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

Task shifting for the delivery of pediatric antiretroviral treatment: a systematic review.

PubMed

Penazzato, Martina; Davies, Mary-Ann; Apollo, Tsitsi; Negussie, Eyerusalem; Ford, Nathan

2014-04-01

Pediatric antiretroviral treatment coverage in resource-limited settings continues to lag behind adults. Task shifting is an effective approach broadly used for adults, which some countries have also adopted for children, but implementation is limited by lack of confidence and skills among nonspecialist staff. A systematic review was conducted by combining key terms for task shifting, antiretroviral therapy (ART), and children. Five databases and two conferences were searched from inception till August 01, 2013. Eight observational studies provided outcome data for 11,828 children who received ART from nonphysician providers across 10 countries in sub-Saharan Africa. The cumulative pooled proportion of deaths was 3.2% [95% confidence interval (CI): 2.0 to 4.5] at 6 months, 4.6% (95% CI: 2.1 to 7.1) at 12 months, 6.2% (95% CI: 3.7 to 8.8) at 24 months, and 5.9% (95% CI: 3.5 to 8.3) at 36 months. Mortality and loss to follow-up in task-shifting programs were comparable to those reported by programs providing doctor- or specialist-led care. Our review suggests that task shifting of ART care can result in outcomes comparable to routine physician care, and this approach should be considered as part of a strategy to scale-up pediatric treatment. Specialist care will remain important for management of sick patients and complicated cases. Further qualitative research is needed to inform optimal implementation of task shifting for pediatric patients.

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

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.

Stock-outs of antiretroviral drugs and coping strategies used to prevent changes in treatment regimens in Kinondoni District, Tanzania: a cross-sectional study.

PubMed

Mori, Amani Thomas; Owenya, Joyce

2014-01-01

Since 2004, the government of Tanzania has been rolling out antiretroviral treatment programs all over the country. However, the capacity of the health system to cope with the rapid scale-up of these programs is a major concern, and problems may result in drug stock-outs that force changes in treatment regimens. This study aims to explore stock-outs of antiretroviral drugs and further determine the coping strategies employed to prevent changes in treatment regimens in HIV/AIDS care and treatment clinics in Kinondoni District, Dar es Salaam, Tanzania. A cross-sectional study was conducted in 20 HIV/AIDS care and treatment clinics. Interviews were conducted with the person in charge and a member of the pharmacy staff from each clinic using a pre-tested semi-structured interview guide. Verbal responses were transcribed, coded and analysed by thematic approach. Quantitative data were analysed using Excel spreadsheet (Microsoft Excel®, Microsoft Corporation). The total number of clients enrolled in the visited clinics was 32,147, of whom 20,831 (64.8%) had already been initiated onto antiretroviral therapies (ART). Stock-out of antiretroviral drugs was reported in 16 out of the 20 clinics, causing 210 patients to change their ART regimens, during the 12 months preceding the survey. Inefficient supply systems, quantification problems and short expiry duration were cited as the main causes of stock-outs. The coping strategies utilised to prevent changes in ART regimens were: shortening of the refill period, borrowing and moving patients to other clinics. Changes in ART regimens due to stock-outs of antiretroviral drugs occurred in a small but significant number of patients. This increases the risk of the emergence of drug-resistant HIV strains. Healthcare workers use various coping strategies to prevent changes in ART regimens but, unfortunately, some of these strategies are likely to increase patient-borne costs, which may discourage them from attending their routine

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

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

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

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.

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.

Simplified tools for measuring retention in care in antiretroviral treatment program in Ethiopia: cohort and current retention in care.

