.

An update and review of antiretroviral therapy.

PubMed

Piacenti, Frank J

2006-08-01

The human immunodeficiency virus (HIV) was discovered in 1982, but treatment strategies were not introduced until 5 years later. Early regimens consisted of one or two drugs and often led to treatment failure. Since the advent in 1995 of highly active antiretroviral therapy (HAART), which consists of at least three agents, a dramatic improvement has been seen in the number of patients attaining undetectable viral loads, improved CD4 counts, and improved survival. However, early HAART often consisted of drugs with complex dosing schedules, strict food requirements, treatment-limiting adverse effects, and the need to take 16-20 pills/day. These treatment barriers often led to patient nonadherence, with subsequent treatment failure and development of resistant strains. The CD4 count and viral load are the most important surrogate markers used to determine if treatment is indicated. Current guidelines suggest starting treatment in patients who are symptomatic with an acquired immunodeficiency syndrome-defining illness regardless of CD4 count or viral load, as well as in asymptomatic patients with a CD4 count of 350 cells/mm(3) or below. In patients with CD4 counts above 350 cells/mm(3) and viral loads above 100,000 copies/ml, some clinicians prefer to defer treatment, whereas others will consider starting therapy; treatment is deferred in patients with CD4 counts above 350 cells/mm(3) and viral load s below 100,000 copies/ml. If therapy is started, the selection of appropriate agents is based on comorbidities (liver disease, depression, cardiovascular disease), pregnancy status, adherence potential (dosage regimen, pill burden, dosing frequency), food restrictions (dosing with regard to meals), adverse drug effects, and potential drug-drug interactions. Within the last 8 years, newer antiretroviral agents have focused on ways to improve adherence, such as convenient dosing (fewer pills), pharmacokinetic and formulation changes to reduce dosing frequency or pill burden, and coformulated dosage forms that contain two or three drugs in one convenient pill. Other improvements include increased potency of newer agents, agents sensitive to a highly resistant virus, improved adverse-effect profile (e.g., less gastrointestinal effects, improved lipid profiles), as well as protease inhibitor boosting with ritonavir, which takes advantage of the potent cytochrome P450 inhibitory action of ritonavir. This review focuses on the concepts of antiretroviral therapy, barriers to successful antiretroviral treatment, developments to limit treatment barriers, and new drug entities for the treatment of HIV.

Loss to follow-up and mortality amongst pregnant women referred to a community clinic for antiretroviral treatment

PubMed Central

Orrell, Catherine; Zwane, Eugene; Bekker, Linda-Gail; Wood, Robin

2009-01-01

Summary In a retrospective cohort analysis, loss to follow-up (LTFU) and mortality rates were compared between pregnant and non-pregnant women referred to a community-based antiretroviral treatment (ART) program in South Africa. While there was no significant difference in adjusted mortality rates between the two groups, the pregnant women had a substantially higher risk of LTFU both pre and on-treatment. This finding highlights the need for programmatic interventions to address retention in care for this patient population. PMID:18670232

Treatment of HIV in the Central Nervous System.

PubMed

Yilmaz, Aylin; Gisslén, Magnus

2014-02-01

Central nervous system (CNS) infection is an important part of systemic human immunodeficiency disease (HIV) infection. It is most often asymptomatic, but can sometimes lead to severe neurologic disease, particularly in advanced stages of immunosuppression. CNS HIV infection usually responds well to antiretroviral treatment, but there are concerns that treatment may not always be fully effective in treating or preventing milder CNS disease and that it, under certain circumstances, might be important to consider antiretroviral drug distribution and effects within the CNS. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Impact of Inpatient Versus Outpatient Total Joint Arthroplasty on 30-Day Hospital Readmission Rates and Unplanned Episodes of Care.

PubMed

Springer, Bryan D; Odum, Susan M; Vegari, David N; Mokris, Jeffrey G; Beaver, Walter B

2017-01-01

This article describes a study comparing 30-day readmission rates between patients undergoing outpatient versus inpatient total hip (THA) and knee (TKA) arthroplasty. A retrospective review of 137 patients undergoing outpatient total joint arthroplasty (TJA) and 106 patients undergoing inpatient (minimum 2-day hospital stay) TJA was conducted. Unplanned hospital readmissions and unplanned episodes of care were recorded. All patients completed a telephone survey. Seven inpatients and 16 outpatients required hospital readmission or an unplanned episode of care following hospital discharge. Readmission rates were higher for TKA than THA. The authors found no statistical differences in 30-day readmission or unplanned care episodes. Copyright © 2016 Elsevier Inc. All rights reserved.

10 CFR 70.50 - Reporting requirements.

Code of Federal Regulations, 2011 CFR

2011-01-01

... requires unplanned medical treatment at a medical facility of an individual with spreadable radioactive... material or any device, container, or equipment containing licensed material when: (i) The quantity of... all factors that contributed to the event and the manufacturer and model number (if applicable) of any...

10 CFR 70.50 - Reporting requirements.

Code of Federal Regulations, 2010 CFR

2010-01-01

... requires unplanned medical treatment at a medical facility of an individual with spreadable radioactive... material or any device, container, or equipment containing licensed material when: (i) The quantity of... all factors that contributed to the event and the manufacturer and model number (if applicable) of any...

10 CFR 76.120 - Reporting requirements.

Code of Federal Regulations, 2011 CFR

2011-01-01

... available and operable to perform the required safety function. (3) An event that requires unplanned medical treatment at a medical facility of an individual with radioactive contamination on the individual's clothing or body. (4) A fire or explosion damaging any radioactive material or any device, container, or...

10 CFR 76.120 - Reporting requirements.

Code of Federal Regulations, 2010 CFR

2010-01-01

... available and operable to perform the required safety function. (3) An event that requires unplanned medical treatment at a medical facility of an individual with radioactive contamination on the individual's clothing or body. (4) A fire or explosion damaging any radioactive material or any device, container, or...

Integrating Antiretroviral Strategies for Human Immunodeficiency Virus Prevention: Post- and Pre-Exposure Prophylaxis and Early Treatment.

PubMed

Grant, Robert M; Smith, Dawn K

2015-12-01

Best practices for integrating human immunodeficiency virus (HIV) testing and antiretroviral interventions for prevention and treatment are suggested based on research evidence and existing normative guidance. The goal is to provide high-impact prevention services during periods of substantial risk. Antiretroviral medications are recommended for postexposure prophylaxis (PEP), pre-exposure prophylaxis (PrEP), and treatment of HIV infection. We reviewed research evidence and current normative guidelines to identify best practices for integrating these high-impact prevention strategies. More sensitive HIV tests used for screening enable earlier diagnosis and treatment of HIV infection, more appropriate counseling, and help limit drug resistance. A fully suppressive PEP regimen should be initiated based on exposure history or physical findings when sensitive diagnostic testing is delayed or not available and antibody tests are negative. Transitions from PEP to PrEP are often warranted because HIV exposure events may continue to occur. This algorithmic approach to integrating PEP, PrEP, and early treatment decisions may increase the uptake of these interventions by a greater number and diversity of knowledgeable healthcare providers.

Integrating Antiretroviral Strategies for Human Immunodeficiency Virus Prevention: Post- and Pre-Exposure Prophylaxis and Early Treatment

PubMed Central

Grant, Robert M.; Smith, Dawn K.

2015-01-01

Best practices for integrating human immunodeficiency virus (HIV) testing and antiretroviral interventions for prevention and treatment are suggested based on research evidence and existing normative guidance. The goal is to provide high-impact prevention services during periods of substantial risk. Antiretroviral medications are recommended for postexposure prophylaxis (PEP), pre-exposure prophylaxis (PrEP), and treatment of HIV infection. We reviewed research evidence and current normative guidelines to identify best practices for integrating these high-impact prevention strategies. More sensitive HIV tests used for screening enable earlier diagnosis and treatment of HIV infection, more appropriate counseling, and help limit drug resistance. A fully suppressive PEP regimen should be initiated based on exposure history or physical findings when sensitive diagnostic testing is delayed or not available and antibody tests are negative. Transitions from PEP to PrEP are often warranted because HIV exposure events may continue to occur. This algorithmic approach to integrating PEP, PrEP, and early treatment decisions may increase the uptake of these interventions by a greater number and diversity of knowledgeable healthcare providers. PMID:26512356

Unplanned admissions in day-case surgery as a clinical indicator for quality assurance.

PubMed

Margovsky, A

2000-03-01

Day surgery is a modern, effective and economical way to treat patients while maintaining the same level of quality of patient care. Quality improvement in day surgery units, however, continues to be an issue due to high rates of unplanned admissions. The aim of the present retrospective study was to investigate reasons for and methods of preventing unplanned postoperative admissions in a day surgical unit over a 12-month period in respect to different surgical specialties. The study was based on an audit from the Endoscopy and Day Surgery Unit (EDSU) at Launceston General Hospital, which provides health care to a population of more than 120000. For the accounted period 920 outpatients had elective day surgical procedures. Overall the unplanned admission rate was 4.7%, and surgical, anaesthetic and social reasons accounted for 58.2, 37.2 and 4.6% of the unplanned admissions, respectively. The highest rate of unplanned admissions was for plastic and reconstructive surgery (12.8%) and orthopaedic surgery (7.5%) despite the relatively small number of patients who underwent such procedures in the day surgery unit. The results also showed a correlation between age group, pre-operative medical status of the patients found suitable for the day surgical procedure and unplanned admissions. Strategies to reduce the unplanned admission rate which include patient selection and pre-operative assessment, patient waiting time and education, pre-operative anaesthesia, follow-up with nursing care and postoperative analgesia are discussed.

Unplanned Pregnancy among Sailors: Background and Opportunities

DTIC Science & Technology

2005-01-05

health assessment. - free, on-line, ready-to-use materials are available to Navy health care professionals for use in patient education and “all-hands...in “all- hands” training and patient education , may help reduce the incidence of unplanned pregnancy among the active duty force. Unplanned

PKC-mediated HuD-GAP43 pathway activation in a mouse model of antiretroviral painful neuropathy.

PubMed

Sanna, M D; Quattrone, A; Ghelardini, C; Galeotti, N

2014-03-01

Patients treated with nucleoside reverse transcriptase inhibitors (NRTIs) develop painful neuropathies that lead to discontinuation of antiretroviral therapy thus limiting viral suppression strategies. The mechanisms by which NRTIs contribute to the development of neuropathy are not known. In order to elucidate the mechanisms underlying this drug-induced neuropathy, we have characterized cellular events in the central nervous system following antiretroviral treatment. Systemic administration of the antiretroviral agent, 2',3'-dideoxycytidine (ddC) considerably increased the expression and phosphorylation of protein kinase C (PKC) γ and ɛ, enzymes highly involved in pain processes, within periaqueductal grey matter (PAG), and, to a lesser extent, within thalamus and prefrontal cortex. These events appeared in coincidence with thermal and mechanical allodynia, but PKC blockade did not prevent the antiretroviral-induced pain hypersensitivity, ruling out a major involvement of PKC in the ddC-induced nociceptive behaviour. An increased expression of GAP43, a marker of neuroregeneration, and decreased levels of ATF3, a marker of neuroregeneration, were detected in all brain areas. ddC treatment also increased the expression of HuD, a RNA-binding protein target of PKC known to stabilize GAP43 mRNA. Pharmacological blockade of PKC prevented HuD and GAP43 overexpression. Silencing of both PKCγ and HuD reduced GAP43 levels in control mice and prevented the ddC-induced GAP43 enhanced expression. Present findings illustrate the presence of a supraspinal PKC-mediated HuD-GAP43 pathway activated by ddC. Based on our results, we speculate that antiretroviral drugs may recruit the HuD-GAP43 pathway, potentially contributing to a response to the antiretroviral neuronal toxicity. Copyright © 2014 Elsevier Ltd. All rights reserved.

Patients' Ways of Speaking about Antiretroviral Medications and Possible Implications for Adherence

ERIC Educational Resources Information Center

Delbene, Roxana

2012-01-01

The medical literature reports that antiretrovirals (ARVs) are considered attitudinal objects (Dunbar-Jacob, 1995). Drawing on the pragmatics of emotion (Caffi & Janney, 1994), this study analyzes how patients' stances about their ARTs shape their emotional relationships with their treatments. The data, collected in a public hospital in…

Clinical implications of fixed-dose coformulations of antiretrovirals on the outcome of HIV-1 therapy.

PubMed

Llibre, Josep M; Arribas, José R; Domingo, Pere; Gatell, Josep M; Lozano, Fernando; Santos, José R; Rivero, Antonio; Moreno, Santiago; Clotet, Bonaventura

2011-09-10

The substitution by generic equivalents of some of the drugs included in fixed-dose antiretroviral coformulations (FDACs) poses the potential risk of disrupting these combinations and administering the components separately in order to incorporate the new generic drug, which offers a more competitive sales price. This may represent a step backwards in the advances achieved in simplicity and adherence to therapy, posing an increased risk of selective noncompliance of some of the separately administered drug substances. Available antiretroviral drugs must be administered for life in the affected individuals - both children and adults. The FDACs represent a significant advance in the simplification of antiretroviral therapy, facilitating adherence to complex and chronic treatments, and contributing to a quantifiable improvement in patient quality of life. These drug coformulations reduce the risk of treatment error, are associated with a lower risk of hospitalization, and can lessen the possibility of covert monotherapy in situations of selective noncompliance. Thus, FDACs can reduce the risk of selection of HIV-1 resistances, which not only adversely affect the treatment options of the individual patient but also constitute a public health problem, and further increase the cost and complexity of therapy. With the exception of those cases requiring dose adjustments, the preferential use of FDACs should be recommended for the treatment of HIV-1 infection in those situations when the agents included in the coformulation are drugs of choice.

A Call for Research on Planned vs. Unplanned Suicidal Behavior

ERIC Educational Resources Information Center

Conner, Kenneth R.

2004-01-01

Unplanned acts of suicidal behavior involve little preparation or forethought whereas planned acts may be carefully conceived and implemented. Planned acts are associated with greater depression, hopelessness, and lethality, but there are meager data on other factors associated with planning. The prevention of planned and unplanned acts may…

Targets for inhibition of HIV replication: entry, enzyme action, release and maturation.

PubMed

Sierra-Aragón, Saleta; Walter, Hauke

2012-01-01

Inhibition of HIV replication initially targeted viral enzymes, which are exclusively expressed by the virus and not present in the human cell. The development of reverse transcriptase (RT) inhibitors started with the discovery of antiretroviral activity of the nucleoside analog zidovudine in March 1987. Currently, six major classes of antiretroviral drugs are used for the treatment of HIV-infected patients: the RT inhibitors, nucleoside inhibitors and nonnucleoside inhibitors, the protease inhibitors, the integrase inhibitor raltegravir, the fusion inhibitor enfuvirtide (T-20), and the chemokine receptor 5 antagonist maraviroc. A seventh class, the maturation inhibitors, has not yet been approved as their effectiveness is impaired by HIV-1 polymorphisms naturally occurring in 30-40% of HIV-1 therapy-naive isolates. The use of antiretroviral combination therapy has proven to be effective in delaying progression to AIDS and to reconstitute the immune system of HIV-infected individuals. During the last 5 years, the introduction of the newest antiretrovirals has increased treatment efficacy tremendously. However, the development and accumulation of resistance to all antiretroviral drug classes are still a major problem. Additional targets will have to be defined to achieve the ultimate goal: the eradication of the virus from the infected human body. Copyright © 2012 S. Karger AG, Basel.

Antiretroviral Drug Susceptibility Among HIV-Infected Adults Failing Antiretroviral Therapy in Rakai, Uganda

PubMed Central

Laeyendecker, Oliver; Nakigozi, Gertrude; Gallant, Joel E.; Huang, Wei; Hudelson, Sarah E.; Quinn, Thomas C.; Newell, Kevin; Serwadda, David; Gray, Ronald H.; Wawer, Maria J.; Eshleman, Susan H.

2012-01-01

Abstract We analyzed antiretroviral drug susceptibility in HIV-infected adults failing first- and second-line antiretroviral treatment (ART) in Rakai, Uganda. Samples obtained from participants at baseline (pretreatment) and at the time of failure on first-line ART and second-line ART were analyzed using genotypic and phenotypic assays for antiretroviral drug resistance. Test results were obtained from 73 samples from 38 individuals (31 baseline samples, 36 first-line failure samples, and six second-line failure samples). Four (13%) of the 31 baseline samples had mutations associated with resistance to nucleoside or nonnucleoside reverse transcriptase inhibitors (NRTIs and NNRTIs, respectively). Among the 36 first-line failure samples, 31 (86%) had NNRTI resistance mutations and 29 (81%) had lamivudine resistance mutations; only eight (22%) had other NRTI resistance mutations. None of the six individuals failing a second-line protease inhibitor (PI)-based regimen had PI resistance mutations. Six (16%) of the participants had discordant genotypic and phenotypic test results. Genotypic resistance to drugs included in first-line ART regimens was detected prior to treatment and among participants failing first-line ART. PI resistance was not detected in individuals failing second-line ART. Surveillance for transmitted and acquired drug resistance remains a priority for scale-up of ART. PMID:22443282

Waste Management in Greater Dhaka City.

ERIC Educational Resources Information Center

Rahman, M. H.

1993-01-01

This study focuses on the environmental degradation of Greater Dhaka City (GDC) resulting from pollution created by the indiscriminate disposal of industrial wastes, open dumping of solid wastes, inadequate treatment and disposal of domestic sewage, and unplanned disposal of leachate from agricultural land. Measures to protect the GDC environment…

Emerging nanotechnology approaches for HIV/AIDS treatment and prevention

PubMed Central

Mamo, Tewodros; Moseman, E Ashley; Kolishetti, Nagesh; Salvador-Morales, Carolina; Shi, Jinjun; Kuritzkes, Daniel R; Langer, Robert; von Andrian, Ulrich

2010-01-01

Currently, there is no cure and no preventive vaccine for HIV/AIDS. Combination antiretroviral therapy has dramatically improved treatment, but it has to be taken for a lifetime, has major side effects and is ineffective in patients in whom the virus develops resistance. Nanotechnology is an emerging multidisciplinary field that is revolutionizing medicine in the 21st century. It has a vast potential to radically advance the treatment and prevention of HIV/AIDS. In this review, we discuss the challenges with the current treatment of the disease and shed light on the remarkable potential of nanotechnology to provide more effective treatment and prevention for HIV/AIDS by advancing antiretroviral therapy, gene therapy, immunotherapy, vaccinology and microbicides. PMID:20148638

Nonadherence as 4-day Antiretroviral Therapy Interruptions: Do Depression and Race/Ethnicity Matter as Much in the Modern Antiretroviral Therapy Era?

PubMed

Sauceda, John A; Johnson, Mallory O; Saberi, Parya

2016-11-01

HIV + White, Latino, and African Americans (N = 1131) completed a survey advertised on social media to re-examine the effect of depressive symptoms (via the Patient Health Questionnaire; PHQ-9) and race/ethnicity on antiretroviral therapy nonadherence (defined as past 3-month, 4-day treatment interruption). An adjusted logistic regression showed a 15 % increase in odds for a treatment interruption per 1-unit increase on the PHQ-9. The effect of depressive symptoms on nonadherence was greater for Latinos (OR = 1.80, p < 0.05), but not for African Americans, compared to Whites. The benefits of modern ART (e.g., simpler, forgiving to minor lapses) may not circumvent the effect of depressive symptomatology.

HIV-1 treatment as prevention: the good, the bad, and the challenges.

PubMed

Smith, Kumi; Powers, Kimberly A; Kashuba, Angela D M; Cohen, Myron S

2011-07-01

This work focuses on the use of antiretroviral agents to prevent the sexual transmission of HIV-1. Two randomized clinical trials demonstrated that antiretroviral agents provided before exposure to HIV-1 offer substantial protection, ostensibly directly proportional to the concentration of antiretroviral therapy (ART) in the genital secretions. Intense focus on the use of HIV treatment as prevention has led to publication of modeling exercises, ecological studies, and observational studies, most of which support the potential benefits of ART. However, the logistical requirements for successful use of ART for prevention are considerable. ART will serve as a cornerstone of combination prevention of HIV-1. Continued research will be essential to measure anticipated benefits and to detect implementation barriers and untoward consequences of such a program, especially increases in primary ART resistance.

Antiretroviral Resistance in HIV/AIDS Patients

NASA Astrophysics Data System (ADS)

Manosuthi, W.; MD

2018-03-01

The higher prevalence of HIV drug resistance was observed in areas with greater ART coverage. The HIV resistance-associated mutations occur when people have inadequate levels of antiretroviral drugs as well as inadequate potency, inadequate adherence, and preexisting resistance. The degree to drug cross-resistance is observed depends on the specific mutations and number of mutation accumulation. In the Southeast Asia region, the challenging of people with treatment failure is the availability and accessibility to subsequent new antiretroviral drugs to construct he second and salvage regimen. Genotypic resistance testing is a useful tool because it can identify the existing drug resistance-associated mutations under the selective drug pressure. Thus, understanding the basic interpretation of HIV drug resistance- associated mutation is useful in guiding clinical decisions for treatment-experienced people living with HIV.

‘Not Until I'm Absolutely Half-Dead and Have To:’ Accounting for Non-Use of Antiretroviral Therapy in Semi-Structured Interviews with People Living with HIV in Australia

PubMed Central

Mao, Limin; Persson, Asha; Holt, Martin; Slavin, Sean; Kidd, Michael R.; Post, Jeffrey J.; Wright, Edwina; de Wit, John

2015-01-01

Abstract Current debates regarding the use of antiretroviral therapy (ART) to promote both individual- and population-level health benefits underscore the importance of understanding why a subpopulation of people with diagnosed HIV and access to treatment choose not to use it. Semi-structured interviews were conducted between 2012 and 2014 with 27 people living with HIV in Australia who were not using ART at the time of interview. Analytic triangulation permitted an appreciation of not only the varied personal reasons for non-use of treatment, but also underlying views on HIV treatment, and the ideal conditions imagined necessary for treatment initiation. Policy goals to increase the number of people with HIV using ART must recognize the diverse explanations for non-use of ART, which include concerns about the various impacts of committing to lifelong pharmaceutical treatment use. Our research identified distinctive subgroups among people who are not using antiretroviral therapy, with a range of individual and social needs that may affect treatment decisions. These findings challenge assumptions about treatment non-use in resource-rich settings, revealing persistent consumer fears about the potent and unknown effects of HIV medications that deserve greater recognition in policy debate on treatment uptake. PMID:25806574

Prevalence of drug resistance and importance of viral load measurements in Honduran HIV-infected patients failing antiretroviral treatment.

PubMed

Murillo, Wendy; de Rivera, I L; Parham, L; Jovel, E; Palou, E; Karlsson, A C; Albert, J

2010-02-01

The Honduran HIV/AIDS Program began to scale up access to HIV therapy in 2002. Up to May 2008, more than 6000 patients received combination antiretroviral therapy (cART). As HIV drug resistance is the major obstacle for effective treatment, the purpose of this study was to assess the prevalence of antiretroviral drug resistance in Honduran HIV-1-infected individuals. We collected samples from 138 individuals (97 adults and 41 children) on cART with virological, immunological or clinical signs of treatment failure. HIV-1 pol sequences were obtained using an in-house method. Resistance mutations were identified according to the 2007 International AIDS Society (IAS)-USA list and predicted susceptibility to cART was scored using the ANRS algorithm. Resistance mutations were detected in 112 patients (81%), 74% in adults and 98% in children. Triple-, dual- and single-class drug resistance was documented in 27%, 43% and 11% of the study subjects, respectively. Multiple logistic regression showed that resistance was independently associated with type of treatment failure [virological failure (odds ratio (OR) = 1) vs. immunological failure (OR = 0.11; 95% confidence interval (CI) 0.030-0.43) vs. clinical failure (OR = 0.037; 95% CI 0.0063-0.22)], route of transmission (OR = 42.8; 95% CI 3.73-491), and years on therapy (OR = 1.81; 95% CI 1.11-2.93). The prevalence of antiretroviral resistance was high in Honduran HIV-infected patients with signs of treatment failure. A majority of study subjects showed dual- or triple-class resistance to nucleoside reverse transcriptase inhibitors, nonnucleoside reverse transcriptase inhibitors and protease inhibitors. Virologically defined treatment failure was a strong predictor of resistance, indicating that viral load testing is needed to correctly identify patients with treatment failure attributable to resistance.

Drug susceptibility to etravirine and darunavir among Human Immunodeficiency Virus Type 1-derived pseudoviruses in treatment-experienced patients with HIV/AIDS in South Korea.

PubMed

Kwon, Oh-Kyung; Kim, Sung Soon; Rhee, Jee Eun; Kee, Mee-Kyung; Park, Mina; Oh, Hye-Ri; Choi, Ju-Yeon

2015-04-09

In South Korea, about 20 types of antiretroviral drugs are used in the treatment of patients with human immunodeficiency virus/acquired immune deficiency syndrome. Since 2010, raltegravir, etravirine, and darunavir have been spotlighted as new drugs for highly active antiretroviral therapy (HAART)-experienced adults with resistant HIV-1 in South Korea. In this study, we investigated potential susceptibility of pseudoviruses derived from treatment-experienced Korean patients to etravirine vs efavirenz and to darunavir vs amprenavir and indinavir using a modified single-round assay. Pseudoviruses derived from nine treatment-experienced patients infected with HIV-1 were investigated by comparison with the wild-type strain pNL4-3. The 50% inhibitory concentration (IC50) values were calculated and drug susceptibility was compared. The intensity of genotypic drug resistance was classified based on the 'SIR' interpretation of the Stanford data base. Drug susceptibility was generally higher for etravirine and darunavir compared with efavirenz, amprenavir, and indinavir in pseudoviruses derived from treatment-experienced patients. Pseudoviruses derived from patients KRB4025 and KRB8014, who exhibited long-term use of protease inhibitors, showed an outside of tested drug concentration, especially for amprenavir and indinavir. However, they exhibited a lower fold-change in resistance to darunavir. Etravirine and darunavir have been used in HAART since 2010 in South Korea. Therefore, these antiretroviral drugs together with other newly introduced antiretroviral drugs are interesting for the optimal treatment of patients with treatment failure. This study may help to find a more effective HAART in the case of HIV-1 infected patients that have difficulty being treated.

Absence of transmission from HIV-infected individuals with HAART to their heterosexual serodiscordant partners.

PubMed

Del Romero, Jorge; Río, Isabel; Castilla, Jesús; Baza, Begoña; Paredes, Vanessa; Vera, Mar; Rodríguez, Carmen

2015-12-01

Further studies are needed to evaluate the level of effectiveness and durability of HAART to reduce the risk of HIV sexual transmission in serodiscordant couples having unprotected sexual practices. A cross-sectional study was conducted with prospective cohort of heterosexual HIV serodiscordant couples where the only risk factor for HIV transmission to the uninfected partner (sexual partner) was the sexual relationship with the infected partner (index case). HIV prevalence in sexual partners at enrolment and seroconversions in follow-up were compared by antiretroviral treatment in the index partner, HIV plasma viral load in index cases and sexual risk exposures in sexual partners. In each visit, an evaluation of the risks for HIV transmission, preventive counselling and screening for genitourinary infections in the sexual partner was performed, as well as the determination of the immunological and virological situation and antiretroviral treatment in the index case. At enrolment no HIV infection was detected in 202 couples where the index case was taking HAART. HIV prevalence in sexual partners was 9.6% in 491 couples where the index case was not taking antiretroviral treatment (p<0.001). During follow-up there was no HIV seroconversion among 199 partners whose index case was taking HAART, accruing 7600 risky sexual exposures and 85 natural pregnancies. Among 359 couples whose index case was not under antiretroviral treatment, over 13,000 risky sexual exposures and 5 HIV seroconversions of sexual partners were recorded. The percentage of seroconversion among couples having risky sexual intercourse was 2.5 (95% confidence interval [CI]: 1.1-5.6) when the index case did not undergo antiretroviral treatment and zero (95% CI: 0-3.2) when the index case received HAART. The risk of sexual transmission of HIV from individuals with HAART to their heterosexual partners can become extremely low. Copyright © 2014. Published by Elsevier España, S.L.U.

Risk factors of hospitalization and readmission of patients with COPD in Hong Kong population: analysis of hospital admission records.

PubMed

Chan, Frank W K; Wong, Fiona Y Y; Yam, Carrie H K; Cheung, Wai-ling; Wong, Eliza L Y; Leung, Michael C M; Goggins, William B; Yeoh, Eng-kiong

2011-08-10

Chronic Obstructive Pulmonary Disease (COPD) accounts for around 4% of all public hospital annual admissions in Hong Kong. By year 2020, COPD will be ranked fifth among the conditions with the highest burden to the society. This study identifies admission and unplanned readmission of COPD patients, factors affecting unplanned readmission, and estimates its cost burden on the public healthcare system in Hong Kong. This is a retrospective study analyzing COPD admissions to all public hospitals in Hong Kong. All admission episodes to acute medical wards with the principal diagnosis of COPD (ICD-9:490-492, 494-496) from January 2006 to December 2007 were captured. Unplanned readmission was defined as an admission which followed a previous admission within 30 days. In 2006 and 2007, 65497 (8.0%) of episodes from medical wards were identified as COPD admissions, and among these, 15882 (24.2%) were unplanned readmissions. The mean age of COPD patients was 76.81 ± 9.59 years and 77% were male. Unplanned readmission was significantly associated with male gender, receiving public assistance and living in nursing homes while no association was found with the Charlson comorbidity index. Patients who were readmitted unplanned had a significant longer acute length of stay (β = 0.3894, P < 0.001) after adjustment for other covariates. Unplanned readmission of COPD patients has a huge impact on the public healthcare system. A systematic approach in programme provision and a good discharge planning process targeting on COPD patients who are at high risk of unplanned readmission are essential.

[HIV retinal vasculitis].

PubMed

Drake-Casanova, P; Moreno-Arrones, J Paz; Gorroño Echebarría, M; Dapena-Sevilla, I; Pareja-Esteban, J; Vleming-Pinilla, E

2010-01-01

We present a case of a 47 year-old woman, infected with human immunodeficiency virus (HIV) diagnosed 5 years ago without receiving any treatment, who had floaters in her left eye. A peripheral retinal vasculitis was discovered and confirmed by an angiography. No source of infection was found, antiretroviral and corticosteroid treatment was given, with a complete resolution of the vasculitis. From 70-80% of positive untreated HIV patients develop ocular complications, with intraocular inflammation in more than half of them. Intraocular inflammation can be associated with opportunistic infections, tumours and as in our case, secondary to the HIV. Antiretroviral therapy is the proper treatment in these patients.

Bilateral Mastectomy as Radical Treatment of Gynecomastia Secondary to Antiretroviral Therapy in a Low-Income Setting: A Case Report.

PubMed

Antunes, Mario; Schiavone, Marcella; Pizzol, Damiano; Di Gennaro, Francesco; Ludovico, Rossana; De Palma, Angela

2018-05-11

Gynecomastia is a common finding in males, with an incidence that varies widely globally. In 10-25% of cases, it is caused by drugs. Its pathophysiologic mechanism includes exposure to exogenous estrogens and medications that cause hypogonadism, antiandrogenic effects and hyperprolactinemia. Gynecomastia is associated with exposure to antiretroviral therapy (ART), particularly efavirenz. Sometimes surgery may be required as treatment. We report a case of a 46-year-old man receiving ART presenting with a marked bilateral breast enlargement who underwent bilateral mastectomy as the only successful treatment in a low-income setting.

40 CFR 264.51 - Purpose and implementation of contingency plan.

Code of Federal Regulations, 2014 CFR

2014-07-01

...) SOLID WASTES (CONTINUED) STANDARDS FOR OWNERS AND OPERATORS OF HAZARDOUS WASTE TREATMENT, STORAGE, AND... plan must be designed to minimize hazards to human health or the environment from fires, explosions, or any unplanned sudden or non-sudden release of hazardous waste or hazardous waste constituents to air...

40 CFR 265.51 - Purpose and implementation of contingency plan.

Code of Federal Regulations, 2014 CFR

2014-07-01

...) SOLID WASTES (CONTINUED) INTERIM STATUS STANDARDS FOR OWNERS AND OPERATORS OF HAZARDOUS WASTE TREATMENT... contingency plan must be designed to minimize hazards to human health or the environment from fires, explosions, or any unplanned sudden or non-sudden release of hazardous waste or hazardous waste constituents...

40 CFR 265.51 - Purpose and implementation of contingency plan.

Code of Federal Regulations, 2012 CFR

2012-07-01

...) SOLID WASTES (CONTINUED) INTERIM STATUS STANDARDS FOR OWNERS AND OPERATORS OF HAZARDOUS WASTE TREATMENT... contingency plan must be designed to minimize hazards to human health or the environment from fires, explosions, or any unplanned sudden or non-sudden release of hazardous waste or hazardous waste constituents...

40 CFR 265.51 - Purpose and implementation of contingency plan.

Code of Federal Regulations, 2013 CFR

2013-07-01

...) SOLID WASTES (CONTINUED) INTERIM STATUS STANDARDS FOR OWNERS AND OPERATORS OF HAZARDOUS WASTE TREATMENT... contingency plan must be designed to minimize hazards to human health or the environment from fires, explosions, or any unplanned sudden or non-sudden release of hazardous waste or hazardous waste constituents...

40 CFR 264.51 - Purpose and implementation of contingency plan.

Code of Federal Regulations, 2012 CFR

2012-07-01

...) SOLID WASTES (CONTINUED) STANDARDS FOR OWNERS AND OPERATORS OF HAZARDOUS WASTE TREATMENT, STORAGE, AND... plan must be designed to minimize hazards to human health or the environment from fires, explosions, or any unplanned sudden or non-sudden release of hazardous waste or hazardous waste constituents to air...

40 CFR 264.51 - Purpose and implementation of contingency plan.

Code of Federal Regulations, 2013 CFR

2013-07-01

...) SOLID WASTES (CONTINUED) STANDARDS FOR OWNERS AND OPERATORS OF HAZARDOUS WASTE TREATMENT, STORAGE, AND... plan must be designed to minimize hazards to human health or the environment from fires, explosions, or any unplanned sudden or non-sudden release of hazardous waste or hazardous waste constituents to air...

40 CFR 265.51 - Purpose and implementation of contingency plan.

Code of Federal Regulations, 2011 CFR

2011-07-01

...) SOLID WASTES (CONTINUED) INTERIM STATUS STANDARDS FOR OWNERS AND OPERATORS OF HAZARDOUS WASTE TREATMENT..., explosions, or any unplanned sudden or non-sudden release of hazardous waste or hazardous waste constituents to air, soil, or surface water. (b) The provisions of the plan must be carried out immediately...

40 CFR 264.51 - Purpose and implementation of contingency plan.

Code of Federal Regulations, 2011 CFR

2011-07-01

...) SOLID WASTES (CONTINUED) STANDARDS FOR OWNERS AND OPERATORS OF HAZARDOUS WASTE TREATMENT, STORAGE, AND... any unplanned sudden or non-sudden release of hazardous waste or hazardous waste constituents to air, soil, or surface water. (b) The provisions of the plan must be carried out immediately whenever there...

New Insights into HIV-1 Persistence in Sanctuary Sites During Antiretroviral Therapy.

PubMed

Poveda, Eva; Tabernilla, Andrés

2016-01-01

Current combinations of antiretroviral drugs for the treatment of HIV infection can successfully achieve and maintain long-term suppression of HIV-1 replication in plasma. Still, none of these therapies is capable of eradicating the virus from the long-lived cellular reservoir that represents the major barrier to HIV cure.

CDC staging based on absolute CD4 count and CD4 percentage in an HIV-1-infected Indian population: treatment implications

PubMed Central

Vajpayee, M; Kaushik, S; Sreenivas, V; Wig, N; Seth, P

2005-01-01

CD4+ T-cell levels are an important criterion for categorizing HIV-related clinical conditions according to the CDC classification system and are therefore important in the management of HIV by initiating antiretroviral therapy and prophylaxis for opportunistic infections due to HIV among HIV-infected individuals. However, it has been observed that the CD4 counts are affected by the geographical location, race, ethnic origin, age, gender and changes in total and differential leucocyte counts. In the light of this knowledge, we classified 600 HIV seropositive antiretroviral treatment (ART)-naïve Indian individuals belonging to different CDC groups A, B and C on the basis of CDC criteria of both CD4% and CD4 counts and receiver operating characteristic (ROC) curves were generated. Importantly, CDC staging on the basis of CD4% indicated significant clinical implications, requiring an early implementation of effective antiretroviral treatment regimen in HIV-infected individuals deprived of treatment when classified on the basis of CD4 counts. PMID:16045738

Treatment of HIV infection: Swedish recommendations 2009.

PubMed

Josephson, Filip; Albert, Jan; Flamholc, Leo; Gisslén, Magnus; Karlström, Olof; Moberg, Lars; Navér, Lars; Svedhem, Veronica; Svennerholm, Bo; Sönnerborg, Anders

2009-01-01

On 4 previous occasions, in 2002, 2003, 2005 and 2007, the Swedish Medical Products Agency (Läkemedelsverket) and the Swedish Reference Group for Antiviral Therapy (RAV) have jointly published recommendations for the treatment of HIV infection. In November 2008, an expert group under the guidance of RAV once more revised the guidelines, of which this is a translation into English. The most important updates in the present guidelines include the following: (a) treatment initiation is now recommended at a CD4 cell count of approximately 350/microl; (b) new recommendations for first-line therapy: abacavir/lamivudine or tenofovir/emtricitabine in combination with efavirenz or a boosted protease inhibitor (PI/r); (c) an increased focus on reducing the use of antiretroviral drugs that may cause lipoatrophy; (d) an emphasis on quality assurance of HIV care through the use of InfCare HIV; (e) considerably altered recommendations for the initiation of antiretroviral therapy in children. All infants (<1 y) should start antiretroviral therapy, regardless of immune status. Also, absolute CD4+ cell counts, rather than percentage, may be used to guide treatment initiation in children above the age of 5 y.

Contribution of substance use disorders on HIV treatment outcomes and antiretroviral medication adherence among HIV-infected persons entering jail.

PubMed

Chitsaz, Ehsan; Meyer, Jaimie P; Krishnan, Archana; Springer, Sandra A; Marcus, Ruthanne; Zaller, Nick; Jordan, Alison O; Lincoln, Thomas; Flanigan, Timothy P; Porterfield, Jeff; Altice, Frederick L

2013-10-01

HIV and substance use are inextricably intertwined. One-sixth of people living with HIV/AIDS (PLWHA) transition through the correctional system annually. There is paucity of evidence on the impact of substance use disorders on HIV treatment engagement among jail detainees. We examined correlates of HIV treatment in the largest sample of PLWHA transitioning through jail in 10 US sites from 2007 to 2011. Cocaine, alcohol, cannabis, and heroin were the most commonly used substances. Drug use severity was negatively and independently correlated with three outcomes just before incarceration: (1) having an HIV care provider (AOR = 0.28; 95 % CI 0.09-0.89); (2) being prescribed antiretroviral therapy (AOR = 0.12; 95 % CI 0.04-0.35) and (3) high levels (>95 %) of antiretroviral medication adherence (AOR = 0.18; 95 % CI 0.05-0.62). Demographic, medical and psychiatric comorbidity, and social factors also contributed to poor outcomes. Evidence-based drug treatments that include multi-faceted interventions, including medication-assisted therapies, are urgently needed to effectively engage this vulnerable population.

Global Response to HIV: Treatment as Prevention, or Treatment for Treatment?

PubMed Central

Sigaloff, Kim C. E.; Lange, Joep M. A.; Montaner, Julio

2014-01-01

The concept of “treatment as prevention” has emerged as a means to curb the global HIV epidemic. There is, however, still ongoing debate about the evidence on when to start antiretroviral therapy in resource-poor settings. Critics have brought forward multiple arguments against a “test and treat” approach, including the potential burden of such a strategy on weak health systems and a presumed lack of scientific support for individual patient benefit of early treatment initiation. In this article, we highlight the societal and individual advantages of treatment as prevention in resource-poor settings. We argue that the available evidence renders the discussion on when to start antiretroviral therapy unnecessary and that, instead, efforts should be aimed at offering treatment as soon as possible. PMID:24926037

Audiological and electrophysiological alterations in HIV-infected individuals subjected or not to antiretroviral therapy.

PubMed

Matas, Carla Gentile; Samelli, Alessandra Giannella; Magliaro, Fernanda Cristina Leite; Segurado, Aluisio

2017-08-02

The Human Immunodeficiency Virus (HIV) and infections related to it can affect multiple sites in the hearing system. The use of High-Activity Anti-Retroviral Therapy (HAART) can cause side effects such as ototoxicity. Thus, no consistent patterns of hearing impairment in adults with Human Immunodeficiency Virus / Acquired Immune Deficiency Syndrome have been established, and the problems that affect the hearing system of this population warrant further research. This study aimed to compare the audiological and electrophysiological data of Human Immunodeficiency Virus-positive patients with and without Acquired Immune Deficiency Syndrome, who were receiving High-Activity Anti-Retroviral Therapy, to healthy individuals. It was a cross-sectional study conducted with 71 subjects (30-48 years old), divided into groups: Research Group I: 16 Human Immunodeficiency Virus-positive individuals without Acquired Immunodeficiency Syndrome (not receiving antiretroviral treatment); Research Group II: 25 Human Immunodeficiency Virus-positive individuals with Acquired Immunodeficiency Syndrome (receiving antiretroviral treatment); Control Group: 30 healthy subjects. All individuals were tested by pure-tone air conduction thresholds at 0.25-8kHz, extended high frequencies at 9-20kHz, electrophysiological tests (Auditory Brainstem Response - ABR, Middle Latency Responses - MLR, Cognitive Potential - P300). Research Group I and Research Group II had higher hearing thresholds in both conventional and high frequency audiometry when compared to the control group, prolonged latency of waves I, III, V and interpeak I-V in Auditory Brainstem Response and prolonged latency of P300 Cognitive Potential. Regarding Middle Latency Responses, there was a decrease in the amplitude of the Pa wave of Research Group II compared to the Research Group I. Both groups with Human Immunodeficiency Virus had higher hearing thresholds when compared to healthy individuals (group exposed to antiretroviral treatment showed the worst hearing threshold) and seemed to have lower neuroelectric transmission speed along the auditory pathway in the brainstem, subcortical and cortical regions. Copyright © 2017. Published by Elsevier Editora Ltda.

Antiretroviral therapy for adults infected with HIV: Guidelines for health care professionals from the Quebec HIV care committee

PubMed Central

Rouleau, Danielle; Fortin, Claude; Trottier, Benoît; Lalonde, Richard; Lapointe, Normand; Côté, Pierre; Routy, Jean-Pierre; Matte, Marie-France; Tsarevsky, Irina; Baril, Jean-Guy

2011-01-01

The appropriate use of antiretrovirals reduces morbidity and mortality caused by HIV infection. The present article provides health care professionals with a practical guide for the use of antiretrovirals. Therapy should be initiated based predominantly on clinical presentation and CD4 count, and should consist of three active drugs or at least two active drugs when this is not possible, as in cases of some treatment-experienced patients. This is the most effective way to achieve long-term suppression of viral replication. Selection of individual drugs in the regimen should consider the weight of the evidence supporting these choices, as well as their tolerability profiles and ease of use, the patients’ comorbidities and treatment history. Treatment interruption is not recommended, either in aviremic patients or in those who have experienced virological failure. Instead, the therapeutic regimen should be adjusted to minimize side effects, promote adherence and suppress viral replication. PMID:22654926

Human immunodeficiency virus/acquired immunodeficiency syndrome and infertility: emerging problems in the era of highly active antiretrovirals.

PubMed

Kushnir, Vitaly A; Lewis, William

2011-09-01

To review the effects of human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) in terms of its associated comorbid conditions and the side effects of antiretroviral treatment on fertility. PubMed computer search to identify relevant articles. Research institution. None. None. None. Biological alterations in reproductive physiology may account for subfertility in patients infected with HIV. Psychosocial factors in patients with HIV infection may affect their reproductive desires and outcomes. Antiretroviral medications may have direct toxicity on gametes and embryos. Available evidence indicates that fertility treatments can be a safe option for couples with HIV-discordant infection status, although the potential risk of viral transmission cannot be completely eliminated. Because their potential reproductive desires are increasingly becoming a concern in the health care of young HIV-infected patients, additional data are needed to address the effect of HIV and its treatments on their fertility and reproductive outcomes. Copyright © 2011 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Starting or changing therapy - a prospective study exploring antiretroviral decision-making.

PubMed

Fehr, J S; Nicca, D; Sendi, P; Wolf, E; Wagels, T; Kiss, A; Bregenzer, T; Vernazza, P; Jäger, H; Spirig, R; Battegay, M

2005-08-01

When to start or change antiretroviral treatment against HIV infection is of major importance. Patients' readiness is considered a major factor influencing such treatment decisions, in particular because no objective, absolute time point when to start antiretroviral therapy exists. We aimed at evaluating patients' readiness to start or change antiretroviral therapy (ART). HIV-infected patients starting or changing ART between July 2002 and February 2003, treating physicians and nurses participated in this prospective, observational multicenter study. We assessed shared decision-making including qualitative aspects, expected treatment decisions and treatment status after 3 months. 75 patients were included. Of 34 patients for whom starting ART was considered, 27 (79%) indicated that they were willing to start treatment. After 3 months, 21 of 27 (78%) actually started therapy, six did not. Patients with depression were less likely to be ready for ART (p < 0.05). Of 41 patients for whom changing ART was considered, 35 (85%) indicated that they were willing to change treatment. Of the latter 35 patients, 33 (94%) finally changed ART within 3 months. Physicians and nurses were too optimistic in predicting the start or change of ART. The main reason to start or change ART was the sole recommendation of the physician (52% in those starting, 61% in those changing ART). Patients mainly judged the decision as shared and were very satisfied (71%) with the process. Qualitative findings revealed the importance of a dialectic decisionmaking, described with two categories: "dealing with oneself and others"' and "understanding and being understood." Patients mainly shared the decision made during consultation. Although physicians have an essential role concerning ART, patients, physicians, and nurses all contribute to the decision. Qualitative findings indicate the importance for health-care providers to include patients' expertise and contributions.

HIV-1 Viral Escape in Cerebrospinal Fluid of Subjects on Suppressive Antiretroviral Treatment

PubMed Central

Edén, Arvid; Fuchs, Dietmar; Hagberg, Lars; Nilsson, Staffan; Spudich, Serena; Svennerholm, Bo; Price, Richard W.; Gisslén, Magnus

2010-01-01

Background. Occasional cases of viral escape in cerebrospinal fluid (CSF) despite suppression of plasma human immunodeficiency virus type 1 (HIV-1) RNA have been reported. We investigated CSF viral escape in subjects treated with commonly used antiretroviral therapy regimens in relation to intrathecal immune activation and central nervous system penetration effectiveness (CPE) rank. Methods. Sixty-nine neurologically asymptomatic subjects treated with antiretroviral therapy >6 months and plasma HIV-1 RNA <50 copies/mL were cross-sectionally included in the analysis. Antiretroviral therapy regimens included efavirenz, lopinavir/ritonavir or atazanavir/ritonavir combined with tenofovir, abacavir, or zidovudine and emtricitabine or lamivudine. HIV-1 RNA was analyzed with real-time polymerase chain reaction assays. Neopterin was analyzed by enzyme-linked immunosorbent assay. Results. Seven (10%) of the 69 subjects had detectable CSF HIV-1 RNA, in median 121 copies/mL (interquartile range, 54–213 copies/mL). Subjects with detectable CSF virus had significantly higher CSF neopterin and longer duration of treatment. Previous treatment interruptions were more common in subjects with CSF escape. Central nervous system penetration effectiveness rank was not a significant predictor of detectable CSF virus or CSF neopterin levels. Conclusions. Viral escape in CSF is more common than previously reported, suggesting that low-grade central nervous system infection may continue in treated patients. Although these findings need extension in longitudinal studies, they suggest the utility of monitoring CSF responses, as new treatment combinations and strategies modify clinical practice. PMID:21050119

HIV-1 viral escape in cerebrospinal fluid of subjects on suppressive antiretroviral treatment.

PubMed

Edén, Arvid; Fuchs, Dietmar; Hagberg, Lars; Nilsson, Staffan; Spudich, Serena; Svennerholm, Bo; Price, Richard W; Gisslén, Magnus

2010-12-15

Occasional cases of viral escape in cerebrospinal fluid (CSF) despite suppression of plasma human immunodeficiency virus type 1 (HIV-1) RNA have been reported. We investigated CSF viral escape in subjects treated with commonly used antiretroviral therapy regimens in relation to intrathecal immune activation and central nervous system penetration effectiveness (CPE) rank. Sixty-nine neurologically asymptomatic subjects treated with antiretroviral therapy >6 months and plasma HIV-1 RNA <50 copies/mL were cross-sectionally included in the analysis. Antiretroviral therapy regimens included efavirenz, lopinavir/ritonavir or atazanavir/ritonavir combined with tenofovir, abacavir, or zidovudine and emtricitabine or lamivudine. HIV-1 RNA was analyzed with real-time polymerase chain reaction assays. Neopterin was analyzed by enzyme-linked immunosorbent assay. Seven (10%) of the 69 subjects had detectable CSF HIV-1 RNA, in median 121 copies/mL (interquartile range, 54-213 copies/mL). Subjects with detectable CSF virus had significantly higher CSF neopterin and longer duration of treatment. Previous treatment interruptions were more common in subjects with CSF escape. Central nervous system penetration effectiveness rank was not a significant predictor of detectable CSF virus or CSF neopterin levels. Viral escape in CSF is more common than previously reported, suggesting that low-grade central nervous system infection may continue in treated patients. Although these findings need extension in longitudinal studies, they suggest the utility of monitoring CSF responses, as new treatment combinations and strategies modify clinical practice.

Optimising the manufacture, formulation, and dose of antiretroviral drugs for more cost-efficient delivery in resource-limited settings: a consensus statement.

PubMed

Crawford, Keith W; Ripin, David H Brown; Levin, Andrew D; Campbell, Jennifer R; Flexner, Charles

2012-07-01

It is expected that funding limitations for worldwide HIV treatment and prevention in resource-limited settings will continue, and, because the need for treatment scale-up is urgent, the emphasis on value for money has become an increasing priority. The Conference on Antiretroviral Drug Optimization--a collaborative project between the Clinton Health Access Initiative, the Johns Hopkins University School of Medicine, and the Bill & Melinda Gates Foundation--brought together process chemists, clinical pharmacologists, pharmaceutical scientists, physicians, pharmacists, and regulatory specialists to explore strategies for the reduction of antiretroviral drug costs. The antiretroviral drugs discussed were prioritised for consideration on the basis of their market impact, and the objectives of the conference were framed as discussion questions generated to guide scientific assessment of potential strategies. These strategies included modifications to the synthesis of the active pharmaceutical ingredient (API) and use of cheaper sources of raw materials in synthesis of these ingredients. Innovations in product formulation could improve bioavailability thus needing less API. For several antiretroviral drugs, studies show efficacy is maintained at doses below the approved dose (eg, efavirenz, lopinavir plus ritonavir, atazanavir, and darunavir). Optimising pharmacoenhancement and extending shelf life are additional strategies. The conference highlighted a range of interventions; optimum cost savings could be achieved through combining approaches. Copyright © 2012 Elsevier Ltd. All rights reserved.

Preventing Unplanned Pregnancy and Completing College: An Evaluation of Online Lessons. 2nd Edition

ERIC Educational Resources Information Center

Antonishak, Jill; Connolly, Chelsey

2014-01-01

The National Campaign to Prevent Teen and Unplanned Pregnancy published free online lessons that help students take action to prevent unplanned pregnancy and complete their education. From the fall of 2012 to the spring of 2014, approximately 2,800 students took the online lessons and participated in pre- and post-lesson evaluation surveys at four…

Dynamics of the HIV infection under antiretroviral therapy: A cellular automata approach

NASA Astrophysics Data System (ADS)

González, Ramón E. R.; Coutinho, Sérgio; Zorzenon dos Santos, Rita Maria; de Figueirêdo, Pedro Hugo

2013-10-01

The dynamics of human immunodeficiency virus infection under antiretroviral therapy is investigated using a cellular automata model where the effectiveness of each drug is self-adjusted by the concentration of CD4+ T infected cells present at each time step. The effectiveness of the drugs and the infected cell concentration at the beginning of treatment are the control parameters of the cell population’s dynamics during therapy. The model allows describing processes of mono and combined therapies. The dynamics that emerges from this model when considering combined antiretroviral therapies reproduces with fair qualitative agreement the phases and different time scales of the process. As observed in clinical data, the results reproduce the significant decrease in the population of infected cells and a concomitant increase of the population of healthy cells in a short timescale (weeks) after the initiation of treatment. Over long time scales, early treatment with potent drugs may lead to undetectable levels of infection. For late treatment or treatments starting with a low density of CD4+ T healthy cells it was observed that the treatment may lead to a steady state in which the T cell counts are above the threshold associated with the onset of AIDS. The results obtained are validated through comparison to available clinical trial data.

Long-term impact of highly active antiretroviral therapy on HIV-related health care costs.

PubMed

Keiser, P; Nassar, N; Kvanli, M B; Turner, D; Smith, J W; Skiest, D

2001-05-01

Highly active antiretroviral therapy (HAART) is associated with decreased opportunistic infections, hospitalization, and HIV-related health care costs over relatively short periods of time. We have previously demonstrated that decreases in total HIV cost are proportional to penetration of protease inhibitor therapy in our clinic. To determine the effects of HAART on HIV health care use and costs over 44 months. A comprehensive HIV service within a Veterans Affairs Medical Center. A cost-effectiveness analysis of HAART. The mean monthly number of hospital days, infectious diseases clinic visits, emergency room visits, non-HIV-related outpatient visits, inpatient costs, and antiretroviral treatment costs per patient were determined by dividing these during the period from January 1995 through June 1998 into four intervals. Viral load tests were available from October 1996. Cost-effectiveness of HAART was evaluated by determining the costs of achieving an undetectable viral load over time. Mean monthly hospitalization and associated inpatient costs decreased and remained low 2 years after the introduction of protease inhibitors (37 hospital days per 100 patients). Total cost decreased from $1905 per patient per month during the first quarter to $1090 per patient per month in the third quarter but increased to $1391 per patient per month in the fourth quarter. Antiretroviral treatment costs increased throughout the entire observation period from $79 per patient per month to $518 per patient per month. Hospitalization costs decreased from $1275 per patient per month in the first quarter to less than $500 per patient per month in each of the third and fourth quarters. The percentage of patients with a viral load <500 copies/mL increased from 21% in October 1996 to 47% in June of 1997 (p =.014). The cost of achieving an undetectable viral load decreased from $4438 per patient per month to $2669 per patient per month, but this trend did not reach statistical significance (p =.18). After an initial decrease, there was an increase in the total monthly cost of caring for HIV patients. Cost increases were primarily due to antiretroviral treatment costs, but these costs were offset by a marked decrease in inpatient-related costs. Increases in costs were not related to antiretroviral treatment failures as measured by the proportion of patients with low or undetectable viral loads. The cost of achieving an undetectable viral load remained stable despite increases in the cost of procuring antiretroviral agents.

Earlier initialization of highly active antiretroviral therapy is associated with long-term survival and is cost-effective: findings from a deterministic model of a 10-year Ugandan cohort.

PubMed

Mills, Fergal P; Ford, Nathan; Nachega, Jean B; Bansback, Nicholas; Nosyk, Bohdan; Yaya, Sanni; Mills, Edward J

2012-11-01

Raising the guidelines for the initiation of antiretroviral therapy in resource-limited settings at CD4 T-cell counts of 350 cells per microliter raises concerns about feasibility and cost. We examined costs of this shift using data from Uganda for almost 10 years. We projected total costs of earlier initiation with combined antiretroviral therapy, including inpatient and outpatient services, antiretroviral treatment and treatment for limited HIV-related opportunistic diseases, and benefits expressed in years-of-life-saved over 5- and 30-year time horizons using a deterministic economic model to examine the incremental cost-effectiveness ratio (ICER), expressed in cost per year-of-life-saved (YLS). The model generated ICERs for 5- and 30-year time horizons. Discounting both costs and benefits at 3% annually, for the 5-year analysis, the ICER was $695/YLS and $769 in the 30-year analysis. The results were most sensitive to program cost and the discount rate applied, but they were less sensitive to opportunistic infection treatment costs or the relative-risk reduction from earlier initiation. Program costs varied from 25% to 125%, and the ICER for the lower bound decreased to $491/YLS at 5-years and $574/YLS at 30 years. For the upper bound, the ICER increased to $899 for 5-years and $964 at 30-years. The budget impact of adoption, assuming the same level of program penetration in the community, is $261,651,942 for 5 years and $872,685,561 for 30 years. Our model showed that earlier initiation of combined antiretroviral therapy in Uganda is associated with improved long-term survival and is highly cost-effective, as defined by WHO-CHOICE.

Impact of late diagnosis and treatment on life expectancy in people with HIV-1: UK Collaborative HIV Cohort (UK CHIC) Study

PubMed Central

Gompels, Mark; Delpech, Valerie; Porter, Kholoud; Post, Frank; Johnson, Margaret; Dunn, David; Palfreeman, Adrian; Gilson, Richard; Gazzard, Brian; Hill, Teresa; Walsh, John; Fisher, Martin; Orkin, Chloe; Ainsworth, Jonathan; Bansi, Loveleen; Phillips, Andrew; Leen, Clifford; Nelson, Mark; Anderson, Jane; Sabin, Caroline

2011-01-01

Objectives To estimate life expectancy for people with HIV undergoing treatment compared with life expectancy in the general population and to assess the impact on life expectancy of late treatment, defined as CD4 count <200 cells/mm3 at start of antiretroviral therapy. Design Cohort study. Setting Outpatient HIV clinics throughout the United Kingdom. Population Adult patients from the UK Collaborative HIV Cohort (UK CHIC) Study with CD4 count ≤350 cells/mm3 at start of antiretroviral therapy in 1996-2008. Main outcome measures Life expectancy at the exact age of 20 (the average additional years that will be lived by a person after age 20), according to the cross sectional age specific mortality rates during the study period. Results 1248 of 17 661 eligible patients died during 91 203 person years’ follow-up. Life expectancy (standard error) at exact age 20 increased from 30.0 (1.2) to 45.8 (1.7) years from 1996-9 to 2006-8. Life expectancy was 39.5 (0.45) for male patients and 50.2 (0.45) years for female patients compared with 57.8 and 61.6 years for men and women in the general population (1996-2006). Starting antiretroviral therapy later than guidelines suggest resulted in up to 15 years’ loss of life: at age 20, life expectancy was 37.9 (1.3), 41.0 (2.2), and 53.4 (1.2) years in those starting antiretroviral therapy with CD4 count <100, 100-199, and 200-350 cells/mm3, respectively. Conclusions Life expectancy in people treated for HIV infection has increased by over 15 years during 1996-2008, but is still about 13 years less than that of the UK population. The higher life expectancy in women is magnified in those with HIV. Earlier diagnosis and subsequent timely treatment with antiretroviral therapy might increase life expectancy. PMID:21990260

Medical resource utilization and cost of HIV-related care in the highly active antiretroviral therapy era at a University Clinic in Sweden.

PubMed

Ghatnekar, Ola; Hjortsberg, Catharina; Gisslén, Magnus; Lindbäck, Stefan; Löthgren, Mickael

2010-01-01

Little is known regarding healthcare costs for HIV/AIDS patients in the era of highly active antiretroviral therapy (HAART) and subgroups of patients according to the severity and progression of HIV infection in Sweden. The objective of this study is therefore to describe the direct medical resource use and cost of healthcare for HIV patients at a university clinic in Sweden. A patient registry database for HIV treatment at the Department of Infectious Diseases, Sahlgrenska University Hospital, between 2000 and 2005 provided information on patient characteristics, antiretroviral drugs and dosages, tests and diagnostic procedures, outpatient visits and inpatient stays. The review used publicly available unit costs with a county council perspective, expressed in 2006 Euros. Two hundred and eighty-five patients with a mean age of 38 years in 2000 (64% men) were followed for 1368 patient-years. They had a mean (median) of 6.3 (0) inpatient days, 4.1 (3.7) physician visits, 4.2 (3.8) nurse visits, 2.6 (0.7) counsellor visits and 11.5 (7.7) tests and diagnostic procedures per patient-year. Only 12 deaths were recorded during the study period, and the proportion of treated patients with successful treatment (HIV-RNA < 50 copies/mL) increased from 74% to 92% during the period. The mean cost per patient-month amounted to €1069. The main cost driver was HIV drugs (51%), followed by inpatient stays (including hospitalizations for opportunistic infections; 22%), outpatient physician, nurse or therapist visits (19%) and diagnostics and tests (7%). All non-drug costs increased with a decreasing CD4 cell count. Overall, approximately half of the direct costs of HIV treatment were not related to antiretroviral treatment. The non-antiretroviral costs were inversely correlated with HIV-induced immune deficiency.

Reduced sTWEAK and Increased sCD163 Levels in HIV-Infected Patients: Modulation by Antiretroviral Treatment, HIV Replication and HCV Co-Infection

PubMed Central

Beltrán, Luis M.; García Morillo, José S.; Egido, Jesús; Noval, Manuel Leal; Ferrando-Martinez, Sara; Blanco-Colio, Luis M.; Genebat, Miguel; Villar, José R.; Moreno-Luna, Rafael; Moreno, Juan Antonio

2014-01-01

Background Patients infected with the human immunodeficiency virus (HIV) have an increased risk of cardiovascular disease due to increased inflammation and persistent immune activation. CD163 is a macrophage scavenger receptor that is involved in monocyte-macrophage activation in HIV-infected patients. CD163 interacts with TWEAK, a member of the TNF superfamily. Circulating levels of sTWEAK and sCD163 have been previously associated with cardiovascular disease, but no previous studies have fully analyzed their association with HIV. Objective The aim of this study was to analyze circulating levels of sTWEAK and sCD163 as well as other known markers of inflammation (hsCRP, IL-6 and sTNFRII) and endothelial dysfunction (sVCAM-1 and ADMA) in 26 patients with HIV before and after 48 weeks of antiretroviral treatment (ART) and 23 healthy subjects. Results Patients with HIV had reduced sTWEAK levels and increased sCD163, sVCAM-1, ADMA, hsCRP, IL-6 and sTNFRII plasma concentrations, as well as increased sCD163/sTWEAK ratio, compared with healthy subjects. Antiretroviral treatment significantly reduced the concentrations of sCD163, sVCAM-1, hsCRP and sTNFRII, although they remained elevated when compared with healthy subjects. Antiretroviral treatment had no effect on the concentrations of ADMA and sTWEAK, biomarkers associated with endothelial function. The use of protease inhibitors as part of antiretroviral therapy and the presence of HCV-HIV co-infection and/or active HIV replication attenuated the ART-mediated decrease in sCD163 plasma concentrations. Conclusion HIV-infected patients showed a proatherogenic profile characterized by increased inflammatory, immune-activation and endothelial-dysfunction biomarkers that partially improved after ART. HCV-HIV co-infection and/or active HIV replication enhanced immune activation despite ART. PMID:24594990

Prevalence and predictors of anaemia in patients with HIV infection at the initiation of combined antiretroviral therapy in Xinjiang, China.

PubMed

Mijiti, Peierdun; Yuexin, Zhang; Min, Liu; Wubuli, Maimaitili; Kejun, Pan; Upur, Halmurat

2015-03-01

We retrospectively analysed routinely collected baseline data of 2252 patients with HIV infection registered in the National Free Antiretroviral Treatment Program in Xinjiang province, China, from 2006 to 2011 to estimate the prevalence and predictors of anaemia at the initiation of combined antiretroviral therapy. Anaemia was diagnosed using the criteria set forth by the World Health Organisation, and univariate and multivariate logistic regression analyses were performed to determine its predictors. The prevalences of mild, moderate, and severe anaemia at the initiation of combined antiretroviral therapy were 19.2%, 17.1%, and 2.6%, respectively. Overall, 38.9% of the patients were anaemic at the initiation of combined antiretroviral therapy. The multivariate logistic regression analysis indicated that Uyghur ethnicity, female gender, lower CD4 count, lower body mass index value, self-reported tuberculosis infection, and oral candidiasis were associated with a higher prevalence of anaemia, whereas higher serum alanine aminotransferase level was associated with a lower prevalence of anaemia. The results suggest that the overall prevalence of anaemia at the initiation of combined antiretroviral therapy in patients with HIV infection is high in Xinjiang, China, but severe anaemia is uncommon. Patients in China should be routinely checked for anaemia prior to combined antiretroviral therapy initiation, and healthcare providers should carefully select the appropriate first-line combined antiretroviral therapy regimens for anaemic patients. © The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

Follow-up on long-term antiretroviral therapy for cats infected with feline immunodeficiency virus.