PubMed

Assefa, Yibeltal; Worku, Alemayehu; Wouters, Edwin; Koole, Olivier; Haile Mariam, Damen; Van Damme, Wim

2012-01-01

Patient retention in care is a critical challenge for antiretroviral treatment programs. This is mainly because retention in care is related to adherence to treatment and patient survival. It is therefore imperative that health facilities and programs measure patient retention in care. However, the currently available tools, such as Kaplan Meier, for measuring retention in care have a lot of practical limitations. The objective of this study was to develop simplified tools for measuring retention in care. Retrospective cohort data were collected from patient registers in nine health facilities in Ethiopia. Retention in care was the primary outcome for the study. Tools were developed to measure "current retention" in care during a specific period of time for a specific "ART-age group" and "cohort retention" in care among patients who were followed for the last "Y" number of years on ART. "Probability of retention" based on the tool for "cohort retention" in care was compared with "probability of retention" based on Kaplan Meier. We found that the new tools enable to measure "current retention" and "cohort retention" in care. We also found that the tools were easy to use and did not require advanced statistical skills. Both "current retention" and "cohort retention" are lower among patients in the first two "ART-age groups" and "ART-age cohorts" than in subsequent "ART-age groups" and "ART-age cohorts". The "probability of retention" based on the new tools were found to be similar to the "probability of retention" based on Kaplan Meier. The simplified tools for "current retention" and "cohort retention" will enable practitioners and program managers to measure and monitor rates of retention in care easily and appropriately. We therefore recommend that health facilities and programs start to use these tools in their efforts to improve retention in care and patient outcomes.

Developing a program for enhancing youth HIV treatment adherence and risk reduction.

PubMed

Fongkaew, Warunee; Udomkhamsuk, Warawan; Viseskul, Nongkran; Guptaruk, Marisa

2017-12-01

Youth living with HIV face difficult and challenging situations that decrease their adherence to antiretroviral medications. In this study, we developed a pilot program to enhance HIV treatment adherence and risk reduction among youth living with HIV based on collaboration with a community hospital involving a multi-disciplinary healthcare team. Participants were 25 youth living with HIV/AIDS, 18 caregivers, and 12 healthcare providers. The action research process comprised a preliminary stage and four phases of assessment, planning, implementation, and evaluation. This program used "edutainment", participatory learning, and multi-disciplinary collaboration to improve HIV treatment adherence and HIV risk behavior knowledge, motivation, and behavior. Education aimed to improve knowledge of antiretroviral drugs and HIV risk-taking behaviors. Motivation was directed at reframing beliefs and increasing positive attitudes of youth toward treatment adherence and raising awareness about safer sex behaviors. The behavioral skills focused on medication management in daily life activities, problem-solving, refusal and negotiation, and condom use. Findings provided preliminary evidence that the program was practical in a clinical context in a community hospital. © 2017 John Wiley & Sons Australia, Ltd.

Outcomes of Nigeria's HIV/AIDS Treatment Program for Patients Initiated on Antiretroviral Treatment between 2004-2012

PubMed Central

Odafe, Solomon; Abiri, Oseni; Debem, Henry; Agolory, Simon; Shiraishi, Ray W.; Auld, Andrew F.; Swaminathan, Mahesh; Dokubo, Kainne; Ngige, Evelyn; Asadu, Chukwuemeka; Abatta, Emmanuel; Ellerbrock, Tedd V.

2016-01-01

Background The Nigerian Antiretroviral therapy (ART) program started in 2004 and now ranks among the largest in Africa. However, nationally representative data on outcomes have not been reported. Methods We evaluated retrospective cohort data from a nationally representative sample of adults aged ≥15 years who initiated ART during 2004 to 2012. Data were abstracted from 3,496 patient records at 35 sites selected using probability-proportional-to-size (PPS) sampling. Analyses were weighted and controlled for the complex survey design. The main outcome measures were mortality, loss to follow-up (LTFU), and retention (the proportion alive and on ART). Potential predictors of attrition were assessed using competing risk regression models. Results At ART initiation, 66.4 percent (%) were females, median age was 33 years, median weight 56 kg, median CD4 count 161 cells/mm3, and 47.1% had stage III/IV disease. The percentage of patients retained at 12, 24, 36 and 48 months was 81.2%, 74.4%, 67.2%, and 61.7%, respectively. Over 10,088 person-years of ART, mortality, LTFU, and overall attrition (mortality, LTFU, and treatment stop) rates were 1.1 (95% confidence interval (CI): 0.7–1.8), 12.3 (95%CI: 8.9–17.0), and 13.9 (95% CI: 10.4–18.5) per 100 person-years (py) respectively. Highest attrition rates of 55.4/100py were witnessed in the first 3 months on ART. Predictors of LTFU included: lower-than-secondary level education (reference: Tertiary), care in North-East and South-South regions (reference: North-Central), presence of moderate/severe anemia, symptomatic functional status, and baseline weight <45kg. Predictor of mortality was WHO stage higher than stage I. Male sex, severe anemia, and care in a small clinic were associated with both mortality and LTFU. Conclusion Moderate/Advanced HIV disease was predictive of attrition; earlier ART initiation could improve program outcomes. Retention interventions targeting men and those with lower levels of education are