PubMed

Medeiros, Sheila de Oliveira; Abreu, Celina Monteiro; Delvecchio, Rodrigo; Ribeiro, Anísia Praxedes; Vasconcelos, Zilton; Brindeiro, Rodrigo de Moraes; Tanuri, Amilcar

2016-04-01

Feline immunodeficiency virus (FIV) is a lentivirus that induces AIDS-like disease in cats. Some of the antiretroviral drugs available to treat patients with HIV type 1 are used to treat FIV-infected cats; however, antiretroviral therapy (ART) is not used in cats as a long-term treatment. In this study, the effects of long-term ART were evaluated in domestic cats treated initially with the nucleoside transcriptase reverse inhibitor (NTRI) zidovudine (AZT) over a period ranging from 5-6 years, followed by a regimen of the NTRI lamivudine (3TC) plus AZT over 3 years. Viral load, sequencing of pol (reverse transcriptase [RT]) region and CD4:CD8 lymphocyte ratio were evaluated during and after treatment. Untreated cats were evaluated as a control group. CD4:CD8 ratios were lower, and uncharacterized resistance mutations were found in the RT region in the group of treated cats. A slight increase in viral load was observed in some cats after discontinuing treatment. The data strongly suggest that treated cats were resistant to therapy, and uncharacterized resistance mutations in the RT gene of FIV were selected for by AZT. Few studies have been conducted to evaluate the effect of long-term antiretroviral therapy in cats. To date, resistance mutations have not been described in vivo. © ISFM and AAFP 2015.

Access to antiretroviral drugs and AIDS management in Senegal.

PubMed

Desclaux, Alice; Ciss, Mounirou; Taverne, Bernard; Sow, Papa S; Egrot, Marc; Faye, Mame A; Lanièce, Isabelle; Sylla, Omar; Delaporte, Eric; Ndoye, Ibrahima

2003-07-01

Description and analysis of the Senegalese Antiretroviral Drug Access Initiative (ISAARV), the first governmental highly active antiretroviral therapy (HAART) treatment programme in Africa, launched in 1998. ISAARV was initially an experimental project designed to evaluate the feasibility, efficacy and acceptability of HAART in an African context. It was based on four principles: collective definition of the strategy, with involvement of the health professionals who would be called on to execute the programme; matching the objectives to available means (gradual enrollment according to drug availability); monitoring by several research programmes; and ongoing adaptation of treatment and follow-up according to the latest international recommendations. Persons qualifying for antiretroviral (ARV) therapy are selected on the basis of immunological and clinical criteria, regardless of economic and social considerations. A system of subsidies was created to favor access to ARV. Following the ARV price reductions that occurred in November 2000, 100% subsidies were created for the poorest participants. Optimal adherence was ensured by monthly follow-up by pharmacists and support groups held by social workers and patient associations. The chosen supply and distribution system allowed drug dispensing to be strictly controlled. The ISAARV programme demonstrates that HAART can be successfully prescribed in Africa. This experience has served as the basis for the creation of a national treatment programme in Senegal planned to treat 7000 patients by 2006.

Acceptability and preferences for safer conception HIV prevention strategies: a qualitative study.

PubMed

Schwartz, Sheree R; West, Nora; Phofa, Rebecca; Yende, Nompumelelo; Sanne, Ian; Bassett, Jean; Van Rie, Annelies

2016-10-01

Safer conception strategies to reduce the HIV transmission risk include antiretroviral therapy for HIV-positive partners, pre-exposure prophylaxis for HIV-negative partners, condomless sex limited to fertile periods, and home-based self-insemination. Resistance to taking treatment or cultural concerns may limit uptake of strategies and intervention success. Understanding the acceptability and preferences between different approaches is important to optimise service delivery. Between February and July 2013, 42 adults (21 HIV-positive and 21 HIV-negative) receiving primary care at Witkoppen Health and Welfare Centre in Johannesburg, South Africa, participated in focus group discussions or in-depth interviews. Themes were analysed using a grounded theory approach. Acceptability of antiretroviral-based strategies varied. Concerns over side effects, antiretroviral treatment duration and beliefs that treatment is only for the sick were common barriers; however, desperation for a child was noted as a facilitator for uptake. HIV-negative men and HIV-positive women had favourable attitudes towards self-insemination, though paternity and safety concerns were raised. Self-insemination was generally preferred over pre-exposure prophylaxis by HIV-negative men, and antiretroviral-based strategies were preferred by couples with HIV-negative female partners, despite concerns raised about condomless sex while virally suppressed. Knowledge about the fertile window was low. A strong counselling component will be required for effective uptake and adherence to safer conception services. © The Author(s) 2016.

Do Older Rural and Urban Veterans Experience Different Rates of Unplanned Readmission to VA and Non-VA Hospitals?

ERIC Educational Resources Information Center

Weeks, William B.; Lee, Richard E.; Wallace, Amy E.; West, Alan N.; Bagian, James P.

2009-01-01

Context: Unplanned readmission within 30 days of discharge is an indicator of hospital quality. Purpose: We wanted to determine whether older rural veterans who were enrolled in the VA had different rates of unplanned readmission to VA or non-VA hospitals than their urban counterparts. Methods: We used the combined VA/Medicare dataset to examine…

Crusted scabies-associated immune reconstitution inflammatory syndrome

PubMed Central

2012-01-01

Background Despite the widely accepted association between crusted scabies and human immunodeficiency virus (HIV)-infection, crusted scabies has not been included in the spectrum of infections associated with immune reconstitution inflammatory syndrome in HIV-infected patients initiating antiretroviral therapy. Case presentation We report a case of a 28-year-old Mexican individual with late HIV-infection, who had no apparent skin lesions but soon after initiation of antiretroviral therapy, he developed an aggressive form of crusted scabies with rapid progression of lesions. Severe infestation by Sarcoptes scabiei was confirmed by microscopic examination of the scale and skin biopsy. Due to the atypical presentation of scabies in a patient responding to antiretroviral therapy, preceded by no apparent skin lesions at initiation of antiretroviral therapy, the episode was interpreted for the first time as “unmasking crusted scabies-associated immune reconstitution inflammatory syndrome”. Conclusion This case illustrates that when crusted scabies is observed in HIV-infected patients responding to antiretroviral therapy, it might as well be considered as a possible manifestation of immune reconstitution inflammatory syndrome. Patient context should be considered for adequate diagnosis and treatment of conditions exacerbated by antiretroviral therapy-induced immune reconstitution. PMID:23181485

Potential drug interactions in patients given antiretroviral therapy

PubMed Central

dos Santos, Wendel Mombaque; Secoli, Silvia Regina; Padoin, Stela Maris de Mello

2016-01-01

ABSTRACT Objective: to investigate potential drug-drug interactions (PDDI) in patients with HIV infection on antiretroviral therapy. Methods: a cross-sectional study was conducted on 161 adults with HIV infection. Clinical, socio demographic, and antiretroviral treatment data were collected. To analyze the potential drug interactions, we used the software Micromedex(r). Statistical analysis was performed by binary logistic regression, with a p-value of ≤0.05 considered statistically significant. Results: of the participants, 52.2% were exposed to potential drug-drug interactions. In total, there were 218 potential drug-drug interactions, of which 79.8% occurred between drugs used for antiretroviral therapy. There was an association between the use of five or more medications and potential drug-drug interactions (p = 0.000) and between the time period of antiretroviral therapy being over six years and potential drug-drug interactions (p < 0.00). The clinical impact was prevalent sedation and cardiotoxicity. Conclusions: the PDDI identified in this study of moderate and higher severity are events that not only affect the therapeutic response leading to toxicity in the central nervous and cardiovascular systems, but also can interfere in tests used for detection of HIV resistance to antiretroviral drugs. PMID:27878224

Risk Factors of Clinical and Immunological Failure in South Indian Cohort on Generic Antiretroviral Therapy.

PubMed

Sadashiv, Mucheli Shravan; Rupali, Priscilla; Manesh, Abi; Kannangai, Rajesh; Abraham, Ooriapadickal Cherian; Pulimood, Susanne A; Karthik, Rajiv; Rajkumar, S; Thomas, Kurien

2017-12-01

Since the time of NACO Antiretroviral (ART) roll-out, generic ART has been the mainstay of therapy. There are many studies documenting the efficacy of generic ART but with the passage of time, failure of therapy is on the rise. As institution of second line ART has significant financial implications both for a program and for an individual it is imperative that we determine factors which contribute towards treatment failure in a cohort of patients on generic antiretroviral therapy. This was a nested matched case-control study assessing the predictors for treatment failure in our cohort who had been on Anti-retroviral therapy for at least a year. We identified 42 patients (Cases) with documented treatment failure out of our cohort of 823 patients and 42 sex, age and duration of therapy-matched controls. Using a structured proforma, we collected information from the out-patient and in-patient charts of the Infectious Diseases clinic Cohort in CMC, Vellore. A set of predetermined variables were studied as potential risk factors for treatment failure on ART. Univariate analysis showed significant association with 1) Self-reported nonadherence<95% [OR 12.81 (95%CI 1.54-281.45)]. 2) Treatment interruptions in adherent cases (OR 9.56 (95% CI 1.11-213.35)]. 3) Past inappropriate therapies [OR 9.65 (95% CI 1.12-215.94)]. 4) Diarrhoea [OR 16.40 (95% CI 2.02-3.55.960]. 5) GI opportunistic infections (OR 11.06 (95% CI 1.31 -244.27)] and 6) Drug Toxicity [OR 3.69 (95% CI 1.15-12.35).In multiple logistic regression analysis, we found independent risk factors of treatment failure to be: Self-reported non-adherence (<95%) with OR 15.46(95%CI 1.55 - 154.08), drug toxicity - OR 4.13(95%CI 1.095 - 15.534) and history of diarrhoea - OR 23.446(95%CI 2.572 - 213.70). This study reveals that besides adherence to therapy, presence of diarrhoea and occurrence of drug toxicity are significant risk factors associated with failure of anti-retroviral therapy. There is a need for further prospective studies to assess their role in development of treatment failure on ART and thus help development of targeted interventions.

Current practices in laboratory monitoring of HIV infection

PubMed Central

Vajpayee, Madhu; Mohan, Teena

2011-01-01

After a diagnosis of HIV infection is made, the patient needs to be monitored using both clinical assessment and laboratory markers. HIV/AIDS monitoring is essential in guiding when to recommend initiation of therapy. Clinical monitoring will include staging of the HIV/AIDS disease using either the presence or absence of HIV-related signs and symptoms using the WHO staging system. Various laboratory methods can be used to monitor the disease progression and to guide whether the patient will need antiretroviral therapy or not. Laboratory monitoring for patients who are not on drugs is done to provide information about the stage of illness; to enable the clinician to make decisions on treatment and to give information on prognosis of the patient. Patients on drugs are monitored to assess their response to treatment with antiretroviral drugs and to detect any possible toxicity and improvement associated with the antiretroviral drugs. PMID:22310815

Prevention and treatment of opportunistic infections and other coinfections in HIV-infected patients: May 2015.

PubMed

Iribarren, José Antonio; Rubio, Rafael; Aguirrebengoa, Koldo; Arribas, Jose Ramón; Baraia-Etxaburu, Josu; Gutiérrez, Félix; Lopez Bernaldo de Quirós, Juan Carlos; Losa, Juan Emilio; Miró, José Ma; Moreno, Santiago; Pérez Molina, José; Podzamczer, Daniel; Pulido, Federico; Riera, Melchor; Rivero, Antonio; Sanz Moreno, José; Amador, Concha; Antela, Antonio; Arazo, Piedad; Arrizabalaga, Julio; Bachiller, Pablo; Barros, Carlos; Berenguer, Juan; Caylá, Joan; Domingo, Pere; Estrada, Vicente; Knobel, Hernando; Locutura, Jaime; López Aldeguer, José; Llibre, Josep Ma; Lozano, Fernando; Mallolas, Josep; Malmierca, Eduardo; Miralles, Celia; Miralles, Pilar; Muñoz, Agustín; Ocampo, Agustín; Olalla, Julián; Pérez, Inés; Pérez Elías, Ma Jesús; Pérez Arellano, José Luis; Portilla, Joaquín; Ribera, Esteban; Rodríguez, Francisco; Santín, Miguel; Sanz Sanz, Jesús; Téllez, Ma Jesús; Torralba, Miguel; Valencia, Eulalia; Von Wichmann, Miguel Angel

2016-10-01

Despite the huge advance that antiretroviral therapy represents for the prognosis of infection by the human immunodeficiency virus (HIV), opportunistic infections (OIs) continue to be a cause of morbidity and mortality in HIV-infected patients. OIs often arise because of severe immunosuppression resulting from poor adherence to antiretroviral therapy, failure of antiretroviral therapy, or unawareness of HIV infection by patients whose first clinical manifestation of AIDS is an OI. The present article updates our previous guidelines on the prevention and treatment of various OIs in HIV-infected patients, namely, infections by parasites, fungi, viruses, mycobacteria, and bacteria, as well as imported infections. The article also addresses immune reconstitution inflammatory syndrome. Copyright © 2016 Elsevier España, S.L.U. and Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. All rights reserved.

The importance of the patient-clinician relationship in adherence to antiretroviral medication.

PubMed

Molassiotis, Alex; Morris, Kate; Trueman, Ian

2007-12-01

The aim of the study was to assess dimensions of the patient-clinician relationship in relation to adherence with antiretroviral medication in a sample of HIV patients. This was a correlational evaluation, using a cross-sectional design. Thirty-eight HIV patients in two UK HIV units provided complete data. Analysis suggested that the elements of the patient-clinician relationship contributing to adherence with medication were the patient perception of being valued and respected by the clinician, the patients' ability to initiate discussions about the treatment, empowerment and level of trust placed in the nurse. The latter, and the time since starting antiretroviral treatment, were the only two variables that could predict adherence in a regression model, explaining 41% of the variance in adherence. Building trusted relationships with the patients and investing in educational and communication techniques to improve the therapeutic relationship could strongly contribute to HIV patients to maintaining high adherence rates.

Antiretroviral-based HIV-1 Prevention: Antiretroviral Treatment and Pre-Exposure Prophylaxis

PubMed Central

Celum, Connie; Baeten, Jared

2012-01-01

Antiretroviral-based HIV-1 prevention strategies – including antiretroviral treatment (ART) to reduce the infectiousness of HIV-1 infected persons and oral and topical pre-exposure prophylaxis (PrEP) for uninfected persons to prevent HIV-1 acquisition – are the most promising new approaches for decreasing HIV-1 spread. Observational studies among HIV-1 serodiscordant couples have associated ART initiation with a reduction in HIV-1 transmission risk of 80–92%, and a recent randomized trial demonstrated that earlier initiation of ART (i.e., at CD4 counts between 350 and 550 cells/mm3), in the context of virologic monitoring and adherence support, resulted in a 96% reduction in HIV-1 transmission. A number of ongoing and recently-completed clinical trials have assessed the efficacy of PrEP for HIV-1 prevention as peri-coitally administered or daily-administered 1% tenofovir gel and daily oral tenofovir and combination emtricitabine/tenofovir. Completed studies have demonstrated HIV-1 protection efficacies ranging from 39% to 75%. However, two trials in African women have shown no HIV-1 protection with PrEP; the reasons for lack of efficacy in those trials are being investigated. Adherence is likely key to efficacy of antiretrovirals for HIV-1 prevention, both as ART and PrEP. Critical unanswered questions for successful delivery of antiretroviral-based HIV-1 prevention include how to target ART and PrEP to realize maximum population benefits, whether HIV-1 infected persons at earlier stages of infection would accept ART to reduce their risk for transmitting HIV-1 and highest-risk HIV-1 negative persons would use PrEP, and whether high adherence could be sustained to achieve high effectiveness. PMID:23221365

Sex education attitudes and outcomes among North American women.

PubMed

Williams, Monnica T; Bonner, Laura

2006-01-01

Attitudes and outcomes of sex education received by North American women are examined via an Internet survey (N = 1,400). Mean age was 19.5, with 24% reporting one or more unplanned pregnancies. Women were more satisfied with sex education from informal sources than from parents, schools, and physicians. Those receiving sex education from parents or schools reported fewer pregnancies and abortions. In school, women receiving a combination of contraceptive and abstinence education and those receiving primarily abstinence education were least likely to experience unplanned pregnancy. Religious identification was significantly related to unplanned pregnancy and type of sex education received from parents. These factors seem to play a significant role in reducing unplanned pregnancy and abortion.

A Mobile Gaming Intervention to Increase Adherence to Antiretroviral Treatment for Youth Living With HIV: Development Guided by the Information, Motivation, and Behavioral Skills Model.

PubMed

Whiteley, Laura; Brown, Larry; Lally, Michelle; Heck, Nicholas; van den Berg, Jacob J

2018-04-23

Highly active combination antiretroviral treatment has been shown to markedly improve the health of HIV-infected adolescents and young adults. Adherence to antiretroviral treatment leads to decreased morbidity and mortality and decreases the number of hospitalizations. However, these clinical achievements can only occur when young persons with HIV are adherent to care. Unfortunately, adolescents and young adults have poorer rates of adherence to antiretroviral medications and poorer rates of retention in care than older adults. Novel and engaging digital approaches are needed to help adolescents and young adults living with HIV be adherent to treatment. The aim of this study was to develop an immersive, action-oriented iPhone gaming intervention to improve adherence to antiretroviral medication and treatment. Game development was guided by social learning theory, taking into consideration the perspectives of adolescents and young adults living with HIV. A total of 20 adolescents and young adults were recruited from an HIV care clinic in Rhode Island, and they participated in qualitative interviews guided by the information-motivation-behavioral skills model of behavior change. The mean age of participants was 22 years, 60% (12/20) of the participants identified as male, and 60% (12/20) of the sample reported missing a dose of antiretroviral medication in the previous week. Acceptability of the game was assessed with client service questionnaire and session evaluation form. A number of themes emerged that informed game development. Adolescents and young adults living with HIV desired informational game content that included new and comprehensive details about HIV, details about HIV as it relates to doctors' visits, and general health information. Motivational themes that emerged were the desire for enhancement of future orientation; reinforcement of positive influences from partners, parents, and friends; collaboration with health care providers; decreasing stigma; and increasing personal relevance of HIV care. Behavioral skills themes centered on self-efficacy and strategies for medical adherence and self-care. On the client service questionnaire, 10 out of the 11 participants indicated they were "satisfied with the game activities," and 9 out of 11 "would recommend it to a friend." On the session evaluation form, 9 out of 11 agreed that they "learned a lot from the game." We utilized youth feedback, social learning theory (information-motivation-behavioral skills), and agile software development to create a multilevel, immersive, action-oriented iPhone gaming intervention to measure and improve treatment adherence for adolescents and young adults living with HIV. There is a dearth of gaming interventions for this population, and this study is a significant step in working toward the development and testing of an iPhone gaming app intervention to promote adherence to antiretroviral treatment. ClinicalTrials.gov NCT01887210; http://clinicaltrials.gov/ct2/show/NCT01887210 (Archived by WebCite at http://www.webcitation.org/6xHMW0NI1). ©Laura Whiteley, Larry Brown, Michelle Lally, Nicholas Heck, Jacob J van den Berg. Originally published in JMIR Mhealth and Uhealth (http://mhealth.jmir.org), 23.04.2018.

A Mobile Gaming Intervention to Increase Adherence to Antiretroviral Treatment for Youth Living With HIV: Development Guided by the Information, Motivation, and Behavioral Skills Model

PubMed Central

2018-01-01

Background Highly active combination antiretroviral treatment has been shown to markedly improve the health of HIV-infected adolescents and young adults. Adherence to antiretroviral treatment leads to decreased morbidity and mortality and decreases the number of hospitalizations. However, these clinical achievements can only occur when young persons with HIV are adherent to care. Unfortunately, adolescents and young adults have poorer rates of adherence to antiretroviral medications and poorer rates of retention in care than older adults. Novel and engaging digital approaches are needed to help adolescents and young adults living with HIV be adherent to treatment. Objective The aim of this study was to develop an immersive, action-oriented iPhone gaming intervention to improve adherence to antiretroviral medication and treatment. Methods Game development was guided by social learning theory, taking into consideration the perspectives of adolescents and young adults living with HIV. A total of 20 adolescents and young adults were recruited from an HIV care clinic in Rhode Island, and they participated in qualitative interviews guided by the information-motivation-behavioral skills model of behavior change. The mean age of participants was 22 years, 60% (12/20) of the participants identified as male, and 60% (12/20) of the sample reported missing a dose of antiretroviral medication in the previous week. Acceptability of the game was assessed with client service questionnaire and session evaluation form. Results A number of themes emerged that informed game development. Adolescents and young adults living with HIV desired informational game content that included new and comprehensive details about HIV, details about HIV as it relates to doctors’ visits, and general health information. Motivational themes that emerged were the desire for enhancement of future orientation; reinforcement of positive influences from partners, parents, and friends; collaboration with health care providers; decreasing stigma; and increasing personal relevance of HIV care. Behavioral skills themes centered on self-efficacy and strategies for medical adherence and self-care. On the client service questionnaire, 10 out of the 11 participants indicated they were “satisfied with the game activities,” and 9 out of 11 “would recommend it to a friend.” On the session evaluation form, 9 out of 11 agreed that they “learned a lot from the game.” Conclusions We utilized youth feedback, social learning theory (information-motivation-behavioral skills), and agile software development to create a multilevel, immersive, action-oriented iPhone gaming intervention to measure and improve treatment adherence for adolescents and young adults living with HIV. There is a dearth of gaming interventions for this population, and this study is a significant step in working toward the development and testing of an iPhone gaming app intervention to promote adherence to antiretroviral treatment. Trial Registration ClinicalTrials.gov NCT01887210; http://clinicaltrials.gov/ct2/show/NCT01887210 (Archived by WebCite at http://www.webcitation.org/6xHMW0NI1) PMID:29685863

Brazil may stop HIV drug access; problems also reported from Argentina.

PubMed

1999-09-03

Brazil's financial crisis is threatening its HIV treatment programs, as well as programs for other diseases such as hemophilia, tuberculosis, diabetes, and malaria. The government is expected to stop providing antiretroviral therapy through the public health system in October. Meanwhile, the Argentine government stopped providing antiretroviral medications in August. Drug recycling programs are also discussed. Contact information is provided.

Knowledge, Stigma, and Behavioral Outcomes among Antiretroviral Therapy Patients Exposed to Nalamdana's Radio and Theater Program in Tamil Nadu, India

ERIC Educational Resources Information Center

Nambiar, Devaki; Ramakrishnan, Vimala; Kumar, Paresh; Varma, Rajeev; Balaji, Nithya; Rajendran, Jeeva; Jhona, Loretta; Chandrasekar, Chokkalingam; Gere, David

2011-01-01

Arts-based programs have improved HIV-related knowledge, attitudes, and behavior in general and at-risk populations. With HIV transformed into a chronic condition, this study compares patients at consecutive stages of receiving antiretroviral treatment, coinciding with exposure to a radio-and-theater-based educational program (unexposed [N = 120],…

Retrospective study of CMV retinitis in patients with AIDS.

PubMed

Pauriah, M; Ong, E L

2000-01-01

To study the characteristics of clinical presentations and treatment outcome of patients with HIV infection who developed cytomegalovirus(CMV) retinitis. A retrospective study for the period 1986-97 at the regional Unit of Infectious Diseases, Newcastle General Hospital; a teaching hospital in the north-east of England. Twenty-seven patients with advanced HIV disease and clinically confirmed CMV retinitis were studied. The mean age was 40.8 years, standard deviation +/-6.3 years. The male : female ratio was 25 : 2. Twenty-six of the patients were white Caucasians and one was of Afro-Caribbean origin. The median time between the first AIDS-defining diagnosis and development of CMV retinitis was 1.5 years and the CD4+ cell count at the time of diagnosis of CMV retinitis was 7/mm3. After 14 months of treatment. 80% of patients on mono antiretroviral therapy had impairment of sight (visual acuity 3/60) versus 30% for those on triple antiretroviral therapy. In the same period, the survival rate was 18 versus 70% for mono versus triple antiretroviral therapy, respectively. The outcome for patients with CMV retinitis was significantly better for those who were on triple than for those on mono antiretroviral therapy.

Challenges and potential barriers to the uptake of antiretroviral-based prevention in Asia and the Pacific region.

PubMed

Lo, Ying-Ru; Kato, Masaya; Phanuphak, Nittaya; Fujita, Masami; Duc, Duong Bui; Sopheap, Seng; Pendse, Razia; Yu, Dongbao; Wu, Zunyou; Chariyalertsak, Suwat

2014-07-01

Evidence has emerged over the past few years on the effectiveness of antiretroviral-based prevention technologies to prevent (i) HIV transmission while decreasing morbidity and mortality in HIV-infected persons, and (ii) HIV acquisition in HIV-uninfected individuals through pre-exposure prophylaxis (PrEP). Only few of the planned studies on treatment as prevention (TasP) are conducted in Asia. TasP might be more feasible and effective in concentrated rather than in generalised epidemics, as resources for HIV testing and antiretroviral treatment could focus on confined and much smaller populations than in the generalised epidemics observed in sub-Saharan Africa. Several countries such as Cambodia, China, Thailand and Vietnam, are now paving the way to success. Similar challenges arise for both TasP and PrEP. However, the operational issues for PrEP are amplified by the need for frequent retesting and ensuring adherence. This paper describes challenges for the implementation of antiretroviral-based prevention and makes the case that TasP and PrEP implementation research in Asia is much needed to provide insights into the feasibility of these interventions in populations where firm evidence of 'real world' effectiveness is still lacking.

Neurotoxicity in the Post-HAART Era: Caution for the Antiretroviral Therapeutics

PubMed Central

Shah, Ankit; Gangwani, Mohitkumar R.; Chaudhari, Nitish S.; Glazyrin, Alexy; Bhat, Hari K.; Kumar, Anil

2016-01-01

Despite the advent of highly active antiretroviral therapy (HAART), HIV-associated neurological disorders (HAND) remain a major challenge in human immunodeficiency virus (HIV) treatment. The early implementation of HAART in the infected individuals helps suppress the viral replication in the plasma and other compartments. Several studies also report the beneficial effect of drugs that successfully penetrate central nervous system (CNS). However, recent data in both clinical setup and in in vitro studies indicate CNS toxicity of the antiretrovirals (ARVs). Although the evidence is limited, correlation between prolonged use of ARVs and neurotoxicity strongly suggests that it is essential to study the underlying mechanisms responsible for such toxicity. Furthermore, closer attention toward clinical outcomes is required to screen various ARV regimens for their association with HAND and other comorbidities. A growing body of literature also indicates a possible role of accelerated aging in the antiretroviral therapy-associated neurotoxicity. Lastly, owing to high pill burden, multiple drugs in the HIV treatment also invite a possible role of drug–drug interaction via various cytochrome P450 enzymes. The particular emphasis of this review is to highlight the need to identify alternative approaches in reducing the CNS toxicity of the ARV drugs in HIV-infected individuals. PMID:27364698

Gynaecomastia in two men on stable antiretroviral therapy who commenced treatment for tuberculosis.

PubMed

Kratz, Jeremy D; El-Shazly, Ahmad Y; Mambuque, Santos G; Demetria, Elpidio; Veldkamp, Peter; Anderson, Timothy S

2016-12-01

Gynaecomastia is a common clinical presentation that varies from benign presentations in stages of human development to hormonal pathology, mainly due to hepatic dysfunction, malignancy, and adverse pharmacologic effects. We describe the development of significant bilateral gynaecomastia after starting treatment for pulmonary tuberculosis (TB) in two males with WHO stage III Human Immunodeficiency Virus (HIV) infection on stable antiretroviral regimens. Emerging reports suggest that distinct hepatic impairment in efavirenz metabolism modulates oestrogenic activity, which may be potentiated by anti-tuberculosis therapy. Clinical application includes early recognition of efavirenz-induced gynaecomastia, especially after commencing tuberculosis treatment. To avoid decreased adherence resulting from the distressing side effect of gynecomastia, transition to an alternative ART regimen over the course of tuberculosis treatment should be considered.

Reduction in Mortality Following Pediatric Rapid Response Team Implementation.

PubMed

Kolovos, Nikoleta S; Gill, Jeff; Michelson, Peter H; Doctor, Allan; Hartman, Mary E

2018-05-01

To evaluate the effectiveness of a physician-led rapid response team program on morbidity and mortality following unplanned admission to the PICU. Before-after study. Single-center quaternary-referral PICU. All unplanned PICU admissions from the ward from 2005 to 2011. The dataset was divided into pre- and post-rapid response team groups for comparison. A Cox proportional hazards model was used to identify the patient characteristics associated with mortality following unplanned PICU admission. Following rapid response team implementation, Pediatric Risk of Mortality, version 3, illness severity was reduced (28.7%), PICU length of stay was less (19.0%), and mortality declined (22%). Relative risk of death following unplanned admission to the PICU after rapid response team implementation was 0.685. For children requiring unplanned admission to the PICU, rapid response team implementation is associated with reduced mortality, admission severity of illness, and length of stay. Rapid response team implementation led to more proximal capture and aggressive intervention in the trajectory of a decompensating pediatric ward patient.

Decision-Making Influences Tibial Impact Accelerations During Lateral Cutting.

PubMed

Lucas, Logan A; England, Benjamin S; Mason, Travis W; Lanning, Christopher R; Miller, Taylor M; Morgan, Alexander M; Almonroeder, Thomas G

2018-05-29

Lower extremity musculoskeletal injuries are common in sports such as basketball and soccer. Athletes competing in sports of this nature must maneuver in response to the actions of their teammates, opponents, etc. This limits their ability to pre-plan movements. The purpose of this study was to compare impact accelerations during pre-planned vs. un-planned lateral cutting. Thirty subjects (15 males, 15 females) performed pre-planned and un-planned cuts while we analyzed impact accelerations using an accelerometer secured to their tibia. For the pre-planned condition, subjects were aware of the movement to perform before initiating a trial. For the un-planned condition, subjects initiated their movement and then reacted to the illumination of one of three visual stimuli which dictated whether they would cut, land, or land-and-jump. A mixed-model ANOVA with a between factor of sex (male, female) and a within factor of condition (pre-planned, un-planned) was used to analyze the magnitude and variability of the impact accelerations for the cutting trials. Both males and females demonstrated higher impact accelerations (p = .010) and a trend toward greater inter-trial variability (p = .073) for the un-planned cutting trials (vs. pre-planned cuts). Un-planned cutting may place greater demands on the musculoskeletal system.

Influence of the number of daily pills and doses on adherence to antiretroviral treatment: a 7-year study.

PubMed

Hernández Arroyo, M J; Cabrera Figueroa, S E; Sepúlveda Correa, R; Valverde Merino, M P; Luna Rodrigo, G; Domínguez-Gil Hurlé, A

2016-02-01

Antiretroviral treatment (ART) is hampered by complicated regimens, high pill burden, drug-drug interactions, and frequent short- and long-term adverse effects, leading to decreased adherence. Over recent years, considerable effort has been directed at developing regimens that are less burdening. We undertook a 7-year retrospective study of the records of 264 HIV-infected subjects enrolled in a pharmaceutical care programme to document the progress made and to study the influence of the number of ART pills and doses on the level of treatment adherence. Antiretroviral dispensing records were analysed for the number of pills and doses administered and the ART adherence rate estimated. In 2005, the patients took a mean of 6·2 pills daily (CI 95%: 5·9-6·6), and 92·9% of them were on a twice-a-day (BID) dosage regimen. By 2012, the mean number of pills was reduced to 4·1 (CI 95%: 3·8-4·4), and only 50·9% were on a BID regimen. No statistically significant relation was observed between number of daily pills and doses and ART adherence reached by the patients in any of the analyses performed. There has been a continuous reduction in the number of pills and doses of antiretrovirals taken by individual patients over the last 7 years due largely to the introduction of improved treatments and regimens. More daily pills or doses was not associated with worse ART adherence in our pharmaceutical care programme. © 2015 John Wiley & Sons Ltd.

Unplanned admission to intensive care after emergency hospitalisation: risk factors and development of a nomogram for individualising risk.

PubMed

Frost, Steven A; Alexandrou, Evan; Bogdanovski, Tony; Salamonson, Yenna; Parr, Michael J; Hillman, Ken M

2009-02-01

Unplanned admission to an intensive care unit (ICU) is associated with high mortality, having the highest incidence among patients who are emergency admissions to the hospital. This study was designed to identify factors associated with unplanned ICU admission in emergency admissions to hospital and develop an absolute risk tool to individualise the risk of an event during a hospital stay. Emergency department (ED) and in-patient hospital data from a large teaching hospital of consecutive admissions from 1 January 1997 to 31 December 2007 aged over 14 years was included in this study. Patient data extracted from 126826 emergency presentations admitted as in-patients consisted of demographic and clinical variables. During an 11-year period 1582 incident unplanned ICU admissions occurred. Predictors of unplanned ICU admission included older age, being male, having a higher acuity triage category and a history of co-morbid conditions. Emergency department diagnostic groups associated with higher incidence of unplanned ICU admission included: sepsis, acute renal failure, lymphatic-hematopoietic tissue neoplasms, pneumonia, chronic-airways disease and bowel obstruction. The final model used to develop the nomogram had an ROC curve AUC of 0.7. This study identified factors associated with unplanned ICU admission and developed a nomogram to individualise risk prior to a patient being transferred from the ED. This nomogram provides clinicians the opportunity prior to transfer from the ED, to either (1) review the appropriateness of the ward level of planned transfer or (2) flag patients for follow-up on the general ward to assess for deterioration.

Combination nucleoside/nucleotide reverse transcriptase inhibitors for treatment of HIV infection.

PubMed

Akanbi, Maxwell O; Scarsi, Kimberly K; Scarci, Kimberly; Taiwo, Babafemi; Murphy, Robert L

2012-01-01

The combination of two nucleoside/nucleotide reverse transcriptase inhibitors (N(t)RTIs) and a third agent from another antiretroviral class is currently recommended for initial antiretroviral therapy. In general, N(t)RTIs remain relevant in subsequent regimens. There are currently six nucleoside reverse transcriptase inhibitors and one nucleotide reverse transcriptase inhibitor drug entities available, and several formulations that include two or more N(t)RTIs in a fixed-dose combination. These entities have heterogeneous pharmacological and clinical properties. Accordingly, toxicity, pill burden, dosing frequency, potential drug-drug interaction, preexisting antiretroviral drug resistance and comorbid conditions should be considered when constructing a regimen. This approach is critical in order to optimize virologic efficacy and clinical outcomes. This article reviews N(t)RTI combinations used in the treatment of HIV-infected adults. The pharmacological properties of each N(t)RTI, and the clinical trials that have influenced treatment guidelines are discussed. It is likely that N(t)RTIs will continue to dominate the global landscape of HIV treatment and prevention, despite emerging interest in N(t)RTI-free combination therapy. Clinical domains where only few alternatives to N(t)RTIs exist include treatment of HIV/HBV coinfection and HIV-2. There is a need for novel N(t)RTIs with enhanced safety and resistance profiles compared with current N(t)RTIs.

A Systematic Review of the Impact of Alcohol Use Disorders on HIV Treatment Outcomes, Adherence to Antiretroviral Therapy and Health Care Utilization *

PubMed Central

Azar, Marwan M.; Springer, Sandra A.; Meyer, Jaimie P.; Altice, Frederick L.

2010-01-01

Background Alcohol use disorders (AUDs) are highly prevalent and associated with non-adherence to antiretroviral therapy, decreased health care utilization and poor HIV treatment outcomes among HIV-infected individuals. Objectives To systematically review studies assessing the impact of AUDs on: (1) medication adherence, (2) health care utilization and (3) biological treatment outcomes among people living with HIV/AIDS (PLWHA). Data Sources Six electronic databases and Google Scholar were queried for articles published in English, French and Spanish from 1988 to 2010. Selected references from primary articles were also examined. Review Methods Selection criteria included: 1) AUD and adherence (N=20); 2) AUD and health services utilization (N=11); or 3) AUD with CD4 count or HIV-1 RNA treatment outcomes (N=10). Reviews, animal studies, non-peer reviewed documents and ongoing studies with unpublished data were excluded. Studies that did not differentiate HIV+ from HIV- status and those that did not distinguish between drug and alcohol use were also excluded. Data were extracted, appraised and summarized. Data Synthesis and Conclusions Our findings consistently support an association between AUDs and decreased adherence to antiretroviral therapy and poor HIV treatment outcomes among HIV-infected individuals. Their effect on health care utilization, however, was variable. PMID:20705402

The impact of HIV clinical pharmacists on HIV treatment outcomes: a systematic review

PubMed Central

Saberi, Parya; Dong, Betty J; Johnson, Mallory O; Greenblatt, Ruth M; Cocohoba, Jennifer M

2012-01-01

Objective Due to the rapid proliferation of human immunodeficiency virus (HIV) treatment options, there is a need for health care providers with knowledge of antiretroviral therapy intricacies. In a HIV multidisciplinary care team, the HIV pharmacist is well-equipped to provide this expertise. We conducted a systematic review to assess the impact of HIV pharmacists on HIV clinical outcomes. Methods We searched six electronic databases from January 1, 1980 to June 1, 2011 and included all quantitative studies that examined pharmacist’s roles in the clinical care of HIV-positive adults. Primary outcomes were antiretroviral adherence, viral load, and CD4+ cell count and secondary outcomes included health care utilization parameters, antiretroviral modifications, and other descriptive variables. Results Thirty-two publications were included. Despite methodological limitation, the involvement of HIV pharmacists was associated with statistically significant adherence improvements and positive impact on viral suppression in the majority of studies. Conclusion This systematic review provides evidence of the beneficial impact of HIV pharmacists on HIV treatment outcomes and offers suggestions for future research. PMID:22536064

Efficacy and safety of three antiretroviral regimens for initial treatment of HIV-1: a randomized clinical trial in diverse multinational settings.

PubMed

Campbell, Thomas B; Smeaton, Laura M; Kumarasamy, N; Flanigan, Timothy; Klingman, Karin L; Firnhaber, Cynthia; Grinsztejn, Beatriz; Hosseinipour, Mina C; Kumwenda, Johnstone; Lalloo, Umesh; Riviere, Cynthia; Sanchez, Jorge; Melo, Marineide; Supparatpinyo, Khuanchai; Tripathy, Srikanth; Martinez, Ana I; Nair, Apsara; Walawander, Ann; Moran, Laura; Chen, Yun; Snowden, Wendy; Rooney, James F; Uy, Jonathan; Schooley, Robert T; De Gruttola, Victor; Hakim, James Gita

2012-01-01

Antiretroviral regimens with simplified dosing and better safety are needed to maximize the efficiency of antiretroviral delivery in resource-limited settings. We investigated the efficacy and safety of antiretroviral regimens with once-daily compared to twice-daily dosing in diverse areas of the world. 1,571 HIV-1-infected persons (47% women) from nine countries in four continents were assigned with equal probability to open-label antiretroviral therapy with efavirenz plus lamivudine-zidovudine (EFV+3TC-ZDV), atazanavir plus didanosine-EC plus emtricitabine (ATV+DDI+FTC), or efavirenz plus emtricitabine-tenofovir-disoproxil fumarate (DF) (EFV+FTC-TDF). ATV+DDI+FTC and EFV+FTC-TDF were hypothesized to be non-inferior to EFV+3TC-ZDV if the upper one-sided 95% confidence bound for the hazard ratio (HR) was ≤1.35 when 30% of participants had treatment failure. An independent monitoring board recommended stopping study follow-up prior to accumulation of 472 treatment failures. Comparing EFV+FTC-TDF to EFV+3TC-ZDV, during a median 184 wk of follow-up there were 95 treatment failures (18%) among 526 participants versus 98 failures among 519 participants (19%; HR 0.95, 95% CI 0.72-1.27; p = 0.74). Safety endpoints occurred in 243 (46%) participants assigned to EFV+FTC-TDF versus 313 (60%) assigned to EFV+3TC-ZDV (HR 0.64, CI 0.54-0.76; p<0.001) and there was a significant interaction between sex and regimen safety (HR 0.50, CI 0.39-0.64 for women; HR 0.79, CI 0.62-1.00 for men; p = 0.01). Comparing ATV+DDI+FTC to EFV+3TC-ZDV, during a median follow-up of 81 wk there were 108 failures (21%) among 526 participants assigned to ATV+DDI+FTC and 76 (15%) among 519 participants assigned to EFV+3TC-ZDV (HR 1.51, CI 1.12-2.04; p = 0.007). EFV+FTC-TDF had similar high efficacy compared to EFV+3TC-ZDV in this trial population, recruited in diverse multinational settings. Superior safety, especially in HIV-1-infected women, and once-daily dosing of EFV+FTC-TDF are advantageous for use of this regimen for initial treatment of HIV-1 infection in resource-limited countries. ATV+DDI+FTC had inferior efficacy and is not recommended as an initial antiretroviral regimen. www.ClinicalTrials.gov NCT00084136. Please see later in the article for the Editors' Summary.

[Kidney transplantation in HIV positive patients: two case reports from Hospital de Clínicas de Porto Alegre initial experience].

PubMed

Spuldaro, Fábio; Ribeiro, Adriana Reginato; Vicari, Alessandra Rosa; Denicol, Nancy Tamara; Dini, Leonardo Infantini; dos Santos, Emanuel Burck; Pegas, Karla Laís; Gonçalves, Luiz Felipe Santos; Manfro, Roberto Ceratti

2012-01-01

Recently kidney transplantation has become an accepted treatment modality for the treatment of HIV infected patients with end-stage renal diseases. For such treatment it is required stability of clinical and laboratory parameters related to HIV infection and the use of highly active antiretroviral therapy. In this report we present the first two cases in Brazil of patients with HIV infection transplanted with organs from deceased donors performed successfully in our institution. The interactions between immunosuppressive and antiretroviral drugs, the co-infections, cardiovascular risk profile and the high incidence of acute rejection remain the major problems to be dealt with in these patients.

Unplanned releases and injuries associated with aerial application of chemicals, 1995-2002.

PubMed

Rice, Nancy; Messing, Rita; Souther, Larry; Berkowitz, Zahava

2005-11-01

For this article, records of the Hazardous Substances Emergency Events Surveillance (HSEES) system were reviewed to identify and describe acute, unplanned releases of agricultural chemicals and associated injuries related to aerial application during 1995-2002. Records of aerial-application accidents from the National Transportation Safety Board were also reviewed. Of the 54,090 events in the HSEES system for 1995-2002, 91 were identified as aerial-application events. The most commonly released substance was malathion. There were 56 victims; 12 died, and 34 required treatment at a hospital. A higher percentage of HSEES aerial-applicator events involved injury and death than did other HSEES transportation events. The relatively high number of injuries and fatalities underscores the need for precautions such as monitoring and limiting pilot cumulative exposures to pesticides, and using appropriate personal protective equipment and decontamination equipment. Emergency responders should be educated about the hazards associated with chemicals at aerial-application crash sites.

[HIV-1 resistance to antiretroviral drugs in pregnant women from Buenos Aires metropolitan area].

PubMed

Zapiola, Inés; Cecchini, Diego; Fernández Giuliano, Silvina; Martínez, Marina; Rodríguez, Claudia; Bouzas, María Belén

The study aimed to determine the prevalence of antiretroviral resistance associated mutations in HIV-1 infected pregnant woman treated in Buenos Aires metropolitan area (period 2008-2014). A total of 136 women with viral load = 500 copies/ml were included: 77 (56.6%) were treatment-naïve and 59 (43.4%) were antiretroviral-experienced patients either with current (n: 24) or previous (n = 35) antiretroviral therapy. Genotypic baseline resistance was investigated in plasma of antiretroviral-naïve patients and antiretroviral-experienced patients. The resistance mutations were identified according to the lists of the World Health Organization and the International Antiviral Society, respectively. Frequencies of resistance associated mutations detected in 2008-2011 and 2012-2014 were compared. A total of 37 (27.2%) women presented at least one resistance associated mutation: 25/94 (26.5%) in 2008-2011 and 12/42 (28.5%) in 2012-2014 (p > 0.05). Among naïves, 15 (19.5%) had at least one mutation: 10/49 (20.4%) in the period 2008-2011 and 5/28 (17.8%) in 2012-2014 (p > 0.05). The resistance mutations detected in naïves were associated with non nucleoside reverse transcriptase inhibitors, being K103N the most common mutation in both periods. In antiretroviral experienced patients, 22/59 (37.3%) had at least one resistance mutation. This study demonstrates a high frequency of resistance associated mutations which remained stable in the period analyzed. These levels suggest an increased circulation of HIV-1 antiretroviral resistant strains in our setting compared to previous reports from Argentina.

Examining the production costs of antiretroviral drugs.

PubMed

Pinheiro, Eloan; Vasan, Ashwin; Kim, Jim Yong; Lee, Evan; Guimier, Jean Marc; Perriens, Joseph

2006-08-22

To present direct manufacturing costs and price calculations of individual antiretroviral drugs, enabling those responsible for their procurement to have a better understanding of the cost structure of their production, and to indicate the prices at which these antiretroviral drugs could be offered in developing country markets. Direct manufacturing costs and factory prices for selected first and second-line antiretroviral drugs were calculated based on cost structure data from a state-owned company in Brazil. Prices for the active pharmaceutical ingredients (API) were taken from a recent survey by the World Health Organization (WHO). The calculated prices for antiretroviral drugs are compared with quoted prices offered by privately-owned, for-profit manufacturers. The API represents the largest component of direct manufacturing costs (55-99%), while other inputs, such as salaries, equipment costs, and scale of production, have a minimal impact. The calculated prices for most of the antiretroviral drugs studied fall within the lower quartile of the range of quoted prices in developing country markets. The exceptions are those drugs, primarily for second-line therapy, for which the API is either under patent, in short supply, or in limited use in developing countries (e.g. abacavir, lopinavir/ritonavir, nelfinavir, saquinavir). The availability of data on the cost of antiretroviral drug production and calculation of factory prices under a sustainable business model provide benchmarks that bulk purchasers of antiretroviral drugs could use to negotiate lower prices. While truly significant price decreases for antiretroviral drugs will depend largely on the future evolution of API prices, the present study demonstrates that for several antiretroviral drugs price reduction is currently possible. Whether or not these reductions materialize will depend on the magnitude of indirect cost and profit added by each supplier over the direct production costs. The ability to achieve price reductions in line with production costs will have critical implications for sustainable treatment for HIV/AIDS in the developing world.

Factors associated with antiretroviral adherence among HIV-infected women with children.

PubMed

Murphy, Debra A; Greenwell, Lisa; Hoffman, Dannie

2002-01-01

HIV symptomatic or AIDS diagnosed women who had a young well child were recruited for a study investigating their adherence to antiretrovirals (N = 46). Very poor rates of adherence were found, ranging from 43% (pill count assessment) to 56% (self-report of 3-day adherence to dose). Several factors were associated with nonadherence, including alcohol use, perceived stress, having a partner and age of youngest child, poor self-efficacy to stay with treatment, and poor outcome expectancies regarding the benefits of following the treatment regimen. Interventions to assist these women in improving adherence are urgently needed.

Knee mechanics during planned and unplanned sidestepping: a systematic review and meta-analysis.

PubMed

Brown, Scott R; Brughelli, Matt; Hume, Patria A

2014-11-01

Knee joint mechanics during sidestepping are associated with anterior cruciate ligament injury. Unplanned sidestepping more closely emulates game scenarios when compared with planned sidestepping by limiting decision time, increasing knee loading and challenging the integrity of soft-tissue structures in the knee. It is important to quantify the loads that may challenge the integrity of the knee during planned and unplanned sidestepping. Our objective was to review literature on knee mechanics during planned and unplanned phases of sidestepping. PubMed, CINAHL, MEDLINE (EBSCO), SPORTDiscus and Web of Science were searched using the terms knee mechanics OR knee kine*, AND plan*, unplan*, anticipat*, unanticipat*, side*, cut* or chang*. A systematic approach was used to evaluate 4,629 records. Records were excluded when not available in English, only available in abstract of conference proceedings, not involving a change-of-direction sidestep, not comparing planned and unplanned or maintaining a running velocity greater than 2 m s(−1). Included studies were evaluated independently by two authors using a custom-designed methodological quality assessment derived from the Physiotherapy Evidence Database (PEDro) scale and then confirmed by a third author. Only six studies met the inclusion criteria and were retained for meta-analysis. Magnitude-based inferences were used to assess the standardised effect of the differences between planned and unplanned sidestepping. Knee angles and knee moments were extracted and reported for flexion/extension, abduction/adduction and internal/external rotation for initial contact, weight acceptance, peak push-off and final push-off phases of sidestepping. For kinematic variables, unplanned sidestepping produced a wide range of small to large increases in knee extension angles, small and moderate increases in knee abduction angles and a small increase in internal rotation angle relative to planned sidestepping during the sidestepping manoeuvre. For kinetic variables, unplanned sidestepping produced mostly small (small to large) increases in knee flexor moments, small to moderate increases in knee abductor moments and mostly moderate (small to large) increases in internal rotator moments relative to planned sidestepping. Approach velocity constraints during the sidestepping manoeuvre were lifted due to the low number of eligible studies. The varying approach velocities included (ranging from 3.0 to 5.5 m s(−1)) may impact the kinematic and kinetic variables examined in this review. Differences in knee mechanics between planned and unplanned sidestepping exist. The most substantial effects occurred during the weight acceptance phase of sidestepping. It seems that biomechanical factors commonly associated with anterior cruciate ligament injury risk are affected the most during the loading phase compared with peak push-off; made evident in the coronal (abductor) and transverse (internal rotator) knee kinetic data presented in this review. The authors of this review propose a rationale for the incorporation of unplanned sport tasks in the development of anterior cruciate ligament injury screening and in prophylactic training programmes.

A large head circumference is more strongly associated with unplanned cesarean or instrumental delivery and neonatal complications than high birthweight.

PubMed

Lipschuetz, Michal; Cohen, Sarah M; Ein-Mor, Eliana; Sapir, Hanna; Hochner-Celnikier, Drorith; Porat, Shay; Amsalem, Hagai; Valsky, Dan V; Ezra, Yossef; Elami-Suzin, Matan; Paltiel, Ora; Yagel, Simcha

2015-12-01

Fetal size impacts on perinatal outcomes. We queried whether the fetal head, as the fetal part interfacing with the birth canal, might impact on obstetric outcomes more than birthweight (BW). We examined associations between neonatal head circumference (HC) and delivery mode and risk of perinatal complications as compared to high BW. This was an electronic medical records-based study of term singleton births (37-42 weeks' gestation) from January 2010 through December 2012 (N = 24,780, 6343 primiparae). We assessed risks of unplanned cesarean or instrumental delivery and maternal and fetal complications in cases with HC or BW ≥95th centile (large HC, high BW) vs those with parameters <95th centile (normal). Newborns were stratified into 4 subgroups: normal HC/normal BW (reference, n = 22,548, primiparae 5862); normal HC/high BW (n = 817, P = 213); large HC/normal BW (n = 878, P = 265); and large HC/high BW (n = 537, P = 103). Multinomial multivariable regression provided adjusted odds ratio (aOR) while controlling for potential confounders. Infants with HC ≥95th centile (n = 1415) were delivered vaginally in 62% of cases, unplanned cesarean delivery 16%, and instrumental delivery 11.2%; 78.4% of infants with HC <95th centile were delivered vaginally, 7.8% unplanned cesarean, and 6.7% instrumental delivery. Odds ratio (OR) for unplanned cesarean was 2.58 (95% confidence interval [CI], 2.22-3.01) and for instrumental delivery OR was 2.13 (95% CI, 1.78-2.54). In contrast, in those with BW ≥95th centile (n = 1354) 80.3% delivered vaginally, 10.2% by unplanned cesarean (OR, 1.2; 95% CI, 1.01-1.44), and 3.4% instrumental delivery (OR, 0.46; 95% CI, 0.34-0.62) compared to infants with BW <95th centile: spontaneous vaginal delivery, 77.3%, unplanned cesarean 8.2%, instrumental 7.1%. Multinomial regression with normal HC/normal BW as reference group showed large HC/normal BW infants were more likely to be delivered by unplanned cesarean (aOR, 3.08; 95% CI, 2.52-3.75) and instrumental delivery (aOR, 3.03; 95% CI, 2.46-3.75). Associations were strengthened in primiparae. Normal HC/high BW was not associated with unplanned cesarean (aOR, 1.18; 95% CI, 0.91-1.54), while large HC/high BW was (aOR, 1.93; 95% CI, 1.47-2.52). Analysis of unplanned cesarean indications showed large HC infants had more failure to progress (27.7% vs 14.1%, P < .001), while smaller HC infants had more fetal distress (23.4% vs 16.9%, P < .05). A large HC is more strongly associated with unplanned cesarean and instrumental delivery than high BW. Prospective studies are needed to test fetal HC as a predictive parameter for prelabor counseling of women with "big babies." Copyright © 2015 Elsevier Inc. All rights reserved.

Differences in Colonoscopy Quality Among Facilities: Development of a Post-Colonoscopy Risk-Standardized Rate of Unplanned Hospital Visits.

PubMed

Ranasinghe, Isuru; Parzynski, Craig S; Searfoss, Rana; Montague, Julia; Lin, Zhenqiu; Allen, John; Vender, Ronald; Bhat, Kanchana; Ross, Joseph S; Bernheim, Susannah; Krumholz, Harlan M; Drye, Elizabeth E

2016-01-01

Colonoscopy is a common procedure, yet little is known about variations in colonoscopy quality among outpatient facilities. We developed an outcome measure to profile outpatient facilities by estimating risk-standardized rates of unplanned hospital visits within 7 days of colonoscopy. We used a 20% sample of 2010 Medicare outpatient colonoscopy claims (331,880 colonoscopies performed at 8140 facilities) from patients ≥65 years or older, and developed a patient-level logistic regression model to estimate the risk of unplanned hospital visits (ie, emergency department visits, observation stays, and inpatient admissions) within 7 days of colonoscopy. We then used the patient-level risk model variables and hierarchical logistic regression to estimate facility rates of risk-standardized unplanned hospital visits using data from the Healthcare Cost and Utilization Project (325,811 colonoscopies at 992 facilities), from 4 states containing 100% of colonoscopies per facility. Outpatient colonoscopies were followed by 5412 unplanned hospital visits within 7 days (16.3/1000 colonoscopies). Hemorrhage, abdominal pain, and perforation were the most common causes of unplanned hospital visits. Fifteen variables were independently associated with unplanned hospital visits (c = 0.67). A history of fluid and electrolyte imbalance (odds ratio [OR] = 1.43; 95% confidence interval [CI]: 1.29-1.58), psychiatric disorders (OR = 1.34; 95% CI: 1.22-1.46), and, in the absence of prior arrhythmia, increasing age past 65 years (aged >85 years vs 65-69 years: OR = 1.87; 95% CI: 1.54-2.28) were most strongly associated. The facility risk-standardized unplanned hospital visits calculated using Healthcare Cost and Utilization Project data showed significant variation (median 12.3/1000; 5th-95th percentile, 10.5-14.6/1000). Median risk-standardized unplanned hospital visits were comparable between ambulatory surgery centers and hospital outpatient departments (each was 10.2/1000), and ranged from 16.1/1000 in the Northeast to 17.2/1000 in the Midwest. We calculated a risk-adjusted measure of outpatient colonoscopy quality, which shows important variation in quality among outpatient facilities. This measure can make transparent the extent to which patients require follow-up hospital care, help inform patient choices, and assist in quality-improvement efforts. Copyright © 2016 AGA Institute. Published by Elsevier Inc. All rights reserved.

Unplanned 30-Day Readmissions in a General Internal Medicine Hospitalist Service at a Comprehensive Cancer Center.

PubMed

Manzano, Joanna-Grace M; Gadiraju, Sahitya; Hiremath, Adarsh; Lin, Heather Yan; Farroni, Jeff; Halm, Josiah

2015-09-01

Hospital readmissions are considered by the Centers for Medicare and Medicaid as a metric for quality of health care delivery. Robust data on the readmission profile of patients with cancer are currently insufficient to determine whether this measure is applicable to cancer hospitals as well. To address this knowledge gap, we estimated the unplanned readmission rate and identified factors influencing unplanned readmissions in a hospitalist service at a comprehensive cancer center. We retrospectively analyzed unplanned 30-day readmission of patients discharged from the General Internal Medicine Hospitalist Service at a comprehensive cancer center between April 1, 2012, and September 30, 2012. Multiple independent variables were studied using univariable and multivariable logistic regression models, with generalized estimating equations to identify risk factors associated with readmissions. We observed a readmission rate of 22.6% in our cohort. The median time to unplanned readmission was 10 days. Unplanned readmission was more likely in patients with metastatic cancer and those with three or more comorbidities. Patients discharged to hospice were less likely to be readmitted (all P values < .01). We observed a high unplanned readmission rate among our population of patients with cancer. The risk factors identified appear to be related to severity of illness and open up opportunities for improving coordination with primary care physicians, oncologists, and other specialists to manage comorbidities, or perhaps transition appropriate patients to palliative care. Our findings will be instrumental for developing targeted interventions to help reduce readmissions at our hospital. Our data also provide direction for appropriate application of readmission quality measures in cancer hospitals. Copyright © 2015 by American Society of Clinical Oncology.

Binge drinking, reflection impulsivity, and unplanned sexual behavior: impaired decision-making in young social drinkers.

PubMed

Townshend, Julia M; Kambouropoulos, Nicolas; Griffin, Alison; Hunt, Frances J; Milani, Raffaella M

2014-04-01

The repeated pattern of heavy intoxication followed by withdrawal from alcohol (i.e., "binge drinking") has been found to have substantial adverse effects on prefrontal neural systems associated with decision-making and impulse control. Repeated binge drinking has been linked to risky and unplanned sexual behavior; however few studies have examined the role of impulsivity and related cognitive processes in understanding this association. The aim of this study was to examine the relationship between binge drinking, "reflection impulsivity" (deficits in gathering and evaluating information during decision-making), alcohol-related expectancies, and unplanned sexual behavior in a sample of young social drinkers. Ninety-two university students completed the alcohol use questionnaire (AUQ) to measure alcohol intake and binge drinking. Two groups (low-binge and high-binge) were generated from the AUQ data. The Information Sampling Task (IST) was used to measure reflection impulsivity; the Alcohol Expectancy Questionnaire (AEQ) for alcohol outcome expectancies; and an unplanned sexual behavior questionnaire, which asked about the number of unplanned sexual events. When compared to the low-binge drinking group, the high-binge drinkers had significantly more unplanned sexual encounters and were impaired on the IST, reflection-impulsivity task. They scored higher on the alcohol expectancy factors of sociability, risk and aggression, negative self-perception, and in particular liquid courage. In a regression analysis, number of unplanned sexual encounters, binge drinking score, and liquid courage were all significantly related. These results support the role of binge drinking in reduced impulse control and decision-making deficits. The findings indicate that high-binge drinkers demonstrate impairments on an impulse control task similar to that observed in dependent samples and this may be a factor in understanding the negative behavioral consequences associated with excessive alcohol use. Copyright © 2014 by the Research Society on Alcoholism.

Caesarean Birth is Associated with Both Maternal and Paternal Origin in Immigrants in Sweden: a Population-Based Study.

PubMed

Juárez, Sol P; Small, Rhonda; Hjern, Anders; Schytt, Erica

2017-11-01

To investigate the association between maternal country of birth and father's origin and unplanned and planned caesarean birth in Sweden. Population-based register study including all singleton births in Sweden between 1999 and 2012 (n = 1 311 885). Multinomial regression was conducted to estimate odds ratios (OR) for unplanned and planned caesarean with 95% confidence intervals for migrant compared with Swedish-born women. Analyses were stratified by parity. Women from Ethiopia, India, South Korea, Chile, Thailand, Iran, and Finland had statistically significantly higher odds of experiencing unplanned (primiparous OR 1.10-2.19; multiparous OR 1.13-2.02) and planned caesarean (primiparous OR 1.18-2.25; multiparous OR 1.13-2.46). Only women from Syria, the former Yugoslavia and Germany had consistently lower risk than Swedish-born mothers (unplanned: primiparous OR 0.76-0.86; multiparous OR 0.74-0.86. Planned; primiparous OR 0.75-0.82; multiparous OR 0.60-0.94). Women from Iraq and Turkey had higher odds of an unplanned caesarean but lower odds of a planned one (among multiparous). In most cases, these results remained after adjustment for available social characteristics, maternal health factors, and pregnancy complications. Both parents being foreign-born increased the odds of unplanned and planned caesarean in primiparous and multiparous women. Unplanned and planned caesarean birth varied by women's country of birth, with both higher and lower rates compared with Swedish-born women, and the father's origin was also of importance. These variations were not explained by a wide range of social, health, or pregnancy factors. © 2017 John Wiley & Sons Ltd.

30-Day Readmission After Spine Surgery: An Analysis of 1400 Consecutive Spine Surgery Patients.

PubMed

Adogwa, Owoicho; Elsamadicy, Aladine A; Han, Jing L; Karikari, Isaac O; Cheng, Joseph; Bagley, Carlos A

2017-04-01

Retrospective cohort review. To identify the rates, causes, and risk factors for 30-day unplanned readmissions in after elective spine surgery at our institution. Early readmission after spine surgery is being used as a proxy for quality of care. One-fifth of patients are rehospitalized within 30 days after spine surgery. Nearly 60% of these readmissions are unplanned, which translates into billions of dollars in healthcare costs. A total of 1400 patients undergoing elective spine surgery at Duke University Hospital between 2008 and 2010 were included in the study. We identified all unplanned readmissions within 30 days of discharge. Unplanned readmissions were defined to have occurred as a result of either a surgical or a nonsurgical complication. Patient records were reviewed to determine the cause of readmission and the length of hospital stay. A total of 132 (9.4%) unplanned early readmissions were identified. The mean ± SD age was 58.6 ± 15.1 years. Lumbar decompression and fusion was the most common procedure The most common causes for readmission were infection or a concern for infection (34.8%) and pain (19.7%), and 26.5% of readmissions required a return to the operating room. The majority of patients that were readmitted presented to the emergency department from home (58.0%) whereas 25.2% were readmitted from a skilled nursing facility. The mean ± SD number of days from discharge to readmission was 9.8 ± 7.9 days and the average length of hospital stay for the readmissions was 7.5 days. This study suggests that infection and refractory pain were the most common primary reasons for unplanned readmission. Efforts at reducing unplanned early readmission after elective spine surgery should be focused on more effective post discharge care.

Unplanned cigarette purchases and tobacco point of sale advertising: a potential barrier to smoking cessation.

PubMed

Clattenburg, Eben J; Elf, Jessica L; Apelberg, Benjamin J

2013-11-01

In the USA, tobacco marketing expenditure is increasingly concentrated at the point of sale (POS). Previous studies have demonstrated an association between exposure to tobacco POS advertising and increased smoking initiation, but limited evidence is available on adult smokers' decisions and behaviours. An immediate post-cigarette purchase survey was administered to 301 cigarette purchasers outside of two grocery stores in Vermont to assess the prevalence of unplanned purchases and opinions about POS tobacco advertising and displays. In total, 11.3% of purchases were reported as unplanned. Certain groups were more likely to make unplanned purchases including: 18-24-year-olds (OR: 2.1, 95% CI 1.0 to 4.4), less than daily smokers (OR: 5.6, 95% CI 1.9 to 16.9), smokers who made 3+ quit attempts in the previous year (OR: 2.4, 95% CI 0.9 to 6.0), those who plan to quit in the next month (OR: 3.7, 95% CI 1.6 to 9.0), and those who agreed that tobacco POS advertising makes quitting smoking harder (OR: 2.3, 95% CI 1.1 to 4.8). Overall, 31.2% of participants agreed that tobacco POS advertising makes quitting smoking harder. Individuals who intended to quit within the next month, made 3+ quit attempts in the last year, or made an unplanned cigarette purchase were the most likely to agree. Young adults and individuals making multiple quit attempts or planning to quit in the next month are more likely to make unplanned cigarette purchases. Reducing unplanned purchases prompted by tobacco POS advertising could improve the likelihood of successful cessation among smokers.

[Association between unplanned pregnancy and adolescence onset asthma].

PubMed

Vázquez-Nava, Francisco; Gil-Lara, Bertoldo; Cruz-Torres, Leoncio; Vázquez-Rodríguez, Carlos F; Vázquez-Rodríguez, Eliza M; Felizardo-Ávalos, Jorge; Llanes-Castillo, Arturo; Córdova-Fernández, José A

2013-01-01

The association between asthma and pregnancy has been documented previously. The relationship between unplanned pregnancy and onset asthma in adolescence has not been studied. To determine the association between unplanned pregnancy and adolescence onset asthma. A cross-sectional study was done gathering information about asthma, unplanned pregnancy, family atopy and active or passive smoking in 3,130 adolescents aged 13-19 years. Asthma diagnosis was established through a selfquestionnaire based on the International Study of Asthma and Allergy in Childhood. Odds ratios for asthma were determined using logistic regression model and chi-squared test. Mean age of the participants was 16.37 ± 1.93 years. The prevalence of active smoking was 16.1%, of passive smoking 40% and of family atopy 9.8%. From the pregnant adolescents (785), 59.5% reported had planned not to have a child before pregnancy. Prevalence of wheezing during the year prior to the study was 9.3% and of wheezing during the pregnancy 2%. The prevalence of adolescence onset asthma was 5.4%. The age of initiation of asthma in the adolescence was 14.75 ± 1.60 years. The analysis showed that unplanned pregnancy has a slight risk for the development of asthma during adolescence. (Crude OR=1.03; CI 95% 1.02-1.05; p=0.000). Unplanned pregnancy, family atopy, active smoking and smoking friends are associated with the onset-asthma in the adolescence.

Efficacy and safety of darunavir (Prezista®) with low-dose ritonavir and other antiretroviral medications in subtype F HIV-1 infected, treatment-experienced subjects in Romania: a post-authorization, open-label, one-cohort, non-interventional, prospective study

PubMed Central

Benea, Otilia Elisabeta; Streinu-Cercel, Adrian; Dorobăţ, Carmen; Rugină, Sorin; Negruţiu, Lucian; Cupşa, Augustin; Duiculescu, Dan; Chiriac, Carmen; Itu, Corina; Prisăcariu, Liviu Jany; Iosif, Ionel

2014-01-01

Introduction The aim of the study was to assess the safety and efficacy of darunavir (Prezista®) used in subtype F human immunodeficiency virus – type 1 (HIV-1) infected, antiretroviral therapy (ART)-experienced patients in Romania in routine clinical practice. Methods This was a post-authorization, open-label, one-cohort, non-interventional, prospective study conducted at multiple sites in Romania to assess efficacy (CD4 cell count, viral load, and treatment compliance) and safety ([serious] adverse events, clinical laboratory evaluation, and vital signs) of darunavir in combination with low-dose ritonavir (DRV/r) and other antiretroviral (ARV) medications in subtype F HIV-1 infected subjects in naturalistic settings. Seventy-eight subjects were recruited by 9 investigational sites and received 600/100 mg DRV/r twice daily. Results Treatment with DRV/r administered with other ARV medications resulted in the expected, statistically relevant improvement of CD4 cell count and viral load in subjects eligible for such treatment. In addition, adherence to treatment was high and the treatment-emergent safety profile observed during this study was consistent with the established safety profile of darunavir. Conclusion DRV/r administered in combination with other ARV medications in subtype F HIV-1 infected subjects in naturalistic settings proved to be an effective and safe treatment in Romania. Trial registration NCT01253967 PMID:25276665

Integrating nutrition security with treatment of people living with HIV: lessons from Kenya.

PubMed

Byron, Elizabeth; Gillespie, Stuart; Nangami, Mabel

2008-06-01

The increased caloric requirements of HIV-positive individuals, undesirable side effects of treatment that may be worsened by malnutrition (but alleviated by nutritional support), and associated declines in adherence and possible increased drug resistance are all justifications for developing better interventions to strengthen the nutrition security of individuals receiving antiretroviral treatment. To highlight key benefits and challenges relating to interventions aimed at strengthening the nutrition security of people living with HIV who are receiving antiretroviral treatment. Qualitative research was undertaken on a short-term nutrition intervention linked to the provision of free antiretroviral treatment for people living with HIV in western Kenya in late 2005 and early 2006. Patients enrolled in the food program while on treatment regimens self-reported greater adherence to their medication, fewer side effects, and a greater ability to satisfy increased appetite. Most clients self-reported weight gain, recovery of physical strength, and the resumption of labor activities while enrolled in dual (food supplementation and treatment) programs. Such improvements were seen to catalyze increased support from family and community. These findings provide further empirical support to calls for a more holistic and comprehensive response to the coexistence of AIDS epidemics with chronic nutrition insecurity. Future work is needed to clarify ways of bridging the gap between short-term nutritional support to individuals and longer-term livelihood security programming for communities affected by AIDS. Such interdisciplinary research will need to be matched by intersectoral action on the part of the agriculture and health sectors in such environments.

Unplanned Complex Suicide-A Consideration of Multiple Methods.

PubMed

Ateriya, Navneet; Kanchan, Tanuj; Shekhawat, Raghvendra Singh; Setia, Puneet; Saraf, Ashish

2018-05-01

Detailed death investigations are mandatory to find out the exact cause and manner in non-natural deaths. In this reference, use of multiple methods in suicide poses a challenge for the investigators especially when the choice of methods to cause death is unplanned. There is an increased likelihood that doubts of homicide are raised in cases of unplanned complex suicides. A case of complex suicide is reported where the victim resorted to multiple methods to end his life, and what appeared to be an unplanned variant based on the death scene investigations. A meticulous crime scene examination, interviews of the victim's relatives and other witnesses, and a thorough autopsy are warranted to conclude on the cause and manner of death in all such cases. © 2017 American Academy of Forensic Sciences.

Dyslipidemia in HIV Infected Children Receiving Highly Active Antiretroviral Therapy.

PubMed

Mandal, Anirban; Mukherjee, Aparna; Lakshmy, R; Kabra, Sushil K; Lodha, Rakesh

2016-03-01

To assess the prevalence of dyslipidemia and lipodystrophy in Indian children receiving non-nucleoside reverse transcriptase inhibitor (NNRTI) based highly active antiretroviral therapy (HAART) and to determine the associated risk factors for the same. The present cross-sectional study was conducted at a Pediatric Clinic of a tertiary care teaching center in India, from May 2011 through December 2012. HIV infected children aged 5-15 y were enrolled if they did not have any severe disease or hospital admission within last 3 mo or receive any medications known to affect the lipid profile. Eighty-one children were on highly active antiretroviral therapy (HAART) for at least 6 mo and 16 were receiving no antiretroviral therapy (ART). Participants' sociodemographic, nutritional, clinical, and laboratory data were recorded in addition to anthropometry and evidence of lipodystrophy. Fasting lipid profile, apolipoprotein A1 and B levels were done for all the children. Among the children on highly active antiretroviral therapy (HAART), 38.3 % had dyslipidemia and 80.2 % had lipodystrophy, while 25 % antiretroviral therapy (ART) naïve HIV infected children had dyslipidemia. No clinically significant risk factors could be identified that increased the risk of dyslipidemia or lipodystrophy in children on highly active antiretroviral therapy (HAART). There is a high prevalence of dyslipidemia and lipodystrophy in Indian children with HIV infection with an imminent need to establish facilities for testing and treatment of these children for metabolic abnormalities.

Effect of therapeutic intensification followed by HIV DNA prime and rAd5 boost vaccination on HIV-specific immunity and HIV reservoir (EraMune 02): a multicentre randomised clinical trial.

PubMed

Achenbach, Chad J; Assoumou, Lambert; Deeks, Steven G; Wilkin, Timothy J; Berzins, Baiba; Casazza, Joseph P; Lambert-Niclot, Sidonie; Koup, Richard A; Costagliola, Dominique; Calvez, Vincent; Katlama, Christine; Autran, Brigitte; Murphy, Robert L

2015-03-01

Achievement of a cure for HIV infection might need reactivation of latent virus and improvement of HIV-specific immunity. As an initial step, in this trial we assessed the effect of antiretroviral therapy intensification and immune modulation with a DNA prime and recombinant adenovirus 5 (rAd5) boost vaccine. In this multicentre, randomised, open-label, non-comparative, phase 2 clinical trial, we enrolled eligible adults 18-70 years of age with chronic HIV-1 infection on suppressive antiretroviral therapy with current CD4 count of at least 350 cells per μL and HIV DNA between 10 and 1000 copies per 10(6) peripheral blood mononuclear cells. After an 8 week lead-in of antiretroviral intensification therapy (standard dose raltegravir and dose-adjusted maraviroc based on baseline antiretroviral therapy), patients were randomly assigned (1:1) to receive antiretroviral therapy intensification alone or intensification plus injections of HIV DNA prime vaccine (4 mg VRC-HIVDNA016-00-VP) at weeks 8, 12, and 16, followed by HIV rAd5 boost vaccine (10(10) particle units of VRC-HIVADV014-00-VP) at week 32. Randomisation was computer generated in permuted blocks of six and was stratified by study site. The primary endpoint was a 0·5 log10 or greater decrease in HIV DNA in peripheral blood mononuclear cells at week 56. This study is registered with ClinicalTrials.gov, number NCT00976404. Between Nov 29, 2010, and Oct 28, 2011, we enrolled 28 eligible patients from three academic HIV clinics in the USA. After the 8 week lead-in of antiretroviral intensification therapy, 14 patients were randomly assigned to continue antiretroviral therapy intensification alone and 14 to intensification plus vaccine. Enrolled participants had median CD4 count of 636 cells per μL, median HIV DNA 170 copies per 10(6) peripheral blood mononuclear cells, and duration of antiretroviral therapy of 13 years. The median amount of HIV DNA did not change significantly between baseline and week 56 in the antiretroviral therapy intensification plus vaccine group. One participant in the antiretroviral therapy intensification alone group reached the primary endpoint, with 0·55 log10 decrease in HIV DNA in peripheral blood mononuclear cells. Both treatments were well tolerated. No severe or systemic reactions to vaccination occurred, and five serious adverse events were recorded during the study, most of which resolved spontaneously or were judged unrelated to study treatments. Antiretroviral therapy intensification followed by DNA prime and rAd5 boost vaccine did not significantly increase HIV expression or reduce the latent HIV reservoir. A multifaceted approach that includes stronger activators of HIV expression and novel immune modulators will probably be needed to reduce the latent HIV reservoir and allow for long-term control in patients off antiretroviral therapy. Objectif Recherche Vaccin SIDA (ORVACS). Copyright © 2015 Elsevier Ltd. All rights reserved.

Non-nucleoside reverse transcriptase inhibitors (NNRTIs), their discovery, development, and use in the treatment of HIV-1 infection: a review of the last 20 years (1989-2009).

PubMed

de Béthune, Marie-Pierre

2010-01-01

It is almost 20 years since NNRTIs were identified as a new class of antiretroviral drugs for the treatment of HIV-1 infection. Although they belong to different and diverse chemical families, they share a common and unique mechanism of action: their interaction with HIV-1 reverse transcriptase induces conformational changes that inhibit the catalytic activities of the enzyme. They are characterized by their specificity for HIV-1, which makes them very selective inhibitors of the virus. First generation NNRTIs nevirapine and efavirenz, in combination with other antiretroviral drugs, have become a cornerstone for the treatment of HIV-1 infection, in patients initiating antiretroviral therapy. Further research has led to the discovery and development of next generation NNRTIs with an increased genetic barrier to the development of resistance. Etravirine is the first NNRTI to show sustained virologic efficacy in patients with NNRTI resistant HIV-1. This review covers the NNRTI class of anti-HIV-1 drugs, from the initial discovery of the class in 1990 to the current compounds in clinical development, i.e. around 20 years of research and development efforts. It describes the characteristics of the NNRTIs, their mechanisms of action, HIV-1 resistance to the inhibitors, and the drugs that have been approved for the treatment of HIV-1 infection, or are currently in clinical development. The role of NNRTIs in prevention of HIV transmission is also addressed. This article forms part of a special issue of Antiviral Research marking the 25th anniversary of antiretroviral drug discovery and development, vol. 85, issue 1, 2010. Copyright 2009 Elsevier B.V. All rights reserved.

Pre-exposure prophylaxis (PrEP) for men who have sex with men in Europe: review of evidence for a much needed prevention tool.

PubMed

Reyniers, Thijs; Hoornenborg, Elske; Vuylsteke, Bea; Wouters, Kristien; Laga, Marie

2017-08-01

In many Western countries with good coverage of antiretroviral treatment (ART) programmes the annual number of HIV infections is still high and not (yet) declining among men who have sex with men (MSM). This might indicate that antiretroviral treatment roll-out alone will not turn around the course of the epidemic and that new, additional tools are needed. Antiretrovirals used as prevention tools for people not yet infected with HIV, such as pre-exposure prophylaxis (PrEP) could be such important additional tools. PrEP is a new type of biomedical prevention, which involves the use of antiretrovirals before, during and after (periods of) sexual exposure to HIV. In this review, we will focus on PrEP as a new prevention tool for MSM at high risk in Europe, including its evidence for effectiveness, challenges for implementation, ongoing European demonstration studies; as well as how PrEP relates to other existing prevention tools. In light of European Medicines Agency's recent recommendation for approval of PrEP we briefly review the potential implications. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Risk factors for unplanned and unwanted teenage pregnancies occurring over two years of follow-up among a cohort of young South African women.

PubMed

Christofides, Nicola J; Jewkes, Rachel K; Dunkle, Kristin L; McCarty, Frances; Jama Shai, Nwabisa; Nduna, Mzikazi; Sterk, Claire

2014-01-01

Although teenage pregnancies in South Africa have declined, the short and longer term health and social consequences are a potential public health concern. This longitudinal study aimed to describe the range of risk and protective factors for incident unwanted and unplanned pregnancies occurring over 2 years of follow-up among a cohort of adolescent women in the Eastern Cape, South Africa. It also investigated the relationship between gender inequality and gender-based violence and subsequent unplanned and unwanted pregnancies among the cohort. Teenage girls, aged 15-18 years (n=19), who were volunteer participants in a cluster randomized controlled trial and who had data from at least one follow-up were included in this analysis. To assess risk and protective factors for incident unwanted or unplanned pregnancies, we constructed multivariate polytomous regression models adjusting for sampling clusters as latent variables. Covariates included age, having a pregnancy prior to baseline, education, time between interviews, study intervention arm, contraceptive use, experience of intimate partner violence, belief that the teenage girl and her boyfriend are mutual main partners, and socioeconomic status. Overall, 174 pregnancies occurred over the 2-year follow-up period. Beliefs about relationship control were not associated with unwanted and unplanned pregnancies, nor were experiences of forced first sex or coerced sex under the age of 15. Hormonal contraception was protective against unplanned pregnancies (OR 0.40; 95% CI 0.21-0.79); however, using condoms was not protective. Physical abuse (OR 1.69; 95% CI 1.05-2.72) was a risk factor for, and having a pregnancy prior to baseline was protective against an unwanted pregnancy (OR 0.25; 95% CI 0.07-0.80). Higher socioeconomic status was protective for both unplanned and unwanted pregnancies (OR 0.69; 95% CI 0.58-0.83 and OR 0.78; 95% CI 0.64-0.96). Believing that the teenage girl and her boyfriend were mutual main partners doubled the odds of reporting both an unplanned and unwanted pregnancy (OR 2.58 95% CI 1.07-6.25, and OR 2.21 95% CI 1.13-4.29). Although some of the measures of gender inequity were not associated with unplanned and unwanted pregnancies, there is evidence of the role of both gender power and socioeconomic status. This was evident in teenage girls who experienced physical violence being more likely to have an unwanted pregnancy. Interventions to prevent teenage pregnancies need to be tailored by socioeconomic status because some teenagers may see having a pregnancy as a way to have a more secure future. Interventions that engage with relationship dynamics of teenagers are essential if unwanted and unplanned pregnancies are to be prevented.

Unplanned pregnancy and subsequent psychological distress in partnered women: a cross-sectional study of the role of relationship quality and wider social support.

PubMed

Barton, Katherine; Redshaw, Maggie; Quigley, Maria A; Carson, Claire

2017-01-26

Research into the impact of unintended pregnancy on the wellbeing of women tends to focus on pregnancies ending in either termination or lone motherhood. Unintended pregnancy is common in partnered women, but little is known about the association between unintended pregnancy and postpartum affective disorders, such as depression and anxiety in this group. Poor relationship quality and lack of social support are considered risk factors for psychological distress (PD). We examined the association between unplanned motherhood and subsequent PD in partnered women, for whom evidence is sparse, accounting for the role of relationship quality and social support. Data for 12,462 partnered mothers were drawn from the first survey of Millennium Cohort Study, completed at 9 months postpartum. Women reported whether their baby was planned, and how they felt when they discovered that they were pregnant. Pregnancy intention is categorised as "planned", "unplanned/happy", "unplanned/ambivalent" and "unplanned/unhappy". PD was assessed using the modified 9-item Rutter Malaise Inventory. Social support was measured by a composite score for perceived support, and a measure of actual support from friends and family. Relationship quality was assessed using a modified Golombok-Rust Inventory of Marital State. The effect of pregnancy intention on the odds of PD at 9 months was estimated, adjusting for potential confounding factors. All analyses were weighted for response and design effects. In total 32.8%(weighted) (4343/12462) of mothers reported an unplanned pregnancy: 23.3 wt% (3087) of mothers felt happy, 3.5 wt% (475) ambivalent, and 6.0 wt% (781) unhappy upon discovery. Unplanned pregnancy was associated with a significantly increased odds of PD compared to planned (OR 1.73 (95%CI: 1.53, 1.95)). This was more pronounced among women who reported negative or ambivalent feelings in early pregnancy (OR 2.72 (95%CI:2.17, 3.41) and 2.56 (95%CI:1.95, 3.34), respectively), than those who reported positive feelings (OR 1.39 (95%CI:1.21, 1.60)). Adjustment for relationship quality, in particular, reduced odds of PD after unplanned pregnancy (e.g. from 2.19 (95%C: 1.74, 2.74) to 1.63 (95% CI: 1.29, 2.07 in the unplanned, unhappy group compared to the planned). A third of partnered mothers reported that their pregnancy was unintended, yet this group is under-researched. Unplanned motherhood was associated with increased risk of PD at 9 months postpartum, particularly among women who felt unhappy or ambivalent at the start. The roles of relationship quality and social support require further investigation, as possible means to intervene and improve maternal wellbeing.

Variables associated with emergency department and/or unplanned hospital utilization for children with epilepsy.

PubMed

Patel, Anup D

2014-02-01

In the United States, approximately one million people are evaluated annually in an emergency department (ED) for the diagnosis of a seizure or epilepsy. The highest percentages of these patients are less than five years of age. No studies have been performed on assessing potential variables associated with recurrent ED visits and/or unplanned hospitalizations for children with epilepsy. Institutional review board approval from Nationwide Children's Hospital was obtained prior to study initiation. An accountable care organization (ACO), Partner for Kids (PFK), database was searched for patients with the highest and the lowest number of ED visits and/or unplanned hospitalizations from 2007 through 2011 using ICD-9 codes of 345.xx and 780.39. The patients were stratified into a high and a low utilizer group. The total number of visits and their associated health care costs were noted for each patient. In total, 120 patients were included for review. Information on the total number of no-shows to outpatient neurology clinic visits and telephone calls to neurology triage nursing was noted. A chart review was performed by a pediatric epileptologist to determine if each individual patient was an appropriate candidate for an emergency seizure treatment. The dose of emergency seizure medication was cross-checked to the patient's actual dose during the time of ED or hospital presentation to determine if the dose given was high, low, or accurate based on dosing recommendations. Multivariable logistic regression was used to test the effects of factors. When controlling for other factors, patients who were given an incorrect or no emergency seizure dosing had a high probability of having multiple ED visits/unplanned hospitalizations compared with patients who were given correct dosing (odds ratio=11.28, 95% CI of odds ratio=(2.42, 52.63), p value<0.01 (p=0.0021)). Using a similar model, patients who experienced a higher number of no-shows to clinic visits had a higher probability of having multiple ED visits/unplanned hospitalizations (odds ratio=5.73 per 1 more number of no-show, 95% CI of odds ratio=(1.78, 18.44), p value<0.01 (p=0.0034)). Future studies are planned to target these risk factors with the goal of decreased ED and/or hospital utilization for children with epilepsy. Copyright © 2013 Elsevier Inc. All rights reserved.

Classical and alternative macrophages have impaired function during acute and chronic HIV-1 infection.

PubMed

Galvão-Lima, Leonardo J; Espíndola, Milena S; Soares, Luana S; Zambuzi, Fabiana A; Cacemiro, Maira; Fontanari, Caroline; Bollela, Valdes R; Frantz, Fabiani G

Three decades after HIV recognition and its association with AIDS development, many advances have emerged - especially related to prevention and treatment. Undoubtedly, the development of Highly Active Antiretroviral Therapy (HAART) dramatically changed the future of the syndrome that we know today. In the present study, we evaluate the impact of Highly Active Antiretroviral Therapy on macrophage function and its relevance to HIV pathogenesis. PBMCs were isolated from blood samples and monocytes (CD14+ cells) were purified. Monocyte-Derived Macrophages (MDMs) were activated on classical (M GM-CSF+IFN-γ ) or alternative (M IL-4+IL13 ) patterns using human recombinant cytokines for six days. After this period, Monocyte-Derived Macrophages were stimulated with TLR2/Dectin-1 or TLR4 agonists and we evaluated the influence of HIV-1 infection and Highly Active Antiretroviral Therapy on the release of cytokines/chemokines by macrophages. The data were obtained using Monocyte-Derived Macrophages derived from HIV naïve or from patients on regular Highly Active Antiretroviral Therapy. Classically Monocyte-Derived Macrophages obtained from HIV-1 infected patients on Highly Active Antiretroviral Therapy released higher levels of IL-6 and IL-12 even without PAMPs stimuli when compared to control group. On the other hand, alternative Monocyte-Derived Macrophages derived from HIV-1 infected patients on Highly Active Antiretroviral Therapy released lower levels of IL-6, IL-10, TNF-α, IP-10 and RANTES after LPS stimuli when compared to control group. Furthermore, healthy individuals have a complex network of cytokines/chemokines released by Monocyte-Derived Macrophages after PAMP stimuli, which was deeply affected in MDMs obtained from naïve HIV-1 infected patients and only partially restored in MDMs derived from HIV-1 infected patients even on regular Highly Active Antiretroviral Therapy. Our therapy protocols were not effective in restoring the functional alterations induced by HIV, especially those found on macrophages. These findings indicate that we still need to develop new approaches and improve the current therapy protocols, focusing on the reestablishment of cellular functions and prevention/treatment of opportunistic infections. Copyright © 2016 Sociedade Brasileira de Infectologia. Published by Elsevier Editora Ltda. All rights reserved.

Antiretroviral Drugs for Treatment and Prevention of HIV Infection in Adults: 2016 Recommendations of the International Antiviral Society-USA Panel.

PubMed

Günthard, Huldrych F; Saag, Michael S; Benson, Constance A; del Rio, Carlos; Eron, Joseph J; Gallant, Joel E; Hoy, Jennifer F; Mugavero, Michael J; Sax, Paul E; Thompson, Melanie A; Gandhi, Rajesh T; Landovitz, Raphael J; Smith, Davey M; Jacobsen, Donna M; Volberding, Paul A

2016-07-12

New data and therapeutic options warrant updated recommendations for the use of antiretroviral drugs (ARVs) to treat or to prevent HIV infection in adults. To provide updated recommendations for the use of antiretroviral therapy in adults (aged ≥18 years) with established HIV infection, including when to start treatment, initial regimens, and changing regimens, along with recommendations for using ARVs for preventing HIV among those at risk, including preexposure and postexposure prophylaxis. A panel of experts in HIV research and patient care convened by the International Antiviral Society-USA reviewed data published in peer-reviewed journals, presented by regulatory agencies, or presented as conference abstracts at peer-reviewed scientific conferences since the 2014 report, for new data or evidence that would change previous recommendations or their ratings. Comprehensive literature searches were conducted in the PubMed and EMBASE databases through April 2016. Recommendations were by consensus, and each recommendation was rated by strength and quality of the evidence. Newer data support the widely accepted recommendation that antiretroviral therapy should be started in all individuals with HIV infection with detectable viremia regardless of CD4 cell count. Recommended optimal initial regimens for most patients are 2 nucleoside reverse transcriptase inhibitors (NRTIs) plus an integrase strand transfer inhibitor (InSTI). Other effective regimens include nonnucleoside reverse transcriptase inhibitors or boosted protease inhibitors with 2 NRTIs. Recommendations for special populations and in the settings of opportunistic infections and concomitant conditions are provided. Reasons for switching therapy include convenience, tolerability, simplification, anticipation of potential new drug interactions, pregnancy or plans for pregnancy, elimination of food restrictions, virologic failure, or drug toxicities. Laboratory assessments are recommended before treatment, and monitoring during treatment is recommended to assess response, adverse effects, and adherence. Approaches are recommended to improve linkage to and retention in care are provided. Daily tenofovir disoproxil fumarate/emtricitabine is recommended for use as preexposure prophylaxis to prevent HIV infection in persons at high risk. When indicated, postexposure prophylaxis should be started as soon as possible after exposure. Antiretroviral agents remain the cornerstone of HIV treatment and prevention. All HIV-infected individuals with detectable plasma virus should receive treatment with recommended initial regimens consisting of an InSTI plus 2 NRTIs. Preexposure prophylaxis should be considered as part of an HIV prevention strategy for at-risk individuals. When used effectively, currently available ARVs can sustain HIV suppression and can prevent new HIV infection. With these treatment regimens, survival rates among HIV-infected adults who are retained in care can approach those of uninfected adults.

Brief Report: HIV Drug Resistance in Adults Failing Early Antiretroviral Treatment: Results From the HIV Prevention Trials Network 052 Trial.

PubMed

Fogel, Jessica M; Hudelson, Sarah E; Ou, San-San; Hart, Stephen; Wallis, Carole; Morgado, Mariza G; Saravanan, Shanmugam; Tripathy, Srikanth; Hovind, Laura; Piwowar-Manning, Estelle; Sabin, Devin; McCauley, Marybeth; Gamble, Theresa; Zhang, Xinyi C; Eron, Joseph J; Gallant, Joel E; Kumwenda, Johnstone; Makhema, Joseph; Kumarasamy, Nagalingeswaran; Chariyalertsak, Suwat; Hakim, James; Badal-Faesen, Sharlaa; Akelo, Victor; Hosseinipour, Mina C; Santos, Breno R; Godbole, Sheela V; Pilotto, Jose H; Grinsztejn, Beatriz; Panchia, Ravindre; Mayer, Kenneth H; Chen, Ying Q; Cohen, Myron S; Eshleman, Susan H

2016-07-01

Early initiation of antiretroviral treatment (ART) reduces HIV transmission and has health benefits. HIV drug resistance can limit treatment options and compromise use of ART for HIV prevention. We evaluated drug resistance in 85 participants in the HIV Prevention Trials Network 052 trial who started ART at CD4 counts of 350-550 cells per cubic millimeter and failed ART by May 2011; 8.2% had baseline resistance and 35.3% had resistance at ART failure. High baseline viral load and less education were associated with emergence of resistance at ART failure. Resistance at ART failure was observed in 7 of 8 (87.5%) participants who started ART at lower CD4 cell counts.

Ethical use of antiretroviral resources for HIV prevention in resource poor settings.

PubMed

Rennie, Stuart

2013-08-01

The effectiveness of antiretroviral regimes (ARVs) to reduce risk of HIV transmission from mother to child and as post-exposure prophylaxis has been known for almost two decades. Recent research indicates ARVs can also reduce the risk of HIV transmission via sexual intercourse in two other ways. With pre-exposure prophylaxis (PrEP), ARVs are used to reduce risk of HIV acquisition among persons who are HIV negative and significantly exposed to the virus. With treatment as prevention (TasP), ARVs are used to reduce risk of HIV transmission from persons who are already HIV positive. The development of these new prevention strategies raises a rationing problem: given the chronic shortage of ARVs for HIV-infected persons in need of treatment, is it ethically justified to allocate ARVs for PrEP and/or TasP? This article examines the intuitively appealing view that allocation of ARVs for treatment should be the highest priority, the use of ARVs for TasP should be a secondary priority, and that utilizing ARVs for PrEP would be unethical. I will argue that selective, evidence-based allocation of ARVs for prevention in certain cases could be ethically justified even when there is insufficient anti-retroviral access for all those needing it for treatment. © 2013 John Wiley & Sons Ltd.

Therapeutic Immunization In HIV Infected Ugandans Receiving Stable Antiretroviral Treatment: A Phase I Safety Study4

PubMed Central

Kityo, Cissy; Bousheri, Stephanie; Akao, Juliette; Ssali, Francis; Byaruhanga, Rose; Ssewanyana, Isaac; Muloma, Prossy; Myalo, Sula; Magala, Rose; Lu, Yichen; Mugyenyi, Peter; Cao, Huyen

2011-01-01

Therapeutic immunizations in HIV infection may boost immunity during antiretroviral treatment. We report on the first therapeutic vaccine trial in Uganda, Africa. This open label Phase I trial was designed to assess the safety, tolerability and immunogenicity of a therapeutic HIV-1 vaccine candidate. Thirty HIV positive volunteers receiving a stable regimen of antiretroviral therapy with CD4 counts > 400 were recruited for the safety evaluation of LFn-p24C, a detoxified anthrax-derived polypeptide fused to the subtype C HIV gag protein p24. The vaccine was well tolerated and HIV RNA levels remained undetectable following three immunizations. CD4 counts in vaccine recipients were significantly higher compared to the control individuals after 12 months. HIV-specific responses were associated with higher gain in CD4 counts following LFn-p24C immunizations. Volunteers were subsequently asked to undergo a 30-day period of observed treatment interruption. 8/24 (30%) individuals showed no evidence of viral rebound during treatment interruption. All demonstrated prompt suppression of viral load following resumption of ART. Our data demonstrates the safety of LFn-p24C and suggests that adjunct therapeutic immunization may benefit select individuals in further boosting an immune response. PMID:21211581

Determinants of access to experimental antiretroviral drugs in an Italian cohort of patients with HIV: a multilevel analysis.

PubMed

Girardi, Enrico; Scognamiglio, Paola; Angeletti, Claudio; Gori, Andrea; Buonfrate, Dora; Arlotti, Massimo; Mazzarello, Giovanni; Castagna, Antonella; Andreoni, Massimo; d'Arminio Monforte, Antonella; Antinori, Andrea; Ippolito, Giuseppe

2012-02-15

Identification of the determinants of access to investigational drugs is important to promote equity and scientific validity in clinical research. We aimed to analyze factors associated with the use of experimental antiretrovirals in Italy. We studied participants in the Italian Cohort of Antiretroviral-Naive Patients (ICoNA). All patients 18 years or older who had started cART (≥ 3 drugs including at least two NRTI) after their enrolment and during 1997-2007 were included in this analysis. We performed a random effect logistic regression analysis to take into account clustering observations within clinical units. The outcome variable was the use of an experimental antiretroviral, defined as an antiretroviral started before commercial availability, in any episode of therapy initiation/change. Use of an experimental antiretroviral obtained through a clinical trial or an expanded access program (EAP) was also analyzed separately. A total of 9,441 episodes of therapy initiation/change were analyzed in 3,752 patients. 392 episodes (360 patients) involved an experimental antiretroviral. In multivariable analysis, factors associated with the overall use of experimental antiretrovirals were: number of experienced drugs (≥ 8 drugs versus "naive": adjusted odds ratio [AOR] = 3.71) or failed antiretrovirals(3-4 drugs and ≥ 5 drugs versus 0-2 drugs: AOR = 1.42 and 2.38 respectively); calendar year (AOR = 0.80 per year) and plasma HIV-RNA copies/ml at therapy change (≥ 4 log versus < 2 log: AOR = 1.55). The probability of taking an experimental antiretroviral through a trial was significantly lower for patients suffering from liver co-morbidity(AOR = 0.65) and for those who experienced 3-4 drugs (vs naive) (AOR = 0.55), while it increased for multi-treated patients(AOR = 2.60). The probability to start an experimental antiretroviral trough an EAP progressively increased with the increasing number of experienced and of failed drugs and also increased for patients with liver co-morbidity (AOR = 1.44; p = 0.053). and for male homosexuals (vs heterosexuals: AOR = 1.67). Variability of the random effect associated to clinical units was statistically significant (p < 0.001) although no association was found with specific characteristics of clinical unit examined. Among patients with HIV infection in Italy, access to experimental antiretrovirals seems to be influenced mainly by exhaustion of treatment options and not by socio-demographic factors.

Leading unplanned change.

PubMed

Erickson, Jeanette Ives

2014-03-01

The article presents reflections on how Magnet® principles help nurse leaders through unplanned change using the 1-year anniversary of the Boston Marathon bombings and the response at Massachusetts General Hospital as an exemplar.

Mutations Related to Antiretroviral Resistance Identified by Ultra-Deep Sequencing in HIV-1 Infected Children under Structured Interruptions of HAART

PubMed Central

Vazquez-Guillen, Jose Manuel; Palacios-Saucedo, Gerardo C.; Rivera-Morales, Lydia G.; Garcia-Campos, Jorge; Ortiz-Lopez, Rocio; Noguera-Julian, Marc; Paredes, Roger; Vielma-Ramirez, Herlinda J.; Ramirez, Teresa J.; Chavez-Garcia, Marcelino; Lopez-Guillen, Paulo; Briones-Lara, Evangelina; Sanchez-Sanchez, Luz M.; Vazquez-Martinez, Carlos A.; Rodriguez-Padilla, Cristina

2016-01-01

Although Structured Treatment Interruptions (STI) are currently not considered an alternative strategy for antiretroviral treatment, their true benefits and limitations have not been fully established. Some studies suggest the possibility of improving the quality of life of patients with this strategy; however, the information that has been obtained corresponds mostly to studies conducted in adults, with a lack of knowledge about its impact on children. Furthermore, mutations associated with antiretroviral resistance could be selected due to sub-therapeutic levels of HAART at each interruption period. Genotyping methods to determine the resistance profiles of the infecting viruses have become increasingly important for the management of patients under STI, thus low-abundance antiretroviral drug-resistant mutations (DRM’s) at levels under limit of detection of conventional genotyping (<20% of quasispecies) could increase the risk of virologic failure. In this work, we analyzed the protease and reverse transcriptase regions of the pol gene by ultra-deep sequencing in pediatric patients under STI with the aim of determining the presence of high- and low-abundance DRM’s in the viral rebounds generated by the STI. High-abundance mutations in protease and high- and low-abundance mutations in reverse transcriptase were detected but no one of these are directly associated with resistance to antiretroviral drugs. The results could suggest that the evaluated STI program is virologically safe, but strict and carefully planned studies, with greater numbers of patients and interruption/restart cycles, are still needed to evaluate the selection of DRM’s during STI. PMID:26807922

[Genetic analysis of the mutations in HIV-1 infected population in Ecuador].

PubMed

González-González, Manuel; Correa-Sierra, Consuelo; Hermida-Álava, Katherine; Machado-Díaz, Ana; Gómez-Andrade, L Fernando; Castillo-Segovia, Martha; Pérez-Santos, C Lissette; Kourí-Cardellá, Vivian

Background The international recommendations of antiretroviral treatment include resistance tests to guide the treatment regimen in each patient, which is not available on a regular basis in Ecuador. Aim To describe mutations that confer resistance to antiretrovirals in a population of Ecuadorian patients. Methods Plasma samples from 101 HIV-1 patients with failure to antiretroviral therapy, divided into 15 children and 86 adults, were studied with the GS Junior (Roche) and the sequences were analyzed with the DeepChek program. Results The most frequent mutations were M184V/I, K101E/P/H, K103N/S, D30N, M46L/I, I54L/M, V82T/F/A/S/L and L90M in adults and F77L, K103N/S, M46L/I, V82T/F/A/S/L and L90M in children. High resistance to non-nucleoside reverse transcriptase (RT) inhibitors in minority viral populations of adults and children (34.9% and 70%) was detected; in children both viral populations (majority and minority viral populations) (> 45%) were protease inhibitor resistant. Patients who had a greater number of therapeutic regimens had higher levels of resistance to antiretrovirals. Most of the samples were subtype B in the TR and protease region, and CRF25_cpx in integrase. Conclusions Mutations and resistance to antiretrovirals are shown in a population of Ecuadorian patients with HIV-1. These results will make it possible to issue a warning to health authorities about the need for resistance studies.

Prevalence of antiretroviral drug resistance and resistance-associated mutations in antiretroviral therapy-naïve HIV-infected individuals from 40 United States cities.

PubMed

Ross, Lisa; Lim, Michael L; Liao, Qiming; Wine, Brian; Rodriguez, Allan E; Weinberg, Winkler; Shaefer, Mark

2007-01-01

Transmission of drug-resistant HIV strains to antiretroviral therapy (ART)-naïve subjects can negatively impact therapy response. As treatment strategies and utilization of antiretroviral drugs evolve, patterns of transmitted mutations may shift. Paired genotypic and phenotypic susceptibility data were retrospectively analyzed for 317 ART-naïve, HIV-infected subjects from 40 small and major metropolitan cities in the Northeastern, Midwestern, Southern, Southwestern, and Northwestern United States during 2003. Using current (January 2007) PhenoSense cutoffs, HIV-from 8% of subjects had reduced susceptibility to > or = 1 drug. By class, < 1% had reduced susceptibility to protease inhibitors (PIs), and 1% had reduced susceptibility to nucleoside reverse transcriptase inhibitors (NRTIs); reduced susceptibility to > or = 1 non-nucleoside reverse transcriptase inhibitor (NNRTIs) was seen in 7% of subjects, with 4% of all subjects having reduced susceptibility to all NNRTIs. IAS-USA-defined NRTI, NNRTI, and/or major PI HIV-drug resistance-associated mutations were detected for 0% of the subjects. HIV risk factors included homosexual contact (74%), heterosexual contact (28%), and injectable drug use/transfusion/other (7%). Reduced susceptibility to > or = 1 drug was significantly higher (p = .034) for white subjects than African Americans and Hispanics/others. The high prevalence of drug resistance in these ART-naïve subjects suggests that transmitted resistance is occurring widely within the United States. HIV genotyping and/or phenotyping for antiretroviral-naïve patients seeking treatment should be considered, especially if the therapy will include an NNRTI.

Incidence, Risk Factors, and Costs for Hospital Returns After Total Joint Arthroplasties.

PubMed

Sibia, Udai S; Mandelblatt, Abigail E; Callanan, Maura A; MacDonald, James H; King, Paul J

2017-02-01

Unplanned hospital returns after total joint arthroplasty (TJA) reduce any cost savings in a bundled reimbursement model. We examine the incidence, risk factors, and costs for unplanned emergency department (ED) visits and readmissions within 30 days of index TJA. We retrospectively reviewed a consecutive series of 655 TJAs (382 total knee arthroplasty and 273 total hip arthroplasty) performed between April 2014 and March 2015. Preoperative diagnosis was osteoarthritis of the hip or knee (97%) or avascular necrosis of the hip (3%). Hospital costs were recorded for each ED visit and readmission episode. Of the 655 TJAs reviewed, 55 (8.4%) returned to the hospital. Of these hospital returns, 35 patients (5.3%) returned for a total of 36 unplanned ED visits whereas the remaining 20 patients (3.1%) presented 22 readmissions within 30 days of index TJA. The 2 most common reasons for unplanned ED visits were postoperative pain/swelling (36%) and medication-related side effects (22%). Avascular necrosis of the hip was a significant risk factor for an unplanned ED visit (7.27 odds ratio [OR], 95% confidence interval [CI] 1.67-31.61, P = .008). Multiple logistic regression analysis revealed the following risk factors for readmission: body mass index (1.10 OR, 95% CI 1.02-1.78, P = .013), comorbidity >2 (2.07 OR, 95% CI 1.06-6.95, P = .037), and prior total knee arthroplasty (2.61 OR, 95% CI 1.01-6.72, P = .047). Ambulating on the day of surgery trended toward a lower risk for readmission (0.13 OR, 95% CI 0.02-1.10, P = .061). The 2 most common reasons for readmission were ileus (23%) and cellulitis (18%). The total cost associated with unplanned ED visits were $15,427 whereas costs of readmissions totaled $142,654. Unplanned ED visits and readmissions in the forthcoming bundled payments reimbursement model will reduce cost savings from rapid recovery protocols for TJA. Identifying and mitigating preventable causes of unplanned visits and readmissions will be critical to improving care and controlling costs. Copyright © 2016 Elsevier Inc. All rights reserved.

The risk of placenta accreta following primary cesarean delivery.

PubMed

Zeevi, Gil; Tirosh, Dan; Baron, Joel; Sade, Maayan Yitshak; Segal, Adi; Hershkovitz, Reli

2018-05-01

To (a) evaluate the risk for placenta accreta following primary cesarean section (CS), in regard to the stage of labor, the cesarean section was taken (elective prelabor vs. unplanned during labor); and (b) investigate whether the association between placenta accreta and maternal and neonatal complications is modified by the type of the primary CS. In a population-based retrospective cohort study, we included all singleton deliveries occurred in Soroka University Medical Center between 1991 and 2015, of women who had a history of a single CS. The deliveries were divided into three groups according to the delivery stage the primary CS was carried out: 'Unplanned 1' (first stage-up to 10 cm), 'Unplanned 2' (second stage-10 cm) and 'Elective' prelabor CS. We assessed the association between the study group and placenta accreta using logistic generalized estimation equation (GEE) models. We additionally assessed maternal and neonatal complications associated with placenta accreta among women who had elective and unplanned CS separately. We included 22,036 deliveries to 13,727 women with a history of one CS, of which 0.9% (n = 207) had placenta accreta in the following pregnancies: 12% (n = 25) in the 'Unplanned 1' group, 7.2% (n = 15) in the ' Unplanned 2' group and 80.8% (n = 167) in the 'elective' group. We found no difference in the risk for subsequent placenta accreta between the groups. In a stratified analysis by the timing of the primary cesarean delivery, the risk for maternal complications, associated with placenta accreta, was more pronounced among women who had an unplanned CS (OR 27.96, P < 0.01) compared to women who had an elective cesarean delivery (OR 13.72, P < 0.01). The stage in which CS is performed has no influence on the risk for placenta accreta in the following pregnancies, women who had an unplanned CS are in a higher risk for placenta accrete-associated maternal complications. This should be taken into consideration while counselling women about their risk while considering trial of labor after cesarean section.

Antiretroviral drug susceptibility among drug-naive adults with recent HIV infection in Rakai, Uganda

PubMed Central

Eshleman, Susan H.; Laeyendecker, Oliver; Parkin, Neil; Huang, Wei; Chappey, Colombe; Paquet, Agnes C.; Serwadda, David; Reynolds, Steven J.; Kiwanuka, Noah; Quinn, Thomas C.; Gray, Ronald; Wawer, Maria

2009-01-01

Objective To analyze antiretroviral drug susceptibility in HIV from recently infected adults in Rakai, Uganda, prior to the availability of antiretroviral drug treatment. Methods Samples obtained at the time of HIV seroconversion (1998–2003) were analyzed using the GeneSeq HIV and PhenoSense HIV assays (Monogram Biosciences, Inc., South San Francisco, California, USA). Results Test results were obtained for 104 samples (subtypes: 26A, 1C, 66D, 9A/D, 1C/D, 1 intersubtype recombinant). Mutations used for genotypic surveillance of transmitted antiretroviral drug resistance were identified in six samples: three had nucleoside reverse transcriptase inhibitor (NRTI) surveillance mutations (two had M41L, one had K219R), and three had protease inhibitor surveillance mutations (I47V, F53L, N88D); none had nonnucleoside reverse transcriptase inhibitor (NNRTI) surveillance mutations. Other resistance-associated mutations were identified in some samples. However, none of the samples had a sufficient number of mutations to predict reduced antiretroviral drug susceptibility. Ten (9.6%) of the samples had reduced phenotypic susceptibility to at least one drug (one had partial susceptibility to didanosine, one had nevirapine resistance, and eight had resistance or partial susceptibility to at least one protease inhibitor). Fifty-three (51%) of the samples had hypersusceptibility to at least one drug (seven had zidovudine hypersusceptibility, 28 had NNRTI hypersusceptibility, 34 had protease inhibitor hypersusceptibility). Delavirdine hyper-susceptibility was more frequent in subtype A than D. In subtype D, efavirenz hypersusceptibility was associated with substitutions at codon 11 in HIV-reverse transcriptase. Conclusion Phenotyping detected reduced antiretroviral drug susceptibility and hypersusceptibility in HIV from some antiretroviral-naive Ugandan adults that was not predicted by genotyping. Phenotyping may complement genotyping for analysis of antiretroviral drug susceptibility in populations with nonsubtype B HIV infection. PMID:19276794

Antiretroviral drug susceptibility among drug-naive adults with recent HIV infection in Rakai, Uganda.

PubMed

Eshleman, Susan H; Laeyendecker, Oliver; Parkin, Neil; Huang, Wei; Chappey, Colombe; Paquet, Agnes C; Serwadda, David; Reynolds, Steven J; Kiwanuka, Noah; Quinn, Thomas C; Gray, Ronald; Wawer, Maria

2009-04-27

To analyze antiretroviral drug susceptibility in HIV from recently infected adults in Rakai, Uganda, prior to the availability of antiretroviral drug treatment. Samples obtained at the time of HIV seroconversion (1998-2003) were analyzed using the GeneSeq HIV and PhenoSense HIV assays (Monogram Biosciences, Inc., South San Francisco, California, USA). Test results were obtained for 104 samples (subtypes: 26A, 1C, 66D, 9A/D, 1C/D, 1 intersubtype recombinant). Mutations used for genotypic surveillance of transmitted antiretroviral drug resistance were identified in six samples: three had nucleoside reverse transcriptase inhibitor (NRTI) surveillance mutations (two had M41L, one had K219R), and three had protease inhibitor surveillance mutations (I47V, F53L, N88D); none had nonnucleoside reverse transcriptase inhibitor (NNRTI) surveillance mutations. Other resistance-associated mutations were identified in some samples. However, none of the samples had a sufficient number of mutations to predict reduced antiretroviral drug susceptibility. Ten (9.6%) of the samples had reduced phenotypic susceptibility to at least one drug (one had partial susceptibility to didanosine, one had nevirapine resistance, and eight had resistance or partial susceptibility to at least one protease inhibitor). Fifty-three (51%) of the samples had hypersusceptibility to at least one drug (seven had zidovudine hypersusceptibility, 28 had NNRTI hypersusceptibility, 34 had protease inhibitor hypersusceptibility). Delavirdine hypersusceptibility was more frequent in subtype A than D. In subtype D, efavirenz hypersusceptibility was associated with substitutions at codon 11 in HIV-reverse transcriptase. Phenotyping detected reduced antiretroviral drug susceptibility and hypersusceptibility in HIV from some antiretroviral-naive Ugandan adults that was not predicted by genotyping. Phenotyping may complement genotyping for analysis of antiretroviral drug susceptibility in populations with nonsubtype B HIV infection.

Drug Treatment Centers in Afghanistan: Creating a Participatory Approach to Tackling the Drug Trade

DTIC Science & Technology

2012-12-01

Anti-Government Forces AIDS: Acquired Immunodeficiency Syndrome ANP: Afghan National Police ART: Anti-Retroviral Treatment BPHS: Basic Package of...treatment centers do performance reviews, corruption within the drug treatment clinics, and how management monitor staff burnout . While clinical governance

HIV genotype resistance testing in antiretroviral (ART) exposed Indian children--a need of the hour.

PubMed

Shah, Ira; Parikh, Shefali

2013-04-01

Development of drug resistance in HIV infected children with treatment failure is a major impediment to selection of appropriate therapy. HIV genotype resistance assays predict drug resistance on the basis of mutations in the viral genome. However, their clinical utility, especially in a resource limited setting is still a subject of debate. The authors report two cases in which both the children suffered from treatment failure of various antiretroviral therapy regimes. In both the cases, Genotype Resistance Testing (GRT) prompted a radical change from proposed failure therapy as per existing guidelines. GRT was specifically important for the selection of a new dual Nucleoside reverse transcriptase inhibitors (NRTI) component of failure regimen by identifying TAMS and M184V mutations in the HIV genome. These case reports highlight the importance of GRT in children failing multiple antiretroviral regimes; and emphasizes the need to recognize situations where GRT is absolutely essential to guide appropriate therapy, even in a resource limited setting.

Factors influencing utilization of postpartum CD4 count testing by HIV-positive women not yet eligible for antiretroviral treatment.

PubMed

Gilles, Kate P; Zimba, Chifundo; Mofolo, Innocent; Bobrow, Emily; Hamela, Gloria; Martinson, Francis; Hoffman, Irving; Hosseinipour, Mina

2011-03-01

Delayed antiretroviral initiation is associated with increased mortality, but individuals frequently delay seeking treatment. To increase early antiretroviral therapy (ART) enrollment of HIV-positive women, antenatal clinics are implementing regular, postpartum CD4 count testing. We examined factors influencing women's utilization of extended CD4 count testing. About 53 in-depth interviews were conducted with nurses, patients, social support persons, and government health officials at three antenatal clinics in Lilongwe, Malawi. Counseling and positive interactions with staff emerged as facilitating factors. Women wanted to know their CD4 count, but didn't understand the importance of early ART initiation. Support from husbands facilitated women's return to the clinic. Reminders were perceived as helpful but ineffectively employed. Staff identified lack of communication, difficulty in tracking, and referring women as barriers. Counseling messages should emphasize the importance of starting ART early. Clinics should focus on male partner involvement, case management, staff communication, and appointment reminders. Follow-up should be offered at multiple service points.

Predictors of Nonadherence to Antiretroviral Therapy among HIV-Infected Adults in Dar es Salaam, Tanzania.

PubMed

Muya, Aisa N; Geldsetzer, Pascal; Hertzmark, Ellen; Ezeamama, Amara E; Kawawa, Hawa; Hawkins, Claudia; Sando, David; Chalamilla, Guerino; Fawzi, Wafaie; Spiegelman, Donna

2015-01-01

Adherence rates of ≥95% to antiretroviral therapy (ART) are necessary to maintain viral suppression in HIV-infected individuals. We identified predictors of nonadherence to scheduled antiretroviral drug pickup appointments in a large HIV care and treatment program in Tanzania. We performed a prospective cohort study of 44, 204 HIV-infected adults on ART between November 2004 and September 2012. Multivariate generalized estimating equation for repeated binary data was used to estimate the relative risk and 95% confidence intervals of nonadherence. Nonadherence was significantly greater among patients with high CD4 counts, high body mass indices, males, younger patients, patients with longer durations on ART, and those with perceived low social support. Targeted interventions should be developed to improve ART adherence among healthier, younger, and more experienced patients who are on ART for longer durations within HIV care and treatment programs. Social support for patients on ART should be emphasized. © The Author(s) 2014.

Correlation of virus load in plasma and lymph node tissue in human immunodeficiency virus infection. INCAS Study Group. Italy, Netherlands, Canada, Australia, and (United) States.

PubMed

Harris, M; Patenaude, P; Cooperberg, P; Filipenko, D; Thorne, A; Raboud, J; Rae, S; Dailey, P; Chernoff, D; Todd, J; Conway, B; Montaner, J S

1997-11-01

The impact of long-term changes in plasma viremia, produced by effective combination antiretroviral therapy, on human immunodeficiency virus (HIV) burden within tissue reservoirs is unknown. Fifteen patients who had received at least 1 year of therapy with two or three drug combinations of zidovudine, didanosine, and nevirapine had suitable samples of lymph node tissue obtained by ultrasound-guided core needle biopsy. HIV RNA was extracted from homogenized tissue samples and quantitated using a modified branched DNA assay. Results were correlated with antiretroviral treatment effect on the basis of plasma virus load measurements over the preceding 12-18 months. A statistically significant negative correlation was observed between magnitude of treatment effect on plasma viremia and lymph node virus load. These data suggest that combinations of antiretroviral drugs that produce sustained suppression of plasma HIV RNA may also be able to reduce the virus burden in lymphoid tissues.

Introduction: the realities of antiretroviral therapy rollout: overcoming challenges to successful programmatic implementation.

PubMed

Ojikutu, Bisola

2007-12-01

In 2006, 2 million human immunodeficiency virus (HIV)-infected people living in low- to middle-income countries were receiving antiretroviral therapy (ART). Although this is an improvement over previous years, significant operational challenges have inhibited progress toward universal access to HIV care and treatment. Despite these challenges, the intense efforts focused on addressing the HIV epidemic present an opportunity for overall health systems improvement in developing nations. In October 2006, Harvard University's Centers for AIDS Research, the Nelson Mandela School of Medicine, the Department of Health of KwaZulu-Natal, and the Medical Research Council of South Africa held a conference entitled "The Realities of Antiretroviral Therapy Rollout: Challenges to Successful Programmatic Implementation" in Durban, South Africa. The goal of the meeting was to bring together international and local leadership, including policy makers, health care workers, and funders, to propose an agenda that would address the challenges to more expeditious provision of HIV care and treatment in resource-limited settings.

Lay Social Resources for Support of Adherence to Antiretroviral Prophylaxis for HIV Prevention Among Serodiscordant Couples in sub-Saharan Africa: A Qualitative Study.

PubMed

Ware, Norma C; Pisarski, Emily E; Haberer, Jessica E; Wyatt, Monique A; Tumwesigye, Elioda; Baeten, Jared M; Celum, Connie L; Bangsberg, David R

2015-05-01

Effectiveness of antiretroviral pre-exposure prophylaxis (PrEP) for HIV prevention will require high adherence. Using qualitative data, this paper identifies potential lay social resources for support of PrEP adherence by HIV serodiscordant couples in Uganda, laying the groundwork for incorporation of these resources into adherence support initiatives as part of implementation. The qualitative analysis characterizes support for PrEP adherence provided by HIV-infected spouses, children, extended family members, and the larger community. Results suggest social resources for support of PrEP adherence in Africa are plentiful outside formal health care settings and health systems and that couples will readily use them. The same shortage of health professionals that impeded scale-up of antiretroviral treatment for HIV/AIDS in Africa promises to challenge delivery of PrEP. Building on the treatment scale-up experience, implementers can address this challenge by examining the value of lay social resources for adherence support in developing strategies for delivery of PrEP.

Animal models for HIV/AIDS research

PubMed Central

Hatziioannou, Theodora; Evans, David T.

2015-01-01

The AIDS pandemic continues to present us with unique scientific and public health challenges. Although the development of effective antiretroviral therapy has been a major triumph, the emergence of drug resistance requires active management of treatment regimens and the continued development of new antiretroviral drugs. Moreover, despite nearly 30 years of intensive investigation, we still lack the basic scientific knowledge necessary to produce a safe and effective vaccine against HIV-1. Animal models offer obvious advantages in the study of HIV/AIDS, allowing for a more invasive investigation of the disease and for preclinical testing of drugs and vaccines. Advances in humanized mouse models, non-human primate immunogenetics and recombinant challenge viruses have greatly increased the number and sophistication of available mouse and simian models. Understanding the advantages and limitations of each of these models is essential for the design of animal studies to guide the development of vaccines and antiretroviral therapies for the prevention and treatment of HIV-1 infection. PMID:23154262

Treatment switch guided by HIV-1 genotyping in Brazil.

PubMed

Tupinambás, Unaí; Ribeiro, Flávia Andrade; Aleixo, Agdemir; Greco, Dirceu

2006-04-01

We assessed the performance of HIV-1 genotyping tests in rescue therapy. Patients were divided into two groups: group 1 (genotyped), included those switching to new antiretroviral drugs based on HIV-1 genotyping data, and group 2 (standard of care -SOC), comprised those in rescue therapy who had not used this test. This was an open and non-randomized study, with 74 patients, followed up for a mean period of 12 months, from February 2002 to May 2003. The groups differed in the duration of antiretroviral use, experience with diverse drug classes (non-nucleoside reverse transcriptase inhibitors and protease inhibitors) and viral load <2.6 log10 copies/mL at any time during treatment. In 23 patients (group 1), the switch in antiretroviral (ARV) regimen was based on genotyping data; this test was not used for 51 patients (group 2). Two CD4 + lymphocyte counts and viral load counts were made for each patient during the study. Data from the pharmacy where patients received antiretroviral agents, medical charts, and direct interviews with patients to assess compliance to treatment, were analyzed. In the genotyped group, the average drop in viral load was 2.8 log10, compared with a 1.5 log10 difference in group 2; the difference was significant in the first assessment performed six months after switching (p=0.001). Considering the patients with viral load < 2.6 log10 (400 copies/mL) after switching, the patients in group 1 had a better performance in the first assessment (73.9% versus 31.1% in groups 1 and 2, respectively); this difference was significant (p=0.001). In multivariate analysis, the variables associated with a greater drop in viral load in the first assessment were the patients whose switching was based on genotyping (group 1), those with a past history of viral load < 2.6 log10 and correct use of antiretroviral agents. In conclusion, the genotyping test and adherence were found to be independent factors for success in the management of patients who failed treatment.

Treatment Outcomes for Extensively Drug-Resistant Tuberculosis and HIV Co-infection

PubMed Central

Padayatchi, Nesri; Kvasnovsky, Charlotte; Werner, Lise; Master, Iqbal; Horsburgh, C. Robert

2013-01-01

High mortality rates have been reported for patients co-infected with extensively drug-resistant tuberculosis (XDR-TB) and HIV, but treatment outcomes have not been reported. We report treatment outcomes for adult XDR TB patients in KwaZulu-Natal Province, South Africa. Initial data were obtained retrospectively, and outcomes were obtained prospectively during 24 months of treatment. A total of 114 XDR TB patients were treated (median 6 drugs, range 3–9 drugs); 82 (73%) were HIV positive and 50 (61%) were receiving antiretroviral therapy. After receiving treatment for 24 months, 48 (42%) of 114 patients died, 25 (22%) were cured or successfully completed treatment, 19 (17%) withdrew from the study, and 22 (19%) showed treatment failure. A higher number of deaths occurred among HIV-positive patients not receiving antiretroviral therapy and among patients who did not show sputum culture conversion. Culture conversion was a major predictor of survival but was poorly predictive (51%) of successful treatment outcome. PMID:23622055

Genetic characterization and antiretroviral resistance mutations among treatment-naive HIV-infected individuals in Jiaxing, China.

PubMed

Guo, Jinlei; Yan, Yong; Zhang, Jiafeng; Ji, Jimei; Ge, Zhijian; Ge, Rui; Zhang, Xiaofei; Wang, Henghui; Chen, Zhongwen; Luo, Jianyong

2017-03-14

The aim of this study was to characterize HIV-1 genotypes and antiretroviral resistance mutations among treatment-naive HIV-infected individuals in Jiaxing, China. The HIV-1 partial polymerase (pol) genes in 93 of the 99 plasma samples were successfully amplified and analyzed. Phylogenetic analysis revealed the existence of five HIV-1 genotypes, of which the most prevalent genotype was CRF01_AE (38.7%), followed by CRF07_BC (34.4%), CRF08_BC (16.1%), subtype B/B' (5.4%), and CRF55_01B (2.1%). Besides, three types of unique recombination forms (URFs) were also observed, including C/F2/A1, CRF01_AE/B, and CRF08_BC/CRF07_BC. Among 93 amplicons, 46.2% had drug resistance-associated mutations, including 23.7% for protease inhibitors (PIs) mutations, 1.1% for nucleoside reverse transcriptase inhibitors (NRTIs) mutations, and 20.4% for non-nucleoside reverse transcriptase inhibitors (NNRTIs) mutations. Six (6.5%) out of 93 treatment-naive subjects were identified to be resistant to one or more NNRTIs, while resistance to NRTIs or PIs was not observed. Our study showed the genetic diversity of HIV-1 strains circulating in Jiaxing and a relative high proportion of antiretroviral resistance mutations among treatment-naive patients, indicating a serious challenge for HIV prevention and treatment program.

Where are we now? A multicountry qualitative study to explore access to pre-antiretroviral care services: a precursor to antiretroviral therapy initiation

PubMed Central

Bukenya, Dominic; Wringe, Alison; Skovdal, Morten; Ssekubugu, Robert; Paparini, Sara; McLean, Estelle; Bonnington, Oliver; Wamoyi, Joyce; Seeley, Janet

2017-01-01

Objective To explore barriers and facilitators to accessing postdiagnosis HIV care in five sub-Saharan African countries. Methods In-depth interviews were conducted with 77 people living with HIV (PLHIV) in pre-antiretroviral therapy care or not-yet-in care and 46 healthcare workers. Participants were purposely selected from health and demographic surveillance sites in Karonga (Malawi), Manicaland (Zimbabwe), uMkhanyakude (South Africa), Kisesa (Tanzania) and Rakai and Kyamulibwa (Uganda). Thematic content analysis was conducted, guided by the constructs of affordability, availability and acceptability of care.- Results Affordability: Transport and treatment costs were a barrier to HIV care, although some participants travelled to distant clinics to avoid being seen by people who knew them or for specific services. Broken equipment and drug stock-outs in local clinics could also necessitate travel to other facilities. Availability: Some facilities did not offer full HIV care, or only offered all services intermittently. PLHIV who frequently travelled complained that care was seldom available to them in places they visited. Acceptability: Severe pain or sickness was a key driver for accessing postdiagnosis care, whereas asymptomatic PLHIV often delayed care-seeking. A belief in witchcraft was a deterrent to accessing clinical care following diagnosis. Changing antiretroviral therapy guidelines generated uncertainty among PLHIV about when to start treatment and delayed postdiagnosis care. PLHIV reported that healthcare workers’ knowledge, attitudes and behaviours, and their ability to impart health education, also influenced whether they accessed HIV care. Conclusion Despite efforts to decentralise services over the past decade, many barriers to accessing HIV care persist. There is a need to increase sustained access to care for PLHIV not yet on treatment, with initiatives that encompass biomedical aspects of care alongside considerations for individual and collective challenges they faced. A failure to do so may undermine efforts to achieve universal access to antiretroviral therapy. PMID:28615327

Pharmacokinetics of piperaquine and safety profile of dihydroartemisinin-piperaquine co-administered with antiretroviral therapy in malaria-uninfected HIV-positive Malawian adults.

PubMed

Banda, Clifford G; Dzinjalamala, Fraction; Mukaka, Mavuto; Mallewa, Jane; Maiden, Victor; Terlouw, Dianne J; Lalloo, David G; Khoo, Saye H; Mwapasa, Victor

2018-05-21

There are limited data on the pharmacokinetic and safety profiles of dihydroartemisinin-piperaquine (DHA-PQ) among human immunodeficiency virus infected (HIV+) individuals taking antiretroviral therapy (ART). In a two step (parallel-group) pharmacokinetic trial with intensive blood sampling, we compared area under the concentration-time curve (AUC 0-28 days ) and safety outcomes of piperaquine among malaria-uninfected HIV+ adults. In step 1, half the adult dose of DHA-PQ was administered for three days as an intitial safety check in four groups (n=6/group) of HIV+ adults (age≥18 years): (i) antiretroviral-naïve, (ii) on nevirapine-based ART, (iii) on efavirenz-based ART, and (iv) on ritonavir-boosted lopinavir-based ART. In step 2, a full adult treatment course of DHA-PQ was administered to a different cohort of participants in three groups: (i) antiretroviral naïve, (ii) on efavirenz-based ART and (iii) on nevirapine-based ART (n=10-15/group). Ritonavir-boosted lopinavir-based ART group was dropped in step 2 due to limited number of participants who were on this second line ART and were eligible for recruitment. Piperaquine's AUC 0-28 days in both steps was 43% lower among participants on efavirenz-based ART compared to ART naïve participants. There were no significant differences in AUC 0-28 days between the other ART groups and the ART naïve group in each of the two steps. Furthermore, no differences in treatment-emergent clinical and laboratory adverse events were observed across the groups in steps 1 and 2. Although well tolerated at half and full standard adult treatment courses, efavirenz based antiretroviral regimen was associated with reduced piperaquine exposure which may compromise dihydroartemisinin-piperaquine's effectiveness in programmatic settings. Copyright © 2018 Banda et al.

Unplanned health care tourism.

PubMed

Powell, Suzanne K

2015-01-01

Health care tourism is often a preplanned event carefully laying out all the details. Sometimes, when one least expects it, medical care is needed outside of the mainland. This Editorial speaks to an unplanned experience.

The socioeconomic consequences of teenage childbearing: findings from a natural experiment.

PubMed

Grogger, J; Bronars, S

1993-01-01

A study based on census data from 1970 and 1980 examines the socioeconomic effects of unplanned teenage childbearing by comparing teenage mothers whose first birth was to twins with those whose first birth was to a single infant. Among black women, an unplanned teenage birth--represented by the secondborn twin--results in significantly lower rates of high school graduation and labor-force participation and significantly higher rates of poverty and welfare recipiency. Ten years after giving birth, black women who have an unplanned child are also significantly less likely than women who have not to be currently married, but are not less likely to have ever been married. Like black women, white women who have an unplanned teenage birth have significantly higher rates of poverty and welfare recipiency; they also have significantly lower family earnings and household income.

Causes of unplanned hemodialysis initiation.

PubMed

Gomis Couto, A; Teruel Briones, J L; Fernández Lucas, M; Rivera Gorrin, M; Rodríguez Mendiola, N; Jiménez Álvaro, S; Quereda Rodríguez-Navarro, C

2011-01-01

Half of patients starting chronic hemodialysis used a transient vascular catheter as a vascular access (unplanned initiation). An objective of the Quality Management Group of the Spanish Society of Nephrology is to achieve that 80% of the patients starting hemodialysis do it with an arteriovenous fistula. We want to review the causes of non-planned hemodialysis nowadays. In 2010, 43 patients had started chronic hemodialysis in the Hospital Ramón y Cajal in Madrid (Spain). Mean age was 61 years, 79% were men, the most frequent cause of chronic renal disease was the diabetes (23%) and Charlson Comorbidity Index was 6.3 ± 2.6. The unplanned hemodialysis occurred in 20 patients (47%), without any differences with the 23 patients who began planned hemodialysis, in none of the clinical or demographic parameters analyzed. The main cause of unplanned hemodialysis was the acute exacerbation of chronic kidney disease stage 3 or 4, previously stable, secondary to an unforeseeable intercurrent process (8 patients, 40% of the cases). One patient began after a non-recovery acute renal failure and in other 6 patients, the reason of unplanned hemodialysis initiation was not attributable to the operation Health System (in 3 cases unknown kidney chronic disease and in the other 3 cases it was patient´s responsibility). Only in 5 cases (25%), the cause could be corrigible. Most causes of unplanned hemodialysis does not come from the healthcare organization and therefore not easy to resolve it. Consequently, the objective of the Quality Group will be difficult to be achieved.

Prevention of HIV-1 Infection with Early Antiretroviral Therapy: Treatment as -

NASA Astrophysics Data System (ADS)

Gilada, Ishwar; Gilada, T.

2014-07-01

There are 34.2 million living with HIV/AIDS globally according to the UNAIDS. The incidence is 2.5 million new infections every year. Out of the 24.8 million patients eligible for antiretroviral treatment, only 8 million are actually receiving it. Nearly 1.7 million people (4658 per day) die of the disease every year i.e., 4658/day, making HIV/AIDS a planetary emergency. The most disturbing fact is that more than 50% of the infected people do not reveal their HIV status to their sexual partners. The UN Sec-Gen Ban Ki-moon suggested "3 Zeros"--Zero Infection, Zero Stigma, Zero AIDS-deaths in 2008...

Initiating therapy: when to start, what to use.

PubMed

Hirsch, Martin S

2008-05-15

Decisions regarding whether to start combination antiretroviral therapy (cART) during primary infection and when to initiate treatment during chronic infection continue to evolve. Although current data suggest that there may be a benefit to therapy during primary infection, results are inconclusive. Once begun, treatment probably should be continued indefinitely, since its potential advantages disappear over time if treatment is stopped. Recent studies suggest that cART may be useful at higher CD4 cell count thresholds than are currently recommended in several guidelines. Several regimens are acceptable as initial therapy, with tenofovir/emtricitabine/efavirenz favored by many because of potency and ease of administration. Other favored regimens include combinations of 2 nucleoside (or nucleotide) reverse-transcriptase inhibitors and a ritonavir-boosted protease inhibitor. Some new antiretroviral drugs under study, particularly integrase inhibitors, may prove useful in treatment-naive patients.

Estimated mortality of adult HIV-infected patients starting treatment with combination antiretroviral therapy

PubMed Central

Yiannoutsos, Constantin Theodore; Johnson, Leigh Francis; Boulle, Andrew; Musick, Beverly Sue; Gsponer, Thomas; Balestre, Eric; Law, Matthew; Shepherd, Bryan E; Egger, Matthias

2012-01-01

Objective To provide estimates of mortality among HIV-infected patients starting combination antiretroviral therapy. Methods We report on the death rates from 122 925 adult HIV-infected patients aged 15 years or older from East, Southern and West Africa, Asia Pacific and Latin America. We use two methods to adjust for biases in mortality estimation resulting from loss from follow-up, based on double-sampling methods applied to patient outreach (Kenya) and linkage with vital registries (South Africa), and apply these to mortality estimates in the other three regions. Age, gender and CD4 count at the initiation of therapy were the factors considered as predictors of mortality at 6, 12, 24 and >24 months after the start of treatment. Results Patient mortality was high during the first 6 months after therapy for all patient subgroups and exceeded 40 per 100 patient years among patients who started treatment at low CD4 count. This trend was seen regardless of region, demographic or disease-related risk factor. Mortality was under-reported by up to or exceeding 100% when comparing estimates obtained from passive monitoring of patient vital status. Conclusions Despite advances in antiretroviral treatment coverage many patients start treatment at very low CD4 counts and experience significant mortality during the first 6 months after treatment initiation. Active patient tracing and linkage with vital registries are critical in adjusting estimates of mortality, particularly in low- and middle-income settings. PMID:23172344

Efficacy and Safety of Three Antiretroviral Regimens for Initial Treatment of HIV-1: A Randomized Clinical Trial in Diverse Multinational Settings

PubMed Central

Campbell, Thomas B.; Smeaton, Laura M.; Kumarasamy, N.; Flanigan, Timothy; Klingman, Karin L.; Firnhaber, Cynthia; Grinsztejn, Beatriz; Hosseinipour, Mina C.; Kumwenda, Johnstone; Lalloo, Umesh; Riviere, Cynthia; Sanchez, Jorge; Melo, Marineide; Supparatpinyo, Khuanchai; Tripathy, Srikanth; Martinez, Ana I.; Nair, Apsara; Walawander, Ann; Moran, Laura; Chen, Yun; Snowden, Wendy; Rooney, James F.; Uy, Jonathan; Schooley, Robert T.; De Gruttola, Victor; Hakim, James Gita; Swann, Edith; Barnett, Ronald L.; Brizz, Barbara; Delph, Yvette; Gettinger, Nikki; Mitsuyasu, Ronald T.; Eshleman, Susan; Safren, Steven; Fiscus, Susan A.; Andrade, Adriana; Haas, David W.; Amod, Farida; Berthaud, Vladimir; Bollinger, Robert C.; Bryson, Yvonne; Celentano, David; Chilongozi, David; Cohen, Myron; Collier, Ann C.; Currier, Judith Silverstein; Cu-Uvin, Susan; Eron, Joseph; Flexner, Charles; Gallant, Joel E.; Gulick, Roy M.; Hammer, Scott M.; Hoffman, Irving; Kazembe, Peter; Kumwenda, Newton; Lama, Javier R.; Lawrence, Jody; Maponga, Chiedza; Martinson, Francis; Mayer, Kenneth; Nielsen, Karin; Pendame, Richard B.; Ramratnam, Bharat; Sanne, Ian; Severe, Patrice; Sirisanthana, Thira; Solomon, Suniti; Tabet, Steve; Taha, Taha; van der Horst, Charles; Wanke, Christine; Gormley, Joan; Marcus, Cheryl J.; Putnam, Beverly; Loeliger, Edde; Pappa, Keith A.; Webb, Nancy; Shugarts, David L.; Winters, Mark A.; Descallar, Renard S.; Steele, Joseph; Wulfsohn, Michael; Said, Farideh; Chen, Yue; Martin, John C; Bischofberger, Norbert; Cheng, Andrew; Jaffe, Howard; Sharma, Jabin; Poongulali, S.; Cardoso, Sandra Wagner; Faria, Deise Lucia; Berendes, Sima; Burke, Kelly; Mngqibisa, Rosie; Kanyama, Cecelia; Kayoyo, Virginia; Samaneka, Wadzanai P.; Chisada, Anthony; Faesen, Sharla; Chariyalertsak, Suwat; Santos, Breno; Lira, Rita Alves; Joglekar, Anjali A.; Rosa, Alberto La; Infante, Rosa; Jain, Mamta; Petersen, Tianna; Godbole, Sheela; Dhayarkar, Sampada; Feinberg, Judith; Baer, Jenifer; Pollard, Richard B.; Asmuth, David; Gangakhedkar, Raman R; Gaikwad, Asmita; Ray, M. Graham; Basler, Cathi; Para, Michael F.; Watson, Kathy J.; Taiwo, Babafemi; McGregor, Donna; Balfour, Henry H.; Mullan, Beth; Kim, Ge-Youl; Klebert, Michael K.; Cox, Gary Matthew; Silberman, Martha; Mildvan, Donna; Revuelta, Manuel; Tashima, Karen T.; Patterson, Helen; Geiseler, P. Jan; Santos, Bartolo; Daar, Eric S; Lopez, Ruben; Frarey, Laurie; Currin, David; Haas, David H.; Bailey, Vicki L.; Tebas, Pablo; Zifchak, Larisa; Noel-Connor, Jolene; Torres, Madeline; Sha, Beverly E.; Fritsche, Janice M.; Cespedes, Michelle; Forcht, Janet; O'Brien, William A.; Mogridge, Cheryl; Hurley, Christine; Corales, Roberto; Palmer, Maria; Adams, Mary; Luque, Amneris; Lopez-Detres, Luis; Stroberg, Todd

2012-01-01

Background Antiretroviral regimens with simplified dosing and better safety are needed to maximize the efficiency of antiretroviral delivery in resource-limited settings. We investigated the efficacy and safety of antiretroviral regimens with once-daily compared to twice-daily dosing in diverse areas of the world. Methods and Findings 1,571 HIV-1-infected persons (47% women) from nine countries in four continents were assigned with equal probability to open-label antiretroviral therapy with efavirenz plus lamivudine-zidovudine (EFV+3TC-ZDV), atazanavir plus didanosine-EC plus emtricitabine (ATV+DDI+FTC), or efavirenz plus emtricitabine-tenofovir-disoproxil fumarate (DF) (EFV+FTC-TDF). ATV+DDI+FTC and EFV+FTC-TDF were hypothesized to be non-inferior to EFV+3TC-ZDV if the upper one-sided 95% confidence bound for the hazard ratio (HR) was ≤1.35 when 30% of participants had treatment failure. An independent monitoring board recommended stopping study follow-up prior to accumulation of 472 treatment failures. Comparing EFV+FTC-TDF to EFV+3TC-ZDV, during a median 184 wk of follow-up there were 95 treatment failures (18%) among 526 participants versus 98 failures among 519 participants (19%; HR 0.95, 95% CI 0.72–1.27; p = 0.74). Safety endpoints occurred in 243 (46%) participants assigned to EFV+FTC-TDF versus 313 (60%) assigned to EFV+3TC-ZDV (HR 0.64, CI 0.54–0.76; p<0.001) and there was a significant interaction between sex and regimen safety (HR 0.50, CI 0.39–0.64 for women; HR 0.79, CI 0.62–1.00 for men; p = 0.01). Comparing ATV+DDI+FTC to EFV+3TC-ZDV, during a median follow-up of 81 wk there were 108 failures (21%) among 526 participants assigned to ATV+DDI+FTC and 76 (15%) among 519 participants assigned to EFV+3TC-ZDV (HR 1.51, CI 1.12–2.04; p = 0.007). Conclusion EFV+FTC-TDF had similar high efficacy compared to EFV+3TC-ZDV in this trial population, recruited in diverse multinational settings. Superior safety, especially in HIV-1-infected women, and once-daily dosing of EFV+FTC-TDF are advantageous for use of this regimen for initial treatment of HIV-1 infection in resource-limited countries. ATV+DDI+FTC had inferior efficacy and is not recommended as an initial antiretroviral regimen. Trial Registration www.ClinicalTrials.gov NCT00084136 Please see later in the article for the Editors' Summary. PMID:22936892

Exploring fertility decisions among pregnant HIV-positive women on antiretroviral therapy at a health centre in Balaka, Malawi: A descriptive qualitative.

PubMed

Biseck, T; Kumwenda, S; Kalulu, K; Chidziwisano, K; Kalumbi, L

2015-12-01

The proportions of women of reproductive age living with the human immunodeficiency virus (HIV) vary between different regions of the world, with significantly higher proportions in sub-Saharan Africa. Family planning is one of the major issues that couples and families affected with HIV must confront. We aimed to assess the cultural and social factors associated with childbearing and family planning knowledge, decision-making, and practices among HIV-positive pregnant women attending antenatal clinic at a health centre in Balaka, Malawi. This was a qualitative descriptive study carried out at Kalembo Health Centre in Balaka. A purposive sampling technique was used to select pregnant women enroled in the antiretroviral therapy (ART) programme. A sample size of thirty-five women was decided upon after data saturation. Qualitative inquiry was used during data collection. Data were analysed using systematic text condensation, while numbers and percentages were generated using Microsoft Excel. Out of 35 participants, 20 were aged between 25 and 34 years, and 18 had been married at least three times. All 35 women wished to have their own biological child. Factors, reported by participants, that promote childbearing included: the desire to please their husbands, fear of losing their husbands to others if they did not bear children, the knowledge that ART would help prevent their children from acquiring the virus, the desire to prove to others that they can also bear children, and a lack of family planning leading to unplanned pregnancies. The factors that lead to pregnancies among women on ART in Balaka ranged from assured safety of the child from HIV, lack of contraception, to other factors related to their partners. The authors recognize and support the freedom for women to become pregnant and bear children, and, in the context of HIV infection, fertility and reproductive services should include a comprehensive approach towards addressing issues of HIV and AIDS and childbearing among infected women.

Reproductive behaviour among women on antiretroviral therapy in Botswana: mismatched pregnancy plans and contraceptive use.

PubMed

Schaan, Michelle M; Taylor, Myra; Marlink, Richard

2014-09-01

Understanding pregnancy planning and contraceptive use is important in preventing unplanned/unwanted pregnancies among women on antiretroviral therapy (ART). Through a cross-sectional survey of 155 women living with HIV on ART in Botswana (mean age = 36), bivariate/multivariate analyses were used to identify and understand pregnancy planning and contraceptive use. Women who did not plan to have a child (n = 85) were older, less educated, had more children and worried about stigmatisation from family and healthcare workers (HCWs). Multivariate analyses found age (OR:3.41; CI:1.57-7.45; p = 0.002); perceived stigmatisation from family and healthcare workers (OR:3.62; CI:1.47-8.96; p = 0.005); and believing it is irresponsible for women living with HIV to want a child (OR:2.40; CI:1.10-5.24; p = 0.028) to be significantly associated with not planning to have a child. Although reported condom use among 85 women who did not plan to have a child was nearly 90%, a total of 26 of these women (34%) believed they did not have control over condom use. Lack of contraception was reported by 6 women who did not plan a child; this, coupled with the lack of control over condom use, puts unmet need for contraception at 38%. Most women reported feeling comfortable talking with HCWs about contraceptives. However, almost a quarter of the women indicated they were infrequently advised about contraceptives at ART clinics. This study found discordance between pregnancy planning and contraceptive use among women on ART. Lack of control over condom use coupled with low hormonal contraceptive use creates unmet need for contraception and increases the risk of unwanted pregnancies. Regular clinic visits for women on ART present excellent opportunities to address contraceptive needs in a considerate and comprehensive manner.

Telomere length is a prognostic biomarker in elderly advanced ovarian cancer patients: a multicenter GINECO study

PubMed Central

Falandry, Claire; Horard, Béatrice; Bruyas, Amandine; Legouffe, Eric; Cretin, Jacques; Meunier, Jérôme; Alexandre, Jérôme; Delecroix, Valérie; Fabbro, Michel; Certain, Marie-Noëlle; Maraval-Gaget, Raymonde; Pujade-Lauraine, Eric; Gilson, Eric; Freyer, Gilles

2015-01-01

Purpose Age induces a progressive decline in functional reserve and impacts cancer treatments. Telomere attrition leads to tissue senescence. We tested the hypothesis that telomere length (TL) could predict patient vulnerability and outcome with cancer treatment. Patients and methods An ancillary study in the Elderly Women GINECO Trial 3 was performed to evaluate the impact of geriatric covariates on survival in elderly advanced ovarian cancer patients receiving six cycles of carboplatin. TL was estimated from peripheral blood at inclusion using standard procedures. Results TL (in base pairs) was estimated for 109/111 patients (median 6.1 kb; range [4.5-8.3 kb]). With a cut-off of 5.77 kb, TL discriminated two patient groups, long telomere (LT) and short telomeres (ST), with significantly different treatment completion rates of 0.80 (95%CI [0.71-0.89]) and 0.59 (95%CI [0.41-0.76]), respectively (odds ratio [OR]=2.8, p=0.02). ST patients were at higher risk of serious adverse events (SAE, OR=2.7; p=0.02) and had more unplanned hospital admissions (OR=2.1; p=0.08). After adjustment on FIGO stage, TL shorter than 6 kb was a risk factor of premature death (HR=1.57; p=0.06). Conclusion This exploratory study identifies TL as predictive factor of decreased treatment completion, SAE risk, unplanned hospital admissions and OS after adjustment on FIGO stage. PMID:26638179

Which factors hinder the decision of Polish HIV-positive patients to take up antiretroviral therapy?

PubMed

Rogowska-Szadkowska, D; Chlabicz, S; Oltarzewska, M A; Sawicka-Powierza, J

2009-03-01

The implementation of highly active antiretroviral therapy (HAART) in 1996 has significantly reduced mortality and morbidity for HIV-positive patients worldwide. However not all eligible persons start HAART. To identify reasons for therapy refusal by HIV-positive persons we performed a questionnaire study. The investigation was conducted among 321 HIV-positive individuals and focused on the decision to take up antiretroviral treatment. Out of 71 untreated patients, 34 (47.9%) admitted that in their case the therapy was not indicated, whereas 20 (28.3%) were afraid of potential side effects that might change their appearance, e.g. face lipoatrophy. Only the treated patients had been prepared to take up therapy, although 17 patients (6.0%) had not received any explanation of the therapy principles, aims or necessity to comply with medication regime. The therapy is generally not discussed with the patients for whom it is not currently indicated, which may contribute to the fixation of fears and prejudices. Doctors who treat HIV-positive patients should be aware of the prejudices and fears their patients have towards antiretroviral therapy in order to react properly and by means of the available antiretroviral drugs help prolong life and improve its quality.

Use of first line antiretroviral therapy from a free ART programme clinic in Pune, India - a preliminary report.

PubMed

Ghate, Manisha; Tripathy, Srikanth; Gangakhedkar, Raman; Thakar, Madhuri; Bhattacharya, Jayanta; Choudhury, Ipsita; Risbud, Arun; Bembalkar, Shilpa; Kadam, Dileep; Rewari, Bharat B; Paranjape, Ramesh

2013-05-01

The treatment outcomes under national antiretroviral therapy (ART) programme are being evaluated in some ART centres in the country. We carried out this study to analyze the impact of first line antiretroviral therapy in HIV infected patients attending a free ART roll out national programme clinic in Pune, India. Antiretroviral naive HIV infected patients attending the clinic between December 2005 and April 2008 and followed up till March 31, 2011 were included in the analysis. The enrolment and follow up of these patients were done as per the national guidelines. Viral load estimations were done in a subset of patients. results: One hundred and forty two patients with median CD4 count of 109 cells/μl (IQR: 60-160) were initiated on treatment. The median follow up was 44 months (IQR: 37-53.3 months). Survival analysis showed that the probability of being alive at the end of 5 years was 85 per cent. Overall increase in the median CD4 count was statistically significant (P<0.001). It was significant in patients with >95 per cent adherence (P<0.001). In 14 per cent patients, the absolute CD4 count did not increase by 100 or more cells/μl at the end of 12 months. Viral load estimation in a subset of 68 patients showed undetectable levels in 61 (89.7%) patients after a median duration of 46 months (IQR: 38.3-54.8). The first line treatment was effective in patients attending the programme clinic. The adherence level influenced immunological and virological outcomes of patients.

Challenges in the concurrent management of malaria and HIV in pregnancy in sub-Saharan Africa.

PubMed

Brentlinger, Paula E; Behrens, Christopher B; Micek, Mark A

2006-02-01

Approximately one million pregnancies are complicated by both malaria and HIV infection in sub-Saharan Africa annually. Both infections have been associated with maternal and infant morbidity and mortality. Intermittent preventive treatment, usually with sulfadoxine-pyrimethamine, has been shown to prevent pregnancy-related malaria and its complications. Several different regimens of antiretroviral therapy are now available to prevent mother-to-child transmission of HIV and/or progression of maternal HIV infection during pregnancy. However, no published studies have yet shown whether standard intermittent preventive treatment and antiretroviral regimens are medically and operationally compatible in pregnancy. We reviewed existing policies regarding prevention and treatment of HIV and malaria in pregnancy, as well as published literature on adverse effects of antiretrovirals and antimalarials commonly used in pregnancy in developing countries, and found that concurrent prescription of sulfadoxine-pyrimethamine, co-trimoxazole (trimethoprim-sulfamethoxazole), and antiretroviral agents including nevirapine and zidovudine per existing protocols for prevention of malaria and vertical HIV transmission may result in adverse drug interactions or overlapping, diagnostically challenging drug toxicities. Insecticide-treated bednets should be provided for HIV-infected pregnant women at risk for malaria. Sulfadoxine-pyrimethamine should be prescribed cautiously in women concurrently receiving daily nevirapine and/or zidovudine, and should be avoided in women on daily co-trimoxazole. Further research is urgently needed to define safe and effective protocols for concurrent management of HIV and malaria in pregnancy, and to define appropriate interventions for different populations subject to differing levels of malaria transmission and antimalarial drug resistance.

Clinician perceptions and patient experiences of antiretroviral treatment integration in primary health care clinics, Tshwane, South Africa.

PubMed

Mathibe, Maphuthego D; Hendricks, Stephen J H; Bergh, Anne-Marie

2015-10-02

Primary Health Care (PHC) clinicians and patients are major role players in the South African antiretroviral treatment programme. Understanding their perceptions and experiences of integrated care and the management of people living with HIV and AIDS in PHC facilities is necessary for successful implementation and sustainability of integration. This study explored clinician perceptions and patient experiences of integration of antiretroviral treatment in PHC clinics. An exploratory, qualitative study was conducted in four city of Tshwane PHC facilities. Two urban and two rural facilities following different models of integration were included. A self-administered questionnaire with open-ended items was completed by 35 clinicians and four focus group interviews were conducted with HIV-positive patients. The data were coded and categories were grouped into sub-themes and themes. Workload, staff development and support for integration affected clinicians' performance and viewpoints. They perceived promotion of privacy, reduced discrimination and increased access to comprehensive care as benefits of service integration. Delays, poor patient care and patient dissatisfaction were viewed as negative aspects of integration. In three facilities patients were satisfied with integration or semi-integration and felt common queues prevented stigma and discrimination, whilst the reverse was true in the facility with separate services. Single-month issuance of antiretroviral drugs and clinic schedule organisation was viewed negatively, as well as poor staff attitudes, poor communication and long waiting times. Although a fully integrated service model is preferable, aspects that need further attention are management support from health authorities for health facilities, improved working conditions and appropriate staff development opportunities.

Twenty-Five Years of Lamivudine: Current and Future Use for the Treatment of HIV-1 Infection.

PubMed

Quercia, Romina; Perno, Carlo-Federico; Koteff, Justin; Moore, Katy; McCoig, Cynthia; St Clair, Marty; Kuritzkes, Daniel

2018-06-01

Innovation in medicine is a dynamic, complex, and continuous process that cannot be isolated to a single moment in time. Anniversaries offer opportunities to commemorate crucial discoveries of modern medicine, such as penicillin (1928), polio vaccination (inactivated, 1955; oral, 1961), the surface antigen of the hepatitis B virus (1967), monoclonal antibodies (1975), and the first HIV antiretroviral drugs (zidovudine, 1987). The advent of antiretroviral drugs has had a profound effect on the progress of the epidemiology of HIV infection, transforming a terminal, irreversible disease that caused a global health crisis into a treatable but chronic disease. This result has been driven by the success of antiretroviral drug combinations that include nucleoside reverse transcriptase inhibitors such as lamivudine. Lamivudine, an L-enantiomeric analog of cytosine, potently affects HIV replication by inhibiting viral reverse transcriptase enzymes at concentrations without toxicity against human polymerases. Although lamivudine was approved more than 2 decades ago, it remains a key component of first-line therapy for HIV because of its virological efficacy and ability to be partnered with other antiretroviral agents in traditional and novel combination therapies. The prominence of lamivudine in HIV therapy is highlighted by its incorporation in recent innovative treatment strategies, such as single-tablet regimens that address challenges associated with regimen complexity and treatment adherence and 2-drug regimens being developed to mitigate cumulative drug exposure and toxicities. This review summarizes how the pharmacologic and virologic properties of lamivudine have solidified its role in contemporary HIV therapy and continue to support its use in emerging therapies.

Racial, gender and geographic disparities of antiretroviral treatment among US Medicaid enrolees in 1998

PubMed Central

King, WD; Minor, P; Ramirez Kitchen, C; Oré, LE; Shoptaw, S; Victorianne, GD; Rust, G

2016-01-01

Background In 1998, highly active antiretroviral therapy (HAART) was widespread, but the diffusion of these lifesaving treatments was not uniform. As half of all AIDS patients in the USA have Medicaid coverage, this study of a multistate Medicaid claims dataset was undertaken to assess disparities in the rates of HAART. Methods Data came from 1998 Medicaid claims files from five states with varying HIV prevalence. ICD-9 codes were used to identify people with a diagnosis of HIV/AIDS or AIDS-defining illness. Multivariate analyses assessed associations between age, gender, race and state of residence for antiretroviral regimens consistent with HAART, as defined by 1998 Centers for Disease Control and Prevention (CDC) guidelines. Results Among 7202 Medicaid enrolees with a diagnosis of HIV/AIDS or AIDS, 62% received HAART and 25% received no antiretroviral therapy. Multivariate analyses showed that age, race, gender and state were all significant predictors of receiving HAART: white, non-Hispanic patients were most likely to receive HAART (68.3%), with lower rates in Hispanic and black, non-Hispanic segments of the population (59.3% and 57.5%, respectively, p<0.001). Women were less likely to receive HAART than men (51.8% vs 69.3%, p<0.001). Conclusion Despite similar insurance coverage and drug benefits, life-saving treatments for HIV/AIDS diffused at widely varying rates in different segments of the Medicaid population. Research is needed to determine the extent to which racial, gender, interstate and region disparities currently correspond to barriers to such care. PMID:18701730

Antiretroviral therapy in children: recent advances.

PubMed

Lodha, Rakesh; Manglani, Mamta

2012-12-01

Availability and successful use of various antiretroviral drugs has transformed HIV/AIDS from an incurable to a treatable chronic condition. The antiretroviral therapy can successfully suppress viral replication and preserve the immune system for many years. The implementation of antiretroviral therapy program in resource limited settings using the 'public health approach' of the World Health Organization has had a dramatic impact on the lives of millions of HIV infected individuals. Antiretroviral therapy (ART) in children has many challenges: use of appropriate formulations, regular need for modification of doses as the child grows, adherence issues, etc. To reduce the high morbidity and mortality in HIV infected children, it is currently recommended that all HIV infected children less than 24 mo should receive ART; in older children the indications are based on clinical and/or immunological criteria. Highly active antiretroviral therapy regimens include at least 3 antiretroviral drugs. The first line therapy recommended for children is a combination of two nucleoside reverse transcriptase inhibitors and a non-nucleoside reverse transcriptase inhibitor. Infants who have had exposure to nevirapine should receive a combination of two nucleoside reverse transcriptase inhibitors and a protease inhibitor; the protease inhibitor of choice is ritonavir boosted lopinavir. The success of therapy is dependent on >95 % adherence. The second line regimen, used when the first line therapy fails, is based on a protease inhibitor. The ongoing research focuses on simplification of regimen, discovery of more potent drugs, availability of more pediatric formulations, treatment of drug resistant strains etc. The optimal indications for initiation of therapy in children, are also being studied.

Risk factors for unplanned and unwanted teenage pregnancies occurring over two years of follow-up among a cohort of young South African women

PubMed Central

Christofides, Nicola J.; Jewkes, Rachel K.; Dunkle, Kristin L.; McCarty, Frances; Shai, Nwabisa Jama; Nduna, Mzikazi; Sterk, Claire

2014-01-01

Background Although teenage pregnancies in South Africa have declined, the short and longer term health and social consequences are a potential public health concern. This longitudinal study aimed to describe the range of risk and protective factors for incident unwanted and unplanned pregnancies occurring over 2 years of follow-up among a cohort of adolescent women in the Eastern Cape, South Africa. It also investigated the relationship between gender inequality and gender-based violence and subsequent unplanned and unwanted pregnancies among the cohort. Objective Teenage girls, aged 15–18 years (n=19), who were volunteer participants in a cluster randomized controlled trial and who had data from at least one follow-up were included in this analysis. To assess risk and protective factors for incident unwanted or unplanned pregnancies, we constructed multivariate polytomous regression models adjusting for sampling clusters as latent variables. Covariates included age, having a pregnancy prior to baseline, education, time between interviews, study intervention arm, contraceptive use, experience of intimate partner violence, belief that the teenage girl and her boyfriend are mutual main partners, and socioeconomic status. Results Overall, 174 pregnancies occurred over the 2-year follow-up period. Beliefs about relationship control were not associated with unwanted and unplanned pregnancies, nor were experiences of forced first sex or coerced sex under the age of 15. Hormonal contraception was protective against unplanned pregnancies (OR 0.40; 95% CI 0.21–0.79); however, using condoms was not protective. Physical abuse (OR 1.69; 95% CI 1.05–2.72) was a risk factor for, and having a pregnancy prior to baseline was protective against an unwanted pregnancy (OR 0.25; 95% CI 0.07–0.80). Higher socioeconomic status was protective for both unplanned and unwanted pregnancies (OR 0.69; 95% CI 0.58–0.83 and OR 0.78; 95% CI 0.64–0.96). Believing that the teenage girl and her boyfriend were mutual main partners doubled the odds of reporting both an unplanned and unwanted pregnancy (OR 2.58 95% CI 1.07–6.25, and OR 2.21 95% CI 1.13–4.29). Conclusion Although some of the measures of gender inequity were not associated with unplanned and unwanted pregnancies, there is evidence of the role of both gender power and socioeconomic status. This was evident in teenage girls who experienced physical violence being more likely to have an unwanted pregnancy. Interventions to prevent teenage pregnancies need to be tailored by socioeconomic status because some teenagers may see having a pregnancy as a way to have a more secure future. Interventions that engage with relationship dynamics of teenagers are essential if unwanted and unplanned pregnancies are to be prevented. PMID:25150027

Dual treatment with atazanavir-ritonavir plus lamivudine versus triple treatment with atazanavir-ritonavir plus two nucleos(t)ides in virologically stable patients with HIV-1 (SALT): 48 week results from a randomised, open-label, non-inferiority trial.

PubMed

Perez-Molina, José A; Rubio, Rafael; Rivero, Antonio; Pasquau, Juan; Suárez-Lozano, Ignacio; Riera, Melcior; Estébanez, Miriam; Santos, Jesús; Sanz-Moreno, José; Troya, Jesús; Mariño, Ana; Antela, Antonio; Navarro, Jordi; Navarro, José; Esteban, Herminia; Moreno, Santiago

2015-07-01

Problems associated with lifelong antiretroviral therapy, such as need for strict adherence, drug-related toxic effects, difficulties with treatment schedules, and cost, mean that simplification strategies should be sought. We aimed to explore the efficacy and safety of dual treatment with atazanavir-ritonavir plus lamivudine as an option to switch to from standard combination antiretroviral therapy in patients with an HIV-1 infection who are virologically suppressed. In this randomised, open-label, non-inferiority trial, we recruited patients aged 18 years and older with chronic HIV-1 infection and no previous treatment failure or resistance, and with HIV-1 RNA of less than 50 copies per mL for at least 6 months, negative hepatitis B virus surface antigen, and good general health, from 30 hospitals in Spain. Exclusion criteria were switch in antiretroviral therapy during the previous 4 months, previous virological failure, pregnancy or breastfeeding, Gilbert's syndrome, use of contraindicated drugs, grade 4 laboratory abnormalities, and previous intolerance to any of the study drugs. We randomly assigned patients (1:1; stratified by active hepatitis C virus infection and previous treatment; computer-generated random number sequence) to dual treatment with oral atazanavir (300 mg once daily) and ritonavir (100 mg once daily) plus lamivudine (300 mg once daily) or triple treatment with oral atazanavir (300 mg once daily) and ritonavir (100 mg once daily) plus two nucleos(t)ide reverse transcriptase inhibitors at the discretion of the investigators. The primary endpoint was virological response, defined as HIV-1 RNA of less than 50 copies per mL at week 48, in the per-protocol population, with a non-inferiority margin of 12%. We included patients who received at least one dose of the study drug in the safety analysis. This study is registered at ClinicalTrials.gov, number NCT01307488. Between Sept 29, 2011, and May 2, 2013, we randomly assigned 286 patients (143 [50%] to each group). At week 48 in the per-protocol population, 112 (84%) of 133 patients had virological response in the dual-treatment group versus 105 (78%) of 135 in the triple-treatment group (difference 6% [95% CI -5 to 16%), showing non-inferiority at the prespecified level. 14 (5%) patients developed severe adverse events (dual treatment six [4%]; triple treatment eight [6%]), none of which we deemed related to the study drug. Grade 3-4 adverse events were similar between groups (dual treatment 77 [55%] of 140; triple treatment 78 [55%] of 141). Treatment discontinuations were less frequent in the dual-treatment group (three [2%]) than in the triple-treatment group (ten [7%]; p=0·047). In our trial, dual treatment was effective, safe, and non-inferior to triple treatment in patients with an HIV-1 infection who are virologically suppressed who switch antiretroviral therapy because of toxic effects, intolerance, or simplification. This combination has the potential to suppress some of the long-term toxic effects associated with nucleos(t)ide reverse transcriptase inhibitors, preserve future treatment options, and reduce the cost of antiretroviral therapy. Bristol Myers-Squibb and Fundación SEIMC-GESIDA. Copyright © 2015 Elsevier Ltd. All rights reserved.

Adverse effects of antiretroviral therapy for HIV infection.

PubMed

Montessori, Valentina; Press, Natasha; Harris, Marianne; Akagi, Linda; Montaner, Julio S G

2004-01-20

Long-term remission of HIV-1 disease can be readily achieved by combinations of antiretroviral agents. The suppression of plasma viral loads to less than the limit of quantification of the most sensitive commercially available assays (i.e., less than 50 copies/mL) and the coincident improvement in CD4 T cell counts is associated with resolution of established opportunistic infections and a decrease in the risk of new opportunistic infections. However, prolonged treatment with combination regimens can be difficult to sustain because of problems with adherence and toxic effects. All antiretroviral drugs can have both short-term and long-term adverse events. The risk of specific side effects varies from drug to drug, from drug class to drug class, and from patient to patient. A better understanding of the adverse effects of antiretroviral agents is of interest not only for HIV specialists as they try to optimize therapy, but also for other physicians who care for HIV-positive patients.

Adverse effects of antiretroviral therapy for HIV infection

PubMed Central

Montessori, Valentina; Press, Natasha; Harris, Marianne; Akagi, Linda; Montaner, Julio S.G.

2004-01-01

LONG-TERM REMISSION OF HIV-1 DISEASE CAN BE READILY ACHIEVED by combinations of antiretroviral agents. The suppression of plasma viral loads to less than the limit of quantification of the most sensitive commercially available assays (i.e., less than 50 copies/mL) and the coincident improvement in CD4 T cell counts is associated with resolution of established opportunistic infections and a decrease in the risk of new opportunistic infections. However, prolonged treatment with combination regimens can be difficult to sustain because of problems with adherence and toxic effects. All antiretroviral drugs can have both short-term and long-term adverse events. The risk of specific side effects varies from drug to drug, from drug class to drug class, and from patient to patient. A better understanding of the adverse effects of antiretroviral agents is of interest not only for HIV specialists as they try to optimize therapy, but also for other physicians who care for HIV-positive patients. PMID:14734438

Treatment of HIV in the CNS: effects of antiretroviral therapy and the promise of non-antiretroviral therapeutics.

PubMed

Peluso, Michael J; Spudich, Serena

2014-09-01

The growing recognition of the burden of neurologic disease associated with HIV infection in the last decade has led to renewed efforts to characterize the pathophysiology of the virus within the central nervous system (CNS). The concept of the AIDS-dementia complex is now better understood as a spectrum of HIV-associated neurocognitive disorders (HAND), which range from asymptomatic disease to severe impairment. Recent work has shown that even optimally treated patients can experience not only persistent HAND, but also the development of new neurologic abnormalities despite viral suppression. This has thrown into question what the impact of antiretroviral therapy has been on the incidence and prevalence of neurocognitive dysfunction. In this context, the last few years have seen a concentrated effort to identify the effects that antiretroviral therapy has on the neurologic manifestations of HIV and to develop therapeutic modalities that might specifically alter the trajectory of HIV within the CNS.

Barriers to and facilitators of HIV-positive patients' adherence to antiretroviral treatment regimens.

PubMed

Roberts, K J

2000-03-01

HIV-positive patients must strictly adhere to antiretroviral regimens for the medications to work properly. Little, however, is known about the obstacles that patients face in adhering to the regimens or what, if anything, helps patients to adhere. The goals of the project were to describe, from HIV-positive patients' own perspectives, the barriers they face in adhering to antiretroviral regimens and the strategies they use to maximize their adherence. Five main barriers (forgetfulness, social/physical environment, complexity of the regimens, medication side effects, and inadequate patient knowledge) to adherence and six main facilitators (mechanical devices, "making a commitment," "routinizing," health beliefs, social support, and professional support) emerged from the data. Patients may overcome some of these barriers by receiving better health education about the need for adherence, professional and lay support for their efforts, and mechanical devices such as alarm clocks and medi-sets. Other barriers, however, such as the complexity of the medications, highlight the need for simplified antiretroviral regimens.

An outcome study of a 2-flap pushback palatoplasty used in the treatment of wide cleft palates.

PubMed

Lin, Kant Y; Black, Jonathan S; Wang, Jessica S; Kerpelman, Jocelyn; Ho, Thuy-Van Tina; Borowitz, Kathleen

2015-05-01

Cleft palate remains a common congenital deformity. The wide cleft palate in particular presents a unique challenge when attempting to restore a competent velopharyngeal mechanism. We present an outcome study of a single surgeon's experience using a modified surgical technique designed to specifically address the wide cleft palate. The surgical technique consisted of a 2-flap pushback palatoplasty without nasal mucosa closure combined with an end-to-end intravelar veloplasty and was used in cleft palates greater than or equal to 10 mm in width. A retrospective, longitudinal outcome study from chart review was then performed where age at surgery, sex, Veau classification of the cleft type, and follow-up length were recorded for each patient. Postsurgery speech outcomes were assessed by standardized speech evaluation performed by a speech language pathologist, and the presence and location of unplanned oronasal fistulas were recorded. Our study revealed an overall incidence of velopharyngeal insufficiency (VPI) of 10.8% and an unplanned symptomatic fistula rate of 16.8%. There was a significant correlation between the Veau classification of the cleft type with the incidence of both VPI and the occurrence of an unplanned oronasal fistula. Application of this surgical technique, specifically to wider cleft palates, resulted in VPI and fistula rates comparable to rates reported with other techniques used in clefts of all widths. Additional information regarding subsequent growth disturbances of the craniofacial skeleton in these patients is currently being collected.

Assessing treatment motivation among patients receiving antiretroviral therapy: A multidimensional approach

PubMed Central

Houston, Eric; McKirnan, David J.; Cervone, Daniel; Johnson, Matthew S.; Sandfort, Theo G.M.

2011-01-01

Using multidimensional scaling analysis (MDS), this study examined how patient conceptualisations of treatment motivation compare with theoretically-based assumptions used in current assessment approaches. Patients undergoing antiretroviral therapy for HIV/AIDS (n = 39) rated for similarity all possible pairings of 23 treatment descriptions, including descriptors of intrinsic, extrinsic, approach, and avoidance motivation. MDS analyses revealed that patient perceptions of intrinsic and extrinsic motivation often differ from those based on definitions derived from common interpretations of self-determination theory. Findings also showed that patients reported motivation for avoiding treatment when they associated their medication regimens with side effects and other negatively-valenced outcomes. The study describes new applications of MDS in assessing how patients perceive the relationship between treatment behaviours and specific forms of motivation, such as intrinsic and extrinsic motivation. In addition, the study suggests how MDS may be used to develop behavioural strategies aimed at helping patients follow their regimens consistently by identifying treatment conceptualisations and contexts that facilitate or impede adherence. PMID:21942538

Assessing treatment motivation among patients receiving antiretroviral therapy: a multidimensional approach.

PubMed

Houston, Eric; McKirnan, David J; Cervone, Daniel; Johnson, Matthew S; Sandfort, Theo G M

2012-01-01

Using multidimensional scaling (MDS) analysis, this study examined how patient conceptualisations of treatment motivation compare with theoretically based assumptions used in current assessment approaches. Patients undergoing antiretroviral therapy for HIV/AIDS (n=39) rated for similarity between all possible pairings of 23 treatment descriptions, including descriptors of intrinsic, extrinsic, approach and avoidance motivation. MDS analyses revealed that patient perceptions of intrinsic and extrinsic motivations often differ from those based on definitions derived from common interpretations of self-determination theory. Findings also showed that patients reported motivation for avoiding treatment when they associated their medication regimens with side effects and other negatively valenced outcomes. The study describes new applications of MDS in assessing how patients perceive the relationship between treatment behaviours and specific forms of motivation, such as intrinsic and extrinsic motivations. In addition, the study suggests how MDS may be used to develop behavioural strategies aimed at helping patients follow their regimens consistently by identifying treatment conceptualisations and contexts that facilitate or impede adherence.

CMV infection in a cohort of HIV-exposed infants born to mothers receiving antiretroviral therapy during pregnancy and breastfeeding.

PubMed

Pirillo, Maria Franca; Liotta, Giuseppe; Andreotti, Mauro; Jere, Haswel; Sagno, Jean-Baptiste; Scarcella, Paola; Mancinelli, Sandro; Buonomo, Ersilia; Amici, Roberta; Marazzi, Maria Cristina; Vella, Stefano; Palombi, Leonardo; Giuliano, Marina

2017-02-01

Antiretroviral therapy has been shown to reduce rates of congenital CMV infection. Little information is available on the possible impact of antiretroviral therapy on postnatal breastfeeding-associated CMV infection acquisition. A cohort of 89 HIV-infected mothers and their children was studied. Women received antiretroviral therapy from week 25 of gestation until 6 months postpartum or indefinitely if meeting the criteria for treatment. All women were evaluated for CMV IgG presence and CMV DNA in breast milk. Children were tested for CMV infection by either the presence of IgM or the presence of CMV DNA in plasma at 1, 6 and 12 months and by the presence of IgG at 24 months. All mothers had high titers of CMV DNA in breast milk (5.7 log at Month 1 and 5.1 log at Month 6). Cumulative CMV infection rates were 60.3 % at Month 6, 69 % at Month 12 and 96.4 % at Month 24. There was a significant negative correlation between the duration of antiretroviral treatment during pregnancy and levels of CMV DNA in breast milk at Month 1 (P = 0.033). There was a trend for a correlation between high titers of CMV DNA in breast milk at 6 months and CMV infection at 6 months (P = 0.069). In this cohort, more than 95 % of the children had acquired CMV infection by 2 years of age. Besides breastfeeding, which played a major role, also horizontal transmission between 1 and 2 years was certainly relevant in determining CMV infection acquisition.

HIV Drug Resistance Testing in a Resource Limited Setting with High Viral Diversity: The First Twenty Eight Months Experience.

PubMed

Ngo-Malabo, Elodie Teclaire; Ngoupo, Paul Alain; Sadeuh-Mba, Serge Alain; Akongnwi, Emmanuel; Banaï, Robert; Ngono, Laure; Bilong-Bilong, Charles Felix; Kfutwah, Anfumbom; Njouom, Richard

2017-01-01

First line antiretroviral therapy in a resource-limited setting consists of nucleotide and non-nucleotide reverse transcriptase inhibitors. Protease inhibitors are the hub of second line therapy. The decision to change antiretroviral therapy for a patient is frequently presumptive because of the lack of genotypic resistance tests in routine follow-up. We describe here the resistance profiles observed in patients with varying terms of antiretroviral therapy in Cameroon after implementation of HIV genotypic resistance testing in routine practice. HIV genotypic resistance testing was carried out on consecutive samples received between August 2013 and November 2015. Protease (Prot) and reverse transcriptase (Rt) genes of the HIV genome were amplified, sequenced and analyzed for drug resistance mutations following the algorithm set up by the French National Agency for research on HIV/AIDS and viral hepatitis. Specimens from a total of 167 patients infected with non-B HIV subtypes were received during the study period. Overall 61.7% patients had viral loads of more than 3log copies/ml, suggesting treatment failure. Among the 72 patients on first line, 56 (77.8%) were resistant to Lamivudine, 57 (79.1%) to Efavirenz and 58 (80.6%) to Nevirapine. Overall, more patients (75.0%) on first line antiretroviral therapy harbored multi-drug resistance compared to their counterparts on second line (25.8%). This study revealed that a group of patients with antiretroviral therapy failure harbored multi-drug resistance mutations related to the majority of drugs in the first line regimen. Therefore, HIV resistance testing could be a useful tool to improve HIV care in resource limited settings like Cameroon where treatment options are limited. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

[Use of darunavir in HIV-infected women during pregnancy].

PubMed

Afonina, L Iu; Voronin, E E

2013-01-01

The use of antiretroviral drugs (ARVDs) in a mother and a child can reduce the risk of vertical transmission of human immunodeficiency virus (HIV) to less than 1%; therefore, highly active antiretroviral therapy is used in all pregnant women regardless of indications for HIV-infection treatment. The major requirements for choosing an ARVD to prevent mother-to-child HIV transmission are its high safety for a pregnant woman, a fetus, and a baby and its high therapeutic efficacy. Clinical trials of darunavir (DRV) in adults and children have shown a high virologic response, good tolerance, and safety. Trials and observations have demonstrated the high efficacy and safety of a DRV when used in pregnant women. Pharmacokinetic studies in pregnant women have indicated the effective and well-tolerated concentration of a DRV when it is co-administered with low-dose ritonavir, which permits the use of a DRV for both the prevention of mother-to-child HIV transmission and the treatment of pregnant women who require antiretroviral therapy. The Russian clinical protocol "Use of ARVDs in the package of measures for the prevention of mother-to-child HIV transmission" approved by the National Scientific Society of Infectiologists in 2013 recommends DRV as an alternative drug in antiretroviral therapy regimens for pregnant women to prevent mother-to-child HIV transmission and to treat maternal HIV infection.

Measuring pregnancy planning: A psychometric evaluation and comparison of two scales.

PubMed

Drevin, Jennifer; Kristiansson, Per; Stern, Jenny; Rosenblad, Andreas

2017-11-01

To psychometrically test the London Measure of Unplanned Pregnancy and compare it with the Swedish Pregnancy Planning Scale. The incidence of unplanned pregnancies is an important indicator of reproductive health. The London Measure of Unplanned Pregnancy measures pregnancy planning by taking contraceptive use, timing, intention to become pregnant, desire for pregnancy, partner agreement, and pre-conceptual preparations into account. It has, however, previously not been psychometrically evaluated using confirmatory factor analysis. The Likert-scored single-item Swedish Pregnancy Planning Scale has been developed to measure the woman's own view of pregnancy planning level. Cross-sectional design. In 2012-2013, 5493 pregnant women living in Sweden were invited to participate in the Swedish Pregnancy Planning study, of whom 3327 (61%) agreed to participate and answered a questionnaire. A test-retest pilot study was conducted in 2011-2012. Thirty-two participants responded to the questionnaire on two occasions 14 days apart. Data were analysed using confirmatory factor analysis, Cohen's weighted kappa and Spearman's correlation. All items of the London Measure of Unplanned Pregnancy contributed to measuring pregnancy planning, but four items had low item-reliability. The London Measure of Unplanned Pregnancy and Swedish Pregnancy Planning Scale corresponded reasonably well with each other and both showed good test-retest reliability. The London Measure of Unplanned Pregnancy may benefit from item reduction and its usefulness may be questioned. The Swedish Pregnancy Planning Scale is time-efficient and shows acceptable reliability and construct validity, which makes it more useful for measuring pregnancy planning. © 2017 John Wiley & Sons Ltd.

Assessing Impacts on Unplanned Hospitalisations of Care Quality and Access Using a Structural Equation Method: With a Case Study of Diabetes

PubMed Central

Congdon, Peter

2016-01-01

Background: Enhanced quality of care and improved access are central to effective primary care management of long term conditions. However, research evidence is inconclusive in establishing a link between quality of primary care, or access, and adverse outcomes, such as unplanned hospitalisation. Methods: This paper proposes a structural equation model for quality and access as latent variables affecting adverse outcomes, such as unplanned hospitalisations. In a case study application, quality of care (QOC) is defined in relation to diabetes, and the aim is to assess impacts of care quality and access on unplanned hospital admissions for diabetes, while allowing also for socio-economic deprivation, diabetes morbidity, and supply effects. The study involves 90 general practitioner (GP) practices in two London Clinical Commissioning Groups, using clinical quality of care indicators, and patient survey data on perceived access. Results: As a single predictor, quality of care has a significant negative impact on emergency admissions, and this significant effect remains when socio-economic deprivation and morbidity are allowed. In a full structural equation model including access, the probability that QOC negatively impacts on unplanned admissions exceeds 0.9. Furthermore, poor access is linked to deprivation, diminished QOC, and larger list sizes. Conclusions: Using a Bayesian inference methodology, the evidence from the analysis is weighted towards negative impacts of higher primary care quality and improved access on unplanned admissions. The methodology of the paper is potentially applicable to other long term conditions, and relevant when care quality and access cannot be measured directly and are better regarded as latent variables. PMID:27598184

Assessing Impacts on Unplanned Hospitalisations of Care Quality and Access Using a Structural Equation Method: With a Case Study of Diabetes.

PubMed

Congdon, Peter

2016-09-01

Enhanced quality of care and improved access are central to effective primary care management of long term conditions. However, research evidence is inconclusive in establishing a link between quality of primary care, or access, and adverse outcomes, such as unplanned hospitalisation. This paper proposes a structural equation model for quality and access as latent variables affecting adverse outcomes, such as unplanned hospitalisations. In a case study application, quality of care (QOC) is defined in relation to diabetes, and the aim is to assess impacts of care quality and access on unplanned hospital admissions for diabetes, while allowing also for socio-economic deprivation, diabetes morbidity, and supply effects. The study involves 90 general practitioner (GP) practices in two London Clinical Commissioning Groups, using clinical quality of care indicators, and patient survey data on perceived access. As a single predictor, quality of care has a significant negative impact on emergency admissions, and this significant effect remains when socio-economic deprivation and morbidity are allowed. In a full structural equation model including access, the probability that QOC negatively impacts on unplanned admissions exceeds 0.9. Furthermore, poor access is linked to deprivation, diminished QOC, and larger list sizes. Using a Bayesian inference methodology, the evidence from the analysis is weighted towards negative impacts of higher primary care quality and improved access on unplanned admissions. The methodology of the paper is potentially applicable to other long term conditions, and relevant when care quality and access cannot be measured directly and are better regarded as latent variables.

Unplanned extubations in an intensive care unit: Findings from a critical incident technique.

PubMed

Danielis, Matteo; Chiaruttini, Simona; Palese, Alvisa

2018-05-15

Patients on mechanical ventilation are at risk of experiencing a potentially life-threatening unplanned extubation in the intensive care unit, which can lead to arrhythmias, bronchial aspiration, difficulty in reintubation or even sudden cardiac arrest. Although incidence and outcomes of the phenomenon have been documented in several quantitative studies, no studies have investigated the antecedents as experienced by critical care nurses. To gain a greater understanding of the antecedents of unplanned extubations. A qualitative study design involving the critical-incident technique. A total of 10 registered nurses who reported one or more episodes of unplanned extubations were involved in an in-depth interview. According to the nurses' experience, episodes of unplanned extubations are determined by predisposing, precipitating and mediating factors. The predisposing factors have been recognised in the (a) weaning programme (expected/unexpected decreased sedation) and in the (b) patient factors (increased needs due to discomfort, restlessness and desire to communicate). The precipitating factors have been divided into (a) organisational (failures in multi-professional communication), (b) environmental (excessive environmental chaos and barriers preventing direct surveillance) and (c) nursing care factors (ensuring privacy by creating barriers, avoiding disturbing other patients and poor nurse-to-patient ratio). Among the mediating factors, which are affected by the precipitating factors, decreased surveillance and mechanical restraints' use have been identified. Identifying risk factors of unplanned extubation, specifically those that are modifiable, such as increasing interprofessional communication, reducing excessive environment chaos, implementing strategies aimed at overcoming barriers threatening direct surveillance and ensuring appropriate nurse-to-patient ratio, can prevent the occurrence of these events. Copyright © 2018 Elsevier Ltd. All rights reserved.

Rationale and uses of a public HIV drug-resistance database.

PubMed

Shafer, Robert W

2006-09-15

Knowledge regarding the drug resistance of human immunodeficiency virus (HIV) is critical for surveillance of drug resistance, development of antiretroviral drugs, and management of infections with drug-resistant viruses. Such knowledge is derived from studies that correlate genetic variation in the targets of therapy with the antiretroviral treatments received by persons from whom the variant was obtained (genotype-treatment), with drug-susceptibility data on genetic variants (genotype-phenotype), and with virological and clinical response to a new treatment regimen (genotype-outcome). An HIV drug-resistance database is required to represent, store, and analyze the diverse forms of data underlying our knowledge of drug resistance and to make these data available to the broad community of researchers studying drug resistance in HIV and clinicians using HIV drug-resistance tests. Such genotype-treatment, genotype-phenotype, and genotype-outcome correlations are contained in the Stanford HIV RT and Protease Sequence Database and have specific usefulness.

Lack of specificity for the analysis of raltegravir using online sample clean-up liquid chromatography-electrospray tandem mass spectrometry.

PubMed

Jourdil, Jean François; Bartoli, Mireille; Stanke-Labesque, Françoise

2009-11-01

Raltegravir is the first antiretroviral agent to target the human immunodeficiency virus-1 (HIV-1) integrase. It is indicated, in association with other antiretrovirals, in the treatment of acquired immunodeficiency syndrome (AIDS) in antiretroviral treatment-experienced adult patients with viral resistance. To evaluate the feasibility of raltegravir therapeutic drug monitoring, we developed a rapid and specific analytical method for the quantification of raltegravir in human plasma by online sample clean-up liquid chromatography-tandem mass spectrometry (LC-MS/MS). After protein precipitation (with 100 microL of acetonitrile/methanol (50/50)) of 25 microL of plasma, fast online matrix-clean-up was performed using a column switching program. The chromatographic step was optimized to separate raltegravir and its glucuronide metabolite (G-raltegravir). Multiple reaction monitoring (MRM) was used for detection of raltegravir and G-raltegravir. In the absence of G-raltegravir standard, G-raltegravir identification was confirmed by beta-glucuronidase pre-treatment. A total analysis of 3.8 min was needed to separate raltegravir to G-raltegravir. The method was linear between 10 and 3000 ng/mL for raltegravir. Analytical recovery was 94+/-1%. Variation coefficients ranged between 5% and 8.4%. Pre-treatment of plasma from a patient under raltegravir treatment with beta-glucuronidase suppressed G-raltegravir peak. We describe a fast online LC-MS/MS assay that is valid and reliable for the quantification of raltegravir, despite the lack of specificity that could occur in MRM scanning mode experiments.

Impact of medical and nonmedical factors on physician decision making for HIV/AIDS antiretroviral treatment.

PubMed

Bogart, L M; Kelly, J A; Catz, S L; Sosman, J M

2000-04-15

To examine influences of medical factors (e.g., viral load) and nonmedical factors (e.g., patient characteristics) on treatment decisions for highly active antiretroviral therapy (HAART), we sent a survey to a random sample of 995 infectious disease physicians who treat patients with HIV/AIDS in the United States in August, 1998. The response rate was 53%. Respondents were asked to report their current practices with respect to antiretroviral treatment and the extent to which each of three medical and 17 nonmedical factors would influence them for or against prescribing HAART to a hypothetical HIV-positive patient. Most reported initiating HAART with findings of low CD4+ cell counts and high viral loads, and weighing CD4+ cell counts, viral load, and opportunistic infection heavily in their decisions to prescribe HAART. Patients' prior history of poor adherence was weighed very much against initiating HAART. Patient homelessness, heavy alcohol use, injection drug use, and prior psychiatric hospitalization were cited by most physicians as weighing against HAART initiation. Thus, most physicians in this sample follow guidelines for the use of HAART, and nonmedical factors related to patients' life situations are weighed as heavily as disease severity in treatment decisions. As HIV increasingly becomes a disease associated with economic disadvantage and other social health problems, it will be essential to develop interventions and care support systems to enable patients experiencing these problems to benefit from HIV treatment advances.

Treatment adherence and subjective well-being in HIV/AIDS infection.

PubMed

Reis, Ana Catarina Rodrigues da Silva; Guerra, Marina Natália Prista; Lencastre, Leonor Mendes de Freitas Queirós E

2013-01-01

The aim of this study was to analyze the relationship between treatment adherence and subjective well-being (positive and negative affects and satisfaction with life) in HIV/AIDS infection. The empirical study was conducted at two Portuguese hospitals (Porto and Lisbon) with a sample of 197 outpatients diagnosed with HIV/AIDS attending the Infectology service and on antiretroviral medication, during a 6-month period (February-July 2009). All patients were asked for voluntary fulfillment of the questionnaire which recorded information on different socio-demographic variables. Clinical records were inspected in order to collect additional clinical information from the patients. The "Questionnaire to Assess Adherence to Antiretroviral Treatment-HIV" was used in order to assess the adherence degree in Portuguese version of Reis et al. The Portuguese versions of "Positive and Negative Affect Schedule" (PANAS) and the "Satisfaction with Life Scale" were used to measure subjective well-being. The study collected evidence on the positive correlation between therapeutic adherence (assessed by CEAT-VIH) and positive affect, as well as between adherence and satisfaction with life. Differences in therapeutic adherence and positive affect according to some clinical variables were also found. The multiplicity and the interaction of several determinants are being considered in the adjustment process during treatment for HIV/AIDS. The results may have implications for the psychological intervention directed at improving adherence to antiretroviral therapy.

North-South Corridor Demonstration Project: Ethical and Logistical Challenges in the Design of a Demonstration Study of Early Antiretroviral Treatment for Long Distance Truck Drivers along a Transport Corridor through South Africa, Zimbabwe, and Zambia

PubMed Central

Gomez, G. B.; Venter, W. D. F.; Lange, J. M. A.; Rees, H.; Hankins, C.

2013-01-01

Background. Long-distance truck drivers are at risk of acquiring and transmitting HIV and have suboptimal access to care. New HIV prevention strategies using antiretroviral drugs to reduce transmission risk (early antiretroviral therapy (ART) at CD4 count >350 cells/μL) have shown efficacy in clinical trials. Demonstration projects are needed to evaluate “real world” programme effectiveness. We present the protocol for a demonstration study to evaluate the feasibility, acceptability, and cost of an early ART intervention for HIV-positive truck drivers along a transport corridor across South Africa, Zimbabwe, and Zambia, as part of an enhanced strategy to improve treatment adherence and retention in care. Methods and Analysis. This demonstration study would follow an observational cohort of truck drivers receiving early treatment. Our mixed methods approach includes quantitative, qualitative, and economic analyses. Key ethical and logistical issues are discussed (i.e., choice of drug regimen, recruitment of participants, and monitoring of adherence, behavioural changes, and adverse events). Conclusion. Questions specific to the design of tailored early ART programmes are amenable to operational research approaches but present substantial ethical and logistical challenges. Addressing these in demonstration projects can inform policy decisions regarding strategies to reduce health inequalities in access to HIV prevention and treatment programmes. PMID:23606977

Plasma Metabolomics Biosignature According to HIV Stage of Infection, Pace of Disease Progression, Viremia Level and Immunological Response to Treatment.

PubMed

Scarpellini, Bruno; Zanoni, Michelle; Sucupira, Maria Cecilia Araripe; Truong, Hong-Ha M; Janini, Luiz Mario Ramos; Segurado, Ismael Dale Cotrin; Diaz, Ricardo Sobhie

2016-01-01

We evaluated plasma samples HIV-infected individuals with different phenotypic profile among five HIV-infected elite controllers and five rapid progressors after recent HIV infection and one year later and from 10 individuals subjected to antiretroviral therapy, five of whom were immunological non-responders (INR), before and after one year of antiretroviral treatment compared to 175 samples from HIV-negative patients. A targeted quantitative tandem mass spectrometry metabolomics approach was used in order to determine plasma metabolomics biosignature that may relate to HIV infection, pace of HIV disease progression, and immunological response to treatment. Twenty-five unique metabolites were identified, including five metabolites that could distinguish rapid progressors and INRs at baseline. Severe deregulation in acylcarnitine and sphingomyelin metabolism compatible with mitochondrial deficiencies was observed. β-oxidation and sphingosine-1-phosphate-phosphatase-1 activity were down-regulated, whereas acyl-alkyl-containing phosphatidylcholines and alkylglyceronephosphate synthase levels were elevated in INRs. Evidence that elite controllers harbor an inborn error of metabolism (late-onset multiple acyl-coenzyme A dehydrogenase deficiency [MADD]) was detected. Blood-based markers from metabolomics show a very high accuracy of discriminating HIV infection between varieties of controls and have the ability to predict rapid disease progression or poor antiretroviral immunological response. These metabolites can be used as biomarkers of HIV natural evolution or treatment response and provide insight into the mechanisms of the disease.

Linking HIV and antiretroviral drug resistance surveillance in Peru: a model for a third-generation HIV sentinel surveillance.

PubMed

Lama, Javier R; Sanchez, Jorge; Suarez, Luis; Caballero, Patricia; Laguna, Alberto; Sanchez, Jose L; Whittington, William L H; Celum, Connie; Grant, Robert M

2006-08-01

HIV drug resistance surveillance is limited by recruitment and selection bias and by limited information regarding HIV incidence rates, secondary resistance, and treatment prevalence. A second-generation HIV sentinel surveillance among men who have sex with men (MSM), regardless of prior history of HIV screening, serostatus, or treatment, was conducted in Peru in 2002. Recent HIV infection was estimated using sensitive/less sensitive enzyme immunoassay testing. Genotypic resistance testing was performed. HIV prevalence was 13.9% (456 HIV positive of 3280 participants). HIV incidence was estimated to be 5.1 per 100 person-years (95% confidence interval: 3.1-8.3). Among 143 MSM who were aware of their HIV infection before testing, only 20 (14.0%) were receiving antiretrovirals (ARV). Mutations conferring ARV resistance were found in 12 (3.3%) of 359 treatment-naive and 5 (31.3%) of 16 treatment-experienced participants with successful genotyping. One recently infected man from Lima demonstrated 3-class multidrug resistance. The most frequently observed mutations in treatment-naive, chronically infected persons from Lima were M184V (1.7%), D30N (1.3%), L90M (1.3%), and L10I (1.3%). The prevalence of ARV resistance among treatment-naive MSM in Peru is low, reflecting limited access to treatment before 2004, and contrasts with the history of ARV treatment in developed countries, where high levels of nucleoside reverse transcriptase inhibitor resistance occurred before introduction of highly active antiretroviral therapy. Linking ARV resistance and HIV sentinel surveillance in developing settings is feasible and should be considered in third-generation HIV sentinel surveillance programs.

Cytomegalovirus Retinitis: A Review.

PubMed

Port, Alexander D; Orlin, Anton; Kiss, Szilard; Patel, Sarju; D'Amico, Donald J; Gupta, Mrinali P

2017-05-01

Cytomegalovirus (CMV) is a ubiquitous DNA herpes virus that causes significant morbidity and mortality in immunocompromised individuals. CMV retinitis is a potentially blinding manifestation of CMV infection that was commonly seen in advanced acquired immunodeficiency syndrome (AIDS) in the era before modern combination antiretroviral therapy era, but is also recognized in patients with immune deficiency from multiple causes. The advent of and advances in antiretroviral therapies for human immunodeficiency virus have decreased the incidence of CMV retinitis by over 90% among AIDS patients, and improved visual outcomes in those affected. The diagnosis is generally a clinical one, and treatment modalities include systemic and intravitreal antiviral medications. Retinal detachment and immune recovery uveitis are sight-threatening complications of CMV retinitis that require specific treatments.

Pharmacokinetic Evaluation of Oral Levofloxacin in Human Immunodeficiency Virus-Infected Subjects Receiving Concomitant Antiretroviral Therapy

PubMed Central

Villani, P.; Viale, P.; Signorini, L.; Cadeo, B.; Marchetti, F.; Villani, A.; Fiocchi, C.; Regazzi, M. B.; Carosi, G.

2001-01-01

The purpose of this study was to evaluate the pharmacokinetics (PK) profile of oral levofloxacin in human immunodeficiency virus-positive patients in steady-state treatment with nelfinavir (NFV) or with efavirenz (EFV) and to determine the effects of levofloxacin on the PK parameters of these two antiretroviral agents. For levofloxacin, plasma samples were obtained at steady state during a 24-h dosing interval. Plasma NFV and EFV concentrations were evaluated before and after 4 days of levofloxacin treatment. Levofloxacin PK do not seem affected by NFV and EFV. There was no significant difference between NFV and EFV plasma levels obtained with and without levofloxacin. PMID:11408245

Declining prevalence of HIV-1 drug resistance in antiretroviral treatment-exposed individuals in Western Europe.

PubMed

De Luca, Andrea; Dunn, David; Zazzi, Maurizio; Camacho, Ricardo; Torti, Carlo; Fanti, Iuri; Kaiser, Rolf; Sönnerborg, Anders; Codoñer, Francisco M; Van Laethem, Kristel; Vandamme, Anne-Mieke; Bansi, Loveleen; Ghisetti, Valeria; van de Vijver, David A M C; Asboe, David; Prosperi, Mattia C F; Di Giambenedetto, Simona

2013-04-15

HIV-1 drug resistance represents a major obstacle to infection and disease control. This retrospective study analyzes trends and determinants of resistance in antiretroviral treatment (ART)-exposed individuals across 7 countries in Europe. Of 20 323 cases, 80% carried at least one resistance mutation: these declined from 81% in 1997 to 71% in 2008. Predicted extensive 3-class resistance was rare (3.2% considering the cumulative genotype) and peaked at 4.5% in 2005, decreasing thereafter. The proportion of cases exhausting available drug options dropped from 32% in 2000 to 1% in 2008. Reduced risk of resistance over calendar years was confirmed by multivariable analysis.

[Policy dilemmas in providing antiretroviral treatment in Brazil].

PubMed

do Lago, Regina Ferro; Costa, Nilson do Rosário

2010-11-01

This paper addresses institutional constraints that have affected Brazilian politics regarding provision of anti-retroviral treatment (ART) to HIV/Aids patients. We analyzed the normative conflict resulting from international agreements on intellectual property rights, especially patent protection, and the constitutional rights of Brazilian patients to universal and free access to ART. These constraints have not substantially changed the Brazilian public policy yet, but they may impact the future sustainability of this policy. As the main barrier to the production of patented drugs is not technological but institutional, Brazilian government faces a dilemma. It may either abide by existing monopolistic restrictions or it may incite competitiveness of domestic industries and developing countries in the pharmaceutical market.

Pharmacologic management of types 1 and 2 diabetes mellitus and their complications in women of childbearing age.

PubMed

Mukherjee, Mimi S; Coppenrath, Valerie A; Dallinga, Bree A

2015-02-01

The numbers of women of childbearing age with pregestational diabetes mellitus (diabetes existing before pregnancy) are increasing, primarily because more patients are developing type 2 diabetes at younger ages. The teratogenicity associated with hyperglycemia in early pregnancy is well documented, and tight glucose control minimizes the risk of congenital malformation. Preconception planning is essential; thus contraception that does not worsen complications of diabetes is desirable. In addition, because contraceptives are not 100% effective, the treatment of elevated blood glucose levels, hypertension, and dyslipidemia in these women requires consideration of unplanned pregnancy. We summarized the literature to aid clinicians in choosing individualized treatment that minimizes risk in case pregnancy occurs and maximizes benefit in preventing the complications of diabetes. In women with well-controlled diabetes without vascular disease, all contraceptive methods are safe. Intrauterine devices are recommended due to their minimal effects on risk factors for diabetic complications and their lack of reliance on patient adherence for efficacy. Among insulins, the insulin analogs-insulin lispro, insulin aspart, and insulin detemir-offer patients greater convenience than regular insulin and NPH insulin, and they are safe in case of unplanned pregnancy. Of the noninsulin agents, glyburide and metformin are the safest during pregnancy, but many of the other agents pose minimal risk as long as they are withdrawn during early pregnancy. The risks and benefits of angiotensin-converting enzyme inhibitors in women with compelling indications must be weighed individually. In hypertensive patients at a high risk for unplanned pregnancy, nifedipine should be considered due to literature supporting its safety during early pregnancy. Pravastatin is recommended for women with dyslipidemia who are using effective contraception because there have been no reports of birth defects with this statin when used during early pregnancy in humans and animals. © 2015 Pharmacotherapy Publications, Inc.

Mining transportation information from social media for planned and unplanned events.

DOT National Transportation Integrated Search

2016-05-01

The objective of this project is on mining social media data to deduce useful travelers information with : a special emphasis under events, including both planned events (such as sporting games), and : unplanned events (such as traffic accidents)....

Risk factors for unplanned pregnancy in women with mental illness living in a developing country.

PubMed

du Toit, Elsa; Jordaan, Esme; Niehaus, Dana; Koen, Liezl; Leppanen, Jukka

2018-06-01

Pregnant women in general are at an increased risk of experiencing symptoms of mental illness, and those living in a developing country are even more vulnerable. Research points towards a causal relationship between unplanned pregnancy and perinatal mental illness and suggests that pregnancy planning can aid in reducing the negative impact of mental illness on a woman, her unborn baby, and the rest of the family. In this quantitative, descriptive study, we investigated both socio-demographic factors and variables relating to mental illness itself that may place women at an increased risk of experiencing unplanned pregnancy. Data was gathered at two maternal mental health clinics in Cape Town by means of semi-structured interviews. Univariate analyses of the data revealed five independent key risk factors for unplanned pregnancy: lower levels of education, unmarried status, belonging to the Colored ethnic population, substance use, and having a history of two or more suicide attempts. Some of these factors overlap with findings of similar studies, but others are unique to the specific population (women with mental illness within a developing country). Screening of women based on these risk predictors may pave the way for early interventions and reduce the incidence of unplanned pregnancy and the negative consequences thereof in the South African population.

Predictors and causes of unplanned re-operations in outpatient plastic surgery: a multi-institutional analysis of 6749 patients using the 2011 NSQIP database.

PubMed

Lim, Seokchun; Jordan, Sumanas W; Jain, Umang; Kim, John Y S

2014-08-01

Studies that evaluate the predictors and causes of unplanned re-operation in outpatient plastic surgery. This study retrospectively reviewed the American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) and identified all plastic surgery outpatient cases performed in 2011. Multiple logistic regression analysis was utilised to identify independent risk factors and causes of unplanned reoperations. Of the 6749 outpatient plastic surgery cases identified, there were 125 (1.9%) unplanned re-operations (UR). Regression analysis demonstrated that body mass index (BMI, OR = 1.041, 95% CI = 1.019-1.065), preoperative open wound/wound infection (OR = 3.498, 95% CI = 1.593-7.678), American Society of Anesthesiologists (ASA) class 3 (OR = 2.235, 95% CI = 1.048-4.765), and total work relative value units (RVU, OR = 1.014, 95% CI = 1.005-1.024) were significantly predictive of UR. Additionally, the presence of any complication was significantly associated with UR (OR = 15.065, 95% CI = 5.705-39.781). In an era of outcomes-driven medicine, unplanned re-operation is a critical quality indicator for ambulatory plastic surgery facilities. The identified risk factors will aid in surgical planning and risk adjustment.

What weekday? How acute? An analysis of reported planned and unplanned GP visits by older multi-morbid patients in the Patient Journey Record System database.

PubMed

Surate Solaligue, David Emanuel; Hederman, Lucy; Martin, Carmel Mary

2014-08-01

Timely access to general practitioner (GP) care is a recognized strategy to address avoidable hospitalization. Little is known about patients seeking planned (decided ahead) and unplanned (decided on day) GP visits. The Patient Journey Record System (PaJR) provides a biopsychosocial real-time monitoring and support service to chronically ill and older people over 65 who may be at risk of an avoidable hospital admission. This study aims to describe reported profiles associated with planned and unplanned GP visits during the week in the PaJR database of regular outbound phone calls made by Care Guides to multi-morbid older patients. One hundred fifty consecutive patients with one or more chronic condition (including chronic obstructive pulmonary disease, heart/vascular disease, heart failure and/or diabetes), one or more hospital admission in previous year, and consecutively recruited from hospital discharge, out-of-hour care and GP practices comprised the study sample. Using a semistructured script, Care Guides telephoned the patients approximately every 3 week days, and entered call data into the PaJR database in 2011. The PaJR project identified and prompted unplanned visits according to its algorithms. Logistic regression modelling and descriptive statistics identified significant predictors of planned and unplanned visits and patterns of GP visits on weekdays reported in calls. In 5096 telephone calls, unplanned versus planned GP visits were predicted by change in health state, significant symptom concerns, poor self-rated health, bodily pain and concerns about caregiver or intimates. Calls not reporting visits had significantly fewer of these features. Planned visits were associated with general and medication concerns, reduced social participation and feeling down. Planned visits were highest on Monday and trended downwards to Fridays. Unplanned visits were reported at the same rate each weekday and more frequently when the interval between calls was ≥3 days. The PaJR project Care Guides advised patients to make unplanned visits in 6.3% of calls and advised planned GP visits in 2.5% of calls. Unplanned GP visits consistently indicated a significant change to worse health with planned visits presenting less acuity in this study of older multi-morbid patients in general practice, when monitored by regular calls at about every 3 days. The PaJR study actively prompted GP visits according to its algorithms. Assessing and predicting acuity in older multi-morbid patients appears to be a promising strategy to improve access to primary care, and thus to reducing avoidable hospital utilization. Further research is needed to investigate the topic on a wider scale. © 2014 John Wiley & Sons, Ltd.

Antiretroviral Drugs for Treatment and Prevention of HIV Infection in Adults

PubMed Central

Günthard, Huldrych F.; Saag, Michael S.; Benson, Constance A.; del Rio, Carlos; Eron, Joseph J.; Gallant, Joel E.; Hoy, Jennifer F.; Mugavero, Michael J.; Sax, Paul E.; Thompson, Melanie A.; Gandhi, Rajesh T.; Landovitz, Raphael J.; Smith, Davey M.; Jacobsen, Donna M.; Volberding, Paul A.

2016-01-01

IMPORTANCE New data and therapeutic options warrant updated recommendations for the use of antiretroviral drugs (ARVs) to treat or to prevent HIV infection in adults. OBJECTIVE To provide updated recommendations for the use of antiretroviral therapy in adults (aged ≥18 years) with established HIV infection, including when to start treatment, initial regimens, and changing regimens, along with recommendations for using ARVs for preventing HIV among those at risk, including preexposure and postexposure prophylaxis. EVIDENCE REVIEW A panel of experts in HIV research and patient care convened by the International Antiviral Society-USA reviewed data published in peer-reviewed journals, presented by regulatory agencies, or presented as conference abstracts at peer-reviewed scientific conferences since the 2014 report, for new data or evidence that would change previous recommendations or their ratings. Comprehensive literature searches were conducted in the PubMed and EMBASE databases through April 2016. Recommendations were by consensus, and each recommendation was rated by strength and quality of the evidence. FINDINGS Newer data support the widely accepted recommendation that antiretroviral therapy should be started in all individuals with HIV infection with detectable viremia regardless of CD4 cell count. Recommended optimal initial regimens for most patients are 2 nucleoside reverse transcriptase inhibitors (NRTIs) plus an integrase strand transfer inhibitor (InSTI). Other effective regimens include nonnucleoside reverse transcriptase inhibitors or boosted protease inhibitors with 2 NRTIs. Recommendations for special populations and in the settings of opportunistic infections and concomitant conditions are provided. Reasons for switching therapy include convenience, tolerability, simplification, anticipation of potential new drug interactions, pregnancy or plans for pregnancy, elimination of food restrictions, virologic failure, or drug toxicities. Laboratory assessments are recommended before treatment, and monitoring during treatment is recommended to assess response, adverse effects, and adherence. Approaches are recommended to improve linkage to and retention in care are provided. Daily tenofovir disoproxil fumarate/emtricitabine is recommended for use as preexposure prophylaxis to prevent HIV infection in persons at high risk. When indicated, postexposure prophylaxis should be started as soon as possible after exposure. CONCLUSIONS AND RELEVANCE Antiretroviral agents remain the cornerstone of HIV treatment and prevention. All HIV-infected individuals with detectable plasma virus should receive treatment with recommended initial regimens consisting of an InSTI plus 2 NRTIs. Preexposure prophylaxis should be considered as part of an HIV prevention strategy for at-risk individuals. When used effectively, currently available ARVs can sustain HIV suppression and can prevent new HIV infection. With these treatment regimens, survival rates among HIV-infected adults who are retained in care can approach those of uninfected adults. PMID:27404187

Clinical, nutritional and immunological characteristics of HIV-infected children in an area of high HIV prevalence.

PubMed

Pedrini, Maura; Moraleda, Cinta; Macete, Eusebio; Gondo, Kizito; Brabin, Bernard J; Menéndez, Clara

2015-08-01

To evaluate the clinical, nutritional and neurodevelopment status of HIV-infected children in a high HIV prevalence area. All HIV-infected children under 15 years of age attending an outpatient clinic of Mozambique between April and May 2010 were recruited. Clinical data were collected and physical examination was performed. In all, 140 children were recruited. The median age at HIV diagnosis was 2.1 years. Fifty-one percent of the children were classified in WHO clinical Stages 3 or 4. Median age of antiretroviral treatment commencement was 3.9 years. Overall, 68% were undernourished, mainly stunted. Forty-four percent failed to pass the national psychomotor developmental test. The pathways for early HIV diagnosis and start of antiretrovirals in children should be improved in Mozambique. Malnutrition, especially stunting, and developmental delay were highly prevalent. Further research focused on early diagnosis of neurocognitive disorders and on the indications of antiretroviral treatment commencement based on chronic malnutrition is required. © The Author [2015]. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Economic evaluation of 3-drug antiretroviral regimens for the prevention of mother-to-child HIV transmission in Thailand.

PubMed

Werayingyong, Pitsaphun; Phanuphak, Nittaya; Chokephaibulkit, Kulkunya; Tantivess, Sripen; Kullert, Nareeluk; Tosanguan, Kakanang; Butchon, Rukmanee; Voramongkol, Nipunporn; Boonsuk, Sarawut; Pilasant, Songyot; Kulpeng, Wantanee; Teerawattananon, Yot

2015-03-01

The current program for prevention of mother-to-child HIV transmission in Thailand recommends a 2-drugs regimen for HIV-infected pregnant women with a CD4 count >200 cells/mm(3). This study assesses the value for money of 3 antiretroviral drugs compared with zidovudine (AZT)+single-dose nevirapine (sd-NVP). A decision tree was constructed to predict costs and outcomes using the governmental perspective for assessing cost-effectiveness of 3-drug regimens: (1) AZT, lamivudine, and efavirenz and (2) AZT, 3TC, and lopinavir/ritonavir, in comparison with the current protocol, AZT+sd-NVP. The 3-drug antiretroviral regimens yield lower costs and better health outcomes compared with AZT+sd-NVP. Although these 3-drug regimens offer higher program costs and health care costs for premature birth, they save money significantly in regard to pediatric HIV treatment and treatment costs for drug resistance in mothers. The 3-drug regimens are cost-saving interventions. The findings from this study were used to support a policy change in the national recommendation. © 2013 APJPH.

Information and communication technologies for adherence to antiretroviral treatment in adults with HIV/AIDS.

PubMed

Lima, Ivana Cristina Vieira de; Galvão, Marli Teresinha Gimeniz; Alexandre, Herta de Oliveira; Lima, Francisca Elisângela Teixeira; Araújo, Thelma Leite de

2016-08-01

Information and communication technologies support interventions directed at the prevention of HIV transmission and patient monitoring by promoting improved accessibility and quality of care. To evaluate the efficacy of information and communication technologies in the adherence to antiretroviral treatment in adults with HIV/AIDS. Systematic review conducted from March to May of 2015 in three databases-the Cumulative Index to Nursing and Allied Health Literature (CINAHL); the Latin-American and Caribbean Literature in Health Sciences (LILACS/BIREME) and SCOPUS; and the Cochrane library and the Medical Literature Analysis and Retrieval System Online portal (MEDLINE/PubMed). The sample consisted of nine randomized clinical trials based on the use of information and communication technologies for adherence to antiretroviral treatment in adults with HIV/AIDS. Three studies analysed the use of a short message service - SMS - two phone calls, two alarm devices, one web-enabled Hand-held device and one web electronic intervention. Improvements in the levels of adherence in the group subjected to the intervention were identified in seven studies. The phone was the type of information and communication technology with proven efficacy with respect to adherence. It was used to make calls, as well as to send alert messages and reminders about taking medications. Pagers were not considered to be effective regarding adherence to antiretroviral therapy. The integrated use of information and communication technologies with standard care promotes increased access to care, strengthening the relationship between patients and health services, with the possibility of mitigating the difficulties experienced by people with HIV in achieving optimal levels of adherence to drug therapy. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Trends in Loss to Follow-Up among Migrant Workers on Antiretroviral Therapy in a Community Cohort in Lesotho

PubMed Central

Bygrave, Helen; Kranzer, Katharina; Hilderbrand, Katherine; Whittall, Jonathan; Jouquet, Guillaume; Goemaere, Eric; Vlahakis, Nathalie; Triviño, Laura; Makakole, Lipontso; Ford, Nathan

2010-01-01

Background The provision of antiretroviral therapy (ART) to migrant populations raises particular challenges with respect to ensuring adequate treatment support, adherence, and retention in care. We assessed rates of loss to follow-up for migrant workers compared with non-migrant workers in a routine treatment programme in Morjia, Lesotho. Design All adult patients (≥18 years) initiating ART between January 1, 2008, and December 31, 2008, and followed up until the end of 2009, were included in the study. We described rates of loss to follow-up according to migrant status by Kaplan-Meier estimates, and used Poisson regression to model associations between migrant status and loss to follow-up controlling for potential confounders identified a priori. Results Our cohort comprised 1185 people, among whom 12% (148) were migrant workers. Among the migrant workers, median age was 36.1 (29.6–45.9) and the majority (55%) were male. We found no statistically significant differences between baseline characteristics and migrant status. Rates of lost to follow up were similar between migrants and non-migrants in the first 3 months but differences increased thereafter. Between 3 and 6 months after initiating antiretroviral therapy, migrants had a 2.78-fold increased rate of defaulting (95%CI 1.15–6.73); between 6 and 12 months the rate was 2.36 times greater (95%CI 1.18–4.73), whereas after 1 year the rate was 6.69 times greater (95%CI 3.18–14.09). Conclusions Our study highlights the need for programme implementers to take into account the specific challenges that may influence continuity of antiretroviral treatment and care for migrant populations. PMID:20976289

Strand transfer inhibitors of HIV-1 integrase: bringing IN a new era of antiretroviral therapy.

PubMed

McColl, Damian J; Chen, Xiaowu

2010-01-01

HIV-1 integrase (IN) is one of three essential enzymes (along with reverse transcriptase and protease) encoded by the viral pol gene. IN mediates two critical reactions during viral replication; firstly 3'-end processing (3'EP) of the double-stranded viral DNA ends and then strand transfer (STF) which joins the viral DNA to the host chromosomal DNA forming a functional integrated proviral DNA. IN is a 288 amino acid protein containing three functional domains, the N-terminal domain (NTD), catalytic core domain (CCD) and the C-terminal domain (CTD). The CCD contains three conserved catalytic residues, Asp64, Asp116 and Glu152, which coordinate divalent metal ions essential for the STF reaction. Intensive research over the last two decades has led to the discovery and development of small molecule inhibitors of the IN STF reaction (INSTIs). INSTIs are catalytic inhibitors of IN, and act to chelate the divalent metal ions in the CCD. One INSTI, raltegravir (RAL, Merck Inc.) was approved in late 2007 for the treatment of HIV-1 infection in patients with prior antiretroviral (ARV) treatment experience and was recently approved also for first line therapy. A second INSTI, elvitegravir (EVG, Gilead Sciences, Inc.) is currently undergoing phase 3 studies in ARV treatment-experienced patients and phase 2 studies in ARV naïve patients as part of a novel fixed dose combination. Several additional INSTIs are in early stage clinical development. This review will discuss the discovery and development of this novel class of antiretrovirals. This article forms part of a special issue of Antiviral Research marking the 25th anniversary of antiretroviral drug discovery and development, Vol 85, issue 1, 2010. Copyright 2009. Published by Elsevier B.V.

Medication possession ratio predicts antiretroviral regimens persistence in Peru.

PubMed

Salinas, Jorge L; Alave, Jorge L; Westfall, Andrew O; Paz, Jorge; Moran, Fiorella; Carbajal-Gonzalez, Danny; Callacondo, David; Avalos, Odalie; Rodriguez, Martin; Gotuzzo, Eduardo; Echevarria, Juan; Willig, James H

2013-01-01

In developing nations, the use of operational parameters (OPs) in the prediction of clinical care represents a missed opportunity to enhance the care process. We modeled the impact of multiple measurements of antiretroviral treatment (ART) adherence on antiretroviral treatment outcomes in Peru. Retrospective cohort study including ART naïve, non-pregnant, adults initiating therapy at Hospital Nacional Cayetano Heredia, Lima-Peru (2006-2010). Three OPs were defined: 1) Medication possession ratio (MPR): days with antiretrovirals dispensed/days on first-line therapy; 2) Laboratory monitory constancy (LMC): proportion of 6 months intervals with ≥1 viral load or CD4 reported; 3) Clinic visit constancy (CVC): proportion of 6 months intervals with ≥1 clinic visit. Three multi-variable Cox proportional hazard (PH) models (one per OP) were fit for (1) time of first-line ART persistence and (2) time to second-line virologic failure. All models were adjusted for socio-demographic, clinical and laboratory variables. 856 patients were included in first-line persistence analyses, median age was 35.6 years [29.4-42.9] and most were male (624; 73%). In multivariable PH models, MPR (per 10% increase HR=0.66; 95%CI=0.61-0.71) and LMC (per 10% increase 0.83; 0.71-0.96) were associated with prolonged time on first-line therapies. Among 79 individuals included in time to second-line virologic failure analyses, MPR was the only OP independently associated with prolonged time to second-line virologic failure (per 10% increase 0.88; 0.77-0.99). The capture and utilization of program level parameters such as MPR can provide valuable insight into patient-level treatment outcomes.

Amniocentesis and chorionic villus sampling in HIV-infected pregnant women: a multicentre case series.

PubMed

Floridia, M; Masuelli, G; Meloni, A; Cetin, I; Tamburrini, E; Cavaliere, A F; Dalzero, S; Sansone, M; Alberico, S; Guerra, B; Spinillo, A; Chiadò Fiorio Tin, M; Ravizza, M

2017-07-01

To assess in pregnant women with HIV the rates of amniocentesis and chorionic villus sampling (CVS), and the outcomes associated with such procedures. Observational study. Data from the Italian National Program on Surveillance on Antiretroviral Treatment in Pregnancy were used. University and hospital clinics. Pregnant women with HIV. Temporal trends were analysed by analysis of variance and by the Chi-square test for trend. Quantitative variables were compared by Student's t-test and categorical data by the Chi-square test, with odds ratios and 95% confidence intervals calculated. Rate of invasive testing, intrauterine death, HIV transmission. Between 2001 and 2015, among 2065 pregnancies in women with HIV, 113 (5.5%) had invasive tests performed. The procedures were conducted under antiretroviral treatment in 99 cases (87.6%), with a significant increase over time in the proportion of tests performed under highly active antiretroviral therapy (HAART) (100% in 2011-2015). Three intrauterine deaths were observed (2.6%), and 14 pregnancies were terminated because of fetal anomalies. Among 96 live newborns, eight had no information available on HIV status. Among the remaining 88 cases with either amniocentesis (n = 75), CVS (n = 12), or both (n = 1), two HIV transmissions occurred (2.3%). No HIV transmission occurred among the women who were on HAART at the time of invasive testing, and none after 2005. The findings reinforce the assumption that invasive prenatal testing does not increase the risk of HIV vertical transmission among pregnant women under suppressive antiretroviral treatment. No HIV transmission occurred among women who underwent amniocentesis or CVS under effective anti-HIV regimens. © 2016 Royal College of Obstetricians and Gynaecologists.

Serum 25-Hydroxyvitamin D Response to Vitamin D3 Supplementation 50,000 IU Monthly in Youth with HIV-1 Infection

PubMed Central

Mulligan, Kathleen; Hazra, Rohan; Flynn, Patricia; Rutledge, Brandy; Van Loan, Marta D.; Lujan-Zilbermann, Jorge; Kapogiannis, Bill G.; Wilson, Craig M.; Stephensen, Charles B.

2012-01-01

Context: Vitamin D deficiency and insufficiency occur frequently in youth with HIV infection, particularly among those receiving the antiretroviral drug efavirenz. Optimal vitamin D dosing for treatment is unclear. Objective: Our objective was to evaluate safety and measure change in 25-hydroxyvitamin D (25-OHD) concentration from baseline to study wk 4 and 12 during treatment with vitamin D3, 50,000 IU monthly. Design, Setting, and Participants: We conducted a randomized double-blind, placebo-controlled multicenter trial of HIV-infected youth ages 18–24 yr, with viral load below 5000 copies/ml, on stable antiretroviral therapy. Intervention: Intervention included vitamin D3, 50,000 IU (n = 102), or matching placebo (n = 101) administered in three directly observed oral doses at monthly intervals. Results: At baseline, mean (sd) age was 20.9 (2.0) yr; 37% were female and 52% African-American, and 54% were vitamin D deficient/insufficient (25-OHD < 20 ng/ml), with no randomized group differences. Of evaluable participants vitamin D deficient/insufficient at baseline who were administered vitamin D, 43 of 46 (93%) had sufficient 25-OHD by wk 12. Vitamin D supplementation increased 25-OHD serum concentration from a baseline of 21.9 (13.3) to 35.9 (19.1) ng/ml at wk 12 (P < 0.001) with no change for placebo. Although use of the antiretroviral efavirenz was associated with lower baseline 25-OHD concentration, efavirenz did not diminish the response to vitamin D supplementation. There was no treatment-related toxicity. Conclusions: Supplementation with vitamin D3 50,000 IU monthly for three doses was safe. Increases in 25-OHD occurred in treated participants regardless of antiretroviral regimen. PMID:22933542

Outcomes of antiretroviral treatment: a comparison between hospitals and health centers in Ethiopia.

PubMed

Balcha, Taye T; Jeppsson, Anders

2010-01-01

the objective of this study was to compare the outcomes of antiretroviral therapy (ART) between hospital and health center levels in Ethiopia. medical records of 1709 ART patients followed for 24 months at 2 hospitals and 3 health centers in the Oromia region of Ethiopia were reviewed. Noted outcomes of ART were currently alive and on treatment; lost to follow-up (LTFU); transferred out (TO); and died (D). of 1709 HIV-positive patients started on ART between September 2006 and February 2007, 1044 (61%) remained alive and were on treatment after 24-month follow-up. In all, 835 (57%) of ART patients at hospitals and 209 (83%) at health centers were retained in the program. Of those who were alive and receiving ART, 79% of patients at health centers and 72% at hospitals were clinically or immunologically improving. In addition, 331 (23%) patients at hospitals were LFTU as compared to 24 (10%) of patients at health centers (relative risk [RR] at 95% confidence interval [CI]: .358 [.231-.555]). While 11% was the mortality rate at hospitals, 5% of patients at health centers also died (RR at 95% CI: .360 [.192-.673]). antiretroviral therapy at health centers was associated with more favorable outcomes than at hospitals.

Cognitive impairment and antiretroviral treatment in a Peruvian population of patients with human immunodeficiency virus.

PubMed

Guevara-Silva, E A

2014-05-01

HIV-associated cognitive impairment occurs even in the early stages of infection. Short-term memory, psychomotor speed, attention, and executive functioning are the main capacities affected. Controversy exists regarding whether highly active antiretroviral therapy (HAART) is helpful in combating this process. The objective of the present study is to determine the association between cognitive impairment and HAART in HIV-infected patients from Hospital Regional de Huacho. Prospective study of HIV patients meeting criteria to start HAART. Twenty-one HIV-positive patients were recruited between April and July 2011. Researchers administered a standardised neuropsychological test battery before and 4 weeks after onset of HAART. Psychomotor speed, executive function, short term memory (visual and verbal), attention, and visuospatial performance were evaluated. Nineteen patients completed the study (14 males and 5 females). In the pre-HAART evaluation, most patients scored below average on the executive function and psychomotor speed subtests. Psychomotor speed and immediate visual memory improved significantly after four months of treatment with HAART. Some degree of cognitive decline may present even in the early and asymptomatic stages of HIV infection. The benefits of antiretroviral treatment for cognitive performance can be detected after only a few weeks of follow-up. Copyright © 2013 Sociedad Española de Neurología. Published by Elsevier Espana. All rights reserved.

[Companion Diagnostics for Selecting Antiretroviral Drugs against HIV-1].

PubMed

Fukutake, Katsuyuki

2015-11-01

Currently, the treatment of human immunodeficiency virus involves combination therapy, as antiretroviral therapy(ART). The treatment has improved steadily since the advent of potent combination therapy in 1996. New drugs that offer new mechanisms of action, improvements in potency and activity even against multidrug-resistant viruses, dosing convenience, and tolerability have been approved. Among ART with useful drugs, there are two important examinations before starting the treatment using the two kinds of drug. CCR5 co-receptor antagonists, maraviroc, prevent HIV entry into target cells by binding to CCR5 receptors. Genotypic assays have been developed that can determine or predict the co-receptor tropism(i.e., CCR5, CXCR4, or both) of the patient's dominant virus population. The assay for HIV-1 co-receptor usage should be performed whenever the use of a CCR5 antagonist is being considered. One of the nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs), abacavir, is an important agent to develop recommended regimens for antiretroviral therapy. Serious and sometimes fatal hypersensitivity reactions have been associated with abacavir-containing products, ZIAGEN, Epzicom, and Triumeq. Patients who carry the HLA-B*5701 allele are at high-risk of a hypersensitivity reaction to abacavir. Prior to initiating therapy with abacavir, performing a screening test for the HLA-B*5701 allele is recommended. [Review].

Community-based treatment of advanced HIV disease: introducing DOT-HAART (directly observed therapy with highly active antiretroviral therapy).

PubMed Central

Farmer, P.; Léandre, F.; Mukherjee, J.; Gupta, R.; Tarter, L.; Kim, J. Y.

2001-01-01

In 2000, acquired immunodeficiency syndrome (AIDS) overtook tuberculosis (TB) as the world's leading infectious cause of adult deaths. In affluent countries, however, AIDS mortality has dropped sharply, largely because of the use of highly active antiretroviral therapy (HAART). Antiretroviral agents are not yet considered essential medications by international public health experts and are not widely used in the poor countries where human immunodeficiency virus (HIV) takes its greatest toll. Arguments against the use of HAART have mainly been based on the high cost of medications and the lack of the infrastructure necessary for using them wisely. We re- examine these arguments in the setting of rising AIDS mortality in developing countries and falling drug prices, and describe a small community-based treatment programme based on lessons gained in TB control. With the collaboration of Haitian community health workers experienced in the delivery of home-based and directly observed treatment for TB, an AIDS-prevention project was expanded to deliver HAART to a subset of HIV patients deemed most likely to benefit. The inclusion criteria and preliminary results are presented. We conclude that directly observed therapy (DOT) with HAART, "DOT-HAART", can be delivered effectively in poor settings if there is an uninterrupted supply of high-quality drugs. PMID:11799447

Hybrid data capture for monitoring patients on highly active antiretroviral therapy (HAART) in urban Botswana.

PubMed

Bussmann, Hermann; Wester, C William; Ndwapi, Ndwapi; Vanderwarker, Chris; Gaolathe, Tendani; Tirelo, Geoffrey; Avalos, Ava; Moffat, Howard; Marlink, Richard G

2006-02-01

Individual patient care and programme evaluation are pivotal for the success of antiretroviral treatment programmes in resource-limited countries. While computer-aided documentation and data storage are indispensable for any large programme, several important issues need to be addressed including which data are to be collected, who collects it and how it is entered into an electronic database. We describe a patient-monitoring approach, which uses patient encounter forms (in hybrid paper + electronic format) based on optical character recognition, piloted at Princess Marina Hospital in Gaborone, Botswana's first public highly active antiretroviral therapy (HAART) outpatient clinic. Our novel data capture approach collects "key" data for tracking patient and programme outcomes. It saves physician time and does not detract from clinical care.

Hybrid data capture for monitoring patients on highly active antiretroviral therapy (HAART) in urban Botswana.

PubMed Central

Bussmann, Hermann; Wester, C. William; Ndwapi, Ndwapi; Vanderwarker, Chris; Gaolathe, Tendani; Tirelo, Geoffrey; Avalos, Ava; Moffat, Howard; Marlink, Richard G.

2006-01-01

Individual patient care and programme evaluation are pivotal for the success of antiretroviral treatment programmes in resource-limited countries. While computer-aided documentation and data storage are indispensable for any large programme, several important issues need to be addressed including which data are to be collected, who collects it and how it is entered into an electronic database. We describe a patient-monitoring approach, which uses patient encounter forms (in hybrid paper + electronic format) based on optical character recognition, piloted at Princess Marina Hospital in Gaborone, Botswana's first public highly active antiretroviral therapy (HAART) outpatient clinic. Our novel data capture approach collects "key" data for tracking patient and programme outcomes. It saves physician time and does not detract from clinical care. PMID:16501730

The antiretroviral efficacy of highly active antiretroviral therapy and plasma nevirapine concentrations in HIV-TB co-infected Indian patients receiving rifampicin based antituberculosis treatment

PubMed Central

2011-01-01

Background Rifampicin reduces the plasma concentrations of nevirapine in human immunodeficiency virus (HIV) and tuberculosis (TB) co-infected patients, who are administered these drugs concomitantly. We conducted a prospective interventional study to assess the efficacy of nevirapine-containing highly active antiretroviral treatment (HAART) when co-administered with rifampicin-containing antituberculosis treatment (ATT) and also measured plasma nevirapine concentrations in patients receiving such a nevirapine-containing HAART regimen. Methods 63 cases included antiretroviral treatment naïve HIV-TB co-infected patients with CD4 counts less than 200 cells/mm3 started on rifampicin-containing ATT followed by nevirapine-containing HAART. In control group we included 51 HIV patients without tuberculosis and on nevirapine-containing HAART. They were assessed for clinical and immunological response at the end of 24 and 48 weeks. Plasma nevirapine concentrations were measured at days 14, 28, 42 and 180 of starting HAART. Results 97 out of 114 (85.1%) patients were alive at the end of 48 weeks. The CD4 cell count showed a mean increase of 108 vs.113 cells/mm3 (p=0.83) at 24 weeks of HAART in cases and controls respectively. Overall, 58.73% patients in cases had viral loads of less than 400 copies/ml at the end of 48 weeks. The mean (± SD) Nevirapine concentrations of cases and control at 14, 28, 42 and 180 days were 2.19 ± 1.49 vs. 3.27 ± 4.95 (p = 0.10), 2.78 ± 1.60 vs. 3.67 ± 3.59 (p = 0.08), 3.06 ± 3.32 vs. 4.04 ± 2.55 (p = 0.10) respectively and 3.04 μg/ml (in cases). Conclusions Good immunological and clinical response can be obtained in HIV-TB co-infected patients receiving rifampicin and nevirapine concomitantly despite somewhat lower nevirapine trough concentrations. This suggests that rifampicin-containing ATT may be co administered in resource limited setting with nevirapine-containing HAART regimen without substantial reduction in antiretroviral effectiveness. Larger sample sized studies and longer follow-up are required to identify populations of individuals where the reduction in nevirapine concentration may result in lower ART response or shorter response duration. PMID:22047185

HIV treatment as prevention in Jamaica and Barbados: magic bullet or sustainable response?

PubMed

Barrow, Geoffrey; Barrow, Christine

2015-01-01

This discursive article introduces HIV treatment as prevention (TasP) and identifies various models for its extrapolation to wider population levels. Drawing on HIV surveillance data for Jamaica and Barbados, the article identifies significant gaps in HIV response programming in relation to testing, antiretroviral treatment coverage, and treatment adherence, thereby highlighting the disparity between assumptions and prerequisites for TasP success. These gaps are attributable, in large part, to sociocultural impediments and structural barriers, severe resource constraints, declining political will, and the redefinition of HIV as a manageable, chronic health issue. Antiretroviral treatment and TasP can realize success only within a combination prevention frame that addresses structural factors, including stigma and discrimination, gender inequality and gender-based violence, social inequality, and poverty. The remedicalization of the response compromises outcomes and undermines the continued potential of HIV programming as an entry point for the promotion of sexual, health, and human rights. © The Author(s) 2013.

Antiretroviral Drugs-Loaded Nanoparticles Fabricated by Dispersion Polymerization with Potential for HIV/AIDS Treatment

PubMed Central

Ogunwuyi, Oluwaseun; Kumari, Namita; Smith, Kahli A.; Bolshakov, Oleg; Adesina, Simeon; Gugssa, Ayele; Anderson, Winston A.; Nekhai, Sergei; Akala, Emmanuel O.

2016-01-01

Highly active antiretroviral (ARV) therapy (HAART) for chronic suppression of HIV replication has revolutionized the treatment of HIV/AIDS. HAART is no panacea; treatments must be maintained for life. Although great progress has been made in ARV therapy, HIV continues to replicate in anatomical and intracellular sites where ARV drugs have restricted access. Nanotechnology has been considered a platform to circumvent some of the challenges in HIV/AIDS treatment. Dispersion polymerization was used to fabricate two types (PMM and ECA) of polymeric nanoparticles, and each was successfully loaded with four ARV drugs (zidovudine, lamivudine, nevirapine, and raltegravir), followed by physicochemical characterization: scanning electron microscope, particle size, zeta potential, drug loading, and in vitro availability. These nanoparticles efficiently inhibited HIV-1 infection in CEM T cells and peripheral blood mononuclear cells; they hold promise for the treatment of HIV/AIDS. The ARV-loaded nanoparticles with polyethylene glycol on the corona may facilitate tethering ligands for targeting specific receptors expressed on the cells of HIV reservoirs. PMID:27013886

Once-daily fosamprenavir with ritonavir in the treatment of HIV infection in therapy-naïve patients.

PubMed

Flamholc, Leo; Gisslén, Magnus

2008-12-01

Treatment options for HIV patients have dramatically improved since the introduction of efficacious antiretroviral combination therapy more than a decade ago. Treatment regimens have been simplified with fewer pills and fewer daily dosages. Fosamprenavir is a protease inhibitor with a rather long half-life which makes it a candidate for once-daily use. Once-daily dosage of ritonavir-boosted fosamprenavir is approved in the US, but not in Europe, for treatment in patients without prior antiretroviral treatment. Here we review the background and rationale for once-daily dosage of ritonavir-boosted fosamprenavir. The rather limited studies that have been published so far indicate that fosamprenavir 1400 mg may be used once daily boosted with ritonavir. The optimal ritonavir dose to be given together with fosamprenavir is still to be defined, though available results indicate that a dose of 100 mg may be adequate provided that no protease inhibitor resistance is present.

[Pilot study of antiretroviral therapy in Djibouti].

PubMed

Ahmed, A A; Latoundji, S

2007-01-01

A cross-sectional survey was conducted among 112 HIV positive patients who had received antiretroviral therapy for >3 months to assess the efficacy of treatment (viral load <400 copies/mL). The median age at enrolment was 36 years, 90% of patients were at the AIDS stage and median CD4 rate was 118/mm3. Patients received a combined treatment of 2 NRTI +1 NNRTI (51%), 3 NRTI (45%) and 2 NRTI+1 PI (4%). Virological efficacy was seen in 74% of the patients, irrespective of the prescribed protocol and the initial clinical and immunological profile. Mean improvements measured were 20% on the Karnofsky index (KI), 2.1 kg/m2 in body mass index and 82 cells/mm in CD4. The prevalence of side effects was 84%. The predictors for treatment success were quality of care and KI > 70%.

Five-year trends in antiretroviral usage and drug costs in HIV-infected children in Thailand.

PubMed

Collins, Intira; Cairns, John; Le Coeur, Sophie; Pagdi, Karin; Ngampiyaskul, Chaiwat; Layangool, Prapaisri; Borkird, Thitiporn; Na-Rajsima, Sathaporn; Wanchaitanawong, Vanichaya; Jourdain, Gonzague; Lallemant, Marc

2013-09-01

As antiretroviral treatment (ART) programs mature, data on drug utilization and costs are needed to assess durability of treatments and inform program planning. Children initiating ART were followed up in an observational cohort in Thailand. Treatment histories from 1999 to 2009 were reviewed. Treatment changes were categorized as: drug substitution (within class), switch across drug class (non nucleoside reverse-transcriptase inhibitors (NNRTI) to/from protease inhibitor (PI)), and to salvage therapy (dual PI or PI and NNRTI). Antiretroviral drug costs were calculated in 6-month cycles (US$ 2009 prices). Predictors of high drug cost including characteristics at start of ART (baseline), initial regimen, treatment change, and duration on ART were assessed using mixed-effects regression models. Five hundred seven children initiated ART with a median 54 (interquartile range, 36-72) months of follow-up. Fifty-two percent had a drug substitution, 21% switched across class, and 2% to salvage therapy. When allowing for drug substitution, 78% remained on their initial regimen. Mean drug cost increased from $251 to $428 per child per year in the first and fifth year of therapy, respectively. PI-based and salvage regimens accounted for 16% and 2% of treatments prescribed and 33% and 5% of total costs, respectively. Predictors of high cost include baseline age ≥ 8 years, non nevirapine-based initial regimen, switch across drug class, and to salvage regimen (P < 0.005). At 5 years, 21% of children switched across drug class and 2% received salvage therapy. The mean drug cost increased by 70%. Access to affordable second- and third-line drugs is essential for the sustainability of treatment programs.

Predictors of Residual Disease after Unplanned Excision of Soft Tissue Sarcomas

PubMed Central

Gingrich, Alicia A.; Elias, Alexandra; Michael Lee, Chia-Yuan; Nakache, Yves-Paul N.; Li, Chin-Shang; Shah, Dhruvil R.; Boutin, Robert D.; Canter, Robert J.

2016-01-01

Background Unplanned excision of soft tissue sarcomas (STS) is an important quality of care issue given the morbidity related to tumor bed excision. Since not all patients harbor residual disease at the time of re-excision, we sought to determine predictors of residual STS following unplanned excision. Methods We identified 76 patients from a prospective database (1/1/2008 – 9/30/2014) who received a diagnosis of primary STS following unplanned excision on the trunk or extremities. We used univariable and multivariable analyses to evaluate predictors of residual STS as the primary endpoint. We calculated the sensitivity/specificity and accuracy of interval magnetic resonance imaging (MRI) to predict residual sarcoma at re-excision. Results Mean age was 52 years, and 63.2% were male. 50% had fragmented unplanned excision. Among patients undergoing re-excision, residual STS was identified in 70%. On univariable analysis, MRI showing gross disease and fragmented excision were significant predictors of residual STS (OR 10.59, 95% CI 2.14–52.49, P=0.004 and OR 3.61, 95% CI 1.09–11.94, P=0.035, respectively). On multivariable analysis, tumor size predicted distant recurrence and overall survival. When we combined equivocal and positive MRI, the sensitivity and specificity of MRI for predicting residual STS were 86.7% (95% CI 73.2–95.0%) and 57.9% (95% CI 33.5–79.8%), with an overall accuracy of 78.1% (95% CI 66.0–87.5%). Conclusions 70% of patients undergoing repeat excision after unplanned excision of STS harbor residual sarcoma. Although interval MRI and fragmented excision appear to be the most significant predictors of residual STS, the accuracy of MRI remains modest, especially given the incidence of equivocal MRI. PMID:27993214

Predicting 7-day, 30-day and 60-day all-cause unplanned readmission: a case study of a Sydney hospital.

PubMed

Maali, Yashar; Perez-Concha, Oscar; Coiera, Enrico; Roffe, David; Day, Richard O; Gallego, Blanca

2018-01-04

The identification of patients at high risk of unplanned readmission is an important component of discharge planning strategies aimed at preventing unwanted returns to hospital. The aim of this study was to investigate the factors associated with unplanned readmission in a Sydney hospital. We developed and compared validated readmission risk scores using routinely collected hospital data to predict 7-day, 30-day and 60-day all-cause unplanned readmission. A combination of gradient boosted tree algorithms for variable selection and logistic regression models was used to build and validate readmission risk scores using medical records from 62,235 live discharges from a metropolitan hospital in Sydney, Australia. The scores had good calibration and fair discriminative performance with c-statistic of 0.71 for 7-day and for 30-day readmission, and 0.74 for 60-day. Previous history of healthcare utilization, urgency of the index admission, old age, comorbidities related to cancer, psychosis, and drug-abuse, abnormal pathology results at discharge, and being unmarried and a public patient were found to be important predictors in all models. Unplanned readmissions beyond 7 days were more strongly associated with longer hospital stays and older patients with higher number of comorbidities and higher use of acute care in the past year. This study demonstrates similar predictors and performance to previous risk scores of 30-day unplanned readmission. Shorter-term readmissions may have different causal pathways than 30-day readmission, and may, therefore, require different screening tools and interventions. This study also re-iterates the need to include more informative data elements to ensure the appropriateness of these risk scores in clinical practice.

A prospective analysis of unplanned patient-initiated contacts in an adult cystic fibrosis centre.

PubMed

Burnet, Espérie; Hubert, Dominique; Champreux, Juliette; Honoré, Isabelle; Kanaan, Reem; Panzo, Rosewilta; Burgel, Pierre-Régis

2018-05-07

Timely response should be provided when patients contact the cystic fibrosis (CF) centre in between scheduled visits. Little data exist on unplanned patient-initiated contacts in CF adults. A two-stage prospective study was undertaken from 1 January to 31 December 2015 at Cochin Hospital, Paris (France). The first stage included all adults (≥18 years) who initiated unplanned contacts to the CF centre over four months. Four physicians and three nurses systematically recorded unplanned patient-initiated contacts. The data was analysed to determine why and how patients contacted the CF centre and time spent responding to their request(s). The second stage (one physician, three nurses) lasted twelve months and explored whether high contact frequency was associated with disease severity, using multivariate logistic regression. In the first stage, 259 of 410 patients (63%) initiated at least one unplanned contact, corresponding to 1067 contacts over 4 months. Patients favoured email with physicians (61% of contacts) and telephone with nurses (87% of contacts). Total time spent by the 7 caregivers on providing responses was 8 h/work week. Reasons for contacting the CF centre varied greatly, but <20% of contacts were directly related to symptom management. In the second stage, 180 of 212 patients (85%) initiated 1876 contacts over 12 months. Factors associated with ≥5 contacts/year were female sex, FEV 1  ≤ 30% predicted, ≥5 physician visits/year, and ≥ 1 hospital admission/year. Answering unplanned patient-initiated contacts represented a significant workload for CF caregivers. Increased disease severity was associated with high contact frequency. Copyright © 2018 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.

A preliminary inquiry on the problem of unplanned (extra-quota) second births.

PubMed

Zhao, L; Zhu, C

1984-01-01

The resurgence of child births in China in 1981 was marked by a decline in the multiparity birth rates and a drastic rise in the rate of unplanned 2nd births, resulting in unplanned 2nd births outnumbering multiparity births. The aim of this investigation was to find the objective and subjective causes for the unplanned 2nd births and explore ways to bring them under strict control. In the countryside there are loud voices that give insufficient labor as their reason for wanting 2nd births. An analysis of 923 cases of unplanned 2nd births in connection with the economic conditions of the families, the sex of the 1st births, intervals between the births, and the parents' cultural level shows that 61.87% of the total number of families suffered a decline in their income. The effect of the sex of the 1st birth over the 2nd birth varies with different localities. Among those having unplanned births, illiterates accounted for more than 35% in Nanzheng and Yanchuan counties and over 20% in Mianxian and Wubao counties. The current rise in 2nd births is due mainly not to economic reasons but to social and psychological reasons. To effectively hold down 2nd births under the current conditions, the following suggestions are offered: 1) step up propaganda and education work to gradually raise people's consciousness for practicing family planning, 2) family planning measures of economic restriction and reward must be implemented, 3) on the basis of enforcing the new marriage law, late marriage should be promoted, 4) a population tax should be imposed, and 5) social insurance for the elderly should be enlarged.

Predictors of accessing antiretroviral therapy among HIV-positive drug users in China's National Methadone Maintenance Treatment Programme.

PubMed

Zhao, Yan; Shi, Cynthia X; McGoogan, Jennifer M; Rou, Keming; Zhang, Fujie; Wu, Zunyou

2015-01-01

The objective of this study was to examine factors that predict antiretroviral therapy (ART) access among eligible, HIV-positive methadone maintenance treatment (MMT) clients. We also tested the hypothesis that sustained MMT participation increases the likelihood of accessing ART. A nation-wide cohort study conducted from 1 March 2004 to 31 December 2011. MMT clients were followed from the time of their enrolment in China's national MMT programme until their death or the study end date. Our cohort comprised 7111 ART-eligible, HIV-positive MMT clients, 49.2% of whom remained ART-naive and 50.8% of whom received ART. Demographic variables, drug use history, MMT programme participation and HIV-related clinical characteristics of study participants who remained naive to ART and those who accessed ART were compared by univariate and multivariable analysis. Predictors of accessing ART among this cohort included being retained in MMT at the time of first meeting ART eligibility [adjusted odds ratio (AOR)=1.84, confidence interval (CI)=1.54-2.21, P<0.001] compared to meeting ART eligibility before entering MMT (AOR=0.98, CI=0.80-1.21, P=0.849) or previously entering MMT and dropping out before meeting ART eligibility. Additional predictors were CD4≤200 cells/μl when ART-eligibility requirement was first met (AOR=1.81, CI=1.61-2.05, P<0.001 compared to CD4=201-350 cells/μl), and being in a stable partner relationship (married/cohabitating: AOR=1.14, CI=1.01-1.28, P=0.030). Retained participation in methadone maintenance treatment increases the likelihood that eligible clients will access antiretroviral therapy. These results highlight the potential benefit of colocalization of methadone maintenance treatment and antiretroviral therapy services in a 'one-stop-shop' model. © 2014 Society for the Study of Addiction.

Association between latent proviral characteristics and immune activation in antiretrovirus-treated human immunodeficiency virus type 1-infected adults.

PubMed

Liang, Emily C; Sceats, Lindsay; Bayless, Nicholas L; Strauss-Albee, Dara M; Kubo, Jessica; Grant, Philip M; Furman, David; Desai, Manisha; Katzenstein, David A; Davis, Mark M; Zolopa, Andrew R; Blish, Catherine A

2014-08-01

Generalized immune activation during HIV infection is associated with an increased risk of cardiovascular disease, neurocognitive disease, osteoporosis, metabolic disorders, and physical frailty. The mechanisms driving this immune activation are poorly understood, particularly for individuals effectively treated with antiretroviral medications. We hypothesized that viral characteristics such as sequence diversity may play a role in driving HIV-associated immune activation. We therefore sequenced proviral DNA isolated from peripheral blood mononuclear cells from HIV-infected individuals on fully suppressive antiretroviral therapy. We performed phylogenetic analyses, calculated viral diversity and divergence in the env and pol genes, and determined coreceptor tropism and the frequency of drug resistance mutations. Comprehensive immune profiling included quantification of immune cell subsets, plasma cytokine levels, and intracellular signaling responses in T cells, B cells, and monocytes. These antiretroviral therapy-treated HIV-infected individuals exhibited a wide range of diversity and divergence in both env and pol genes. However, proviral diversity and divergence in env and pol, coreceptor tropism, and the level of drug resistance did not significantly correlate with markers of immune activation. A clinical history of virologic failure was also not significantly associated with levels of immune activation, indicating that a history of virologic failure does not inexorably lead to increased immune activation as long as suppressive antiretroviral medications are provided. Overall, this study demonstrates that latent viral diversity is unlikely to be a major driver of persistent HIV-associated immune activation. Chronic immune activation, which is associated with cardiovascular disease, neurologic disease, and early aging, is likely to be a major driver of morbidity and mortality in HIV-infected individuals. Although treatment of HIV with antiretroviral medications decreases the level of immune activation, levels do not return to normal. The factors driving this persistent immune activation, particularly during effective treatment, are poorly understood. In this study, we investigated whether characteristics of the latent, integrated HIV provirus that persists during treatment are associated with immune activation. We found no relationship between latent viral characteristics and immune activation in treated individuals, indicating that qualities of the provirus are unlikely to be a major driver of persistent inflammation. We also found that individuals who had previously failed treatment but were currently effectively treated did not have significantly increased levels of immune activation, providing hope that past treatment failures do not have a lifelong "legacy" impact. Copyright © 2014, American Society for Microbiology. All Rights Reserved.

High prevalence of HIV-1 drug resistance among patients on first-line antiretroviral treatment in Lomé, Togo.

PubMed

Dagnra, Anoumou Y; Vidal, Nicole; Mensah, Akovi; Patassi, Akouda; Aho, Komi; Salou, Mounerou; Monleau, Marjorie; Prince-David, Mireille; Singo, Assétina; Pitche, Palokinam; Delaporte, Eric; Peeters, Martine

2011-06-10

With widespread use of antiretroviral (ARV) drugs in Africa, one of the major potential challenges is the risk of emergence of ARV drug-resistant HIV strains. Our objective is to evaluate the virological failure and genotypic drug-resistance mutations in patients receiving first-line highly active antiretroviral therapy (HAART) in routine clinics that use the World Health Organization public health approach to monitor antiretroviral treatment (ART) in Togo. Patients on HAART for one year (10-14 months) were enrolled between April and October 2008 at three sites in Lomé, the capital city of Togo. Plasma viral load was measured with the NucliSENS EasyQ HIV-1 assay (Biomérieux, Lyon, France) and/or a Generic viral load assay (Biocentric, Bandol, France). Genotypic drug-resistance testing was performed with an inhouse assay on plasma samples from patients with viral loads of more than 1000 copies/ml. CD4 cell counts and demographic data were also obtained from medical records. A total of 188 patients receiving first-line antiretroviral treatment were enrolled, and 58 (30.8%) of them experienced virologic failure. Drug-resistance mutations were present in 46 patients, corresponding to 24.5% of all patients enrolled in the study. All 46 patients were resistant to non-nucleoside reverse-transcriptase inhibitors (NNRTIs): of these, 12 were resistant only to NNRTIs, 25 to NNRTIs and lamivudine/emtricitabine, and eight to all three drugs of their ARV regimes. Importantly, eight patients were already predicted to be resistant to etravirine, the new NNRTI, and three patients harboured the K65R mutation, inducing major resistance to tenofovir. In Togo, efforts to provide access to ARV therapy for infected persons have increased since 2003, and scaling up of ART started in 2007. The high number of resistant strains observed in Togo shows clearly that the emergence of HIV drug resistance is of increasing concern in countries where ART is now widely used, and can compromise the long-term success of first- and second-line ART.

Cardiovascular risk and dyslipidemia among persons living with HIV: a review.

PubMed

Maggi, Paolo; Di Biagio, Antonio; Rusconi, Stefano; Cicalini, Stefania; D'Abbraccio, Maurizio; d'Ettorre, Gabriella; Martinelli, Canio; Nunnari, Giuseppe; Sighinolfi, Laura; Spagnuolo, Vincenzo; Squillace, Nicola

2017-08-09

Aim of this review is to focus the attention on people living with HIV infection at risk of developing a cardiovascular event. What is or what would be the most suitable antiretroviral therapy? Which statin or fibrate to reduce the risk? How to influence behavior and lifestyles? Prevention of cardiovascular disease (CVD) risk remains the first and essential step in a medical intervention on these patients. The lifestyle modification, including smoking cessation, increased physical activity, weight reduction, and the education on healthy dietary practices are the main instruments. Statins are the cornerstone for the treatment of hypercholesterolemia. They have been shown to slow the progression or promote regression of coronary plaque, and could also exert an anti-inflammatory and immunomodulatory effect. However the current guidelines for the use of these drugs in general population are dissimilar, with important differences between American and European ones. The debate between American and European guidelines is still open and, also considering the independent risk factor represented by HIV, specific guidelines are warranted. Ezetimibe reduces the intestinal absorption of cholesterol. It is effective alone or in combination with rosuvastatin. It does not modify plasmatic concentrations of antiretrovirals. A number of experimental new classes of drugs for the treatment of hypercholesterolemia are being studied. Fibrates represent the first choice for treatment of hypertriglyceridemia, however, the renal toxicity of fibrates and statins should be considered. Omega 3 fatty acids have a good safety profile, but their efficacy is limited. Another concern is the high dose needed. Other drugs are acipimox and tesamorelin. Current antiretroviral therapies are less toxic and more effective than regimens used in the early years. Lipodistrophy and dyslipidemia are the main causes of long-term toxicities. Not all antiretrovirals have similar toxicities. Protease Inhibitors may cause dyslipidemia and lipodystrophy, while integrase inhibitors have a minimal impact on lipids profile, and no evidence of lipodystrophy. There is still much to be written with the introduction of new drugs in clinical practice. Cardiovascular risk among HIV infected patients, interventions on behavior and lifestyles, use of drugs to reduce the risk, and switch in antiretroviral therapy, remain nowadays major issues in the management of HIV-infected patients.

Early antiretroviral therapy: rationale, protease inhibitor-sparing regimens and once daily dosing.

PubMed

Gatell, J M

1998-01-01

In 1998 it seems reasonable and widely accepted that all human immunodeficiency virus type 1 (HIV-1)-infected patients willing to be treated may benefit from receiving antiretroviral therapy. Only those with undetectable plasma HIV-1 RNA, normal CD4 lymphocyte counts and lack of markers of immunological system activation may be possible exceptions. The rationale supporting the early initiation of antiretroviral therapy are (i) data on viral dynamics; (ii) preliminary data pointing toward a better and a quicker restoration of immune function when treatment is initiated in very early stages (during or within a few weeks or months of acute symptomatic or asymptomatic HIV-1 infection); (iii) the lack of a stable viral load set-point even in patients in the early stages (CD4 > 500 cells/mm3) who have a very low viral load (< 5000 copies/ml); (iv) the relatively high likelihood of clinical progression at mid-term of the approximately 50-75% of patients in very early disease stages (CD4 > 500 cells/mm3) who have a plasma viral load above 5000 to 10,000 HIV-1 RNA copies/ml; (v) data from the Spanish Earth-1 study, which used a composite endpoint (virological, immunological or clinical progression), demonstrating that even in these very early stages of HIV-1 disease any antiretroviral therapy (double or triple combination) was better than no treatment. Even in early disease stages, a triple combination is needed to achieve a durable and profound virological and immunological response. In addition, the combination of stavudine plus didanosine has several advantages and can be considered one of the best double nucleoside combinations to combine with a protease inhibitor or with a non-nucleoside reverse transcriptase inhibitor. The INCAS study and the preliminary results of the ongoing Spanish SCAN study have demonstrated the possibility of protease inhibitor-sparing combinations for initial antiretroviral treatment, at least in selected patient subsets, such as those with a relatively low baseline viral load. Furthermore, components of these protease inhibitor-sparing combinations such as didanosine or nevirapine are suitable for once daily administration.

Analyzing the effect of selected control policy measures and sociodemographic factors on alcoholic beverage consumption in Europe within the AMPHORA project: statistical methods.

PubMed

Baccini, Michela; Carreras, Giulia

2014-10-01

This paper describes the methods used to investigate variations in total alcoholic beverage consumption as related to selected control intervention policies and other socioeconomic factors (unplanned factors) within 12 European countries involved in the AMPHORA project. The analysis presented several critical points: presence of missing values, strong correlation among the unplanned factors, long-term waves or trends in both the time series of alcohol consumption and the time series of the main explanatory variables. These difficulties were addressed by implementing a multiple imputation procedure for filling in missing values, then specifying for each country a multiple regression model which accounted for time trend, policy measures and a limited set of unplanned factors, selected in advance on the basis of sociological and statistical considerations are addressed. This approach allowed estimating the "net" effect of the selected control policies on alcohol consumption, but not the association between each unplanned factor and the outcome.

Reoperations within 48 hours following 7942 pediatric neurosurgery procedures.

PubMed

Roy, Anil K; Chu, Jason; Bozeman, Caroline; Sarda, Samir; Sawvel, Michael; Chern, Joshua J

2017-06-01

OBJECTIVE Various indicators are used to evaluate the quality of care delivered by surgical services, one of which is early reoperation rate. The indications and rate of reoperations within a 48-hour time period have not been previously reported for pediatric neurosurgery. METHODS Between May 1, 2009, and December 30, 2014, 7942 surgeries were performed by the pediatric neurosurgery service in the operating rooms at a single institution. Demographic, socioeconomic, and clinical characteristics associated with each of the operations were prospectively collected. The procedures were grouped into 31 categories based on the nature of the procedure and underlying diseases. Reoperations within 48 hours at the conclusion of the index surgery were reviewed to determine whether the reoperation was planned or unplanned. Multivariate logistic regression was employed to analyze risk factors associated with unplanned reoperations. RESULTS Cerebrospinal fluid shunt-and hydrocephalus-related surgeries accounted for 3245 (40.8%) of the 7942 procedures. Spinal procedures, craniotomy for tumor resections, craniotomy for traumatic injury, and craniofacial reconstructions accounted for an additional 8.7%, 6.8%, 4.5%, and 4.5% of surgical volume. There were 221 reoperations within 48 hours of the index surgery, yielding an overall incidence of 2.78%; 159 of the reoperation were unplanned. Of these 159 unplanned reoperations, 121 followed index operations involving shunt manipulations. Using unplanned reoperations as the dependent variable (n = 159), index operations with a starting time after 3 pm and admission through the emergency department (ED) were associated with a two- to threefold increase in the likelihood of reoperations (after-hour surgery, odds ratio [OR] 2.01 [95% CI 1.43-2.83, p < 0.001]; ED admission, OR 1.97 (95% CI 1.32-2.96, p < 0.05]). CONCLUSIONS Approximately 25% of the reoperations within 48 hours of a pediatric neurosurgical procedure were planned. When reoperations were unplanned, contributing factors could be both surgeon related and system related. Further study is required to determine the extent to which these reoperations are preventable. The utility of unplanned reoperation as a quality indicator is dependent on proper definition, analysis, and calculation.

Cost-efficacy analysis of the MONET trial using UK antiretroviral drug prices.

PubMed

Gazzard, Brian; Hill, Andrew; Anceau, Anne

2011-07-01

In virologically suppressed patients, switching to darunavir/ritonavir (DRV/r) monotherapy maintains HIV RNA suppression, and could also lower treatment costs. The purpose of this analysis was to calculate the potential cost savings from the use of DRV/r monotherapy in the UK. In the MONET trial, 256 patients with HIV RNA < 50 copies/mL on current highly active antiretroviral therapy (HAART) for over 24 weeks (non-nucleoside reverse-transcriptase inhibitor [NNRTI] based [43%] or protease inhibitor [PI] based [57%]), switched to DRV/r 800/100 mg once daily, either as monotherapy (n = 127) or with two NRTIs (n = 129). The UK costs per patient with HIV RNA < 50 copies/mL at week 48 (responders) were calculated using a 'switch included' analysis to account for additional antiretrovirals taken after initial treatment failure. By this analysis, efficacy was 93.5% versus 95.1% in the DRV/r monotherapy and triple therapy arms, respectively. British National Formulary 2009 values were used. Before the trial, the mean annual cost of antiretrovirals was £6906 for patients receiving NNRTI-based HAART, and £8348 for patients receiving PI-based HAART. During the MONET trial, the mean annual per-patient cost of antiretrovirals was £8642 in the triple therapy arm, of which 55% was from NRTIs and 45% from PIs. The mean per-patient cost in the monotherapy arm was £4126, a saving of 52% versus triple therapy. The mean cost per responder was £9085 in the triple therapy arm versus £4413 in the DRV/r monotherapy arm. Based on the MONET results, the lower cost of DRV/r monotherapy versus triple therapy in the UK would allow more patients to be treated for fixed budgets, while maintaining HIV RNA suppression at < 50 copies/mL. If all patients meeting the inclusion criteria of the MONET trial in the UK were switched to DRV/r monotherapy, there is the potential to save up to £60 million in antiretroviral drug costs from the UK NHS budget.

Cost-effectiveness of community-based strategies to strengthen the continuum of HIV care in rural South Africa: a health economic modelling analysis.

PubMed

Smith, Jennifer A; Sharma, Monisha; Levin, Carol; Baeten, Jared M; van Rooyen, Heidi; Celum, Connie; Hallett, Timothy B; Barnabas, Ruanne V

2015-04-01

Home HIV counselling and testing (HTC) achieves high coverage of testing and linkage to care compared with existing facility-based approaches, particularly among asymptomatic individuals. In a modelling analysis we aimed to assess the effect on population-level health and cost-effectiveness of a community-based package of home HTC in KwaZulu-Natal, South Africa. We parameterised an individual-based model with data from home HTC and linkage field studies that achieved high coverage (91%) and linkage to antiretroviral therapy (80%) in rural KwaZulu-Natal, South Africa. Costs were derived from a linked microcosting study. The model simulated 10,000 individuals over 10 years and incremental cost-effectiveness ratios were calculated for the intervention relative to the existing status quo of facility-based testing, with costs discounted at 3% annually. The model predicted implementation of home HTC in addition to current practice to decrease HIV-associated morbidity by 10–22% and HIV infections by 9–48% with increasing CD4 cell count thresholds for antiretroviral therapy initiation. Incremental programme costs were US$2·7 million to $4·4 million higher in the intervention scenarios than at baseline, and costs increased with higher CD4 cell count thresholds for antiretroviral therapy initiation; antiretroviral therapy accounted for 48–87% of total costs. Incremental cost-effectiveness ratios per disability-adjusted life-year averted were $1340 at an antiretroviral therapy threshold of CD4 count lower than 200 cells per μL, $1090 at lower than 350 cells per μL, $1150 at lower than 500 cells per μL, and $1360 at universal access to antiretroviral therapy. Community-based HTC with enhanced linkage to care can result in increased HIV testing coverage and treatment uptake, decreasing the population burden of HIV-associated morbidity and mortality. The incremental cost-effectiveness ratios are less than 20% of South Africa's gross domestic product per person, and are therefore classed as very cost effective. Home HTC can be a viable means to achieve UNAIDS' ambitious new targets for HIV treatment coverage. National Institutes of Health, Bill & Melinda Gates Foundation, Wellcome Trust.

Quality of life, anxiety and depression in patients with HIV/AIDS who present poor adherence to antiretroviral therapy: a cross-sectional study in Salvador, Brazil.

PubMed

Betancur, Mónica Narváez; Lins, Liliane; Oliveira, Irismar Reis de; Brites, Carlos

The introduction of highly active antiretroviral therapy marked a major gain in efficacy of HIV/AIDS treatment and a reduction in morbidity and mortality of the infected patients. However, high levels of adherence are required to obtain virologic suppression. In Brazil, the policy of free and universal access to antiretroviral therapy has been in place since 1996, although there are reports of poor adherence. To define the clinical, demographic and psychological characteristics, and quality of life of patients with HIV/AIDS who present poor adherence to highly active antiretroviral therapy. This was a cross-sectional study. To be included in the study patients had to be 18 through 65 years old, diagnosed with HIV/AIDS, having the two previous viral loads above 500 copies, a surrogate for poor adherence to antiretrovirals. The following instruments were applied to all eligible patients: the sociodemographic questionnaire "Adherence Follow-up Questionnaire", the Beck Depression Inventory (BDI-II), the Beck Anxiety Inventory (BAI), and the 36-Item Short Form Survey. 47 patients were evaluated, 70.2% were female, mean age of 41.9 years (±10.5), 46.8% were single, 51.1% self-reported adherence ≥95%, 46.8% mentioned depression as the main reason for not taking the medication, 59.5% presented symptoms of moderate to severe depression, and 44.7% presented symptoms of moderate to severe anxiety. Finally, regarding health-related quality of life these patients obtained low scores in all dimensions, physical component summary of 43.96 (±9.64) and mental component summary of 33.19 (±13.35). The psychological component is considered to be fundamental in the management of HIV/AIDS patients. Psychoeducation should be conducted at the initial evaluation to reduce negative beliefs regarding antiretroviral therapy Assessment of anxiety and depression symptoms should be done throughout therapy as both psycological conditions are associated with patient adherence, success of treatment, and ultimately with patients' quality of life. Copyright © 2017 Sociedade Brasileira de Infectologia. Published by Elsevier Editora Ltda. All rights reserved.

Synergistic vulnerabilities: antiretroviral treatment among women in Uganda.

PubMed

Winchester, Margaret S

2015-01-01

Despite being an early success story in the reduction of HIV infection rates, Uganda faces myriad challenges in the recent era of accelerated antiretroviral treatment (ARV) scale-up. For those able to access treatment, ongoing vulnerabilities of poverty and violence compound treatment-related costs and concerns. This paper explores experiences of one particularly vulnerable population - women on ARVs who have also experienced intimate partner violence (IPV). Data were collected over 12 months in Uganda. They include ethnographic interviews (n = 40) drawn from a larger sample of women on ARV and semi-structured interviews with policy-makers and service providers (n = 42), examining the intersection of experiences and responses to treatment from multiple perspectives. Women's narratives show that due to treatment, immediate health concerns take on secondary importance, while other forms of vulnerability, including IPV and poverty, can continue to shape treatment experiences and the decision to stay in violent relationships. Providers likewise face difficulties in overburdened clinics, though they recognise women's concerns and the importance of considering other forms of vulnerability in treatment. This analysis makes the case for integrating treatment with other types of social services and demonstrates the importance of understanding the ways in which synergistic and compounding vulnerabilities confound treatment scale-up efforts.

Identifying risk factors of immune reconstitution inflammatory syndrome in AIDS patients receiving highly active anti-retroviral therapy.

PubMed

He, Bo; Zheng, Yuhuang; Liu, Meng; Zhou, Guoqiang; Chen, Xia; Mamadou, Diallo; He, Yan; Zhou, Huaying; Chen, Zi

2013-01-01

Immune reconstitution inflammation syndrome typically occurs within days after patients undergo highly active anti-retroviral therapy and is a big hurdle for effective treatment of AIDS patients. In this study, we monitored immune reconstitution inflammation syndrome occurrence in 238 AIDS patients treated with highly active anti-retroviral therapy. Among them, immune reconstitution inflammation syndrome occurred in 47 cases (19.7%). Immune reconstitution inflammation syndrome patients had significantly higher rate of opportunistic infection (p<0.001) and persistently lower CD4(+) cell count (p<0.001) compared to the non-immune reconstitution inflammation syndrome patients. In contrast, no significant differences in HIV RNA loads were observed between the immune reconstitution inflammation syndrome group and non-immune reconstitution inflammation syndrome group. These data suggest that a history of opportunistic infection and CD4(+) cell counts at baseline may function as risk factors for immune reconstitution inflammation syndrome occurrence in AIDS patients as well as potential prognostic markers. These findings will improve the management of AIDS with highly active anti-retroviral therapy. Copyright © 2013 Elsevier Editora Ltda. All rights reserved.

Current and emerging formulation strategies for the effective transdermal delivery of HIV inhibitors.

PubMed

Ham, Anthony S; Buckheit, Robert W

2015-02-01

Current and emerging formulation strategies for skin permeation are poised to open the transdermal drug delivery to a broader range of small molecule compounds that do not fit the traditional requirements for successful transdermal drug delivery, allowing the development of new patch technologies to deliver antiretroviral drugs that were previously incapable of being delivered through transdermal means. Transdermal drug delivery offers several distinct advantages over traditional dosage forms. Current antiretroviral drugs used for the treatment of HIV infection include a variety of highly active small molecule compounds with significantly limited skin permeability, and thus new and novel means of enhancing transport through the skin are needed. Current and emerging formulation strategies are poised to open the transdermal drug delivery to a broader range of compounds that do not fit the traditional requirements for successful transdermal drug delivery, allowing the development of new patch technologies to deliver antiretroviral drugs that were previously incapable of being delivered through transdermal means. Thus, with continuing research into skin permeability and patch formulation strategies, there is a large potential for antiretroviral transdermal drug delivery.

Current and emerging formulation strategies for the effective transdermal delivery of HIV inhibitors

PubMed Central

Ham, Anthony S; Buckheit, Robert W

2015-01-01

Current and emerging formulation strategies for skin permeation are poised to open the transdermal drug delivery to a broader range of small molecule compounds that do not fit the traditional requirements for successful transdermal drug delivery, allowing the development of new patch technologies to deliver antiretroviral drugs that were previously incapable of being delivered through transdermal means. Transdermal drug delivery offers several distinct advantages over traditional dosage forms. Current antiretroviral drugs used for the treatment of HIV infection include a variety of highly active small molecule compounds with significantly limited skin permeability, and thus new and novel means of enhancing transport through the skin are needed. Current and emerging formulation strategies are poised to open the transdermal drug delivery to a broader range of compounds that do not fit the traditional requirements for successful transdermal drug delivery, allowing the development of new patch technologies to deliver antiretroviral drugs that were previously incapable of being delivered through transdermal means. Thus, with continuing research into skin permeability and patch formulation strategies, there is a large potential for antiretroviral transdermal drug delivery. PMID:25690088

Antiretrovirals and safer conception for HIV-serodiscordant couples

PubMed Central

Matthews, Lynn T.; Smit, Jennifer A.; Cu-Uvin, Susan; Cohan, Deborah

2013-01-01

Purpose of review Many men and women living with HIV and their uninfected partners attempt to conceive children. HIV-prevention science can be applied to reduce sexual transmission risk while respecting couples’ reproductive goals. Here we discuss antiretrovirals as prevention in the context of safer conception for HIV-serodiscordant couples. Recent findings Antiretroviral therapy (ART) for the infected partner and pre-exposure prophylaxis (PrEP) for the uninfected partner reduce the risk of heterosexual HIV transmission. Several demonstration projects suggest the feasibility and acceptability of antiretroviral (ARV)s as periconception HIV-prevention for HIV-serodiscordant couples. The application of ARVs to periconception risk reduction may be limited by adherence. Summary For male-infected (M+F−) couples who cannot access sperm processing and female-infected (F+M−) couples unwilling to carry out insemination without intercourse, ART for the infected partner, PrEP for the uninfected partner, combined with treatment for sexually transmitted infections, sex limited to peak fertility, and medical male circumcision (for F+M couples) provide excellent, well tolerated options for reducing the risk of periconception HIV sexual transmission. PMID:23032734

The prevalence of unplanned pregnancy ending in birth, associated factors, and health outcomes.

PubMed

Goossens, J; Van Den Branden, Y; Van der Sluys, L; Delbaere, I; Van Hecke, A; Verhaeghe, S; Beeckman, D

2016-12-01

What are associated factors of unplanned pregnancies ending in birth? Pregnancies that were less planned were associated with women of lower socio-economic status (SES), an unhealthier lifestyle before and during the pregnancy, more stress, and less social support. In Europe, the prevalence of unplanned pregnancy leading to birth varies. Unplanned pregnancy is more common among socially disadvantaged women, and associated with adverse pregnancy outcomes. In a cross-sectional study, 517 women were recruited from May through September 2015. Women were recruited from six hospitals in Flanders, Belgium. Data from self-report and medical records were collected during the first 5 days postpartum. The validated London Measure of Unplanned Pregnancy was used to collect data regarding pregnancy planning. Data were analysed with Mann-Whitney U tests, Kruskal-Wallis tests, and multiple linear regression analysis. The majority of the pregnancies (83%) ending in birth were planned, 15% were ambivalent, and 2% unplanned. Women who are multigravida (95% CI -0.30 to -0.02), less well educated (95% CI 0.07-0.85), single or having a non-cohabiting relationship (95% CI 0.01-2.53), having history of drug abuse (95% CI -2.07 to -0.35), and experiencing intimate partner violence (95% CI -3.82 to -1.59) tended to have a significantly higher risk of a less planned pregnancy. Less planned pregnancies were significantly associated with initially unwanted pregnancies (P < 0.001), no folic acid or vitamin use before pregnancy (P < 0.001), lower number of prenatal visits (P = 0.03), smoking during pregnancy (P < 0.001), more stress (P = 0.002), lower relationship satisfaction (P = 0.001), and less social support (P < 0.001). Less planned pregnancies were also significantly associated with hyperemesis (P < 0.001) and shorter duration of delivery (P = 0.03). No differences were found in neonatal outcomes. The prevalence of unplanned pregnancies is probably underestimated due to overrepresentation of women with higher SES in this study. Women's emotions may have influenced the answer to certain questions. Owing to the cross-sectional design, no causal relationships could be established. This study emphasizes the importance of targeting socially disadvantaged women in the prevention of unplanned pregnancies. This study was funded by the Research Foundation - Flanders (FWO). The authors have no conflict of interests. Not applicable. © The Author 2016. Published by Oxford University Press on behalf of the European Society of HumanReproduction and Embryology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Undisclosed antiretroviral drug use in a multinational clinical trial (HIV Prevention Trials Network 052).

PubMed

Fogel, Jessica M; Wang, Lei; Parsons, Teresa L; Ou, San-San; Piwowar-Manning, Estelle; Chen, Ying; Mudhune, Victor O; Hosseinipour, Mina C; Kumwenda, Johnstone; Hakim, James G; Chariyalertsak, Suwat; Panchia, Ravindre; Sanne, Ian; Kumarasamy, Nagalingeswaran; Grinsztejn, Beatriz; Makhema, Joseph; Pilotto, Jose; Santos, Breno R; Mayer, Kenneth H; McCauley, Marybeth; Gamble, Theresa; Bumpus, Namandjé N; Hendrix, Craig W; Cohen, Myron S; Eshleman, Susan H

2013-11-15

The HIV Prevention Trials Network 052 study enrolled serodiscordant couples. Index participants infected with human immunodeficiency virus reported no prior antiretroviral (ARV) treatment at enrollment. ARV drug testing was performed retrospectively using enrollment samples from a subset of index participants. ARV drugs were detected in 45 of 96 participants (46.9%) with an undetectable viral load, 2 of 48 (4.2%) with a low viral load, and 1 of 65 (1.5%) with a high viral load (P < .0001); they were also detected in follow-up samples from participants who were not receiving study-administered treatment. ARV drug testing may be useful in addition to self-report of ARV drug use in some clinical trial settings.

[Care for women with HIV: gender perspectives].

PubMed

Ko, Nai-Ying

2011-12-01

When women face social and cultural inequality they inevitably bear increased HIV infection risks. The success of antiretroviral therapies in suppressing HIV's viral load and prolonging patient lives has made HIV a treatable chronic disease. Given the same follow-up treatments, research shows no significant differences between men and women in terms of either clinical, immunological or virological parameters at baseline or mortality after one year of antiretroviral therapy. Also, advances in assisted reproductive technologies now makes having HIV-free children possible for HIV couples. Gender equality and human right are essential to effective HIV prevention. Nurses must take all appropriate measures to eliminate discrimination against women in HIV prevention, treatment and care programs in order to ensure equal gender access to critical healthcare services.

The Effect of Antiretroviral Combination Treatment on Epstein-Barr Virus (EBV) Genome Load in HIV-Infected Patients

PubMed Central

Friis, Anna M. C.; Gyllensten, Katarina; Aleman, Anna; Ernberg, Ingemar; Åkerlund, Börje

2010-01-01

We evaluated the effect of combination anti-retroviral treatment (cART) on the host control of EBV infection in moderately immunosuppressed HIV-1 patients. Twenty HIV-1 infected individuals were followed for five years with repeated measurements of EBV DNA load in peripheral blood lymphocytes in relation to HIV-RNA titers and CD4+ cell counts. Individuals with optimal response, i.e. durable non-detectable HIV-RNA, showed a decline of EBV load to the level of healthy controls. Individuals with non-optimal HIV-1 control did not restore their EBV control. Long-lasting suppression of HIV-replication after early initiation of cART is a prerequisite for re-establishing the immune control of EBV. PMID:21994658

Which Patients First? Setting Priorities for Antiretroviral Therapy Where Resources Are Limited

PubMed Central

McGough, Laura J.; Reynolds, Steven J.; Quinn, Thomas C.; Zenilman, Jonathan M.

2005-01-01

The availability of limited funds from international agencies for the purchase of antiretroviral (ARV) treatment in developing countries presents challenges, especially in prioritizing who should receive therapy. Public input and the protection of human rights are crucial in making treatment programs equitable and accountable. By examining historical precedents of resource allocation, we aim to provoke and inform debate about current ARV programs. Through a critical review of the published literature, we evaluate 4 precedents for key lessons: the discovery of insulin for diabetes in 1922, the release of penicillin for civilian use in 1943, the development of chronic hemodialysis programs in 1961, and current allocation of liver transplants. We then describe current rationing mechanisms for ARVs. PMID:15983271

Novel antiretroviral combinations in treatment-experienced patients with HIV infection: rationale and results.

PubMed

Taiwo, Babafemi; Murphy, Robert L; Katlama, Christine

2010-09-10

Novel antiretroviral drugs offer different degrees of improvement in activity against drug-resistant HIV, short- and long-term tolerability, and dosing convenience compared with earlier drugs. Those drugs approved more recently and commonly used in treatment-experienced patients include the entry inhibitor enfuvirtide, protease inhibitors (PIs) [darunavir and tipranavir], a C-C chemokine receptor (CCR) type 5 antagonist (maraviroc), an integrase inhibitor (raltegravir) and etravirine, a non-nucleoside reverse transcriptase inhibitor (NNRTI). Novel agents in earlier stages of development include a CCR5 monoclonal antibody (PRO 140) administered subcutaneously once weekly, once-daily integrase inhibitors (elvitegravir and S/GSK1349572), and several nucleoside (nucleotide) reverse transcriptase inhibitors and NNRTIs. Bevirimat, a maturation inhibitor, has compromised activity in the presence of relatively common Gag polymorphisms. Viral suppression is necessary to control the evolution of drug resistance, reduce chronic immune activation that probably underlies the excess morbidity and mortality in HIV-infected patients, and reduce viral transmission, including transmitted drug resistance. In general, the proportion of viraemic patients who achieve suppression increases with the number of active pharmacokinetically compatible antiretroviral drugs in the regimen. In the ANRS139-TRIO trial, 86% of highly treatment-experienced patients treated with darunavir-ritonavir, etravirine and raltegravir had HIV RNA <50 copies/mL at 48 weeks. In patients who had received at least 12 weeks of a stable regimen and had no darunavir resistance-associated mutations, once-daily darunavir boosted with ritonavir 100 mg was virologically noninferior with better lipid effects than with the twice-daily dosing, which requires a 200 mg total daily dose of ritonavir. Raltegravir plus a boosted PI is being investigated for second-line therapy in patients not responding to NNRTI-based first-line treatment in resource-limited settings (RLS). However, concerns about this potential strategy include the low barrier against resistance of raltegravir, limited penetration of some PIs into the CNS and the unknown impact of integrase polymorphisms seen more commonly in non-B subtype HIV-1. In patients who have already achieved viral suppression, novel agents may be used to simplify the dosing schedule, lower costs (such as by switching to boosted PI monotherapy), reduce adverse events or preserve antiretroviral drug options, especially since the absence of an HIV eradication strategy implies the need for life-long combination antiretroviral therapy. Switching enfuvirtide to raltegravir eliminated painful injection-site reactions without compromising virological suppression. Two studies found different virological outcomes when patients were switched from lopinavir/ritonavir to raltegravir, but there was an improvement in the lipid profile. Simplifying to darunavir-ritonavir monotherapy after suppression of plasma HIV RNA to <50 copies/mL has been found to be safe with no emergence of resistance in cases of viral rebound, but longer-term data are needed. The initial suggestion that maraviroc may possess unique CD4+ T-cell boosting effects was not confirmed in several clinical trials. Improved understanding of HIV pathogenesis has opened new frontiers for research such as identifying the sources, consequences and optimal management of residual viraemia in those with plasma HIV RNA <50 copies/mL. Globally, however, one of the most urgent priorities is providing the increasing number of treatment-experienced virologically failing patients in RLS with access to optimal treatment, including those treatments based on novel antiretroviral agents.

Predicting the Necessity for Extracorporeal Circulation During Lung Transplantation: A Feasibility Study.

PubMed

Hinske, Ludwig Christian; Hoechter, Dominik Johannes; Schröeer, Eva; Kneidinger, Nikolaus; Schramm, René; Preissler, Gerhard; Tomasi, Roland; Sisic, Alma; Frey, Lorenz; von Dossow, Vera; Scheiermann, Patrick

2017-06-01

The factors leading to the implementation of unplanned extracorporeal circulation during lung transplantation are poorly defined. Consequently, the authors aimed to identify patients at risk for unplanned extracorporeal circulation during lung transplantation. Retrospective data analysis. Single-center university hospital. A development data set of 170 consecutive patients and an independent validation cohort of 52 patients undergoing lung transplantation. The authors investigated a cohort of 170 consecutive patients undergoing single or sequential bilateral lung transplantation without a priori indication for extracorporeal circulation and evaluated the predictive capability of distinct preoperative and intraoperative variables by using automated model building techniques at three clinically relevant time points (preoperatively, after endotracheal intubation, and after establishing single-lung ventilation). Preoperative mean pulmonary arterial pressure was the strongest predictor for unplanned extracorporeal circulation. A logistic regression model based on preoperative mean pulmonary arterial pressure and lung allocation score achieved an area under the receiver operating characteristic curve of 0.85. Consequently, the authors developed a novel 3-point scoring system based on preoperative mean pulmonary arterial pressure and lung allocation score, which identified patients at risk for unplanned extracorporeal circulation and validated this score in an independent cohort of 52 patients undergoing lung transplantation. The authors showed that patients at risk for unplanned extracorporeal circulation during lung transplantation could be identified by their novel 3-point score. Copyright © 2017 Elsevier Inc. All rights reserved.

The effect of retail cigarette pack displays on unplanned purchases: results from immediate postpurchase interviews.

PubMed

Carter, O B J; Mills, B W; Donovan, R J

2009-06-01

To assess the influence of point-of-sale (POS) cigarette displays on unplanned purchases. Intercept interviews were conducted with customers observed purchasing cigarettes from retail outlets featuring POS cigarette displays. Measures included intention to purchase cigarettes prior to entering the store, unprompted and prompted salience of POS tobacco displays, urge to buy cigarettes as a result of seeing the POS display, brand switching and support for a ban on POS cigarette displays. In total, 206 daily smokers aged 18-76 years (90 male, 116 female) were interviewed. Unplanned cigarette purchases were made by 22% of participants. POS displays influenced nearly four times as many unplanned purchases as planned purchases (47% vs 12%, p<0.01). Brand switching was reported among 5% of participants, half of whom were influenced by POS displays. Four times as many smokers were supportive of a ban on POS tobacco displays than unsupportive (49% vs 12%), and 28% agreed that such a ban would make it easier to quit. POS tobacco displays act as a form of advertising even in the absence of advertising materials. They stimulate unplanned cigarette purchases, play an important role in brand selection and tempt smokers trying to quit. This justifies removing POS tobacco displays from line of sight-something that very few smokers in our sample would object to.

Metabolic complications associated with HIV protease inhibitor therapy.

PubMed

Nolan, David

2003-01-01

HIV protease inhibitors were introduced into clinical practice over 7 years ago as an important component of combination antiretroviral drug regimens which in many ways revolutionised the treatment of HIV infection. The significant improvements in prognosis that have resulted from the use of these regimens, combined with the need for lifelong treatment, have increasingly focused attention on the adverse effects of antiretroviral drugs and on the metabolic complications of HIV protease inhibitors in particular. In this review, the cluster of metabolic abnormalities characterised by triglyceride-rich dyslipidaemia and insulin resistance associated with HIV protease inhibitor therapy are considered, along with implications for cardiovascular risk in patients affected by these complications. Toxicity profiles of individual drugs within the HIV protease inhibitor class are examined, as there is an increased recognition of significant intra-class differences both in terms of absolute risk of metabolic complications as well as the particular metabolic phenotype associated with these drugs. Guidelines for clinical assessment and treatment are emphasised, along with pathophysiological mechanisms that may provide a rational basis for the treatment of metabolic complications. Finally, these drug-specific effects are considered within the context of HIV-specific effects on lipid metabolism as well as lifestyle factors that have contributed to a rapidly increasing incidence of similar metabolic syndromes in the general population. These data highlight the importance of individualising patient management in terms of choice of antiretroviral regimen, assessment of metabolic outcomes and use of therapeutic interventions, based on the assessment of baseline (pre-treatment) metabolic status as well as the presence of potentially modifiable cardiovascular risk factors.

Modeling the virus-immune system interactions in the peripheral bloodstream of HIV infected individuals using a cellular automata model with considering the effects of antiretroviral therapy.

PubMed

Golpayegani, Gelayol Nazari; Jafari, Amir Homayoun; Dabanloo, Nader Jafarnia

2017-01-01

According to the World Health Organization, by the end of last year, about 37 million people throughout the world were diagnosed with AIDS and millions of people die each year from this disease. To develop an appropriate model which depicts the mechanism of the dynamics involved in the interactions between HIV and immune system in peripheral bloodstream of HIV infected individuals by considering the phenomena of virus mutation and taking into account the role of latently infected cells in speared of infection and considering the effects of antiretroviral drugs and occurrence of drug resistance in our model in order to assess the results obtained from applying different therapeutic methods. Two-dimensional CA model with Moor neighboring was developed. Various agents which they were referring to peripheral bloodstream particles of HIV infected individuals were defined. Then the biological rules were extracted from both expert knowledge and the authoritative articles. The extracted rules were applied for updating the states of these agents. The effects of using antiretroviral drug treatment were considered by applying drug's effectiveness of both of protease and reverse transcriptase inhibitors as two separate inputs of model. Time evolution curves of concentrations of defined agents were shown as our results. In case of considering no treatment, our results showed that concentrations of healthy CD4+T cells reached the threshold of AIDS after a bout 250 weeks. By applying monotherapy method, the concentrations of these cells remained on the threshold of AIDS for a long time and applying combined antiretroviral therapy (cART) method leaded to increase the concentration of these cells 20% upper than threshold of AIDS. Also, by applying monotherapy and cART compared with no treatment, the concentrations of infected CD4+T cells 10% and 40% decreased further, respectively and for the level of viral load, leads to a reduction of almost 55% and 90%, respectively. Belated treatment, comparison with early treatment, caused almost 10% reduce (increase) in steady state concentrations of healthy (infected) cells.

Socio-economic impact of antiretroviral treatment in HIV patients. An economic review of cost savings after introduction of HAART.

PubMed

Gonzalo, Teresa; García Goñi, Manuel; Muñoz-Fernández, María Angeles

2009-01-01

Star celebrities such as Rock Hudson, Freddie Mercury, Magic Johnson, and Isaac Asimov have unfortunately something in common: they were all victims of the HIV global pandemic. Since then HIV infection has become considered a pandemic disease, and it is regarded as a priority in healthcare worldwide. It is ranked as the first cause of death among young people in industrialized countries, and it is recognized as a public healthcare problem due to its human, social, mass media, and economic impact. Incorporation of new and highly active antiretroviral treatment, available since 1996 for HIV/AIDS treatment, has provoked a radical change in the disease pattern, as well as in the impact on patient survival and quality of life. The pharmaceutical industry's contribution, based on the research for more active new drugs, has been pivotal. Mortality rates have decreased significantly in 20 years by 50% and now AIDS is considered a chronic and controlled disease. In this review we have studied the impact of HAART treatment on infected patients, allowing them to maintain their status as active workers and the decreased absenteeism from work derived from this, contributing ultimately to overall social wealth and, thus, to economic growth. Furthermore, an analysis of the impact on healthcare costs, quality of life per year, life per year gained, cost economic savings and cost opportunity among other parameters has shown that society and governments are gaining major benefits from the inclusion of antiretroviral therapies in HIV/AIDS patients.

Plasma Metabolomics Biosignature According to HIV Stage of Infection, Pace of Disease Progression, Viremia Level and Immunological Response to Treatment

PubMed Central

Scarpelini, Bruno; Zanoni, Michelle; Sucupira, Maria Cecilia Araripe; Truong, Hong-Ha M.; Janini, Luiz Mario Ramos; Segurado, Ismael Dale Cotrin; Diaz, Ricardo Sobhie

2016-01-01

Background We evaluated plasma samples HIV-infected individuals with different phenotypic profile among five HIV-infected elite controllers and five rapid progressors after recent HIV infection and one year later and from 10 individuals subjected to antiretroviral therapy, five of whom were immunological non-responders (INR), before and after one year of antiretroviral treatment compared to 175 samples from HIV-negative patients. A targeted quantitative tandem mass spectrometry metabolomics approach was used in order to determine plasma metabolomics biosignature that may relate to HIV infection, pace of HIV disease progression, and immunological response to treatment. Results Twenty-five unique metabolites were identified, including five metabolites that could distinguish rapid progressors and INRs at baseline. Severe deregulation in acylcarnitine and sphingomyelin metabolism compatible with mitochondrial deficiencies was observed. β-oxidation and sphingosine‐1‐phosphate-phosphatase-1 activity were down-regulated, whereas acyl-alkyl-containing phosphatidylcholines and alkylglyceronephosphate synthase levels were elevated in INRs. Evidence that elite controllers harbor an inborn error of metabolism (late-onset multiple acyl-coenzyme A dehydrogenase deficiency [MADD]) was detected. Conclusions Blood-based markers from metabolomics show a very high accuracy of discriminating HIV infection between varieties of controls and have the ability to predict rapid disease progression or poor antiretroviral immunological response. These metabolites can be used as biomarkers of HIV natural evolution or treatment response and provide insight into the mechanisms of the disease. PMID:27941971

Characterization of Nucleoside Reverse Transcriptase Inhibitor-Associated Mutations in the RNase H Region of HIV-1 Subtype C Infected Individuals.

PubMed

Ngcapu, Sinaye; Theys, Kristof; Libin, Pieter; Marconi, Vincent C; Sunpath, Henry; Ndung'u, Thumbi; Gordon, Michelle L

2017-11-08

The South African national treatment programme includes nucleoside reverse transcriptase inhibitors (NRTIs) in both first and second line highly active antiretroviral therapy regimens. Mutations in the RNase H domain have been associated with resistance to NRTIs but primarily in HIV-1 subtype B studies. Here, we investigated the prevalence and association of RNase H mutations with NRTI resistance in sequences from HIV-1 subtype C infected individuals. RNase H sequences from 112 NRTI treated but virologically failing individuals and 28 antiretroviral therapy (ART)-naive individuals were generated and analysed. In addition, sequences from 359 subtype C ART-naive sequences were downloaded from Los Alamos database to give a total of 387 sequences from ART-naive individuals for the analysis. Fisher's exact test was used to identify mutations and Bayesian network learning was applied to identify novel NRTI resistance mutation pathways in RNase H domain. The mutations A435L, S468A, T470S, L484I, A508S, Q509L, L517I, Q524E and E529D were more prevalent in sequences from treatment-experienced compared to antiretroviral treatment naive individuals, however, only the E529D mutation remained significant after correction for multiple comparison. Our findings suggest a potential interaction between E529D and NRTI-treatment; however, site-directed mutagenesis is needed to understand the impact of this RNase H mutation.

The Economic Impact of AIDS Treatment: Labor Supply in Western Kenya

ERIC Educational Resources Information Center

Thirumurthy, Harsha; Zivin, Joshua Graff; Goldstein, Markus

2008-01-01

Using longitudinal survey data collected in collaboration with a treatment program, this paper estimates the economic impacts of antiretroviral treatment. The responses in two outcomes are studied: (1) labor supply of treated adult AIDS patients; and (2) labor supply of individuals in patients' households. Within six months after treatment…

"Damaging what wasn't damaged already": psychological tension and antiretroviral adherence among HIV-infected methadone-maintained drug users.

PubMed

Batchelder, A W; Brisbane, M; Litwin, A H; Nahvi, S; Berg, K M; Arnsten, J H

2013-01-01

Active drug use among HIV-infected persons is associated with poor adherence to highly active antiretroviral therapy (HAART) and suboptimal treatment outcomes. To understand adherence experiences among HIV-infected drug users, we conducted semistructured interviews with 15 participants in a randomized controlled trial evaluating the efficacy of directly observed HAART delivered in methadone maintenance clinics. Interviews were recorded, transcribed, and thematically analyzed. We identified negative and positive psychological themes associated with both drug use and adherence. Participants described tension between negative feelings (denial, shame, and perceived isolation) and positive feelings (acceptance, motivation, empowerment, and perceived connectedness), and they associated this tension with their own drug using and adherence behaviors. Sustained antiretroviral therapy adherence may require increased emphasis on understanding the psychological experience of HIV-infected drug users.

Cellular automata approach for the dynamics of HIV infection under antiretroviral therapies: The role of the virus diffusion

NASA Astrophysics Data System (ADS)

González, Ramón E. R.; de Figueirêdo, Pedro Hugo; Coutinho, Sérgio

2013-10-01

We study a cellular automata model to test the timing of antiretroviral therapy strategies for the dynamics of infection with human immunodeficiency virus (HIV). We focus on the role of virus diffusion when its population is included in previous cellular automata model that describes the dynamics of the lymphocytes cells population during infection. This inclusion allows us to consider the spread of infection by the virus-cell interaction, beyond that which occurs by cell-cell contagion. The results show an acceleration of the infectious process in the absence of treatment, but show better efficiency in reducing the risk of the onset of AIDS when combined antiretroviral therapies are used even with drugs of low effectiveness. Comparison of results with clinical data supports the conclusions of this study.

Prophylaxis and treatment of HIV-1 infection in pregnancy: Swedish recommendations 2010.

PubMed

Navér, Lars; Albert, Jan; Belfrage, Erik; Flamholc, Leo; Gisslén, Magnus; Gyllensten, Katarina; Josephson, Filip; Karlström, Olof; Lindgren, Susanne; Pettersson, Karin; Svedhem, Veronica; Sönnerborg, Anders; Westling, Katarina; Yilmaz, Aylin; Swedish Reference Group for Antiviral Therapy

2011-07-01

Prophylaxis and treatment with antiretroviral drugs and the use of elective caesarean section have resulted in a very low mother-to-child transmission of human immunodeficiency virus (HIV) during recent years. The availability of new antiretroviral drugs, updated general treatment guidelines and increasing knowledge of the importance of drug resistance, have necessitated regular revisions of the "Prophylaxis and treatment of HIV-1 infection in pregnancy" recommendations. For these reasons, The Swedish Reference Group for Antiviral Therapy (RAV) updated the 2007 recommendations at an expert meeting that took place on 25 March 2010. The most important revisions from the previous recommendations are: (1) it is recommended that treatment during pregnancy starts at the latest at gestational week 14-18; (2) ongoing efficient treatment at confirmed pregnancy may, with a few exceptions, be continued; (3) lopinavir/r and atazanavir/r are equally recommended protease inhibitors; (4) if maternal HIV RNA is >50 copies/ml close to delivery, a planned caesarean section, intravenous zidovudine, oral nevirapine for the mother and post-exposure prophylaxis for the infant with 3 antiretroviral drugs are recommended; (5) for delivery at <34 gestational weeks, intravenous zidovudine and oral nevirapine for the mother and at 48-72 h for the infant is recommended, in addition to other prophylaxis; (6) intravenous zidovudine is not recommended when HIV RNA is <50 copies/ml and a caesarean section is performed; (7) it is recommended that prophylaxis for the infant is started within 4 h; (8) prophylactic zidovudine for the infant may be administered twice daily instead of 4 times a day, as was the case previously; and (9) the number of sampling occasions for the infant has been decreased.

Discordant Treatment Responses to Combination Antiretroviral Therapy in Rwanda: A Prospective Cohort Study

PubMed Central

Kayigamba, Felix R.; Franke, Molly F.; Bakker, Mirjam I.; Rodriguez, Carly A.; Bagiruwigize, Emmanuel; Wit, Ferdinand WNM; Rich, Michael L.; Schim van der Loeff, Maarten F.

2016-01-01

Introduction Some antiretroviral therapy naïve patients starting combination antiretroviral therapy (cART) experience a limited CD4 count rise despite virological suppression, or vice versa. We assessed the prevalence and determinants of discordant treatment responses in a Rwandan cohort. Methods A discordant immunological cART response was defined as an increase of <100 CD4 cells/mm3 at 12 months compared to baseline despite virological suppression (viral load [VL] <40 copies/mL). A discordant virological cART response was defined as detectable VL at 12 months with an increase in CD4 count ≥100 cells/mm3. The prevalence of, and independent predictors for these two types of discordant responses were analysed in two cohorts nested in a 12-month prospective study of cART-naïve HIV patients treated at nine rural health facilities in two regions in Rwanda. Results Among 382 patients with an undetectable VL at 12 months, 112 (29%) had a CD4 rise of <100 cells/mm3. Age ≥35 years and longer travel to the clinic were independent determinants of an immunological discordant response, but sex, baseline CD4 count, body mass index and WHO HIV clinical stage were not. Among 326 patients with a CD4 rise of ≥100 cells/mm3, 56 (17%) had a detectable viral load at 12 months. Male sex was associated with a virological discordant treatment response (P = 0.05), but age, baseline CD4 count, BMI, WHO HIV clinical stage, and travel time to the clinic were not. Conclusions Discordant treatment responses were common in cART-naïve HIV patients in Rwanda. Small CD4 increases could be misinterpreted as a (virological) treatment failure and lead to unnecessary treatment changes. PMID:27438000

Essentials from the 2015 European AIDS Clinical Society (EACS) guidelines for the treatment of adult HIV-positive persons.

PubMed

Ryom, L; Boesecke, C; Gisler, V; Manzardo, C; Rockstroh, J K; Puoti, M; Furrer, H; Miro, J M; Gatell, J M; Pozniak, A; Behrens, G; Battegay, M; Lundgren, J D

2016-02-01

The European AIDS Clinical Society (EACS) guidelines are intended for all clinicians involved in the care of HIV-positive persons, and are available in print, online, and as a free App for download for iPhone and Android. The 2015 version of the EACS guidelines contains major revisions in all sections; antiretroviral treatment (ART), comorbidities, coinfections and opportunistic diseases. Among the key revisions is the recommendation of ART for all HIV-positive persons, irrespectively of CD4 count, based on the Strategic Timing of AntiRetroviral Treatment (START) study results. The recommendations for the preferred and the alternative ART options have also been revised, and a new section on the use of pre-exposure prophylaxis (PrEP) has been added. A number of new antiretroviral drugs/drug combinations have been added to the updated tables on drug-drug interactions, adverse drug effects, dose adjustment for renal/liver insufficiency and for ART administration in persons with swallowing difficulties. The revisions of the coinfection section reflect the major advances in anti-hepatitis C virus (HCV) treatment with direct-acting antivirals with earlier start of treatment in individuals at increased risk of liver disease progression, and a phasing out of interferon-containing treatment regimens. The section on opportunistic diseases has been restructured according to individual pathogens/diseases and a new overview table has been added on CD4 count thresholds for different primary prophylaxes. The diagnosis and management of HIV infection and related coinfections, opportunistic diseases and comorbidities continue to require a multidisciplinary effort for which the 2015 version of the EACS guidelines provides an easily accessable and updated overview. © 2015 British HIV Association.

Pregnancy and Single Parenthood in the Navy: Results of a 1997 Survey.

DTIC Science & Technology

1998-09-01

rates for age cohorts. Half of the women experiencing an unplanned pregnancy were not using birth control , whereas the pill was the most failure-prone...shore duty; (2) attempt to reduce unplanned pregnancies by improving birth control education and expanding family planning efforts; and (3) emphasize

Adult Couples Facing a Planned or an Unplanned Pregnancy: Two Realities

ERIC Educational Resources Information Center

Bouchard, Genevieve

2005-01-01

This study examined demographic, individual, and relational factors that differentiate adult couples facing an unplanned pregnancy carried to term from those facing a planned pregnancy. One hundred and eighteen couples expecting their first child completed, along with a demographic questionnaire, measures of personality, perceived stress,…

Gesture, Meaning, and Thinking-for-Teaching in Unplanned Vocabulary Explanations

ERIC Educational Resources Information Center

van Compernolle, Rémi A.; Smotrova, Tetyana

2017-01-01

In this article, we examine the ways in which an ESL instructor constructs contextually relevant meanings through the synchronization of speech and gesture during unplanned vocabulary explanations. Video recorded data are analysed, with focus on an in-class homework review in which students demonstrated difficulty in comprehending several key…

Planned and Unplanned Childbearing among Unmarried Women.

ERIC Educational Resources Information Center

Musick, Kelly

2002-01-01

Uses data from the 1995 National Survey of Family Growth to examine social, demographic, and economic correlates of planned and unplanned childbearing among unmarried women. Finds that low education increases the likelihood such childbearing outside of marriage for all race and ethnic groups. Results suggest ways in which the meaning of…

Prevalence of HIV Drug Resistance Before and 1 Year After Treatment Initiation in 4 Sites in the Malawi Antiretroviral Treatment Program

PubMed Central

Bennett, Diane; van Oosterhout, Joep J.; Moyo, Kundai; Hosseinipour, Mina; DeVos, Josh; Zhou, Zhiyong; Aberle-Grasse, John; Warne, Thomas R.; Mtika, Clement; Chilima, Ben; Banda, Richard; Pasulani, Olesi; Porter, Carol; Phiri, Sam; Jahn, Andreas; Kamwendo, Debbie; Jordan, Michael R.; Kabuluzi, Storn; Chimbwandira, Frank; Kagoli, Mathew; Matatiyo, Blackson; Demby, Austin; Yang, Chunfu

2012-01-01

Since 2004, the Malawi antiretroviral treatment (ART) program has provided a public health–focused system based on World Health Organization clinical staging, standardized first-line ART regimens, limited laboratory monitoring, and no patient-level monitoring of human immunodeficiency virus drug resistance (HIVDR). The Malawi Ministry of Health conducts periodic evaluations of HIVDR development in prospective cohorts at sentinel clinics. We evaluated viral load suppression, HIVDR, and factors associated with HIVDR in 4 ART sites at 12–15 months after ART initiation. More than 70% of patients initiating ART had viral suppression at 12 months. HIVDR prevalence (6.1%) after 12 months of ART was low and largely associated with baseline HIVDR. Better follow-up, removal of barriers to on-time drug pickups, and adherence education for patients 16–24 years of age may further prevent HIVDR. PMID:22544204

Lower urinary tract infections in women.

PubMed

Davis, Cathy; Rantell, Angie

2017-05-11

In her lifetime, a woman is highly likely to develop at least one lower urinary tract infection. Early detection and treatment are key. Being aware of predisposing factors for infection and understanding appropriate diagnosis and treatment regimens will help nurses in both primary and acute care manage these patients correctly. This will not only benefit patients but will also help prevent incorrect antimicrobial management and avoid unplanned admissions. This aim of this article is to provide nurses with the information they need to best advise both colleagues and patients on how to manage lower urinary tract infections in women.

Ledipasvir-Sofosbuvir for 8 Weeks in Non-Cirrhotic Patients with Previously Untreated Genotype 1 HCV Infection ± HIV-1 Co-Infection.

PubMed

Isakov, Vasily; Gankina, Natalia; Morozov, Viacheslav; Kersey, Kathryn; Lu, Sophia; Osinusi, Anu; Svarovskaia, Evguenia; Brainard, Diana M; Salupere, Riina; Orlova-Morozova, Elena; Zhdanov, Konstantin

2018-03-01

BACKGROUND AND OBJECTIVES: The efficacy of < 12 weeks of hepatitis C virus (HCV) treatment in patients co-infected with HCV and human immunodeficiency virus type 1 (HIV-1) has not been established. We assessed the efficacy and safety of ledipasvir-sofosbuvir for 8 weeks in HCV mono-infected and HCV/HIV-1 co-infected patients. We enrolled patients mono-infected with genotype 1 HCV or co-infected with HCV and HIV-1 who were HCV treatment-naive and did not have cirrhosis. HCV/HIV-1 co-infected patients were either not receiving antiretroviral treatment and had a CD4 T-cell count > 500 cells/mm 3 or were receiving a protocol-approved antiretroviral regimen for ≥ 8 weeks (or ≥ 6 months for abacavir-containing regimens) and had HIV-1 RNA < 50 copies/mL and a CD4 T-cell count > 200 cells/mm 3 . Patients received ledipasvir-sofosbuvir (90/400 mg) once daily for 8 weeks. The primary efficacy endpoint was sustained virologic response 12 weeks after treatment discontinuation (SVR12). The SVR12 rate was 100% (67/67) for HCV mono-infected patients and 97% (57/59) for HCV/HIV-1 co-infected patients. Two patients relapsed by the week 4 post-treatment visit. Overall, the most common adverse events were headache (52%) and upper abdominal pain (26%). There were no serious adverse events or treatment discontinuations due to adverse events. No HCV/HIV-1 co-infected patients receiving antiretroviral treatment experienced HIV virologic rebound, and no clinically meaningful changes in CD4 T-cell counts were observed in any co-infected patient. Non-cirrhotic, treatment-naive patients with genotype 1 HCV mono-infection and HCV/HIV-1 co-infection achieved high rates of SVR12 with 8 weeks of treatment with ledipasvir/sofosbuvir. ClinicalTrials.gov identifier: NCT02472886.

Emergence of resistance mutations in simian immunodeficiency virus (SIV)-infected rhesus macaques receiving non-suppressive antiretroviral therapy (ART)

DOE PAGES

Policicchio, Benjamin Bruno; Sette, Paola; Xu, Cuiling; ...

2018-02-21

Two SIVmac251-infected rhesus macaques received tenofovir/emtricitabine with raltegravir intensification. Viral rebound occurred during treatment and sequencing of reverse transcriptase and integrase genes identified multiple resistance mutations. Similar to HIV infection, antiretroviral-resistance mutations may occur in SIV-infected nonhuman primates receiving nonsuppressive ART. As ART administration to nonhuman primates is currently dramatically expanding, fueled by both cure research and the study of HIV-related comorbidities, viral resistance should be factored in the study design and data interpretation

Emergence of resistance mutations in simian immunodeficiency virus (SIV)-infected rhesus macaques receiving non-suppressive antiretroviral therapy (ART)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Policicchio, Benjamin Bruno; Sette, Paola; Xu, Cuiling

Two SIVmac251-infected rhesus macaques received tenofovir/emtricitabine with raltegravir intensification. Viral rebound occurred during treatment and sequencing of reverse transcriptase and integrase genes identified multiple resistance mutations. Similar to HIV infection, antiretroviral-resistance mutations may occur in SIV-infected nonhuman primates receiving nonsuppressive ART. As ART administration to nonhuman primates is currently dramatically expanding, fueled by both cure research and the study of HIV-related comorbidities, viral resistance should be factored in the study design and data interpretation

Potential impact of new World Health Organization criteria for antiretroviral treatment for prevention of mother-to-child HIV transmission

PubMed Central

Kuhn, Louise; Aldrovandi, Grace M.; Sinkala, Moses; Kankasa, Chipepo; Mwiya, Mwiya; Thea, Donald M.

2010-01-01

We reviewed the potential impact of new World Health Organization criteria for antiretroviral therapy using data from 1025 HIV-infected women and infants followed through 24 months in Lusaka, Zambia. The new criteria require initiating therapy among 68% of pregnant women and, if fully effective, would prevent 92% of maternal deaths and 88% of perinatal and postnatal infections. Using CD4 <350 cells/uL, irrespective of clinical stage, is more efficient and stricter CD4 cut-offs would be counter-productive. PMID:20568677

Human Resources for Treating HIV/AIDS: Are the Preventive Effects of Antiretroviral Treatment a Game Changer?

PubMed

Bärnighausen, Till; Bloom, David E; Humair, Salal

2016-01-01

Shortages of human resources for treating HIV/AIDS (HRHA) are a fundamental barrier to reaching universal antiretroviral treatment (ART) coverage in developing countries. Previous studies suggest that recruiting HRHA to attain universal ART coverage poses an insurmountable challenge as ART significantly increases survival among HIV-infected individuals. While new evidence about ART's prevention benefits suggests fewer infections may mitigate the challenge, new policies such as treatment-as-prevention (TasP) will exacerbate it. We develop a mathematical model to analytically study the net effects of these countervailing factors. Using South Africa as a case study, we find that contrary to previous results, universal ART coverage is achievable even with current HRHA numbers. However, larger health gains are possible through a surge-capacity policy that aggressively recruits HRHA to reach universal ART coverage quickly. Without such a policy, TasP roll-out can increase health losses by crowding out sicker patients from treatment, unless a surge capacity exclusively for TasP is also created.

Early nucleoside reverse transcriptase inhibitors for the treatment of HIV: a brief history of stavudine (D4T) and its comparison with other dideoxynucleosides.

PubMed

Martin, John C; Hitchcock, Michael J M; De Clercq, Erik; Prusoff, William H

2010-01-01

The occasion of this 25th anniversary issue encouraged us to reminisce about the important history of the discovery of the dideoxynucleoside analogues for the treatment of HIV/AIDS and to chronicle our thoughts about a particular exciting and rewarding period of our scientific careers. Following the identification of the anti-HIV activity of zidovudine (AZT), we participated in the urgent quest to discover optimal treatments of HIV infection and AIDS. A number of previously synthesized nucleoside analogues were comparatively evaluated, and stavudine (D4T) emerged as a promising candidate for development. Following clinical evaluation, D4T became a mainstay of the initial antiretroviral combination therapy, prolonging and saving numerous lives. It has only recently been supplanted by better-tolerated treatments. This article forms part of a special issue of Antiviral Research marking the 25th anniversary of antiretroviral drug discovery and development, vol. 85, issue 1, 2010. Copyright 2009 Elsevier B.V. All rights reserved.

Human Resources for Treating HIV/AIDS: Are the Preventive Effects of Antiretroviral Treatment a Game Changer?

PubMed Central

2016-01-01

Shortages of human resources for treating HIV/AIDS (HRHA) are a fundamental barrier to reaching universal antiretroviral treatment (ART) coverage in developing countries. Previous studies suggest that recruiting HRHA to attain universal ART coverage poses an insurmountable challenge as ART significantly increases survival among HIV-infected individuals. While new evidence about ART’s prevention benefits suggests fewer infections may mitigate the challenge, new policies such as treatment-as-prevention (TasP) will exacerbate it. We develop a mathematical model to analytically study the net effects of these countervailing factors. Using South Africa as a case study, we find that contrary to previous results, universal ART coverage is achievable even with current HRHA numbers. However, larger health gains are possible through a surge-capacity policy that aggressively recruits HRHA to reach universal ART coverage quickly. Without such a policy, TasP roll-out can increase health losses by crowding out sicker patients from treatment, unless a surge capacity exclusively for TasP is also created. PMID:27716813

Directly administered antiretroviral therapy for HIV-infected drug users does not have an impact on antiretroviral resistance: results from a randomized controlled trial.

PubMed

Maru, Duncan Smith-Rohrberg; Kozal, Michael J; Bruce, R Douglas; Springer, Sandra A; Altice, Frederick L

2007-12-15

Directly administered antiretroviral therapy (DAART) is an effective intervention that improves clinical outcomes among HIV-infected drug users. Its effects on antiretroviral drug resistance, however, are unknown. We conducted a community-based, prospective, randomized controlled trial of DAART compared with self-administered therapy (SAT). We performed a modified intention-to-treat analysis among 115 subjects who provided serum samples for HIV genotypic resistance testing at baseline and at follow-up. The main outcomes measures included total genotypic sensitivity score, future drug options, number of new drug resistance mutations (DRMs), and number of new major International AIDS Society (IAS) mutations. The adjusted probability of developing at least 1 new DRM did not differ between the 2 arms (SAT: 0.41 per person-year [PPY], DAART: 0.49 PPY; adjusted relative risk [RR] = 1.04; P = 0.90), nor did the number of new mutations (SAT: 0.76 PPY, DAART: 0.83 PPY; adjusted RR = 0.99; P = 0.99) or the probability of developing new major IAS new drug mutations (SAT: 0.30 PPY, DAART: 0.33 PPY; adjusted RR = 1.12; P = 0.78). On measures of GSS and FDO, the 2 arms also did not differ. In this trial, DAART provided on-treatment virologic benefit for HIV-infected drug users without affecting the rate of development of antiretroviral medication resistance.

Prevalence of Adverse Drug Reactions to Highly Active Antiretroviral Therapy (HAART) among HIV Positive Patients in Imam Khomeini Hospital of Tehran, Iran.

PubMed

Koochak, Hamid E; Babaii, Azita; Pourdast, Alia; Golrokhy, Raheleh; Rasoolinejad, Mehrnaz; Khodaei, Sepideh; Moghadam, Saeed R J; Taheri, Reza R; Seyed Alinaghi, Seyed Ahmad

2017-01-01

The present study assessed the prevalence of adverse drug reactions (ADRs) among HIV positive patients taking antiretroviral therapy referred to Imam Khomeini Hospital in Tehran, Iran. This is a cross sectional study regarding side effects of Highly Active Antiretroviral Therapy (HAART) in HIV positive patients referred to Voluntary Counseling and Testing (VCT) center in Imam Khomeini Hospital of Tehran, Iran during a period of the year 2009 to 2010. Two hundred patients under antiretroviral treatment evaluated for the side effects of drug based on available records, face to face interviews and written lab data. Data was collected from a sample of 200 HIV positive patients (72% male). Injection drug use was the most common route of HIV transmission. Co-Infections with Hepatitis C virus (HCV) found in the majority of patients (60.5%). Tuberculosis was the most prevalent opportunistic infection. One hundred eighty eight (94%) patients experienced at least one adverse drug reaction. The most frequent clinical and paraclinical findings were skin rash (28%) and abnormal liver function tests (36%). Given the high prevalence of adverse drug reactions among HIV positive patients taking antiretroviral therapy (ART) in this study, clinicians should be aware of ADRs at the initiation of ART as complications can affect patients' adherence to the therapy. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Unplanned pregnancies in the United States.

PubMed

Grimes, D A

1986-03-01

Unplanned pregnancies constitute an epidemic in the United States. Over 3 million unplanned pregnancies occur, and over 1.5 million induced abortions are performed each year. Women of minority races and those with less than 12 years of education are at high risk of having unwanted children. Fear of complications (not the complications themselves) is the most powerful deterrent to women's use of contraception. Much of this fear is due to bad press. Recent good news about contraception, such as protection against ovarian and endometrial cancer, protection against ectopic pregnancy, and absence of teratogenic effects, has not received appropriate media coverage. For healthy women younger than 35 years, failure to use fertility control is more dangerous than use of any method.

Effects of competition on hospital quality: an examination using hospital administrative data.

PubMed

Palangkaraya, Alfons; Yong, Jongsay

2013-06-01

This paper investigates the effects of competition on hospital quality using hospital administration data from the State of Victoria, Australia. Hospital quality is measured by 30-day mortality rates and 30-day unplanned readmission rates. Competition is measured by Herfindahl-Hirschman index and the numbers of competing public and private hospitals. The paper finds that hospitals facing higher competition have lower unplanned admission rates. However, competition is related negatively to hospital quality when measured by mortality, albeit the effects are weak and barely statistically significant. The paper also finds that the positive effect of competition on quality as measured by unplanned readmission differs greatly depending on whether the hospital is publicly or privately owned.

Eating disorders and the oral and maxillofacial surgeon.

PubMed

Blitz, Meredith; Rosen, David S

2010-11-01

Perhaps the most challenging of all patients seeking treatment with the oral and maxillofacial surgeon (OMS) are those with eating disorders (EDs). Complex psychiatric illnesses, with their associated and significant medical sequelae, make a thorough knowledge of these disorders critical in the approach, evaluation, treatment planning, and surgical outcome in this expanding population of patients. Whether surgery for patients with EDs is elective in nature or unplanned, challenges are faced in all aspects of their care, from diagnosis to preoperative preparation, surgery, and treatment. This article identifies and outlines issues of importance for the OMS when encountering patients with known or suspected EDs and provides guidance in the management of their outpatient or inpatient treatment. Copyright © 2010. Published by Elsevier Inc.

Investigational Antiretroviral Drugs: What is Coming Down the Pipeline.

PubMed

Gulick, Roy M

2018-04-01

Over the past 30 years, antiretroviral drug regimens for treating HIV infection have become more effective, safer, and more convenient. Despite 31 currently approved drugs, the pipeline of investigational HIV drugs remains full. Investigational antiretroviral drugs include the nucleoside analogue reverse transcriptase translocation inhibitor (NRTTI) MK-8591, a long-acting compound that could be dosed once weekly. Investigational nonnucleoside analogue reverse transcriptase inhibitors (NNRTIs) include doravirine, which is active in vitro against NNRTI-resistant HIV and was potent and well-tolerated when used in combination with a dual-nucleoside analogue RTI (nRTI) backbone in treatment-naive individuals.New integrase strand transfer inhibitors (InSTIs) include recently approved bictegravir, which is active against InSTI-resistant viral strains in vitro and was potent and well-tolerated in combination regimens in treatment-naive individuals, and investigational cabotegravir, which is being studied with monthly parenteral dosing for HIV maintenance treatment and with bimonthly dosing for HIV preexposure prophylaxis (PrEP). Investigational HIV entry inhibitors include the new CD4 attachment inhibitor fostemsavir, which targets HIV envelope glycoprotein 120, and recently approved ibalizumab, which binds the CD4 receptor. This article summarizes presentations by Roy M. Gulick, MD, MPH, at the IAS-USA continuing education program, Improving the Management of HIV Disease, held in Los Angeles, California, in April 2017, and at the 2017 Ryan White HIV/AIDS Program Clinical Conference, held in San Antonio, Texas, in August 2017.

[HIV drug resistance in ART-experienced patients in Cali, Colombia, 2008-2010].

PubMed

Martínez-Cajas, Jorge L; Mueses-Marín, Héctor F; Galindo-Orrego, Pablo; Agudelo, Juan F; Galindo-Quintero, Jaime

2013-01-01

Little has been published in Colombia on HIV drug resistance in patients taking antiretroviral treatment (ART). Currently, the Colombian guidelines do not recommend the use of genotypic antiretroviral resistance tests (GART) for treatment-naive patients or for those experiencing a first therapeutic failure. To determine the frequency of relevant resistance mutations and the degree of susceptibility/ resistance of HIV to antiretroviral drugs (ARVs) in ART-experienced patients. A non-random sample of 170 ART-experienced HIV patients with virologic failure and who underwent GART was recruited. A study of HIV drug resistance was carried out in two groups of patients: one group that underwent early GART and the other group that received late GART testing. The most frequent type of resistance affected the non-nucleoside class (76%). The late-GART group had higher risk of nucleoside analog and protease inhibitor drug resistance, a higher number of resistance mutations and more complex mutational profiles than the early-GART group. A high cross resistance level (30%) was found in the nucleoside analog class. The least affected medications were tenofovir and darunavir. Our results suggest that performing GART late is associated with levels of ARV resistance that could restrict the use of an important number of essential ARV in subsequent regimens. There is a need to revise the current recommendations to include GART prior to start of treatment and after the first virologic failure.

Understanding the facilitators and barriers of antiretroviral adherence in Peru: A qualitative study

PubMed Central

2010-01-01

Background Antiretroviral scale-up is increasing in resource-constrained settings. To date, few studies have explored the barriers and facilitators of adherence to ART in these settings. Facilitators and barriers of antiretroviral adherence in Peru are not completely understood. Methods At two clinics that serve a large number of HIV-positive individuals in Lima, Peru, 31 in-depth interviews were carried out in 2006 with adult HIV-positive individuals receiving ART. Purposive sampling was used to recruit the participants. Interviews were transcribed and coded using two Spanish-speaking researchers and a content analysis approach to identify themes in the data. Results Among the participants, 28/31 (90%) were male, 25/31 (81%) were self-identified as mestizo, and 19/31 (61%) had an education above high school. The most frequently discussed barriers to adherence included side effects, simply forgetting, inconvenience, dietary requirements, being away from home, and fear of disclosure/stigma. The most frequently discussed facilitators to adherence included having a fixed routine, understanding the need for compliance, seeing positive results, treatment knowledge, and faith in treatment. Conclusions Overall, these findings were similar to the facilitators and challenges experienced by individuals on ART in other resource constrained settings. Further treatment support tools and networks should be developed to decrease the challenges of ART adherence for HIV-positive individuals in Lima, Peru. PMID:20070889

HIV-positive patient with herpes zoster: a manifestation of the immune reconstitution inflammatory syndrome.

PubMed

Lutwak, Nancy; Dill, Curt

2012-01-01

Herpes zoster is a common illness that can lead to serious morbidity. There is now evidence that HIV-infected patients who have been treated with antiretroviral therapy are at greater risk of developing herpes zoster not when they are severely immunocompromised but, paradoxically, when their immune system is recovering. This is a manifestation of the immune reconstitution inflammatory syndrome. The objectives of this report are to (1) inform health care providers that HIV-infected patients may develop multiple infectious, autoimmune, and oncological manifestations after treatment with antiretroviral medication, as they have immune system reconstitution, and (2) discuss herpes zoster, one of the possible manifestations. The patient is a 68-year-old HIV-positive man who presented with herpes zoster after being treated with highly active antiretroviral therapy (HAART) when his immune system was recovering, not when he was most immunosuppressed. Emergency department physicians should be aware that HIV-infected patients treated with HAART may have clinical deterioration despite immune system strengthening. This immune reconstitution inflammatory syndrome can present with infectious, autoimmune, or oncological manifestations. Our case patient, an HIV-positive man with immune system recovery after treatment with HAART, presented with an infectious manifestation, herpes zoster.

HIV antibodies for treatment of HIV infection

PubMed Central

Margolis, David M.; Koup, Richard A.; Ferrari, Guido

2016-01-01

Summary The bar is high to improve on current combination antiretroviral therapy (ART), now highly effective, safe, and simple. However antibodies that bind the HIV envelope are able to uniquely target the virus as it seeks to enter new target cells, or as it is expressed from previously infected cells. Further, the use of antibodies against HIV as a therapeutic may offer advantages. Antibodies can have long half-lives, and are being considered as partners for long-acting antiretrovirals for use in therapy or prevention of HIV infection. Early studies in animal models and in clinical trials suggest that such antibodies can have antiviral activity but, as with small molecule antiretrovirals, the issues of viral escape and resistance will have to be addressed. Most promising, however, are the unique properties of anti-HIV antibodies: the potential ability to opsonize viral particles, to direct antibody-dependent cellular cytotoxicity (ADCC) against actively infected cells, and ultimately the ability to direct the clearance of HIV-infected cells by effector cells of the immune system. These distinctive activities suggest that HIV antibodies and their derivatives may play an important role in the next frontier of HIV therapeutics, the effort to develop treatments that could lead to an HIV cure. PMID:28133794

Adolescents with perinatally acquired HIV: emerging behavioral and health needs for long-term survivors.

PubMed

Koenig, Linda J; Nesheim, Steven; Abramowitz, Susan

2011-10-01

Because of widespread availability of highly active antiretroviral therapy in the developed world, a large proportion of children with perinatally acquired HIV have survived to adolescence and young adulthood. Although their survival is remarkable, many now experience the long-term effects of HIV infection and its treatment. Further, as these youths have entered adolescence, more is known about the impact of normative developmental transitions on health maintenance behaviors. Although perinatally infected adolescents are healthier than they were a decade or more ago, they are significantly experienced with antiretroviral therapy, with increased virological resistance and other consequences of extended antiretroviral use. Three behavioral health challenges have been documented in the first cohort of long-term survivors: decreased medication adherence, sexual debut and accompanying pregnancy and transmission risk, and mental health problems. These issues are consistent with a developmental press for autonomy, mature sexual relationships and future planning, but must be carefully managed to preserve health. Adolescents with perinatally acquired HIV require coordinated multidisciplinary support services - including adherence support, reproductive health counseling addressing both pregnancy planning and disease transmission, and mental health and educational/vocational planning - so that they can fully benefit from treatment advances. (C) 2011 Lippincott Williams & Wilkins, Inc.

HIV disease progression despite suppression of viral replication is associated with exhaustion of lymphopoiesis

PubMed Central

Sauce, Delphine; Larsen, Martin; Fastenackels, Solène; Pauchard, Michèle; Ait-Mohand, Hocine; Schneider, Luminita; Guihot, Amélie; Boufassa, Faroudy; Zaunders, John; Iguertsira, Malika; Bailey, Michelle; Gorochov, Guy; Duvivier, Claudine; Carcelain, Guislaine; Kelleher, Anthony D.; Simon, Anne; Meyer, Laurence; Costagliola, Dominique; Deeks, Steven G.; Lambotte, Olivier; Autran, Brigitte; Hunt, Peter W.; Katlama, Christine

2011-01-01

The mechanisms of CD4+ T-cell count decline, the hallmark of HIV disease progression, and its relationship to elevated levels of immune activation are not fully understood. Massive depletion of CD4+ T cells occurs during the course of HIV-1 infection, so that maintenance of adequate CD4+ T-cell levels probably depends primarily on the capacity to renew depleted lymphocytes, that is, the lymphopoiesis. We performed here a comprehensive study of quantitative and qualitative attributes of CD34+ hematopoietic progenitor cells directly from the blood of a large set of HIV-infected persons compared with uninfected donors, in particular the elderly. Our analyses underline a marked impairment of primary immune resources with the failure to maintain adequate lymphocyte counts. Systemic immune activation emerges as a major correlate of altered lymphopoiesis, which can be partially reversed with prolonged antiretroviral therapy. Importantly, HIV disease progression despite elite control of HIV replication or virologic success on antiretroviral treatment is associated with persistent damage to the lymphopoietic system or exhaustion of lymphopoiesis. These findings highlight the importance of primary hematopoietic resources in HIV pathogenesis and the response to antiretroviral treatments. PMID:21436070

Depression among patients attending antiretroviral treatment program in public health facilities in Bahir Dar City, Ethiopia.

PubMed

Tareke, Minale; Addisu, Fikir; Abate, Andargie

2018-05-01

The magnitude of depression is not well investigated among people living with HIV/AIDS. Thus, this research aimed to assess the magnitude of depression and its influencing factors among people living with HIV/AIDS attending government institutions in Bahir Dar City, North West, Ethiopia. institution based-cross-sectional study was done among randomly selected 415 people living with HIV/AIDS attending antiretroviral therapy program in Bahir Dar city, Ethiopia. Socio-demographic data and medical histories for all respondents were collected using interviewer-administered structured questionnaire. We assessed the odds of association of patient characteristics with depression was assessed using multiple logistic regression. The relative effect estimates of the respective factors were presented with odds ratio accompanied by their 95% uncertainty intervals. From 407 people living with HIV/AIDS interviewed, 198(48.6%) of them had depression. Social support, HIV clinical staging, total daily pill burden, treatment regimen and adherence to highly active antiretroviral therapy were significantly associated with depression. The magnitude of depression among people living with HIV/AIDS was found to be high. Early mental health screening should be done for people living with HIV/AIDS. Copyright © 2018 Elsevier B.V. All rights reserved.

Sticking to it: the effect of maximally assisted therapy on antiretroviral treatment adherence among individuals living with HIV who are unstably housed.

PubMed

Parashar, Surita; Palmer, Alexis K; O'Brien, Nadia; Chan, Keith; Shen, Anya; Coulter, Suzy; Montaner, Julio S G; Hogg, Robert S

2011-11-01

Housing is a known determinant of health behaviors, which includes adherence to Antiretroviral Therapy (ART). Within the Longitudinal Investigations into Supportive and Ancillary Health Services (LISA) study, unstable housing is inversely associated with adherence. Several comprehensive adherence support services have emerged to improve adherence for unstably housed or otherwise vulnerable populations. The Maximally Assisted Therapy (MAT) program in Vancouver, British Columbia uses a multidisciplinary approach to support HIV-positive clients with a history of addictions or mental illness, many of whom also experience episodic homelessness. This study investigated the association between antiretroviral adherence and use of support services, including the MAT program, amongst people living with HIV and AIDS who are unstably housed in the LISA sample. Of the 212 unstably housed participants, those who attended the MAT program were 4.76 times more likely to be ≥95% adherent (95% CI 1.72-13.13; P = 0.003) than those who did not. The findings suggest that in the absence of sustainable housing solutions, programs such as MAT play an important role in supporting treatment adherence in this population.

Anaemia in Pregnancy Is Associated with Advanced HIV Disease

PubMed Central

Nandlal, Vikesh; Moodley, Dhayendre; Grobler, Anneke; Bagratee, Jayanthilall; Maharaj, Niren R.; Richardson, Paul

2014-01-01

Background Anaemia is a common clinical finding in HIV infected women and has been associated with advanced disease. The use of antiretroviral drugs such as Zidovudine (ZDV) either for prevention of mother to child transmission (MTCT) of HIV or used in combination with other antiretrovirals have been implicated in the development or increased severity of anaemia. We report the prevalence, type, severity and incidence of anaemia in a cohort of HIV infected women who initiated antiretroviral prophylaxis or treatment during pregnancy. Methods and Materials This is a retrospective cohort data analysis of 408 HIV infected pregnant women who participated in a breastfeeding intervention study (HPTN 046 Study, ClinicalTrials.gov NCT 00074412) in South Africa. Women initiated zidovudine prophylaxis for PMTCT or triple antiretroviral treatment in pregnancy according to the standard of care. Laboratory and clinical data in pregnancy, <72 hours and 2 weeks postdelivery were extracted from the main database and analysed. Results The mean Hb concentration was 10.6 g/dL at baseline and 262/408 (64.2%) women were diagnosed with anaemia (Hb<11 g/dL) in pregnancy, 48/146 (32.9%) subsequently developed anaemia intrapartum or postpartum and 89/310 (28.7%) of all cases of anaemia remained unresolved by 2 weeks postdelivery. In a univariate analysis, CD4 count and gravidity were significant risk factors for anaemia in pregnancy, RR 1.41; 1.23–1.61 (p<0.001) and 1.10; 1.01–1.18 (p = 0.02) respectively. After adjusting for antiretroviral regimen, age and gravidity in a multivariable analysis, only the CD4 count remains a significant risk factor for anaemia in pregnancy and postdelivery. Conclusion In conclusion, anaemia was most common among women in the advanced stage of HIV infection (CD4<200 cells/mm3). There was no evidence of an association between ZDV or triple ARVs and anaemia. PMID:25222119

Anaemia in pregnancy is associated with advanced HIV disease.

PubMed

Nandlal, Vikesh; Moodley, Dhayendre; Grobler, Anneke; Bagratee, Jayanthilall; Maharaj, Niren R; Richardson, Paul

2014-01-01

Anaemia is a common clinical finding in HIV infected women and has been associated with advanced disease. The use of antiretroviral drugs such as Zidovudine (ZDV) either for prevention of mother to child transmission (MTCT) of HIV or used in combination with other antiretrovirals have been implicated in the development or increased severity of anaemia. We report the prevalence, type, severity and incidence of anaemia in a cohort of HIV infected women who initiated antiretroviral prophylaxis or treatment during pregnancy. This is a retrospective cohort data analysis of 408 HIV infected pregnant women who participated in a breastfeeding intervention study (HPTN 046 Study, ClinicalTrials.gov NCT 00074412) in South Africa. Women initiated zidovudine prophylaxis for PMTCT or triple antiretroviral treatment in pregnancy according to the standard of care. Laboratory and clinical data in pregnancy, <72 hours and 2 weeks postdelivery were extracted from the main database and analysed. The mean Hb concentration was 10.6 g/dL at baseline and 262/408 (64.2%) women were diagnosed with anaemia (Hb<11 g/dL) in pregnancy, 48/146 (32.9%) subsequently developed anaemia intrapartum or postpartum and 89/310 (28.7%) of all cases of anaemia remained unresolved by 2 weeks postdelivery. In a univariate analysis, CD4 count and gravidity were significant risk factors for anaemia in pregnancy, RR 1.41; 1.23-1.61 (p<0.001) and 1.10; 1.01-1.18 (p = 0.02) respectively. After adjusting for antiretroviral regimen, age and gravidity in a multivariable analysis, only the CD4 count remains a significant risk factor for anaemia in pregnancy and postdelivery. In conclusion, anaemia was most common among women in the advanced stage of HIV infection (CD4<200 cells/mm3). There was no evidence of an association between ZDV or triple ARVs and anaemia.

Sex issues in HIV-1-infected persons during highly active antiretroviral therapy: a systematic review.

PubMed

Nicastri, Emanuele; Leone, Sebastiano; Angeletti, Claudio; Palmisano, Lucia; Sarmati, Loredana; Chiesi, Antonio; Geraci, Andrea; Vella, Stefano; Narciso, Pasquale; Corpolongo, Angela; Andreoni, Massimo

2007-10-01

Since the introduction of highly active antiretroviral therapy (HAART), morbidity and mortality rates have sharply decreased among HIV-infected patients. Studies of possible differences between men and women in the course of HIV infection give conflicting results. The objective of this study was to assess sex differences during HAART. A literature search by using the MEDLINE database between March 2002 and February 2007 was performed to identify all published studies on the sex-specific differences on the impact of HAART. All articles with measures of effect (preferably adjusted odds ratio, relative risk or hazard ratio with 95% CI) of sex on viroimmunological and clinical parameters during HAART were included. Five different topics of interest in our research were selected: time of initiation of HAART, adherence, viroimmunological response, clinical response and adverse reactions during HAART. US data report an initiation of HAART at an earlier disease stage in men compared with women. After initiation of HAART, most authors do not report any viroimmunological difference, although a few clinical studies showed a significantly better virological response in women compared with men. Nevertheless, women were more likely to be less adherent to antiretrovirals and to have non-structured treatment interruptions than men. This is likely to be related to the higher number of adverse reactions they experience during HAART. Finally, discordant opinions with regard to clinical benefits during HAART exist, but recent clinical and observational trials suggest a better clinical outcome for women. We found little evidence of sex differences during antiretroviral treatment. Nevertheless, most of these studies were underpowered to detect sex differences and had limited follow-up at 6 or 12 months. Design of new gender-sensitive clinical trials with both prolonged follow-up and sample size representative of the current HIV prevalence among women are strongly needed to detect the likely sex differences of antiretroviral agents during HIV infection.

Planned and Unplanned Aspects of Occupational Choices by Youth. Final Report.

ERIC Educational Resources Information Center

Ellis, Robert A.; And Others

This document includes reports on four subjects relevant to planned and unplanned aspects of occupational choices by youth. (1) "Toward a Morphology of Occupational Choice," by Robert A. Ellis and others, discusses intrinsic features and extrinsic rewards of work, extra-role considerations, and goal perception as major influences on occupational…

It's Not about Me: College Women and Unplanned Pregnancy

ERIC Educational Resources Information Center

Hardy, Jayne W.

2011-01-01

The purpose of this qualitative study was to explore the experiences of single college women who had an unplanned pregnancy while attending a small private four-year university in the upper midwest. The conceptual framework used to provide direction for this study was social constructivism. A phenomenological approach was used to seek the reality…

Reducing unplanned pregnancy and abortion in Zimbabwe through postabortion contraception.

PubMed

Johnson, Brooke R; Ndhlovu, Singatsho; Farr, Sherry L; Chipato, Tsungai

2002-06-01

In many countries, women treated for complications from spontaneous or unsafely induced abortion lack access to contraceptive services. As a result, many of them soon have a subsequent unplanned pregnancy or a repeat abortion, placing their health at increased risk. This report presents the results of a prospective intervention study on postabortion family planning conducted in the two largest public hospitals in Zimbabwe. Women at Harare Central Hospital, in the capital, received a postabortion family planning intervention, and Mpilo Central Hospital, in Bulawayo, served as the control site. The study cohort was 982 women, 527 of whom were followed for a 12-month period. During the follow-up period, significantly more women used highly effective methods of contraception, significantly fewer unplanned pregnancies occurred, and fewer repeat abortions were performed at the intervention site than at the control site. These results offer compelling evidence that ward-based contraceptive services provided to women treated for incomplete abortion can significantly reduce subsequent unplanned pregnancies. The results also suggest that postabortion family planning services can reduce the incidence of repeat abortion.

Rates and risk factors of unplanned 30-day readmission following general and thoracic pediatric surgical procedures.

PubMed

Polites, Stephanie F; Potter, Donald D; Glasgow, Amy E; Klinkner, Denise B; Moir, Christopher R; Ishitani, Michael B; Habermann, Elizabeth B

2017-08-01

Postoperative unplanned readmissions are costly and decrease patient satisfaction; however, little is known about this complication in pediatric surgery. The purpose of this study was to determine rates and predictors of unplanned readmission in a multi-institutional cohort of pediatric surgical patients. Unplanned 30-day readmissions following general and thoracic surgical procedures in children <18 were identified from the 2012-2014 National Surgical Quality Improvement Program- Pediatric. Time-dependent rates of readmission per 30 person-days were determined to account for varied postoperative length of stay (pLOS). Patients were randomly divided into 70% derivation and 30% validation cohorts which were used for creation and validation of a risk model for readmission. Readmission occurred in 1948 (3.6%) of 54,870 children for a rate of 4.3% per 30 person-days. Adjusted predictors of readmission included hepatobiliary procedures, increased wound class, operative duration, complications, and pLOS. The predictive model discriminated well in the derivation and validation cohorts (AUROC 0.710 and 0.701) with good calibration between observed and expected readmission events in both cohorts (p>.05). Unplanned readmission occurs less frequently in pediatric surgery than what is described in adults, calling into question its use as a quality indicator in this population. Factors that predict readmission including type of procedure, complications, and pLOS can be used to identify at-risk children and develop prevention strategies. III. Copyright © 2017 Elsevier Inc. All rights reserved.

Contrasting fire responses to climate and management: insights from two Australian ecosystems.

PubMed

King, Karen J; Cary, Geoffrey J; Bradstock, Ross A; Marsden-Smedley, Jonathan B

2013-04-01

This study explores effects of climate change and fuel management on unplanned fire activity in ecosystems representing contrasting extremes of the moisture availability spectrum (mesic and arid). Simulation modelling examined unplanned fire activity (fire incidence and area burned, and the area burned by large fires) for alternate climate scenarios and prescribed burning levels in: (i) a cool, moist temperate forest and wet moorland ecosystem in south-west Tasmania (mesic); and (ii) a spinifex and mulga ecosystem in central Australia (arid). Contemporary fire activity in these case study systems is limited, respectively, by fuel availability and fuel amount. For future climates, unplanned fire incidence and area burned increased in the mesic landscape, but decreased in the arid landscape in accordance with predictions based on these limiting factors. Area burned by large fires (greater than the 95th percentile of historical, unplanned fire size) increased with future climates in the mesic landscape. Simulated prescribed burning was more effective in reducing unplanned fire activity in the mesic landscape. However, the inhibitory effects of prescribed burning are predicted to be outweighed by climate change in the mesic landscape, whereas in the arid landscape prescribed burning reinforced a predicted decline in fire under climate change. The potentially contrasting direction of future changes to fire will have fundamentally different consequences for biodiversity in these contrasting ecosystems, and these will need to be accommodated through contrasting, innovative management solutions. © 2012 Blackwell Publishing Ltd.

The relevance, biases, and importance of digitising opportunistic non-standardised collections: A case study in Iberian harvestmen fauna with BOS Arthropod Collection datasets (Arachnida, Opiliones).

PubMed

Merino-Sáinz, Izaskun; Torralba-Burrial, Antonio; Anadón, Araceli

2014-01-01

In this study, we analyse the relevance of harvestmen distribution data derived from opportunistic, unplanned, and non-standardised collection events in an area in the north of the Iberian Peninsula. Using specimens deposited in the BOS Arthropod Collection at the University of Oviedo, we compared these data with data from planned, standardised, and periodic collections with pitfall traps in several locations in the same area. The Arthropod Collection, begun in 1977, includes specimens derived from both sampling types, and its recent digitisation allows for this type of comparative analysis. Therefore, this is the first data-paper employing a hybrid approach, wherein subset metadata are described alongside a comparative analysis. The full dataset can be accessed through Spanish GBIF IPT at http://www.gbif.es:8080/ipt/archive.do?r=Bos-Opi, and the metadata of the unplanned collection events at http://www.gbif.es:8080/ipt/resource.do?r=bos-opi_unplanned_collection_events. We have mapped the data on the 18 harvestmen species included in the unplanned collections and provided records for some species in six provinces for the first time. We have also provided the locations of Phalangium opilio in eight provinces without published records. These results highlight the importance of digitising data from unplanned biodiversity collections, as well as those derived from planned collections, especially in scarcely studied groups and areas.

Peritonitis in Rwanda: Epidemiology and risk factors for morbidity and mortality.

PubMed

Ndayizeye, Leonard; Ngarambe, Christian; Smart, Blair; Riviello, Robert; Majyambere, Jean Paul; Rickard, Jennifer

2016-12-01

Few studies discuss causes and outcomes of peritonitis in low-income settings. This study describes epidemiology of patients with peritonitis at a Rwandan referral hospital. Identification of risk factors associated with mortality and unplanned reoperation could improve management of peritonitis. Data were collected on demographics, clinical presentation, operative findings, and outcomes for all patients with peritonitis. Multivariate regression analysis identified factors associated with in-hospital mortality and unplanned reoperation. A total of 280 patients presented with peritonitis over a 6-month period. Causes of peritonitis were complications of intestinal obstruction (39%) and appendicitis (17%). Thirty-six (13%) patients required unplanned reoperation, and in-hospital mortality was 17%. Factors associated with increased odds of in-hospital mortality were unplanned reoperation (adjusted odds ratio 34.12), vasopressor use (adjusted odds ratio 24.91), abnormal white blood cell count (adjusted odds ratio 12.6), intensive care unit admission (adjusted odds ratio 9.06), and American Society of Anesthesiologist score ≥3 (adjusted odds ratio 7.80). Factors associated with increased odds of unplanned reoperation included typhoid perforation (adjusted odds ratio 5.92) and hypoxia on admission (adjusted odds ratio 3.82). Peritonitis in Rwanda presents with high morbidity and mortality. Minimizing delays in care is important, as many patients with intestinal obstruction present with features of peritonitis. A better understanding of patient care and management prior to arrival at the referral hospital is needed to identify areas for improvement at the health center and district hospital. Copyright © 2016 Elsevier Inc. All rights reserved.

The relevance, biases, and importance of digitising opportunistic non-standardised collections: A case study in Iberian harvestmen fauna with BOS Arthropod Collection datasets (Arachnida, Opiliones)

PubMed Central

Merino-Sáinz, Izaskun; Torralba-Burrial, Antonio; Anadón, Araceli

2014-01-01

Abstract In this study, we analyse the relevance of harvestmen distribution data derived from opportunistic, unplanned, and non-standardised collection events in an area in the north of the Iberian Peninsula. Using specimens deposited in the BOS Arthropod Collection at the University of Oviedo, we compared these data with data from planned, standardised, and periodic collections with pitfall traps in several locations in the same area. The Arthropod Collection, begun in 1977, includes specimens derived from both sampling types, and its recent digitisation allows for this type of comparative analysis. Therefore, this is the first data-paper employing a hybrid approach, wherein subset metadata are described alongside a comparative analysis. The full dataset can be accessed through Spanish GBIF IPT at http://www.gbif.es:8080/ipt/archive.do?r=Bos-Opi, and the metadata of the unplanned collection events at http://www.gbif.es:8080/ipt/resource.do?r=bos-opi_unplanned_collection_events. We have mapped the data on the 18 harvestmen species included in the unplanned collections and provided records for some species in six provinces for the first time. We have also provided the locations of Phalangium opilio in eight provinces without published records. These results highlight the importance of digitising data from unplanned biodiversity collections, as well as those derived from planned collections, especially in scarcely studied groups and areas. PMID:24843271

New Utility for an Old Tool

PubMed Central

Odonkor, Charles A.; Schonberger, Robert B.; Dai, Feng; Shelley, Kirk H.; Silverman, David G.; Barash, Paul G.

2013-01-01

Objective The primary aim of this study was to design prediction models based on a functional marker (preoperative gait-speed) to predict readiness for home discharge time of ≤ 90 minutes, and to identify those at risk for unplanned admissions, after elective ambulatory surgery. Design This prospective observational cohort study evaluated all patients scheduled for elective ambulatory surgery. Home discharge readiness and unplanned admissions were the primary outcomes. Independent variables included preoperative gait speed, heart rate, and total anesthesia time. The relationship between all predictors and each primary outcome was determined in separate multivariable logistic regression models. Results After adjustment for covariates, gait speed with adjusted odds ratio = 3.71 (95% CI: 1.21-11.26), p=0.02; was independently associated with early home discharge readiness ≤90 minutes. Importantly, gait speed dichotomized as greater or less than 1 m/s predicted unplanned admissions with odds ratio = 0.35 (95% CI: 0.16 to 0.76, p=0.008) for those with speeds ≥ 1 m/s in comparison to those with speed < 1 m/s. In a separate model, prior history of cardiac surgery with adjusted odds ratio =7.5 (95% CI: 2.34-24.41)(p=0.001) was independently associated with unplanned admissions after elective ambulatory surgery, when other covariates were held constant. Conclusions This study demonstrates use of novel prediction models based on gait speed testing to predict early home discharge and to identify those patients at risk for unplanned admissions, after elective ambulatory surgery. PMID:24051992

Implementing antiretroviral resistance testing in a primary health care HIV treatment programme in rural KwaZulu-Natal, South Africa: early experiences, achievements and challenges.

PubMed

Lessells, Richard J; Stott, Katharine E; Manasa, Justen; Naidu, Kevindra K; Skingsley, Andrew; Rossouw, Theresa; de Oliveira, Tulio

2014-03-07

Antiretroviral drug resistance is becoming increasingly common with the expansion of human immunodeficiency virus (HIV) treatment programmes in high prevalence settings. Genotypic resistance testing could have benefit in guiding individual-level treatment decisions but successful models for delivering resistance testing in low- and middle-income countries have not been reported. An HIV Treatment Failure Clinic model was implemented within a large primary health care HIV treatment programme in northern KwaZulu-Natal, South Africa. Genotypic resistance testing was offered to adults (≥16 years) with virological failure on first-line antiretroviral therapy (one viral load >1000 copies/ml after at least 12 months on a standard first-line regimen). A genotypic resistance test report was generated with treatment recommendations from a specialist HIV clinician and sent to medical officers at the clinics who were responsible for patient management. A quantitative process evaluation was conducted to determine how the model was implemented and to provide feedback regarding barriers and challenges to delivery. A total of 508 specimens were submitted for genotyping between 8 April 2011 and 31 January 2013; in 438 cases (86.2%) a complete genotype report with recommendations from the specialist clinician was sent to the medical officer. The median turnaround time from specimen collection to receipt of final report was 18 days (interquartile range (IQR) 13-29). In 114 (26.0%) cases the recommended treatment differed from what would be given in the absence of drug resistance testing. In the majority of cases (n = 315, 71.9%), the subsequent treatment prescribed was in line with the recommendations of the report. Genotypic resistance testing was successfully implemented in this large primary health care HIV programme and the system functioned well enough for the results to influence clinical management decisions in real time. Further research will explore the impact and cost-effectiveness of different implementation models in different settings.

Lifelong antiretroviral therapy or HIV cure: The benefits for the individual patient.

PubMed

Buell, Kevin G; Chung, Christopher; Chaudhry, Zain; Puri, Aiysha; Nawab, Khizr; Ravindran, Rahul Prashanth

2016-01-01

There are an estimated 35 million people living with human immunodeficiency virus (HIV) globally, 19 million of whom are unaware of their HIV status and, in the absence of antiretroviral therapy (ART), will have a shortened life expectancy. Although ART remains the "gold standard" for treatment of HIV infection, the requirement for lifelong treatment poses multiple challenges for the patient. These include stigma, an untenable pill burden, side effects, and the threat of viral resistance in the case of non-compliance. This review evaluates the challenges of accessing, delivering, and sustaining ART for people living with HIV and will discuss the case for pursuing a goal of HIV cure, the potential benefits of such a cure for the individual patient, and the current potential candidates for such a cure.

[AIDS-related early mortality in Mexico between 2008 and 2012].

PubMed

Silverman-Retana, Omar; Bautista-Arredondo, Sergio; Serván-Mori, Edson; Lozano, Rafael

2015-01-01

To describe the distribution of AIDS-related mortality according to the time of occurrence since entry to the System for the Administration, Logistics and Surveillance of Antiretrovirals (SALVAR, in Spanish), among users of Ministry of Health facilities in Mexico. Descriptive analysis of AIDS mortality and the related clinical and demographic profile of 41847 patients registered in SALVAR. 3195 patients (8.1%) died within the study period, 59% of these deaths occurred within six months after treatment initiation. Among those patients, 87.3% were diagnosed late, given their CD4 levels (CD4cel<200 cel/ml³). Our results underscore the need to strengthen programs aimed to increase opportune HIV diagnosis and linkage to care, as a key component of universal access policy to antiretroviral treatment in Mexico.

Association between age at first sexual intercourse and knowledge, attitudes and practices regarding reproductive health and unplanned pregnancy: a cross-sectional study.

PubMed

Shu, C; Fu, A; Lu, J; Yin, M; Chen, Y; Qin, T; Shang, X; Wang, X; Zhang, M; Xiong, C; Yin, P

2016-06-01

Age at first sexual intercourse (AFSI) is decreasing among adolescents in developed nations. An early sexual debut has been associated, to some extent, with multiple sexual partners, infrequent use of condoms, unplanned pregnancy, unsafe abortion, and sexually transmitted disease and human immunodeficiency virus infection. Unplanned pregnancy among adolescents has both physical and social adverse effects. In total, 78,400 self-administered anonymous questionnaires were distributed to college students in seven cities in China to determine the age at which Chinese college students first engage in sexual activity, and the association between AFSI and knowledge, attitudes and practices (KAP) regarding reproductive health and unplanned pregnancy. Approximately 10,164 students reported that they were sexually active, and most reported that they had engaged in sexual intercourse for the first time during college. The average AFSI was 20.14 [standard deviation (SD) 2.98] years, and the average AFSI by gender was 19.97 (SD 2.97) years for males and 20.41 (SD 2.97) years for females. The unplanned pregnancy rate among the participants was 34.03%. Participants lacked knowledge about contraception and reproductive health, although most believed that it is necessary to have this knowledge. Participants' attitudes towards premarital sex were varied. Factors that were found to be associated with unplanned pregnancy were AFSI, contraceptive methods used for first sexual act, and whether contraceptive methods were used for every sexual act. The college period is a key time for Chinese students in terms of becoming sexually active. As such, comprehensive and informative reproductive health education should be provided before and during the college period. Furthermore, reproductive health education should include appropriate sexual morality education and comprehensive sex education. Gender traits and needs should be considered in sex education. Copyright © 2016 The Royal Society for Public Health. Published by Elsevier Ltd. All rights reserved.

Impact of Socioeconomic Inequality on Access, Adherence, and Outcomes of Antiretroviral Treatment Services for People Living with HIV/AIDS in Vietnam.

PubMed

Tran, Bach Xuan; Hwang, Jongnam; Nguyen, Long Hoang; Nguyen, Anh Tuan; Latkin, Noah Reed Knowlton; Tran, Ngoc Kim; Minh Thuc, Vu Thi; Nguyen, Huong Lan Thi; Phan, Huong Thu Thi; Le, Huong Thi; Tran, Tho Dinh; Latkin, Carl A

2016-01-01

Ensuring an equal benefit across different patient groups is necessary while scaling up free-of-charge antiretroviral treatment (ART) services. This study aimed to measure the disparity in access, adherence, and outcomes of ART in Vietnam and the effects of socioeconomic status (SES) characteristics on the levels of inequality. A cross-sectional study was conducted in 1133 PLWH in Vietnam. ART access, adherence, and treatment outcomes were self-reported using a structured questionnaire. Wealth-related inequality was calculated using a concentration index, and a decomposition analysis was used to determine the contribution of each SES variable to inequality in access, adherence, and outcomes of ART. Based on SES, minor inequality was found in ART access and adherence while there was considerable inequality in ART outcomes. Poor people were more likely to start treatment early, while rich people had better adherence and overall treatment outcomes. Decomposition revealed that occupation and education played important roles in inequality in ART access, adherence, and treatment outcomes. The findings suggested that health services should be integrated into the ART regimen. Furthermore, occupational orientation and training courses should be provided to reduce inequality in ART access, adherence, and treatment outcomes.

Analysis of cognitive variables and sexual risk behaviors among infected and HIV-uninfected people from Spain.

PubMed

Bermúdez, María de la Paz; Araújo, Ludgleydson Fernandes de; Reyes, Antonio Ortega; Hernández-Quero, José; Teva, Inmaculada

2016-07-01

The wider availability of anti-retroviral treatment has brought about an improvement in the immunological situation of human immunodeficiency virus (HIV)-positive individuals, which in turn has led to significant reductions in AIDS-related morbidity and mortality and better quality of life for patients. However, the rate of diagnosis of new cases of HIV among the adult population is on the increase due to high-risk sexual behavior practices, particularly not using condoms, sexual relations with a large number of partners and starting sexual relations at a younger age, with unplanned pregnancies and sexually transmitted infections (STIs), including HIV. For this reason, public health managers have invested considerable effort in recent years in creating STI and HIV prevention programs. Yet, in spite of the implementation of measures for reducing the rates of infection, few studies have been published in Spain comparing individuals living with HIV with the general population about cognitive variables and the link between these variables and high-risk sexual behavior. The objective was to compare a group of individuals living with HIV with another group from the general population in terms of cognitive variables (knowledge about STIs and HIV, concern about STI/HIV and pregnancy, self-efficacy to refuse sexual relations and resilience) and sexual behavior. The sample consisted of 318 adults, 159 were from the general population and 159 were individuals living with HIV. Individuals living with HIV had higher scores for concern about HIV/AIDS, STIs, pregnancy and knowledge of STI/HIV compared with the general population. We concluded that uninfected people who had low and high level of concern about HIV/AIDS began having anal sex at a younger age than those with a medium level of concern. Overall, results indicate that the concern about HIV/AIDS should be addressed in preventive health interventions to minimize the risks of sexual behavior.

Women undergoing aortic surgery are at higher risk for unplanned readmissions compared with men especially when discharged home.

PubMed

Flink, Benjamin J; Long, Chandler A; Duwayri, Yazan; Brewster, Luke P; Veeraswamy, Ravi; Gallagher, Katherine; Arya, Shipra

2016-06-01

Women undergoing vascular surgery have higher morbidity and mortality. Our study explores gender-based differences in patient-centered outcomes such as readmission, length of stay (LOS), and discharge destination (home vs nonhome facility) in aortic aneurysm surgery. Patients were identified from the American College of Surgeons National Surgical Quality Improvement Project database (2011-2013) undergoing abdominal, thoracic, and thoracoabdominal aortic aneurysms (N = 17,763), who were discharged and survived their index hospitalization. The primary outcome was unplanned readmission, and secondary outcomes were discharge to a nonhome facility, LOS, and reasons for unplanned readmission. Univariate, multivariate, and stratified analyses based on gender and discharge destination were used. Overall, 1541 patients (8.7%) experienced an unplanned readmission, with a significantly higher risk in women vs men (10.8% vs 8%; P < .001) overall (Procedure subtypes: abdominal aortic aneurysm [10.1% vs 7.7%; P < .001], thoracic aortic aneurysm [14.1% vs 13.5%; P = .8], and thoracoabdominal aortic aneurysm [14.8% vs 10%; P = .051]). The higher odds of readmission in women compared with men persisted in multivariate analysis after controlling for covariates (odds ratio [OR], 1.21; 95% confidence interval [CI], 1.05-1.4). Similarly, the rate of discharge to a nonhome facility was nearly double in women compared with men (20.6% vs 10.7%; P < .001), but discharge to a nonhome facility was not a significant predictor of unplanned readmission. Upon stratification by discharge destination, the higher odds of readmissions in women compared with men occurred in patients who were discharged home (OR, 1.2; 95% CI, 1.02-1.4) but not in those who were discharged to a nonhome facility (OR, 1.06; 95% CI, 0.8-1.4). Significant differences in LOS were seen in patients who were discharged home. No gender differences were found in reasons for readmission with the three most common reasons being thromboembolic events, wound infections, and pneumonia. Gender disparity exists in the risk of unplanned readmission among aortic aneurysm surgery patients. Women who were discharged home have a higher likelihood of unplanned readmission despite longer LOS than men. These data suggest that further study into the discharge planning processes, social factors, and use of rehabilitation services is needed for women undergoing aortic procedures to decrease readmissions. Published by Elsevier Inc.

Risk factors for unplanned readmission within 30 days after pediatric neurosurgery: a nationwide analysis of 9799 procedures from the American College of Surgeons National Surgical Quality Improvement Program

PubMed Central

Sherrod, Brandon A.; Johnston, James M.; Rocque, Brandon G.

2017-01-01

Objective Readmission rate is increasingly used as a quality outcome measure after surgery. The purpose of this study was to establish, using a national database, the baseline readmission rates and risk factors for readmission after pediatric neurosurgical procedures. Methods The American College of Surgeons National Surgical Quality Improvement Program–Pediatric database was queried for pediatric patients treated by a neurosurgeon from 2012 to 2013. Procedures were categorized by current procedural terminology code. Patient demographics, comorbidities, preoperative laboratory values, operative variables, and postoperative complications were analyzed via univariate and multivariate techniques to find associations with unplanned readmission within 30 days of the primary procedure. Results A total of 9799 cases met the inclusion criteria, 1098 (11.2%) of which had an unplanned readmission within 30 days. Readmission occurred 14.0 ± 7.7 days postoperatively (mean ± standard deviation). The 4 procedures with the highest unplanned readmission rates were CSF shunt revision (17.3%), repair of myelomeningocele > 5 cm in diameter (15.4%), CSF shunt creation (14.1%), and craniectomy for infratentorial tumor excision (13.9%). Spine (6.5%), craniotomy for craniosynostosis (2.1%), and skin lesion (1.0%) procedures had the lowest unplanned readmission rates. On multivariate regression analysis, the odds of readmission were greatest in patients experiencing postoperative surgical site infection (SSI; deep, organ/space, superficial SSI and wound disruption: OR > 12 and p < 0.001 for each). Postoperative pneumonia (OR 4.294, p < 0.001), urinary tract infection (OR 4.262, p < 0.001), and sepsis (OR 2.616, p = 0.006) also independently increased the readmission risk. Independent patient risk factors for unplanned readmission included Native American race (OR 2.363, p = 0.019), steroid use > 10 days (OR 1.411, p = 0.010), oxygen supplementation (OR 1.645, p = 0.010), nutritional support (OR 1.403, p = 0.009), seizure disorder (OR 1.250, p = 0.021), and longer operative time (per hour increase, OR 1.059, p = 0.014). Conclusions This study may aid in identifying patients at risk for unplanned readmission following pediatric neurosurgery, potentially helping to focus efforts at lowering readmission rates, minimizing patient risk, and lowering costs for health care systems. PMID:27184348

Risk factors for unplanned readmission within 30 days after pediatric neurosurgery: a nationwide analysis of 9799 procedures from the American College of Surgeons National Surgical Quality Improvement Program.

PubMed

Sherrod, Brandon A; Johnston, James M; Rocque, Brandon G

2016-09-01

OBJECTIVE Hospital readmission rate is increasingly used as a quality outcome measure after surgery. The purpose of this study was to establish, using a national database, the baseline readmission rates and risk factors for patient readmission after pediatric neurosurgical procedures. METHODS The American College of Surgeons National Surgical Quality Improvement Program-Pediatric database was queried for pediatric patients treated by a neurosurgeon between 2012 and 2013. Procedures were categorized by current procedural terminology (CPT) code. Patient demographics, comorbidities, preoperative laboratory values, operative variables, and postoperative complications were analyzed via univariate and multivariate techniques to find associations with unplanned readmissions within 30 days of the primary procedure. RESULTS A total of 9799 cases met the inclusion criteria, 1098 (11.2%) of which had an unplanned readmission within 30 days. Readmission occurred 14.0 ± 7.7 days postoperatively (mean ± standard deviation). The 4 procedures with the highest unplanned readmission rates were CSF shunt revision (17.3%; CPT codes 62225 and 62230), repair of myelomeningocele > 5 cm in diameter (15.4%), CSF shunt creation (14.1%), and craniectomy for infratentorial tumor excision (13.9%). The lowest unplanned readmission rates were for spine (6.5%), craniotomy for craniosynostosis (2.1%), and skin lesion (1.0%) procedures. On multivariate regression analysis, the odds of readmission were greatest in patients experiencing postoperative surgical site infection (SSI; deep, organ/space, superficial SSI, and wound disruption: OR > 12 and p < 0.001 for each). Postoperative pneumonia (OR 4.294, p < 0.001), urinary tract infection (OR 4.262, p < 0.001), and sepsis (OR 2.616, p = 0.006) also independently increased the readmission risk. Independent patient risk factors for unplanned readmission included Native American race (OR 2.363, p = 0.019), steroid use > 10 days (OR 1.411, p = 0.010), oxygen supplementation (OR 1.645, p = 0.010), nutritional support (OR 1.403, p = 0.009), seizure disorder (OR 1.250, p = 0.021), and longer operative time (per hour increase, OR 1.059, p = 0.029). CONCLUSIONS This study may aid in identifying patients at risk for unplanned readmission following pediatric neurosurgery, potentially helping to focus efforts at lowering readmission rates, minimizing patient risk, and lowering costs for health care systems.

Motor and Cognitive Functional Status Are Associated with 30-day Unplanned Rehospitalization Following Post-Acute Care in Medicare Fee-for-Service Beneficiaries.

PubMed

Middleton, Addie; Graham, James E; Lin, Yu-Li; Goodwin, James S; Bettger, Janet Prvu; Deutsch, Anne; Ottenbacher, Kenneth J

2016-12-01

The Improving Medicare Post-Acute Care Transformation (IMPACT) Act of 2014 stipulates that standardized functional status (self-care and mobility) and cognitive function data will be used for quality reporting in post-acute care settings. Thirty-day post-discharge unplanned rehospitalization is an established quality metric that has recently been extended to post-acute settings. The relationships between the functional domains in the IMPACT Act and 30-day unplanned rehospitalization are poorly understood. To determine the degree to which discharge mobility, self-care, and cognitive function are associated with 30-day unplanned rehospitalization following discharge from post-acute care. This was a retrospective cohort study. Inpatient rehabilitation facilities submitting claims and assessment data to the Centers for Medicare and Medicaid Services in 2012-2013. Medicare fee-for-service enrollees discharged from post-acute rehabilitation in 2012-2013. The sample included community-dwelling adults admitted for rehabilitation following an acute care stay who survived for 32 days following discharge (N = 252,406). Not applicable. Thirty-day unplanned rehospitalization following post-acute rehabilitation. The unadjusted 30-day unplanned rehospitalization rate was 12.0 % (n = 30,179). Overall, patients dependent at discharge for mobility had a 50 % increased odds of rehospitalization (OR = 1.50, 95 % CI: 1.42-1.59), patients dependent for self-care a 36 % increased odds (OR = 1.36, 95 % CI: 1.27-1.47), and patients dependent for cognition a 19 % increased odds (OR = 1.19, 95 % CI: 1.09-1.29). Patients dependent for both self-care and mobility at discharge (n = 8312, 3.3 %) had a 16.1 % (95 % CI: 15.3-17.0 %) adjusted rehospitalization rate versus 8.5 % (95 % CI: 8.3-8.8 %) for those independent for both (n = 74,641; 29.6 %). The functional domains identified in the IMPACT Act were associated with 30-day unplanned rehospitalization following post-acute care in this large national sample. Further research is needed to better understand and improve the functional measures, and to determine if their association with rehospitalizations varies across post-acute settings, patient populations, or episodes of care.

Health care utilisation among older persons with intellectual disability and dementia: a registry study.

PubMed

Axmon, A; Karlsson, B; Ahlström, G

2016-12-01

Both persons with intellectual disability (ID) and persons with dementia have high disease burdens, and consequently also high health care needs. As life expectancy increases for persons with ID, the group of persons with the dual diagnosis of ID and dementia will become larger. Through national registries, we identified 7936 persons who had received support directed to persons with ID during 2012, and an age- and gender-matched sample from the general population. A national registry was also used to collect information on health care utilisation (excluding primary care) for the period 2002-2012. Health care utilisation was measured as presence and number of planned and unplanned in-patient and out-patient visits, as well as length of stay. In comparison with persons with ID but without dementia, persons with ID and dementia were more likely to have at least one planned out-patient visit (odds ratio [OR] 8.07), unplanned out-patient visit (OR 2.41), planned in-patient visit (OR 2.76) or unplanned in-patient visit (OR 4.19). However, among those with at least one of each respective outcome, the average number of visits did not differ between those with and without dementia. Persons with ID and dementia were less likely to have at least one planned out-patient visit than persons with dementia in the general population sample (OR 0.40), but more likely to have at least one unplanned in-patient visit (OR 1.90). No statistically significant differences were found for having at least one unplanned out-patient or planned in-patient visit. Nevertheless, among those with at least one unplanned out-patient visit, the number of visits was higher in the general population sample. Persons with ID and dementia are less likely to receive planned health care than persons with dementia in the general population. They have, however, higher levels of unplanned health care utilisation. This may be an indication that the current support system is not sufficient to meet the challenges of increased longevity among persons with ID. © 2016 The Authors. Journal of Intellectual Disability Research published by MENCAP and International Association of the Scientific Study of Intellectual and Developmental Disibilities and John Wiley & Sons Ltd.

Electrical treatment of atrial arrhythmias in heart failure patients implanted with a dual defibrillator CRT device. Results from the TRADE-HF study.

PubMed

Botto, Giovanni Luca; Padeletti, Luigi; Covino, Gregorio; Pieragnoli, Paolo; Liccardo, Mattia; Mariconti, Barbara; Favale, Stefano; Molon, Giulio; De Filippo, Paolo; Bolognese, Leonardo; Landolina, Maurizio; Raciti, Giovanni; Boriani, Giuseppe

2017-06-01

Ventricular and atrial arrhythmias commonly occur in heart failure patients and are a significant source of symptoms, morbidity and mortality. Some specific generators referred to as dual defibrillators, Dual CRT-Ds, have the ability to treat atrial and ventricular arrhythmias. TRADE-HF is a prospective two-arm randomized study aimed at assessing the benefits of complete automatic management of atrial arrhythmias in patients implanted with a dual CRT-D. Primary objective of the TRADE-HF study was to document reduction of unplanned hospital admission for cardiac reasons or death for cardiovascular causes or progression to permanent AF, by comparing fully-automatic device driven therapy for atrial tachycardia or fibrillation (AT/AF) to an in-hospital approach for treatment of symptomatic AT/AF. Randomized Patients were followed every 6months for 3years to assess the primary objective. Four-hundred-twenty patients have been enrolled in the study. At the end of the study 30 subjects died for cardiovascular causes, 60 had at least one hospitalization for cardiovascular causes and 14 developed permanent AF. Eighty-seven patients experienced a composite event. Hazard Ratio for device-managed automatic therapy arm compared to traditional was 0.987 (95% CI: 0.684-1.503; p=0.951). The primary endpoint analysis resulted in no difference between the device managed and in-hospital treatment arm. The TRADE-HF study failed to demonstrate a reduction in the composite of unplanned hospitalizations for cardiovascular causes or death for cardiovascular causes or progression to permanent AF using automatic atrial therapy compared to a traditional approach including hospitalization for symptomatic episodes and/or in-hospital treatment of AT/AF. Copyright © 2017 Elsevier B.V. All rights reserved.

Management of ganciclovir-resistant cytomegalovirus retinitis in HIV infection in the era of antiretroviral therapy.

PubMed

Adler, Hugh; De Gascun, Cillian F; McSweeney, Fionnuala; Acheson, Robert W; Brannigan, Eimear T; Duffy, Margaret; Keegan, David J; Lambert, John S

2014-10-01

The incidence of cytomegalovirus retinitis has decreased significantly since the advent of antiretroviral therapy. However, it remains an important problem in both the developed and developing worlds. Furthermore, long-term antiviral suppression is associated with a significant increase in viral resistance. We present the case of a 46-year-old man who developed cytomegalovirus retinitis one year after being diagnosed with HIV. While he initially demonstrated an excellent clinical response to ganciclovir, his cytomegalovirus viral load remained persistently elevated. Over the subsequent years, his virus developed ganciclovir resistance with a concomitant deterioration in his visual acuity. He responded poorly to salvage therapy with foscarnet and cidofovir. This case highlights the ongoing difficulty of managing cytomegalovirus disease nearly two decades into the era of antiretroviral therapy and underlines the need to develop new treatment strategies. © The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

Pharmacodynamics of folic acid receptor targeted antiretroviral nanotherapy in HIV-1-infected humanized mice.

PubMed

Puligujja, Pavan; Araínga, Mariluz; Dash, Prasanta; Palandri, Diana; Mosley, R Lee; Gorantla, Santhi; Poluektova, Larisa; McMillan, JoEllyn; Gendelman, Howard E

2015-08-01

Long-acting nanoformulated antiretroviral therapy (nanoART) can sustain plasma drug levels and improve its biodistribution. Cell targeted-nanoART can achieve this and bring drug efficiently to viral reservoirs. However, whether such improvements affect antiretroviral responses remains unknown. To these ends, we tested folic acid (FA)-linked poloxamer407-coated ritonavir-boosted atazanavir (FA-nanoATV/r) nanoparticles for their ability to affect chronic HIV-1 infection in humanized mice. Following three, 100mg/kg FA-nanoATV/r intramuscular injections administered every other week to infected animals, viral RNA was at or below the detection limit, cell-associated HIV-1p24 reduced and CD4+ T cell counts protected. The dosing regimen improved treatment outcomes more than two fold from untargeted nanoATV/r. We posit that these nanoformulations have potential for translation to human use. Copyright © 2015 Elsevier B.V. All rights reserved.

The Promise of Antiretrovirals for HIV Prevention

PubMed Central

Flash, Charlene; Krakower, Douglas; Mayer, Kenneth H.

2013-01-01

With an estimated 2.6 million new HIV infections diagnosed annually, the world needs new prevention strategies to partner with condom use, harm reduction approaches for injection drug users, and male circumcision. Antiretrovirals can reduce the risk of mother-to-child HIV transmission and limit HIV acquisition after occupational exposure. Macaque models and clinical trials demonstrate efficacy of oral or topical antiretrovirals used prior to HIV exposure to prevent HIV transmission, ie pre-exposure prophylaxis (PrEP). Early initiation of effective HIV treatment in serodiscordant couples results in a 96% decrease in HIV transmission. HIV testing to determine serostatus and identify undiagnosed persons is foundational to these approaches. The relative efficacy of different approaches, adherence, cost and long-term safety will affect uptake and impact of these strategies. Ongoing research will help characterize the role for oral and topical formulations and help quantify potential benefits in sub-populations at risk for HIV acquisition. PMID:22351302

Dangerous medicines: Unproven AIDS cures and counterfeit antiretroviral drugs

PubMed Central

Amon, Joseph J

2008-01-01

Background Increasing access to antiretroviral therapy (ART) is a critical goal endorsed by the United Nations and all of its member states. At the same time, anecdotal accounts suggest that the promotion of unproven AIDS 'cures' and remedies are widespread, and in the case of The Gambia, Iran and South Africa, have been promoted by governments directly. Although a range of legislative and regulatory measures have been adopted by some governments, and technical assistance has been provided by international agencies to address counterfeit medicines generally, the threat of counterfeit antiretroviral drugs is not being addressed. Discussion Countries, charged with fulfilling the right to health and committed to expanding access to ART must explicitly recognize their obligation to combat unproven AIDS treatments and ensure the availability of a safe and efficacious drugs supply. International donors must help support and coordinate these efforts. PMID:18304316

Drug Interactions and Antiretroviral Drug Monitoring

PubMed Central

Foy, Matthew; Sperati, C. John; Lucas, Gregory M.

2014-01-01

Due to the improved longevity afforded by combination antiretroviral therapy (cART), HIV-infected individuals are developing several non-AIDS related comorbid conditions. Consequently, medical management of the HIV-infected population is increasingly complex, with a growing list of potential drug-drug interactions (DDIs). This article reviews some of the most relevant and emerging potential interactions between antiretroviral medications and other agents. The most common DDIs are those involving protease inhibitors or non-nucleoside reverse transcriptase inhibitors which alter the cytochrome P450 enzyme system and/or drug transporters such as p-glycoprotein. Of note are the new agents for the treatment of chronic hepatitis C virus infection. These new classes of drugs and others drugs which are increasingly used in this patient population represent a significant challenge with regard to achieving the goals of effective HIV suppression and minimization of drug-related toxicities. Awareness of DDIs and a multidisciplinary approach are imperative in reaching these goals. PMID:24950731

Early versus delayed initiation of antiretroviral therapy for Indian HIV-Infected individuals with tuberculosis on antituberculosis treatment.

PubMed

Sinha, Sanjeev; Shekhar, Rahul C; Singh, Gurjeet; Shah, Nipam; Ahmad, Hafiz; Kumar, Narendra; Sharma, Surendra K; Samantaray, J C; Ranjan, Sanjai; Ekka, Meera; Sreenivas, Vishnu; Mitsuyasu, Ronald T

2012-07-31

For antiretroviral therapy (ART) naive human immunodeficiency virus (HIV) infected adults suffering from tuberculosis (TB), there is uncertainty about the optimal time to initiate highly active antiretroviral therapy (HAART) after starting antituberculosis treatment (ATT), in order to minimize mortality, HIV disease progression, and adverse events. In a randomized, open label trial at All India Institute of Medical Sciences, New Delhi, India, eligible HIV positive individuals with a diagnosis of TB were randomly assigned to receive HAART after 2-4 or 8-12 weeks of starting ATT, and were followed for 12 months after HAART initiation. Participants received directly observed therapy short course (DOTS) for TB, and an antiretroviral regimen comprising stavudine or zidovudine, lamivudine, and efavirenz. Primary end points were death from any cause, and progression of HIV disease marked by failure of ART. A total of 150 patients with HIV and TB were initiated on HAART: 88 received it after 2-4 weeks (early ART) and 62 after 8-12 weeks (delayed ART) of starting ATT. There was no significant difference in mortality between the groups after the introduction of HAART. However, incidence of ART failure was 31% in delayed versus 16% in early ART arm (p = 0.045). Kaplan Meier disease progression free survival at 12 months was 79% for early versus 64% for the delayed ART arm (p = 0.05). Rates of adverse events were similar. Early initiation of HAART for patients with HIV and TB significantly decreases incidence of HIV disease progression and has good tolerability. CTRI/2011/12/002260.

Approaches to rationing antiretroviral treatment: ethical and equity implications.

PubMed Central

Bennett, Sara; Chanfreau, Catherine

2005-01-01

Despite a growing global commitment to the provision of antiretroviral therapy (ART), its availability is still likely to be less than the need. This imbalance raises ethical dilemmas about who should be granted access to publicly-subsidized ART programmes. This paper reviews the eligibility and targeting criteria used in four case-study countries at different points in the scale-up of ART, with the aim of drawing lessons regarding ethical approaches to rationing. Mexico, Senegal, Thailand and Uganda have each made an explicit policy commitment to provide antiretrovirals to all those in need, but are achieving this goal in steps--beginning with explicit rationing of access to care. Drawing upon the case-studies and experiences elsewhere, categories of explicit rationing criteria have been identified. These include biomedical factors, adherence to treatment, prevention-driven factors, social and economic benefits, financial factors and factors driven by ethical arguments. The initial criteria for determining eligibility are typically clinical criteria and assessment of adherence prospects, followed by a number of other factors. Rationing mechanisms reflect several underlying ethical theories and the ethical underpinnings of explicit rationing criteria should reflect societal values. In order to ensure this alignment, widespread consultation with a variety of stakeholders, and not only policy-makers or physicians, is critical. Without such explicit debate, more rationing will occur implicitly and this may be more inequitable. The effects of rationing mechanisms upon equity are critically dependent upon the implementation processes. As antiretroviral programmes are implemented it is crucial to monitor who gains access to these programmes. PMID:16175829

The cost of antiretroviral therapy in Haiti

PubMed Central

Koenig, Serena P; Riviere, Cynthia; Leger, Paul; Severe, Patrice; Atwood, Sidney; Fitzgerald, Daniel W; Pape, Jean W; Schackman, Bruce R

2008-01-01

Background We determined direct medical costs, overhead costs, societal costs, and personnel requirements for the provision of antiretroviral therapy (ART) to patients with AIDS in Haiti. Methods We examined data from 218 treatment-naïve adults who were consecutively initiated on ART at the GHESKIO Center in Port-au-Prince, Haiti between December 23, 2003 and May 20, 2004 and calculated costs and personnel requirements for the first year of ART. Results The mean total cost of treatment per patient was $US 982 including $US 846 in direct costs, $US 114 for overhead, and $US 22 for societal costs. The direct cost per patient included generic ART medications $US 355, lab tests $US 130, nutrition $US 117, hospitalizations $US 62, pre-ART evaluation $US 58, labor $US 51, non-ART medications $US 39, outside referrals $US 31, and telephone cards for patient retention $US 3. Higher treatment costs were associated with hospitalization, change in ART regimen, TB treatment, and survival for one year. We estimate that 1.5 doctors and 2.5 nurses are required to treat 1000 patients in the first year after initiating ART. Conclusion Initial ART treatment in Haiti costs approximately $US 1,000 per patient per year. With generic first-line antiretroviral drugs, only 36% of the cost is for medications. Patients who change regimens are significantly more expensive to treat, highlighting the need for less-expensive second-line drugs. There may be sufficient health care personnel to treat all HIV-infected patients in urban areas of Haiti, but not in rural areas. New models of HIV care are needed for rural areas using assistant medical officers and community health workers. PMID:18275615

Detection of drug resistance mutations at low plasma HIV-1 RNA load in a European multicentre cohort study.

PubMed

Prosperi, Mattia C F; Mackie, Nicola; Di Giambenedetto, Simona; Zazzi, Maurizio; Camacho, Ricardo; Fanti, Iuri; Torti, Carlo; Sönnerborg, Anders; Kaiser, Rolf; Codoñer, Francisco M; Van Laethem, Kristel; Bansi, Loveleen; van de Vijver, David A M C; Geretti, Anna Maria; De Luca, Andrea

2011-08-01

Guidelines indicate a plasma HIV-1 RNA load of 500-1000 copies/mL as the minimal threshold for antiretroviral drug resistance testing. Resistance testing at lower viral load levels may be useful to guide timely treatment switches, although data on the clinical utility of this remain limited. We report here the influence of viral load levels on the probability of detecting drug resistance mutations (DRMs) and other mutations by routine genotypic testing in a large multicentre European cohort, with a focus on tests performed at a viral load <1000 copies/mL. A total of 16 511 HIV-1 reverse transcriptase and protease sequences from 11 492 treatment-experienced patients were identified, and linked to clinical data on viral load, CD4 T cell counts and antiretroviral treatment history. Test results from 3162 treatment-naive patients served as controls. Multivariable analysis was employed to identify predictors of reverse transcriptase and protease DRMs. Overall, 2500/16 511 (15.14%) test results were obtained at a viral load <1000 copies/mL. Individuals with viral load levels of 1000-10000 copies/mL showed the highest probability of drug resistance to any drug class. Independently from other measurable confounders, treatment-experienced patients showed a trend for DRMs and other mutations to decrease at viral load levels <500 copies/mL. Genotypic testing at low viral load may identify emerging antiretroviral drug resistance at an early stage, and thus might be successfully employed in guiding prompt management strategies that may reduce the accumulation of resistance and cross-resistance, viral adaptive changes, and larger viral load increases.

LC-MS/MS determination of antiretroviral drugs in influents and effluents from wastewater treatment plants in KwaZulu-Natal, South Africa.

PubMed

Abafe, Ovokeroye A; Späth, Jana; Fick, Jerker; Jansson, Stina; Buckley, Chris; Stark, Annegret; Pietruschka, Bjoern; Martincigh, Bice S

2018-06-01

South Africa has the largest occurrence of the human immune deficiency virus (HIV) in the world but has also implemented the largest antiretroviral (ARV) treatment programme. It was therefore of interest to determine the presence and concentrations of commonly used antiretroviral drugs (ARVDs) and, also, to determine the capabilities of wastewater treatment plants (WWTPs) for removing ARVDs. To this end, a surrogate standard based LC-MS/MS method was optimized and applied for the detection of thirteen ARVDs used in the treatment and management of HIV/acquired immune deficiency syndrome (HIV/AIDS) in two major and one modular WWTP in the eThekwini Municipality in KwaZulu-Natal, South Africa. The method was validated and the detection limits fell within the range of 2-20 ng L -1 . The analytical recoveries for the ARVDs were mainly greater than 50% with acceptable relative standard deviations. The concentration values ranged from

Prevalence, awareness, treatment, and control rate of hypertension in HIV-infected patients: the HIV-HY study.

PubMed

De Socio, Giuseppe Vittorio; Ricci, Elena; Maggi, Paolo; Parruti, Giustino; Pucci, Giacomo; Di Biagio, Antonio; Calza, Leonardo; Orofino, Giancarlo; Carenzi, Laura; Cecchini, Enisia; Madeddu, Giordano; Quirino, Tiziana; Schillaci, Giuseppe

2014-02-01

We aimed to assess the prevalence of hypertension in an unselected human immunodeficiency virus (HIV)-infected population and to identify factors associated with hypertension prevalence, treatment, and control. We used a multicenter, cross-sectional, nationwide study that sampled 1,182 unselected, consecutive, HIV-infected patients. Office blood pressure was accurately measured with standard procedures. Patients were 71% men and 92% white, with a median age of 47 years (range = 18-78); 6% were antiretroviral treatment naive. The overall prevalence of hypertension was 29.3%; high-normal pressure accounted for an additional 12.3%. Among hypertensive subjects, 64.9% were aware of their hypertensive condition, 52.9% were treated, and 33.0% were controlled (blood pressure < 140/90 mm Hg). Blood pressure-lowering medications were used in monotherapy in 54.3% of the subjects. Angiotensin-converting enzyme inhibitors and angiotensin receptor blockers were the most frequently used drugs (76.1%: monotherapy = 39.1%, combination treatment = 37.0%). In multivariable regression models, hypertension was independently predicted by traditional risk factors, including age ≥50 years, male sex, family history of cardiovascular disease, body mass index ≥25 kg/m2, previous cardiovascular events, diabetes, central obesity, and metabolic syndrome, as well as by duration of HIV infection, duration of antiretroviral therapy, and nadir CD4+ T-cell count <200/μl. The choice of protease inhibitors vs. nonnucleoside reverse transcriptase inhibitors as a third antiretroviral drug was irrelevant. Hypertension affects nearly 30% of HIV adult outpatients in Italy. More than one-third of the hypertensive subjects are unaware of their condition, and more than two-thirds are uncontrolled. A higher level of attention to the diagnosis and treatment of hypertension is mandatory in this setting.

Adverse Drug Reactions to Antiretroviral Therapy: Prospective Study in Children in Sikasso (Mali)

PubMed Central

Oumar, Aboubacar A.; Diallo, Korotoumou; Dembélé, Jean P.; Samaké, Lassana; Sidibé, Issa; Togo, Boubacar; Sylla, Mariam; Tounkara, Anatole; Dao, Sounkalo; Tulkens, Paul M.

2012-01-01

OBJECTIVES Adverse events during antiretroviral treatment are frequent and various. Their diagnosis incurs some various difficulties according to the geographic context. Our aim was to describe the frequency, nature, and preventability of adverse drug reactions (ADRs) due to antiretroviral treatment in Malian outpatient children. METHODS The study was a 6-month (June 1 to November 30, 2010) prospective, observational study of 92 children admitted to a pediatric hospital in Sikasso, Mali. The patients were treated with a generic drug and/or drug combinations. Prior to treatment initiation, demographic characteristics, clinical history, and biologic parameters, including CD4 cell counts, were collected for each patient. The World Health Organization's adverse drug reactions classification was used to characterize the side effects. Adverse effects and toxicities were graded 1, 2, and 3. Analysis of data was performed using SPSS Version 17.0 software. RESULTS Ninety-two human immunodeficiency virus–infected children met the criteria of inclusion. After 24 weeks of treatment, we observed that 14.1% of children had at least one side effect during our study. Side effects were many and varied, with the most frequent being cutaneous rash, nausea, vomiting, and diarrhea (38.5%, 23.1%, 15.4%, and 15.4%, respectively). Side effects were grade 1 in most cases. One case of grade 2 and one case of grade 3 were observed with rash. We observed one case of grade 3 side effects during our study. The treatment regimen was changed in 15.2% of cases, including one case because of side effects. CONCLUSION ADRs are not rare in Mali, particularly in children. These ADRs have an impact on quality of life for patients. We recommend a pharmacovigilance system for sustainable management of side effects in patients infected with human immunodeficiency virus in Mali. PMID:23411444

The Evolving Landscape of HIV Drug Resistance Diagnostics for Expanding Testing in Resource-Limited Settings.

PubMed

Inzaule, Seth C; Hamers, Ralph L; Paredes, Roger; Yang, Chunfu; Schuurman, Rob; Rinke de Wit, Tobias F

2017-01-01

Global scale-up of antiretroviral treatment has dramatically changed the prospects of HIV/AIDS disease, rendering life-long chronic care and treatment a reality for millions of HIV-infected patients. Affordable technologies to monitor antiretroviral treatment are needed to ensure long-term durability of limited available drug regimens. HIV drug resistance tests can complement existing strategies in optimizing clinical decision-making for patients with treatment failure, in addition to facilitating population-based surveillance of HIV drug resistance. This review assesses the current landscape of HIV drug resistance technologies and discusses the strengths and limitations of existing assays available for expanding testing in resource-limited settings. These include sequencing-based assays (Sanger sequencing assays and nextgeneration sequencing), point mutation assays, and genotype-free data-based prediction systems. Sanger assays are currently considered the gold standard genotyping technology, though only available at a limited number of resource-limited setting reference and regional laboratories, but high capital and test costs have limited their wide expansion. Point mutation assays present opportunities for simplified laboratory assays, but HIV genetic variability, extensive codon redundancy at or near the mutation target sites with limited multiplexing capability have restricted their utility. Next-generation sequencing, despite high costs, may have potential to reduce the testing cost significantly through multiplexing in high-throughput facilities, although the level of bioinformatics expertise required for data analysis is currently still complex and expensive and lacks standardization. Web-based genotype-free prediction systems may provide enhanced antiretroviral treatment decision-making without the need for laboratory testing, but require further clinical field evaluation and implementation scientific research in resource-limited settings.

Update on HIV-1 acquired and transmitted drug resistance in Africa.

PubMed

Ssemwanga, Deogratius; Lihana, Raphael W; Ugoji, Chinenye; Abimiku, Alash'le; Nkengasong, John; Dakum, Patrick; Ndembi, Nicaise

2015-01-01

The last ten years have witnessed a significant scale-up and access to antiretroviral therapy in Africa, which has improved patient quality of life and survival. One major challenge associated with increased access to antiretroviral therapy is the development of antiretroviral resistance due to inconsistent drug supply and/or poor patient adherence. We review the current state of both acquired and transmitted drug resistance in Africa over the past ten years (2001-2011) to identify drug resistance associated with the different drug regimens used on the continent and to help guide affordable strategies for drug resistance surveillance. A total of 161 references (153 articles, six reports and two conference abstracts) were reviewed. Antiretroviral resistance data was available for 40 of 53 African countries. A total of 5,541 adult patients from 99 studies in Africa were included in this analysis. The pooled prevalence of drug resistance mutations in Africa was 10.6%, and Central Africa had the highest prevalence of 54.9%. The highest prevalence of nucleoside reverse transcriptase inhibitor mutations was in the west (55.3%) and central (54.8%) areas; nonnucleoside reverse transcriptase inhibitor mutations were highest in East Africa (57.0%) and protease inhibitors mutations highest in Southern Africa (16.3%). The major nucleoside reverse transcriptase inhibitor mutation in all four African regions was M184V. Major nonnucleoside reverse transcriptase inhibitor as well as protease inhibitor mutations varied by region. The prevalence of drug resistance has remained low in several African countries although the emergence of drug resistance mutations varied across countries. Continued surveillance of antiretroviral therapy resistance remains crucial in gauging the effectiveness of country antiretroviral therapy programs and strategizing on effective and affordable strategies for successful treatment.

HIV-1 drug resistance in recently HIV-infected pregnant mother's naïve to antiretroviral therapy in Dodoma urban, Tanzania.

PubMed

Vairo, Francesco; Nicastri, Emanuele; Liuzzi, Giuseppina; Chaula, Zainab; Nguhuni, Boniface; Bevilacqua, Nazario; Forbici, Federica; Amendola, Alessandra; Fabeni, Lavinia; De Nardo, Pasquale; Perno, Carlo Federico; Cannas, Angela; Sakhoo, Calistus; Capobianchi, Maria Rosaria; Ippolito, Giuseppe

2013-09-21

HIV resistance affects virological response to therapy and efficacy of prophylaxis in mother-to-child-transmission. The study aims to assess the prevalence of HIV primary resistance in pregnant women naïve to antiretrovirals. Cross sectional baseline analysis of a cohort of HIV + pregnant women (HPW) enrolled in the study entitled Antiretroviral Management of Antenatal and Natal HIV Infection (AMANI, peace in Kiswahili language). The AMANI study began in May 2010 in Dodoma, Tanzania. In this observational cohort, antiretroviral treatment was provided to all women from the 28th week of gestation until the end of the breastfeeding period. Baseline CD4 cell count, viral load and HIV drug-resistance genotype were collected. Drug-resistance analysis was performed on 97 naïve infected-mothers. The prevalence of all primary drug resistance and primary non-nucleoside reverse-transcriptase inhibitors resistance was 11.9% and 7.5%, respectively. K103S was found in two women with no M184V detection. HIV-1 subtype A was the most commonly identified, with a high prevalence of subtype A1, followed by C, D, C/D recombinant, A/C recombinant and A/D recombinant. HIV drug- resistance mutations were detected in A1 and C subtypes. Our study reports an 11.9% prevalence rate of primary drug resistance in naïve HIV-infected pregnant women from a remote area of Tanzania. Considering that the non-nucleoside reverse-transcriptase inhibitors are part of the first-line antiretroviral regimen in Tanzania and all of Africa, resistance surveys should be prioritized in settings where antiretroviral therapy programs are scaled up.

HIV Resistance Prediction to Reverse Transcriptase Inhibitors: Focus on Open Data.

PubMed

Tarasova, Olga; Poroikov, Vladimir

2018-04-19

Research and development of new antiretroviral agents are in great demand due to issues with safety and efficacy of the antiretroviral drugs. HIV reverse transcriptase (RT) is an important target for HIV treatment. RT inhibitors targeting early stages of the virus-host interaction are of great interest for researchers. There are a lot of clinical and biochemical data on relationships between the occurring of the single point mutations and their combinations in the pol gene of HIV and resistance of the particular variants of HIV to nucleoside and non-nucleoside reverse transcriptase inhibitors. The experimental data stored in the databases of HIV sequences can be used for development of methods that are able to predict HIV resistance based on amino acid or nucleotide sequences. The data on HIV sequences resistance can be further used for (1) development of new antiretroviral agents with high potential for HIV inhibition and elimination and (2) optimization of antiretroviral therapy. In our communication, we focus on the data on the RT sequences and HIV resistance, which are available on the Internet. The experimental methods, which are applied to produce the data on HIV-1 resistance, the known data on their concordance, are also discussed.

A New Classification System to Report Complications in Growing Spine Surgery: A Multicenter Consensus Study.

PubMed

Smith, John T; Johnston, Charles; Skaggs, David; Flynn, John; Vitale, Michael

2015-12-01

The use of growth-sparing instrumentation in pediatric spinal deformity is associated with a significant incidence of adverse events. However, there is no consistent way to report these complications, allowing for meaningful comparison of different growth-sparing techniques and strategies. The purpose of this study is to develop consensus for a new classification system to report these complications. The authors, who represent lead surgeons from 5 major pediatric spine centers, collaborated to develop a classification system to report complications associated with growing spine surgery. Following IRB approval, this system was then tested using a minimum of 10 patients from each center with at least 2-year follow-up after initial implantation of growing instrumentation to assess ease of use and consistency in reporting complications. Inclusion criteria were only patients who had surgical treatment of early onset scoliosis and did not include casting or bracing.Complications are defined as an unplanned medical event in the course of treatment that may or may not affect final outcome. Severity refers to the level of care and urgency required to treat the complication, and can be classified as device related or disease related. Severity grade (SV) I is a complication that does not require unplanned surgery, and can be corrected at the next scheduled surgery. SVII requires an unplanned surgery, with SVIIA requiring a single trip and SVIIB needing multiple trips for resolution. SVIII is a complication that substantially alters the planned course of treatment. Disease-related complications are classified as grade SVI if no hospitalization is required and grade SVII if hospitalization is required. SVIV was defined as death, either disease or device related. A total of 65 patients from 5 institutions met enrollment criteria for the study; 56 patients had at least 1 complication and 9 had no complications. There were 14 growing rods, 47 VEPTRs, ,and 4 hybrid constructs. The average age at implant was 4.7 years. There were an average of 5.4 expansions, 1.6 revisions, and 0.8 exchanges per patient. The minimum follow-up was 2 years. The most common complications were migration (60), infection (31), pneumonia (21), and instrumentation failure (23). When classified, the complications were grade I (57), grade IIA (79), grade IIB (10), and grade III (6). Well-documented uncertainty in clinical decision making in this area highlights the need for more rigorous clinical research. Reporting complications standardized for severity and impact on the course of treatment in growing spine surgery is a necessary prerequisite for meaningful comparative evaluation of different treatment options. This study shows that although complications were common, only 9% (SVIII) were severe enough to change the planned course of treatment. We propose that future studies reporting complications of different methods of growth-sparing spine surgery use this classification moving forward so that meaningful comparisons can be made between different treatment techniques.

Fragment Based Strategies for Discovery of Novel HIV-1 Reverse Transcriptase and Integrase Inhibitors.

PubMed

Latham, Catherine F; La, Jennifer; Tinetti, Ricky N; Chalmers, David K; Tachedjian, Gilda

2016-01-01

Human immunodeficiency virus (HIV) remains a global health problem. While combined antiretroviral therapy has been successful in controlling the virus in patients, HIV can develop resistance to drugs used for treatment, rendering available drugs less effective and limiting treatment options. Initiatives to find novel drugs for HIV treatment are ongoing, although traditional drug design approaches often focus on known binding sites for inhibition of established drug targets like reverse transcriptase and integrase. These approaches tend towards generating more inhibitors in the same drug classes already used in the clinic. Lack of diversity in antiretroviral drug classes can result in limited treatment options, as cross-resistance can emerge to a whole drug class in patients treated with only one drug from that class. A fresh approach in the search for new HIV-1 drugs is fragment-based drug discovery (FBDD), a validated strategy for drug discovery based on using smaller libraries of low molecular weight molecules (<300 Da) screened using primarily biophysical assays. FBDD is aimed at not only finding novel drug scaffolds, but also probing the target protein to find new, often allosteric, inhibitory binding sites. Several fragment-based strategies have been successful in identifying novel inhibitory sites or scaffolds for two proven drug targets for HIV-1, reverse transcriptase and integrase. While any FBDD-generated HIV-1 drugs have yet to enter the clinic, recent FBDD initiatives against these two well-characterised HIV-1 targets have reinvigorated antiretroviral drug discovery and the search for novel classes of HIV-1 drugs.

Gender differences in clinical, immunological, and virological outcomes in highly active antiretroviral-treated HIV–HCV coinfected patients

PubMed Central

Emery, Joel; Pick, Neora; Mills, Edward J; Cooper, Curtis L

2010-01-01

Objective: The influence of biological sex on human immunodeficiency virus (HIV) antiretroviral treatment outcome is not well described in HIV–hepatitis C (HCV) coinfection. Methods: We assessed patients’ clinical outcomes of HIV–HCV coinfected patients initiating antiretroviral therapy attending the Ottawa Hospital Immunodeficiency Clinic from January 1996 to June 2008. Results: We assessed 144 males and 39 females. Although similar in most baseline characteristics, the CD4 count was higher in females (375 vs 290 cells/μL). Fewer females initiated ritonavir-boosted regimens. The median duration on therapy before interruption or change was longer in males (10 versus 4 months) (odds ratio [OR] 1.40 95% confidence interval: 0.95–2.04; P = 0.09). HIV RNA suppression was frequent (74%) and mean CD4 count achieved robust (over 400 cells/μL) at 6 months, irrespective of sex. The primary reasons for therapy interruption in females and males included: gastrointestinal intolerance (25% vs 19%; P = 0.42); poor adherence (22% vs 15%; P = 0.31); neuropsychiatric symptoms (19% vs 5%; P = 0.003); and lost to follow-up (3% vs 13%; P = 0.08). Seven males (5%) and no females discontinued therapy for liver-specific complications. Death rate was higher in females (23% vs 7%; P = 0.003). Conclusion: There are subtle differences in the characteristics of female and male HIV–HCV coinfected patients that influence HIV treatment decisions. The reasons for treatment interruption and change differ by biological sex. This knowledge should be considered when starting HIV therapy and in efforts to improve treatment outcomes. PMID:20517470

Antiretroviral treatment-based cost saving interventions may offset expenses for new patients and earlier treatment start.

PubMed

Angeletti, C; Pezzotti, P; Antinori, A; Mammone, A; Navarra, A; Orchi, N; Lorenzini, P; Mecozzi, A; Ammassari, A; Murachelli, S; Ippolito, G; Girardi, E

2014-03-01

Combination antiretroviral therapy (cART) has become the main driver of total costs of caring for persons living with HIV (PLHIV). The present study estimated the short/medium-term cost trends in response to the recent evolution of national guidelines and regional therapeutic protocols for cART in Italy. We developed a deterministic mathematical model that was calibrated using epidemic data for Lazio, a region located in central Italy with about six million inhabitants. In the Base Case Scenario, the estimated number of PLHIV in the Lazio region increased over the period 2012-2016 from 14 414 to 17 179. Over the same period, the average projected annual cost for treating the HIV-infected population was €147.0 million. An earlier cART initiation resulted in a rise of 2.3% in the average estimated annual cost, whereas an increase from 27% to 50% in the proportion of naïve subjects starting cART with a nonnucleoside reverse transcriptase inhibitor (NNRTI)-based regimen resulted in a reduction of 0.3%. Simplification strategies based on NNRTIs co-formulated in a single tablet regimen and protease inhibitor/ritonavir-boosted monotherapy produced an overall reduction in average annual costs of 1.5%. A further average saving of 3.3% resulted from the introduction of generic antiretroviral drugs. In the medium term, cost saving interventions could finance the increase in costs resulting from the inertial growth in the number of patients requiring treatment and from the earlier treatment initiation recommended in recent guidelines. © 2013 British HIV Association.

Oral adverse effects due to the use of Nevirapine.

PubMed

Moura, Mariela Dutra Gontijo; Senna, Maria Inês Barreiros; Madureira, Davidson Fróis; Fonseca, Linaena Merícy Silva; Mesquita, Ricardo Alves

2008-01-01

The aim of this article is to present the clinical characteristics and management of an oral adverse effect stemming from the use of the antiretroviral medication Nevirapine (NVP). NVP is a non-nucleoside reverse transcriptase inhibitor used in the treatment of Human Immunodeficiency Virus (HIV) infection. A 29-year-old black man, HIV-infected since 1996, began highly active antiretroviral therapy (HAART) with zidovudine, lamivudine, and indinavir. From 1996 to 2002 several medications were changed due to their adverse effects: indinavir (renal colic and fever), nelfinavir (cutaneous rash), and efavirenz (nausea and temporary memory loss). When the patient presented to our service he was taking NVP, zidovudine, and lamivudine. A whitish plaque in the lips and bilateral buccal mucosa, burning, taste disturbance, and xerostomia were observed. The discontinuation of HAART led to the complete resolution of signs and symptoms. The patient has received follow-up treatment for three years and five months without local or systemic effects observed. Unfortunately, the clinical features of the oral adverse effect from NVP are not well known. This paper contributed to the identification of possible reactions in the oral cavity due to antiretroviral medication. Although HAART is very important in the treatment of HIV, its side effects are responsible for patients' non-adherence to medications. While more studies are needed to better understand the mechanism of action after suspending HAART, the complete resolution of the signs and symptoms was observed. Therefore, physicians and dentists alike must understand how to identify and prevent these adverse effects in order to further improve HIV patient treatments.

Structured intermittent interruption of chronic HIV infection treatment with highly active antiretroviral therapy: effects on leptin and TNF-alpha.

PubMed

Arjona, M Montes de Oca; Pérez-Cano, R; Garcia-Juárez, R; Martín-Aspas, A; del Alamo, C Fernández Gutiérrez; Girón-González, J A

2006-04-01

The changes in nutritional parameters and adipocytokines after structured intermittent interruption of highly active antiretroviral treatment of patients with chronic HIV infection are analyzed. Twenty-seven patients with chronic HIV infection (median CD4+ T cell count/microl: nadir, 394; at the beginning of structured interruptions, 1041; HIV viral load: nadir, 41,521 copies/ml; at the beginning of structured interruptions <50 copies/ml; median time of previous treatment: 60 months) were evaluated during three cycles of intermittent interruptions of therapy (8 weeks on/4 weeks off). CD4+ T cell count, HIV viral load, anthropometric measures, and serum concentrations of triglycerides, cholesterol, leptin, and tumor necrosis factor and its soluble receptors I and II were determined. After the three cycles of intermittent interruptions of therapy, no significant differences in CD4+ T cell count/microl, viral load, or serum concentrations of cholesterol or triglycerides with reference to baseline values were found. A near-significant higher fatty mass (skinfold thicknesses, at the end, 121 mm, at the beginning, 100 mm, p = 0.100), combined with a significant increase of concentration of leptin (1.5 vs. 4.7 ng/ml, p = 0,044), as well as a decrease in serum concentrations of soluble receptors of tumor necrosis factor (TNFRI, 104 vs. 73 pg/ml, p = 0.022; TNFRII 253 vs. 195 pg/ml, p = 0.098) were detected. Structured intermittent interruption of highly active antiretroviral treatment of patients with chronic HIV infection induces a valuable positive modification in markers of lipid turnover and adipose tissue mass.

Does an Unplanned Pregnancy Have Long-Term Implications for Mother-Child Relationships?

ERIC Educational Resources Information Center

Nelson, Jackie A.; O'Brien, Marion

2012-01-01

The effect of pregnancy planning on the quality of mother-adolescent relationships 15 years later was examined among 373 first-time parents and 472 experienced parents using a mediated moderation model. Among first-time mothers only, the experience of an unplanned pregnancy was related to higher maternal depressive symptoms when mothers also…

Benefits of Using Planned Comparisons Rather Than Post Hoc Tests: A Brief Review with Examples.

ERIC Educational Resources Information Center

DuRapau, Theresa M.

The rationale behind analysis of variance (including analysis of covariance and multiple analyses of variance and covariance) methods is reviewed, and unplanned and planned methods of evaluating differences between means are briefly described. Two advantages of using planned or a priori tests over unplanned or post hoc tests are presented. In…

Unplanned Terminology Development: A Synchronic and Diachronic Study on Economic Terms in Turkish Newspapers

ERIC Educational Resources Information Center

Karabacak, Erkan

2009-01-01

This study deals with unplanned terminology development in the subject field of economics within media discourse. It examines how economic terms in Turkish newspapers emerge, are used, and cease. This developmental process is also analyzed through productivity of economic terms and the factors affect them. The subject terms are also analyzed as a…

Factors that Adolescent Males Take into Account in Decisions about an Unplanned Pregnancy

ERIC Educational Resources Information Center

Corkindale, Carolyn J.; Condon, John T.; Russell, Alan; Quinlivan, Julie A.

2009-01-01

Little is known about what factors adolescent males consider important when making decisions concerning the resolution of an unplanned pregnancy with a teenage partner. Young men's influence on pregnancy outcome decisions can play an important part in the subsequent psychological adjustment of the female. The present report draws on data from a…

Processes and Factors Underlying Adolescent Males' Attitudes and Decision-Making in Relation to an Unplanned Pregnancy

ERIC Educational Resources Information Center

Condon, John T.; Corkindale, Carolyn J.; Russell, Alan; Quinlivan, Julie A.

2006-01-01

This research examined adolescent males' decision-making when confronted with a hypothetical unplanned pregnancy in a sexual partner. An innovative methodology, involving a computerized simulation game was utilized with 386 Australian males (mean age of 15 years). Data were gathered from responses made during the simulation, and questionnaires…

Strategy, structure, and patient quality outcomes in ambulatory surgery centers (1997-2004).

PubMed

Chukmaitov, Askar; Devers, Kelly J; Harless, David W; Menachemi, Nir; Brooks, Robert G

2011-04-01

The purpose of this study was to examine potential associations among ambulatory surgery centers' (ASCs) organizational strategy, structure, and quality performance. The authors obtained several large-scale, all-payer claims data sets for the 1997 to 2004 period. The authors operationalized quality performance as unplanned hospitalizations at 30 days after outpatient arthroscopy and colonoscopy procedures. The authors draw on related organizational theory, behavior, and health services research literatures to develop their conceptual framework and hypotheses and fitted fixed and random effects Poisson regression models with the count of unplanned hospitalizations. Consistent with the key hypotheses formulated, the findings suggest that higher levels of specialization and the volume of procedures may be associated with a decrease in unplanned hospitalizations at ASCs.

Long-term costs and health impact of continued global fund support for antiretroviral therapy.

PubMed

Stover, John; Korenromp, Eline L; Blakley, Matthew; Komatsu, Ryuichi; Viisainen, Kirsi; Bollinger, Lori; Atun, Rifat

2011-01-01

By the end of 2011 Global Fund investments will be supporting 3.5 million people on antiretroviral therapy (ART) in 104 low- and middle-income countries. We estimated the cost and health impact of continuing treatment for these patients through 2020. Survival on first-line and second-line ART regimens is estimated based on annual retention rates reported by national AIDS programs. Costs per patient-year were calculated from country-reported ARV procurement prices, and expenditures on laboratory tests, health care utilization and end-of-life care from in-depth costing studies. Of the 3.5 million ART patients in 2011, 2.3 million will still need treatment in 2020. The annual cost of maintaining ART falls from $1.9 billion in 2011 to $1.7 billion in 2020, as a result of a declining number of surviving patients partially offset by increasing costs as more patients migrate to second-line therapy. The Global Fund is expected to continue being a major contributor to meeting this financial need, alongside other international funders and domestic resources. Costs would be $150 million less in 2020 with an annual 5% decline in first-line ARV prices and $150-370 million less with a 5%-12% annual decline in second-line prices, but $200 million higher in 2020 with phase out of stavudine (d4T), or $200 million higher with increased migration to second-line regimens expected if all countries routinely adopted viral load monitoring. Deaths postponed by ART correspond to 830,000 life-years saved in 2011, increasing to around 2.3 million life-years every year between 2015 and 2020. Annual patient-level direct costs of supporting a patient cohort remain fairly stable over 2011-2020, if current antiretroviral prices and delivery costs are maintained. Second-line antiretroviral prices are a major cost driver, underscoring the importance of investing in treatment quality to improve retention on first-line regimens.

Improved Neuropsychological and Neurological Functioning Across Three Antiretroviral Regimens in Diverse Resource-Limited Settings: AIDS Clinical Trials Group Study A5199, the International Neurological Study

PubMed Central

Robertson, K.; Jiang, H.; Kumwenda, J.; Supparatpinyo, K.; Evans, S.; Campbell, T. B.; Price, R.; Tripathy, S.; Kumarasamy, N.; La Rosa, A.; Santos, B.; Silva, M. T.; Montano, S.; Kanyama, C.; Faesen, S.; Murphy, R.; Hall, C.; Marra, C. M.; Marcus, C.; Berzins, B.; Allen, R.; Housseinipour, M.; Amod, F.; Sanne, I.; Hakim, J.; Walawander, A.; Nair, A.

2012-01-01

Background. AIDS Clinical Trials Group (ACTG) A5199 compared the neurological and neuropsychological (NP) effects of 3 antiretroviral regimens in participants infected with human immunodeficiency virus type 1 (HIV-1) in resource-limited settings. Methods. Participants from Brazil, India, Malawi, Peru, South Africa, Thailand, and Zimbabwe were randomized to 3 antiretroviral treatment arms: A (lamivudine-zidovudine plus efavirenz, n = 289), B (atazanavir, emtricitabine, and didanosine-EC, n = 293), and C (emtricitabine-tenofovir-disoproxil fumarate plus efavirenz, n = 278) as part of the ACTG PEARLS study (A5175). Standardized neurological and neuropsychological (NP) screening examinations (grooved pegboard, timed gait, semantic verbal fluency, and finger tapping) were administered every 24 weeks from February 2006 to May 2010. Associations with neurological and neuropsychological function were estimated from linear and logistic regression models using generalized estimating equations. Results. The median weeks on study was 168 (Q1 = 96, Q3 = 192) for the 860 participants. NP test scores improved (P < .05) with the exception of semantic verbal fluency. No differences in neurological and neuropsychological functioning between treatment regimens were detected (P > .10). Significant country effects were noted on all NP tests and neurological outcomes (P < .01). Conclusions. The study detected no significant differences in neuropsychological and neurological outcomes between randomized ART regimens. Significant improvement occurred in neurocognitive and neurological functioning over time after initiation of ARTs. The etiology of these improvements is likely multifactorial, reflecting reduced central nervous system HIV infection, better general health, and practice effects. This study suggests that treatment with either of the World Health Organization –recommended first-line antiretroviral regimens in resource-limited settings will improve neuropsychological functioning and reduce neurological dysfunction. Clinical trials registration.  NCT00096824. PMID:22661489

Gender Differences in Adherence and Response to Antiretroviral Treatment in the Stratall Trial in Rural District Hospitals in Cameroon.

PubMed

Boullé, Charlotte; Kouanfack, Charles; Laborde-Balen, Gabrièle; Boyer, Sylvie; Aghokeng, Avelin F; Carrieri, Maria P; Kazé, Serge; Dontsop, Marlise; Mben, Jean-Marc; Koulla-Shiro, Sinata; Peytavin, Gilles; Spire, Bruno; Delaporte, Eric; Laurent, Christian

2015-07-01

Evidence of gender differences in antiretroviral treatment (ART) outcomes in sub-Saharan Africa is conflicting. Our objective was to assess gender differences in (1) adherence to ART and (2) virologic failure, immune reconstitution, mortality, and disease progression adjusting for adherence. Cohort study among 459 ART-naive patients followed up 24 months after initiation in 2006-2010 in 9 rural district hospitals. Adherence to ART was assessed using (1) a validated tool based on multiple patient self-reports and (2) antiretroviral plasma concentrations. The associations between gender and the outcomes were assessed using multivariate mixed models or accelerated time failure models. One hundred thirty-five patients (29.4%) were men. At baseline, men were older, had higher body mass index and hemoglobin level, and received more frequently efavirenz than women. Gender was not associated with self-reported adherence (P = 0.872, 0.169, and 0.867 for moderate adherence, low adherence, and treatment interruption, respectively) or with antiretroviral plasma concentrations (P = 0.549 for nevirapine/efavirenz). In contrast, male gender was associated with virologic failure [odds ratio: 2.18, 95% confidence interval (CI): 1.31 to 3.62, P = 0.003], lower immunologic reconstitution (coefficient: -58.7 at month 24, 95% CI: -100.8 to -16.6, P = 0.006), and faster progression to death (time ratio: 0.30, 95% CI: 0.12 to 0.78, P = 0.014) and/or to World Health Organization stage 4 event (time ratio: 0.27, 95% CI: 0.09 to 0.79, P = 0.017). Our study provides important evidence that African men are more vulnerable to ART failure than women and that the male vulnerability extends beyond adherence issues. Additional studies are needed to determine the causes for this vulnerability to optimize HIV care. However, personalized adherence support remains crucial.

Long-Term Costs and Health Impact of Continued Global Fund Support for Antiretroviral Therapy

PubMed Central

Stover, John; Korenromp, Eline L.; Blakley, Matthew; Komatsu, Ryuichi; Viisainen, Kirsi; Bollinger, Lori; Atun, Rifat

2011-01-01

Background By the end of 2011 Global Fund investments will be supporting 3.5 million people on antiretroviral therapy (ART) in 104 low- and middle-income countries. We estimated the cost and health impact of continuing treatment for these patients through 2020. Methods and Findings Survival on first-line and second-line ART regimens is estimated based on annual retention rates reported by national AIDS programs. Costs per patient-year were calculated from country-reported ARV procurement prices, and expenditures on laboratory tests, health care utilization and end-of-life care from in-depth costing studies. Of the 3.5 million ART patients in 2011, 2.3 million will still need treatment in 2020. The annual cost of maintaining ART falls from $1.9 billion in 2011 to $1.7 billion in 2020, as a result of a declining number of surviving patients partially offset by increasing costs as more patients migrate to second-line therapy. The Global Fund is expected to continue being a major contributor to meeting this financial need, alongside other international funders and domestic resources. Costs would be $150 million less in 2020 with an annual 5% decline in first-line ARV prices and $150–370 million less with a 5%–12% annual decline in second-line prices, but $200 million higher in 2020 with phase out of stavudine (d4T), or $200 million higher with increased migration to second-line regimens expected if all countries routinely adopted viral load monitoring. Deaths postponed by ART correspond to 830,000 life-years saved in 2011, increasing to around 2.3 million life-years every year between 2015 and 2020. Conclusions Annual patient-level direct costs of supporting a patient cohort remain fairly stable over 2011–2020, if current antiretroviral prices and delivery costs are maintained. Second-line antiretroviral prices are a major cost driver, underscoring the importance of investing in treatment quality to improve retention on first-line regimens. PMID:21731646

Early antiretroviral treatment (eART) limits viral diversity over time in a long-term HIV viral suppressed perinatally infected child.

PubMed

Palma, Paolo; Zangari, Paola; Alteri, Claudia; Tchidjou, Hyppolite K; Manno, Emma Concetta; Liuzzi, Giuseppina; Perno, Carlo Federico; Rossi, Paolo; Bertoli, Ada; Bernardi, Stefania

2016-12-09

HIV genetic diversity implicates major challenges for the control of viral infection by the immune system and for the identification of an effective immunotherapeutic strategy. With the present case report we underline as HIV evolution could be effectively halted by early antiretroviral treatment (eART). Few cases supported this evidence due to the difficulty of performing amplification and sequencing analysis in long-term viral suppressed patients. Here, we reported the case of limited HIV-1 viral evolution over time in a successful early treated child. A perinatally HIV-1 infected infant was treated within 7 weeks of age with zidovudine, lamivudine, nevirapine and lopinavir/ritonavir. At antiretroviral treatment (ART) initiation HIV-1 viral load (VL) and CD4 percentage were >500,000 copies/ml and 35%, respectively. Plasma genotypic resistance test showed a wild-type virus. The child reached VL undetectability after 33 weeks of combination antiretroviral therapy (cART) since he maintained a stable VL <40copies/ml. After 116 weeks on ART we were able to perform amplification and sequencing assay on the plasma virus. At this time VL was <40 copies/ml and CD4 percentage was 40%. Again the genotypic resistance test revealed a wild-type virus. The phylogenetic analysis performed on the HIV-1 pol sequences of the mother and the child revealed that sequences clustered with C subtype reference strains and formed a monophyletic cluster distinct from the other C sequences included in the analysis (bootstrap value >90%). Any major evolutionary divergence was detected. eART limits the viral evolution avoiding the emergence of new viral variants. This result may have important implications in host immune control and may sustain the challenge search of new personalized immunotherapeutic approaches to achieve a prolonged viral remission.

HIV treatment 2020: what will it look like?

PubMed

Gulick, Roy

2014-01-01

Currently there are 28 approved antiretroviral drugs in six mechanistic classes, and recommended first-line regimens are highly potent, well tolerated, and as convenient as one pill, once-a-day. How will HIV treatment change by 2020? Over the next few years, we are likely to see potent 2-drug regimens tested head-to-head with standard three-drug regimens, and some of these will likely become standard-of-care. Newer agents with novel drug resistance profiles (e.g. doravirine, an NNRTI) or new mechanisms of action (e.g. BMS 663068, a CD4 attachment inhibitor) will provide virologic activity in patients with drug-resistant viral strains. Comparative studies of current and newer agents such as the investigational prodrug of tenofovir (TAF) will help define less toxic regimens. We will see additional convenient co-formulations developed; with them, we are likely to have second- and even third-line regimens administered one pill, once-daily. Long-acting injectable investigational formulations currently in clinical trials such as rilpivirine LA (administered monthly) and cabotegravir (administered quarterly), and others (including combinations of these agents) could provide additional convenient treatment options. Other novel formulations (e.g. patches, implants, rings) and combinations of antiretrovirals with other kinds of medications (e.g. contraceptives) may be developed and tested. In the developing world, we will see increasing numbers of patients taking potent, well-tolerated convenient first-line and subsequent regimens with the goal of "20 by 20" - 20 million treated people by 2020. Generic formulations of antiretroviral drugs, including combinations, will be increasingly available and used worldwide. With the current appreciation that inflammation and immune activation play an important role in the natural history of treated HIV infection, anti-inflammatory agents will be tested and may supplement (or even be co-formulated with) standard antiretroviral regimens. Recognizing our progress to date, these and other innovations will further improve HIV therapy by 2020.

Prevalence and clinical impact of recreational drug consumption in people living with HIV on treatment: a cross-sectional study

PubMed Central

Zurita, Beatriz; Velasco, Cesar; Feliu, Anna; Gutierrez, Mar; Masip, Montserrat; Mangues, M Antonia

2017-01-01

Objectives Drug interactions, poor adherence to medication and high-risk sexual behaviour may occur in individuals with HIV using recreational drugs. Thus, we aimed to assess the prevalence of recreational drugs use and to explore its clinical impact in HIV patients on treatment. Methods Observational, cross sectional, study conducted in a 700 bed university hospital, Barcelona, Spain. A total of 208 adults living with HIV on treatment were included. A questionnaire was administered by clinical pharmacists, including evaluation of sociodemographic variables, past 12-month drug consumption, adherence to antiretrovirals (Simplified Medication Adherence Questionnaire) and high-risk sexual behaviour (condomless sex/multiple partners). Additional data were obtained from clinical records. Recreational drug-antiretroviral interactions were checked in reference databases. Prevalence was calculated for 5% precision and 95% CI. Crude and adjusted binary logistic regressions were performed to identify associations between recreational drug use and adherence problems, and between recreational drug use and high-risk sexual behaviour. Results From the overall sample, 92 participants (44.2%) consumed recreational drugs over the past 1 year. Of these, 44 (48.8%) had used different types of recreational drugs in this period. We detected 11 recreational substances, including sildenafil and nitrites. The most consumed drugs were: cannabis (68.5%), cocaine (45.5%), nitrites (31.5%), sildenafil (28.3) and ecstasy (19.6%). Relevant interactions occurred in 46 (50%) of the individuals consuming drugs. Recreational drug consumption was found to be related to adherence problems with antiretrovirals (OR: 2.51 (95% CI 1.32 to 4.77) p=0.005) and high-risk sexual behaviour (OR: 2.81 (95% CI 1.47 to 5.39) p=0.002). Conclusions Recreational drugs are frequently used by HIV patients on treatment. Classical drugs and new substances consumed in sexual context are usual. Recreational drug consumption interferes with several clinical outcomes, including potentially relevant interactions between drugs and antiretrovirals, adherence problems and high-risk sexual behaviour. Thus, there is the urgent need of implementing patient-centred care involving recreational drug consumption. PMID:28100565

The effects of HIV self-testing on the uptake of HIV testing and linkage to antiretroviral treatment among adults in Africa: a systematic review protocol.

PubMed

Njau, Bernard; Damian, Damian J; Abdullahi, Leila; Boulle, Andrew; Mathews, Catherine

2016-04-05

HIV is still a global public health problem. More than 75 % of HIV-infected people are in Africa, and most of them are unaware of their HIV status, which is a barrier to accessing antiretroviral treatment. Our review aims, firstly, to determine whether HIV self-testing is an effective method to increase the uptake of testing, the yield of new HIV-positive diagnoses, and the linkage to antiretroviral treatment. Secondly, we aim to review the factors that facilitate or impede the uptake of HIV self-testing. Participants will be adults living in Africa. For the first aim, the intervention will be HIV self-testing either alone or in addition to HIV testing standard of care. The comparison will be HIV testing standard of care. The primary outcomes will be (i) uptake of HIV testing and (ii) yield of new HIV-positive diagnoses. The secondary outcomes will be (a) linkage to antiretroviral (ARV) treatment and (b) incidence of social harms. For the second aim, we will review barriers and facilitators to the uptake of self-testing. We will search PubMed, Cochrane Central Register of Controlled Trials, Scopus, Web of Science, WHOLIS, Africa Wide, and CINAHL for eligible studies from 1998, with no language limits. We will check reference lists of included studies for other eligible reports. Eligible studies will include experimental and observational studies. Two authors will independently screen the search output, select studies, and extract data, resolving discrepancies by consensus and discussion. Two authors will use Cochrane risk of bias tools for experimental studies, the Newcastle-Ottawa Quality Assessment Scale for observational studies, and the Critical Appraisal Skills Programme (CASP) quality assessment tool for qualitative studies. Innovative and cost-effective community-based HIV testing strategies, such as self-testing, will contribute to universal coverage of HIV testing in Africa. The findings from this systematic review will guide development of self-testing policy in African countries. PROSPERO CRD42015023935.

Survival and predictors of mortality among human immunodeficiency virus patients on anti-retroviral treatment at Jinka Hospital, South Omo, Ethiopia: a six years retrospective cohort study

PubMed Central

Ameni, Gobena

2016-01-01

OBJECTIVES The survival rate of human immunodeficiency virus (HIV)-infected patients receiving treatment in Ethiopia is poorly understood. This study aimed to determine the survival rate and predictors of mortality among HIV-infected adults on antiretroviral therapy (ART) at Jinka Hospital, South Omo, Ethiopia. METHODS A 6-year retrospective cohort study was conducted using 350 patient records drawn from 1,899 patients on ART at Jinka Hospital from September 2010 to August 2015. The data were analyzed using Kaplan-Meier statistics and Cox regression models. RESULTS Of the 350 study participants, 315 (90.0%) were censored and 35 (10.0%) died. Twenty-two (62.9%) of the deaths occurred during the first year of treatment. The total follow-up encompassed 1,995 person-years, with an incidence rate of 1.75 deaths per 100 person-years. The mean survival time of patients on highly active antiretroviral therapy (HAART) was 30.84±19.57 months. The overall survival of patients on HAART was 64.00% (95% confidence interval [CI], 61.85 to 66.21%) at 72 months of follow-up. The significant predictors of mortality included non-disclosure of HIV status (adjusted hazard ratio [aHR], 5.82; 95% CI, 1.91 to 17.72), a history of tuberculosis (aHR, 1.82; 95% CI, 1.41 to 3.51), and ambulatory (aHR, 2.97; 95% CI, 1.20 to 8.86) or bedridden (aHR, 4.67; 95% CI, 1.30 to 17.27) functional status, World Health Organization (WHO) clinical stage IV illness (aHR, 24.97; 95% CI, 2.75 to 26.45), and substance abusers (aHR, 3.72; 95% CI, 1.39 to 9.97). CONCLUSIONS Patients with a history of tuberculosis treatment, ambulatory or bedridden functional status, or advanced WHO clinical stage disease, as well substance abusers, should be carefully monitored, particularly in the first few months after initiating antiretroviral therapy. Patients should also be encouraged to disclose their status to their relatives. PMID:27820957

Determinants of anti-retroviral regimen changes among HIV/AIDS patients of east and west Wollega zone health institutions, Oromia region, west Ethiopia: a cross-sectional study.

PubMed

Bokore, Amsalu; Korme, Belay; Bayisa, Getu

2018-06-05

Human Immunodeficiency Virus (HIV) is one of the main causes of morbidity and mortality; because of this it continues to be a major global public health concern. It has believed to kill more than 34 million lives so far. Sub Saharan Africa constitutes about 70% of people living with HIV among the 37 million on the globe. This region, accounted for more than two third of the global new HIV infections and about 15 million (40%) were receiving antiretroviral therapy (ART) at the end of 2014 throught the world. ART has fundamentally changed the treatment of HIV and transformed this infection from a disease of high mortality to chronic and medically managed disease. The issues of drug induced toxicities & complexity of current highly active antiretroviral therapy (HAART) regimens has remained of great concern. The aim of this study was to determine factors leading to antiretroviral regimen changes among HIV/AIDS Patients in the study area. A facility based retrospective cross-sectional study was conducted from April 28, 2017 to May 30, 2017 in the ART clinics of east and west Wollega zone health institutions using a pre-tested data collecting form and chart review. The sample included the 243 patients whose medication had been switched. Majority 145 (59.67%) of the patients had been on ART for > 10 years duration. More than half 126(51.9%) of the patients had received tuberculosis (TB) treatment and almost three out of five patients (57.2%) had received isoniazid & cotrimoxazole prophylaxis. The most common reason for regimen change was peripheral neuropathy 146(60.1%) and the most common medication for this reason was stavudine, lamivudine and neverapine based 108(44.44%). The number of patients who changed ARV drug in our resource constrained setting present a challenge to the restricted treatment choices that we currently own. Less toxic and better-tolerated HIV treatment options should be available and used more frequently.

Programmed initiation of hemodialysis for systemic amyloidosis patients associated with rheumatoid arthritis.

PubMed

Kuroda, Takeshi; Tanabe, Naohito; Kobayashi, Daisuke; Sato, Hiroe; Wada, Yoko; Murakami, Shuichi; Sakatsume, Minoru; Nakano, Masaaki; Narita, Ichiei

2011-09-01

Reactive amyloidosis is a serious systemic disease in rheumatoid arthritis (RA). Amyloid protein can be deposited in kidneys, heart or gastrointestinal tract leading to organ failure. Renal involvement is a well-known complication in amyloidosis as this may culminate in end-stage renal disease (ESRD). Hemodialysis (HD) is always considered the treatment of choice for such patients; however, the prognosis is usually poor due to a large number of sudden deaths immediately following HD therapy. To circumvent the problem of HD initiation while instituting HD safety, we devised a plan to start HD and compare patient's survival with our previous data. Sixty-three patients were treated with HD. They were categorized according to the initiation of first dialysis. All patients were divided into planned, unplanned and programmed initiation groups. First dialysis that had been initiated as not urgent was considered 'planned' (20 patients). First dialysis that had been performed urgently for life-threatening renal insufficiency was considered 'unplanned' (31 patients). First dialysis that had been initiated as not urgent and according to our dialysis program was considered 'programmed' (12 patients). Survival of these 63 patients from the initiation of HD at 38 days was 75%, at 321 days was 50% and at 1,784 days was 25%. Patients with unplanned initiation of HD showed a significant poor survival compared with those of both planned and programmed initiation. Additionally, patients with planned and programmed initiation of HD showed no significant difference for the patients' survival. Our study demonstrates that patients with amyloidosis have a higher mortality rate. Nevertheless, programmed initiation of HD will improve the prognosis of patients with ESRD. Such possibility needs to be considered in more detail in the future.

[Prognostic factors for severe infection after flexible ureteroscopy: Clinical interest of urine culture the day before surgery?].

PubMed

Alezra, E; Lasselin, J; Forzini, T; François, T; Viart, L; Saint, F

2016-01-01

The objectives of this study have been to determine prognostic factors for acute pyelonephritis (AP) after flexible ureteroscopy (FU), to assess the frequency of readmission for AP and to study the usefulness of urinalysis the day before surgery. Between 2010 and 2013, 266 patients have had at least one ureteroscopy (n=325). All infectious complications and unplanned readmissions within the month after FU were retrospectively evaluated. Several data have been collected: age, sex, BMI, surgical indication (calculis or tumor), number of previous ureteroscopies, number of previous surgeries for calculis, stones number, size and location, bilateral interventions, operating time, preoperative ureteral stenting, postoperative stenting, hospitalization stay, urine culture the day before surgery (j-1) and prescription of antibiotic therapy the week before FU. Correlation between these variables and acute pyelonephritis (AP) the month following the USSR was tested (StatView 4.5, SAS Institute) (P<0.05 significant). We observed 24 postoperative APs (7.4%), 17 prior to hospital discharge and 7 requiring rehospitalization. In univariate analysis, the significant prognostic factors of postoperative AP have been: stone size (>14 mm) (P=0.03); operating time (70 minutes) (P<0.005); positive day - 1 urine culture (P<0.001); antibiotics treatment the week before FU (P<0.001). In multivariate analysis, antibiotics prescription during the week before USSR remained significant (P<0.002; RR 5.8 [1.9-15]). Acute pyelonephritis requiring unplanned admission after ureteroscopy is a rare complication (2.4%). Urinalysis one day before ureteroscopy could allow early antibiotic therapy and may reduce 63% of unplanned hospital admissions for acute pyelonephritis. 5. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

Comparison of submuscular and open plating of pediatric femur fractures: a retrospective review.

PubMed

Abbott, Matthew D; Loder, Randall T; Anglen, Jeffrey O

2013-01-01

Plate osteosynthesis is an accepted method of treatment of pediatric femur fractures. Historically, open plating has been used. Submuscular bridge plating has gained recent popularity due to the theoretical advantages of decreased operative time, decreased blood loss, and decreased risk for infection. The purpose of this study was to compare submuscular bridge plating to open plating of pediatric femur fractures. We retrospectively reviewed 79 patients (80 treated femur fractures) between 1999 and 2011 that underwent either open plating (58 femur fractures) or submuscular bridge plating (22 femur fractures). The outcome measures evaluated were operative time, estimated blood loss, malunion, leg length discrepancy, time to union, infection, unplanned return to the operating room, and length of hospital stay after surgery. Among our outcome measures, there was no difference between the 2 groups in terms of operative time, leg length discrepancy, time to union, infection, or length of hospital stay after surgery. There was greater estimated blood loss in the open plating group (P≤0.0001) and greater rotational asymmetry in the submuscular bridge plating group (P=0.005). There was a trend of increased unplanned return to the operating room in the open plating group (5/58 vs. 0/22) although not statistically significant (P=0.32). Submuscular bridge plating and open plating seem to be equally viable options for the management of pediatric diaphyseal femur fractures. In this study, open plating had an increase in estimated blood loss and a trend of more unplanned returns to the operating room, whereas submuscular bridge plating had an increase in asymptomatic rotational asymmetry. Further larger, prospective, randomized studies are necessary to further evaluate these operative techniques. Therapeutic Level III.

Antiretroviral treatment start-time during primary SIV(mac) infection in macaques exerts a different impact on early viral replication and dissemination.

PubMed

Sellier, Pierre; Mannioui, Abdelkrim; Bourry, Olivier; Dereuddre-Bosquet, Nathalie; Delache, Benoit; Brochard, Patricia; Calvo, Julien; Prévot, Sophie; Roques, Pierre

2010-05-11

The time of infection is rarely known in human cases; thus, the effects of delaying the initiation of antiretroviral therapy (ART) on the peripheral viral load and the establishment of viral reservoirs are poorly understood. Six groups of macaques, infected intravenously with SIV(mac251), were given placebo or antiretroviral therapy to explore reservoir establishment; macaques were treated for 2 weeks, with treatment starting 4 hours, 7 or 14 days after infection. Viral replication and dissemination were measured in the gut (rectum), in the lung and in blood and lymphoid tissues (peripheral lymph nodes), by quantifying viral RNA, DNA and 2LTR circles. We used immunohistochemistry (CD4 and CD68) to assess the impact of these treatments on the relative amount of virus target cells in tissue. Treatment that was started 4 hours post-infection (pi) decreased viral replication and dissemination in blood and tissue samples, which were assessed on day 14 (RNA/DNA/2LTR circles). The virus remained detectable and lymphoid tissues were activated in LN and the gut in both placebo- and ART-treated animals. Viral RNA in plasma continued to be lower in macaques treated seven days after infection; however, this was not the case for viral DNA in peripheral blood mononuclear cells. There was a small but significant difference in RNA and DNA levels in tissues between placebo- and ART-treated animals on day 21. When started 14 days after infection, treatment resulted in a limited decrease in the plasma viral load. Treatment that was started 4 hours after infection significantly reduced viral replication and dissemination. When started 7 days after infection, it was of slight virological benefit in peripheral blood and in tissues, and treatment was even less effective if started 14 days pi. These data favor starting ART no longer than one week after intravenous SIV(mac251) exposure.

Human immunodeficiency virus (HIV) in pregnancy: a review of the guidelines for preventing mother-to-child transmission in Malaysia.

PubMed

Azwa, Iskandar; Khong, Su Yen

2012-12-01

Mother-to-child transmission (MTCT) of human immunodefi ciency virus (HIV) is a devastating consequence of HIV infection during pregnancy and is largely preventable. Evidence-based interventions such as universal antenatal screening, provision of antiretroviral therapy, delivery by elective caesarean section and avoidance of breastfeeding have ensured that the rates of MTCT remain low in Malaysia. This review discusses the most recent advances in the management of HIV infection in pregnancy with emphasis on antiretroviral treatment strategies and obstetric care in a middle income country.

[Epidemiology of induced abortion in France].

PubMed

Vigoureux, S

2016-12-01

Conduct a synthesis of existing knowledge about the frequency of induced abortion or termination of pregnancy and unplanned pregnancies, the exposure factors of unplanned pregnancies and abortion and the associated morbidity and mortality. Consultation of The Medline database, and national and international reports on abortions in France and in developed countries. Voluntary termination of pregnancy is an induced abortion, opted for non-medical reasons, which in France can be performed before 14 weeks of gestation. Abortion is a common procedure, with rare complications, amounting to about 220,000 procedures per year in France with a stable rate over decades. Similarly to births, women aged 20 to 24 are most affected. The possibility of an abortion exists for all women; this potential event, however, is not equal for each and varies by age of women, socio-professional situations, geographical origins, marital status and past or present domestic and sexual violence. The French historical analysis shows that for 50 years the increase in contraceptive prevalence rate is associated with a decrease in the frequency of unplanned pregnancies. It is therefore possible that the prevention of unplanned pregnancy through early uptake of contraception and contraception options by women is related to a woman's lifestyle. Nonetheless, the number of abortion remains stable since its decriminalization despite the large increase in medicalized contraceptive prevalence rate. Good knowledge of the epidemiology of voluntary termination of pregnancy and unplanned pregnancies is a prerequisite to better adopt prevention and case management strategies. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Technical performance score is associated with outcomes after the Norwood procedure.

PubMed

Nathan, Meena; Sleeper, Lynn A; Ohye, Richard G; Frommelt, Peter C; Caldarone, Christopher A; Tweddell, James S; Lu, Minmin; Pearson, Gail D; Gaynor, J William; Pizarro, Christian; Williams, Ismee A; Colan, Steven D; Dunbar-Masterson, Carolyn; Gruber, Peter J; Hill, Kevin; Hirsch-Romano, Jennifer; Jacobs, Jeffrey P; Kaltman, Jonathan R; Kumar, S Ram; Morales, David; Bradley, Scott M; Kanter, Kirk; Newburger, Jane W

2014-11-01

The technical performance score (TPS) has been reported in a single center study to predict the outcomes after congenital cardiac surgery. We sought to determine the association of the TPS with outcomes in patients undergoing the Norwood procedure in the Single Ventricle Reconstruction trial. We calculated the TPS (class 1, optimal; class 2, adequate; class 3, inadequate) according to the predischarge echocardiograms analyzed in a core laboratory and unplanned reinterventions that occurred before discharge from the Norwood hospitalization. Multivariable regression examined the association of the TPS with interval to first extubation, Norwood length of stay, death or transplantation, unplanned postdischarge reinterventions, and neurodevelopment at 14 months old. Of 549 patients undergoing a Norwood procedure, 356 (65%) had an echocardiogram adequate to assess atrial septal restriction or arch obstruction or an unplanned reintervention, enabling calculation of the TPS. On multivariable regression, adjusting for preoperative variables, a better TPS was an independent predictor of a shorter interval to first extubation (P=.019), better transplant-free survival before Norwood discharge (P<.001; odds ratio, 9.1 for inadequate vs optimal), shorter hospital length of stay (P<.001), fewer unplanned reinterventions between Norwood discharge and stage II (P=.004), and a higher Bayley II psychomotor development index at 14 months (P=.031). The TPS was not associated with transplant-free survival after Norwood discharge, unplanned reinterventions after stage II, or the Bayley II mental development index at 14 months. TPS is an independent predictor of important outcomes after Norwood and could serve as a tool for quality improvement. Copyright © 2014 The American Association for Thoracic Surgery. All rights reserved.

Unplanned Reoperations in Neurosurgical Patients Due to Postoperative Bleeding

PubMed Central

Zheng, Xin-Rui; Chen, Tao; Yang, Yue-Fan; Rao, Wei; Wang, Guan-Ying; Zhang, Shan-Hong; Fei, Zhou

2015-01-01

Abstract The aim of this study is to investigate the incidence of unplanned reoperations from all causes due to bleeding in neurosurgical patients. The medical records of patients who received neurosurgical procedures at our hospital were retrospectively reviewed and data of patients who received reoperations were extracted and summarized. A literature review was conducted of the Medline, Cochrane, EMBASE, and Google Scholar databases up to November 2013. The main outcome measure was the rate of unplanned reoperations due to bleeding. At our hospital, 68 patients with a mean age of 41.5 ± 21.5 years (range, 7 months to 76 years) received an unplanned reoperation. More than 70% of the patients were older than 18 years, 64.7% were males, and 94.1% had cranial surgery. Almost 60% of the patients received >1 blood transfusion (58.8%) after the first surgery. Of the 68 patients, 35 (51.5%) received a second operation due to bleeding. Univariate logistic regression analysis only showed that an increasing time interval between the first and second surgery was associated with a decreased chance of the reoperation being performed due to bleeding (odds ratio [OR] = 0.843, 95% confidence interval [CI]: 0.720–0.987; P = .033). Of 229 studies identified, 5 retrospective reports with a total of 1375 patients were included in the analysis. The rate of reoperations for bleeding in the 5 studies ranged from 4.2% to 31.5%. Employing measures to reduce postoperative bleeding may help reduce the rate of unplanned neurosurgical reoperations. PMID:26061301

Factors affecting unplanned readmissions from community hospitals to acute hospitals: a prospective observational study.

PubMed

Leong, Ian Y O; Chan, Siew-Pang; Tan, Boon-Yeow; Sitoh, Yih-Yiow; Ang, Yan-Hoon; Merchant, Reshma; Kanagasabai, Kala; Lee, Patricia S Y; Pang, Weng-Sun

2009-02-01

While the readmission rate from community hospitals is known, the factors affecting it are not. Our aim was to determine the factors predicting unplanned readmissions from community hospitals (CHs) to acute hospitals (AHs). This was an observational prospective cohort study, involving 842 patients requiring post-acute rehabilitation in 2 CHs admitted from 3 AHs in Singapore. We studied the role of the Cumulative Illness Rating Scale (CIRS) organ impairment scores, the Mini-mental State Examination (MMSE) score, the Shah modified Barthel Index (BI) score, and the triceps skin fold thickness (TSFT) in predicting the rate of unplanned readmissions (UR), early unplanned readmissions (EUPR) and late unplanned readmissions (LUPR). We developed a clinical prediction rule to determine the risk of UR and EUPR. The rates of EUPR and LUPR were 7.6% and 10.3% respectively. The factors that predicted UR were the CIRS-heart score, the CIRS-haemopoietic score, the CIRS-endocrine / metabolic score and the BI on admission. The MMSE was predictive of EUPR. The TSFT and CIRS-liver score were predictive of LUPR. Upon receiver operator characteristics analysis, the clinical prediction rules for the prediction of EUPR and UR had areas under the curve of 0.745 and 0.733 respectively. The likelihood ratios of the clinical prediction rules for EUPR and UR ranged from 0.42 to 5.69 and 0.34 to 3.16 respectively. Patients who have UR can be identified by the admission BI, the MMSE, the TSFT and CIRS scores in the cardiac, haemopoietic, liver and endocrine/metabolic systems.

New utility for an old tool: can a simple gait speed test predict ambulatory surgical discharge outcomes?

PubMed

Odonkor, Charles A; Schonberger, Robert B; Dai, Feng; Shelley, Kirk H; Silverman, David G; Barash, Paul G

2013-10-01

The primary aims of this study were to design prediction models based on a functional marker (preoperative gait speed) to predict readiness for home discharge time of 90 mins or less and to identify those at risk for unplanned admissions after elective ambulatory surgery. This prospective observational cohort study evaluated all patients scheduled for elective ambulatory surgery. Home discharge readiness and unplanned admissions were the primary outcomes. Independent variables included preoperative gait speed, heart rate, and total anesthesia time. The relationship between all predictors and each primary outcome was determined in separate multivariable logistic regression models. After adjustment for covariates, gait speed with adjusted odds ratio of 3.71 (95% confidence interval, 1.21-11.26), P = 0.02, was independently associated with early home discharge readiness of 90 mins or less. Importantly, gait speed dichotomized as greater or less than 1 m/sec predicted unplanned admissions, with odds ratio of 0.35 (95% confidence interval, 0.16-0.76, P = 0.008) for those with speeds 1 m/sec or greater in comparison with those with speeds less than 1 m/sec. In a separate model, history of cardiac surgery with adjusted odds ratio of 7.5 (95% confidence interval, 2.34-24.41; P = 0.001) was independently associated with unplanned admissions after elective ambulatory surgery, when other covariates were held constant. This study demonstrates the use of novel prediction models based on gait speed testing to predict early home discharge and to identify those patients at risk for unplanned admissions after elective ambulatory surgery.

Definition of Readmission in 3,041 Patients Undergoing Hepatectomy

PubMed Central

Brudvik, Kristoffer W; Mise, Yoshihiro; Conrad, Claudius; Zimmitti, Giuseppe; Aloia, Thomas A; Vauthey, Jean-Nicolas

2015-01-01

Background Readmission rates of 9.7%–15.5% after hepatectomy have been reported. These rates are difficult to interpret due to variability in the time interval used to monitor readmission. The aim of this study was to refine the definition of readmission after hepatectomy. Study Design A prospectively maintained database of 3041 patients who underwent hepatectomy from 1998 through 2013 was merged with the hospital registry to identify readmissions. Area under the curve (AUC) analysis was used to determine the time interval that best captured unplanned readmission. Results Readmission rates at 30 days, 90 days, and 1 year after discharge were 10.7% (n = 326), 17.3% (n = 526), and 31.9% (n = 971) respectively. The time interval that best accounted for unplanned readmissions was 45 days after discharge (AUC, 0.956; p < 0.001), during which 389 patients (12.8%) were readmitted (unplanned: n = 312 [10.3%]; planned: n = 77 [2.5%]). In comparison, the 30 days after surgery interval (used in the ACS-NSQIP database) omitted 65 (26.3%) unplanned readmissions. Multivariate analysis revealed the following risk factors for unplanned readmission: diabetes (odds ratio [OR], 1.6; p = 0.024), right hepatectomy (OR, 2.1; p = 0.034), bile duct resection (OR, 1.9; p = 0.034), abdominal complication (OR, 1.8; p = 0.010), and a major postoperative complication (OR, 2.4; p < 0.001). Neither index hospitalization > 7 days nor postoperative hepatobiliary complications were independently associated with readmission. Conclusions To accurately assess readmission after hepatectomy, patients should be monitored 45 days after discharge. PMID:26047760

Definition of Readmission in 3,041 Patients Undergoing Hepatectomy.

PubMed

Brudvik, Kristoffer W; Mise, Yoshihiro; Conrad, Claudius; Zimmitti, Giuseppe; Aloia, Thomas A; Vauthey, Jean-Nicolas

2015-07-01

Readmission rates of 9.7% to 15.5% after hepatectomy have been reported. These rates are difficult to interpret due to variability in the time interval used to monitor readmission. The aim of this study was to refine the definition of readmission after hepatectomy. A prospectively maintained database of 3,041 patients who underwent hepatectomy from 1998 through 2013 was merged with the hospital registry to identify readmissions. Area under the curve (AUC) analysis was used to determine the time interval that best captured unplanned readmission. Readmission rates at 30 days, 90 days, and 1 year after discharge were 10.7% (n = 326), 17.3% (n = 526), and 31.9% (n = 971) respectively. The time interval that best accounted for unplanned readmissions was 45 days after discharge (AUC, 0.956; p < 0.001), during which 389 patients (12.8%) were readmitted (unplanned: n = 312 [10.3%]; planned: n = 77 [2.5%]). In comparison, the 30 days after surgery interval (used in the ACS-NSQIP database) omitted 65 (26.3%) unplanned readmissions. Multivariate analysis revealed the following risk factors for unplanned readmission: diabetes (odds ratio [OR] 1.6; p = 0.024), right hepatectomy (OR 2.1; p = 0.034), bile duct resection (OR 1.9; p = 0.034), abdominal complication (OR 1.8; p = 0.010), and a major postoperative complication (OR 2.4; p < 0.001). Neither index hospitalization > 7 days nor postoperative hepatobiliary complications were independently associated with readmission. To accurately assess readmission after hepatectomy, patients should be monitored 45 days after discharge. Copyright © 2015 American College of Surgeons. Published by Elsevier Inc. All rights reserved.

STEM CELLS AS A POTENTIAL FUTURE TREATMENT OF PEDIATRIC INTESTINAL DISORDERS

PubMed Central

Markel, Troy A.; Crisostomo, Paul R.; Lahm, Tim; Novotny, Nathan M.; Rescorla, Frederick J.; Tector, A. Joseph; Meldrum, Daniel R.

2008-01-01

All surgical disciplines encounter planned and unplanned ischemic events that may ultimately lead to cellular dysfunction and death. Stem cell therapy has shown promise for the treatment of a variety of ischemic and inflammatory disorders where tissue damage has occurred. As stem cells have proven beneficial in many disease processes, important opportunities in the future treatment of gastrointestinal disorders may exist. Therefore, this manuscript will serve to: review the different types of stem cells that may be applicable to the treatment of gastrointestinal disorders, review the mechanisms suggesting that stem cells may work for these conditions; discuss current practices for harvesting and purifying stem cells; and provide a concise summary of a few of the pediatric intestinal disorders that could be treated with cellular therapy. PMID:18970924

Alaska Native and Rural Youths' Views of Sexual Health: A Focus Group Project on Sexually Transmitted Diseases, HIV/AIDS, and Unplanned Pregnancy

ERIC Educational Resources Information Center

Leston, Jessica D.; Jessen, Cornelia M.; Simons, Brenna C.

2012-01-01

Background: The disparity in rates of sexually transmitted diseases (STDs), HIV/AIDS, and unplanned pregnancy between Alaska Native (AN) and non-AN populations, particularly among young adults and females, is significant and concerning. Focus groups were conducted to better understand the knowledge, attitudes, and beliefs of rural Alaska youth…

Planned versus Unplanned Contrasts: Exactly Why Planned Contrasts Tend To Have More Power against Type II Error.

ERIC Educational Resources Information Center

Wang, Lin

The literature is reviewed regarding the difference between planned contrasts, OVA and unplanned contrasts. The relationship between statistical power of a test method and Type I, Type II error rates is first explored to provide a framework for the discussion. The concepts and formulation of contrast, orthogonal and non-orthogonal contrasts are…

The treatment outcomes of antiretroviral substitutions in routine clinical settings in Asia; data from the TREAT Asia HIV Observational Database (TAHOD).

PubMed

Jung, In Young; Boettiger, David; Wong, Wing Wai; Lee, Man Po; Kiertiburanakul, Sasisopin; Chaiwarith, Romanee; Avihingsanon, Anchalee; Tanuma, Junko; Kumarasamy, Nagalingeswaran; Kamarulzaman, Adeeba; Zhang, Fujie; Kantipong, Pacharee; Ng, Oon Tek; Sim, Benedict Lim Heng; Law, Matthew; Ross, Jeremy; Choi, Jun Yong

2017-12-01

Although substitutions of antiretroviral regimen are generally safe, most data on substitutions are based on results from clinical trials. The objective of this study was to evaluate the treatment outcomes of substituting antiretroviral regimen in virologically suppressed HIV-infected patients in non-clinical trial settings in Asian countries. The study population consisted of HIV-infected patients enrolled in the TREAT Asia HIV Observational Database (TAHOD). Individuals were included in this analysis if they started combination antiretroviral treatment (cART) after 2002, were being treated at a centre that documented a median rate of viral load monitoring ≥0.8 tests/patient/year among TAHOD enrolees, and experienced a minor or major treatment substitution while on virally suppressive cART. The primary endpoint to evaluate outcomes was clinical or virological failure (VF), followed by an ART class change. Clinical failure was defined as death or an AIDS diagnosis. VF was defined as confirmed viral load measurements ≥400 copies/mL followed by an ART class change within six months. Minor regimen substitutions were defined as within-class changes and major regimen substitutions were defined as changes to a drug class. The patterns of substitutions and rate of clinical or VF after substitutions were analyzed. Of 3994 adults who started ART after 2002, 3119 (78.1%) had at least one period of virological suppression. Among these, 1170 (37.5%) underwent a minor regimen substitution, and 296 (9.5%) underwent a major regimen substitution during suppression. The rates of clinical or VF were 1.48/100 person years (95% CI 1.14 to 1.91) in the minor substitution group, 2.85/100 person years (95% CI 1.88 to 4.33) in the major substitution group and 2.53/100 person years (95% CI 2.20 to 2.92) among patients that did not undergo a treatment substitution. The rate of clinical or VF was low in both major and minor substitution groups, showing that regimen substitution is generally effective in non-clinical trial settings in Asian countries. © 2017 The Authors. Journal of the International AIDS Society published by John Wiley & sons Ltd on behalf of the International AIDS Society.

Impact of early initiation versus national standard of care of antiretroviral therapy in Swaziland's public sector health system: study protocol for a stepped-wedge randomized trial.

PubMed

Walsh, Fiona J; Bärnighausen, Till; Delva, Wim; Fleming, Yvette; Khumalo, Gavin; Lejeune, Charlotte L; Mazibuko, Sikhathele; Mlambo, Charmaine Khudzie; Reis, Ria; Spiegelman, Donna; Zwane, Mandisa; Okello, Velephi

2017-08-18

There is robust clinical evidence to support offering early access to antiretroviral treatment (ART) to all HIV-positive individuals, irrespective of disease stage, to both improve patient health outcomes and reduce HIV incidence. However, as the global treatment guidelines shift to meet this evidence, it is still largely unknown if early access to ART for all (also referred to as "treatment as prevention" or "universal test and treat") is a feasible intervention in the resource-limited countries where this approach could have the biggest impact on the course of the HIV epidemics. The MaxART Early Access to ART for All (EAAA) implementation study was designed to determine the feasibility, acceptability, clinical outcomes, affordability, and scalability of offering early antiretroviral treatment to all HIV-positive individuals in Swaziland's public sector health system. This is a three-year stepped-wedge randomized design with open enrollment for all adults aged 18 years and older across 14 government-managed health facilities in Swaziland's Hhohho Region. Primary endpoints are retention and viral suppression. Secondary endpoints include ART initiation, adherence, drug resistance, tuberculosis, HIV disease progression, patient satisfaction, and cost per patient per year. Sites are grouped to transition two at a time from the control (standard of care) to intervention (EAAA) stage at each four-month step. This design will result in approximately one half of the total observation time to accrue in the intervention arm and the other half in the control arm. Our estimated enrolment number, which is supported by conservative power calculations, is 4501 patients over the course of the 36-month study period. A multidisciplinary, mixed-methods approach will be adopted to supplement the randomized controlled trial and meet the study aims. Additional study components include implementation science, social science, economic evaluation, and predictive HIV incidence modeling. A stepped-wedge randomized design is a causally strong and robust approach to determine if providing antiretroviral treatment for all HIV-positive individuals is a feasible intervention in a resource-limited, public sector health system. We expect our study results to contribute to health policy decisions related to the HIV response in Swaziland and other countries in sub-Saharan Africa. ClinicalTrials.gov, NCT02909218 . Registered on 10 July 2016.

Alcohol consumption and its related harms in The Netherlands since 1960: relationships with planned and unplanned factors.

PubMed

Knibbe, Ronald A; Derickx, Mieke; Allamani, Allaman; Massini, Giulia

2014-10-01

to establish which unplanned (social developments) and planned (alcohol policy measures) factors are related to per capita consumption and alcohol-related harms in the Netherlands. linear regression was used to establish which of the planned and unplanned factors were most strongly connected with alcohol consumption and harms. Artificial Neural Analysis (ANN) was used to inspect the interconnections between all variables. mothers age at birth was most strongly associated with increase in consumption. The ban on selling alcoholic beverages at petrol station was associated with a decrease in consumption. The linear regression of harms did not show any relation between alcohol policy measures and harms. The ANN-analyses indicate a very high interconnectedness between all variables allowing no causal inferences. Exceptions are the relation between price of beer and wine and the consumption of these beverages and the relation between a decrease in transport mortality and the increased use of breathalyzers tests and a restriction of paracommercial selling. unplanned factors are most strongly associated with per capita consumption and harms. ANN-analysis indicates that price of alcoholic beverages, breath testing, and restriction of sales may have had some influence. The study's limitations are noted.

Eliminating health disparities in unintended pregnancy with long-acting reversible contraception (LARC).

PubMed

Parks, Caitlin; Peipert, Jeffrey F

2016-06-01

Significant public health disparities exist surrounding teen and unplanned pregnancy in the United States. Women of color and those with lower education and socioeconomic status are at much greater risk of unplanned pregnancy and the resulting adverse outcomes. Unplanned pregnancies reduce educational and career opportunities and may contribute to socioeconomic deprivation and widening income disparities. Long-acting reversible contraception (LARC), including intrauterine devices and implants, offer the opportunity to change the default from drifting into parenthood to planned conception. LARC methods are forgettable; once placed, they offer highly effective, long-term pregnancy prevention. Increasing evidence in the medical literature demonstrates the population benefits of use of these methods. However, barriers to more widespread use of LARC methods persist and include educational, access, and cost barriers. With increasing insurance coverage under the Affordable Care Act and more widespread, no-cost coverage of methods, more and more women are choosing intrauterine devices and the contraceptive implant. Increasing the use of highly effective contraceptive methods may provide one solution to the persistent problem of the health disparities of unplanned and teen pregnancies in the United States and improve women's and children's health. Copyright © 2016 Elsevier Inc. All rights reserved.