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.

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.

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

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

[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.

The International Interlaboratory Quality Control Program for Measurement of Antiretroviral Drugs in Plasma: a global proficiency testing program.

PubMed

Burger, David; Teulen, Marga; Eerland, Jaco; Harteveld, Anneke; Aarnoutse, Rob; Touw, Daan

2011-04-01

The International Interlaboratory Quality Control Program for Measurement of Antiretroviral Drugs in Plasma was initiated in 1999 by Radboud University Nijmegen Medical Center, The Netherlands, and continued later on in collaboration with the Dutch Association for Quality Assessment in Therapeutic Drug Monitoring and Clinical Toxicology (www.kkgt.nl). The aim of this analysis was to evaluate the first 10 years of the Program and to determine variables associated with reporting of less accurate results. Two rounds are organized annually in which blind samples are shipped to participants containing a low, medium, or high concentration of each antiretroviral drug. Any reported result that deviates more than 20% from the spiked concentration is defined as inaccurate. By the end of 2009, the number of laboratories participating in the Program had increased to 56; 44 (79%) are located in Europe. A total of 12,798 test results was available for analysis, of which 2104 (16.4%) were reported as inaccurate. Performance was best for samples containing nevirapine (mean of inadequate scores per round: 11.1%) and lopinavir (11.9%) and worst for indinavir (18.7%), atazanavir (18.9%), saquinavir (19.6%), and nelfinavir (21.3%). High and medium concentrations were less frequently reported as inaccurate than low concentrations: 13.5%, 13.0%, and 22.4%, respectively. Although the overall performance of the laboratories varied per year, a trend was visible for improvement over time with 19.9% of the results being inaccurate in 2002 (n = 20 laboratories) to 15.7% in 2009 (n = 56 laboratories). The Program provides a proficiency testing program in which laboratories are alerted to potential analytical errors while performing therapeutic drug monitoring in HIV-infected patients. Laboratories should put more effort in adequately analyzing concentrations of antiretroviral drugs with low minimum effective concentrations.

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.

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

Antiretroviral Treatment for Children with Peripartum Nevirapine Exposure

PubMed Central

Palumbo, Paul; Lindsey, Jane C.; Hughes, Michael D.; Cotton, Mark F.; Bobat, Raziya; Meyers, Tammy; Bwakura-Dangarembizi, Mutsawashe; Chi, Benjamin H.; Musoke, Philippa; Kamthunzi, Portia; Schimana, Werner; Purdue, Lynette; Eshleman, Susan H.; Abrams, Elaine J.; Millar, Linda; Petzold, Elizabeth; Mofenson, Lynne M.; Jean-Philippe, Patrick; Violari, Avy

2010-01-01

BACKGROUND Single-dose nevirapine is the cornerstone of the regimen for prevention of mother-to-child transmission of human immunodeficiency virus (HIV) in resource-limited settings, but nevirapine frequently selects for resistant virus in mothers and children who become infected despite prophylaxis. The optimal antiretroviral treatment strategy for children who have had prior exposure to single-dose nevirapine is unknown. METHODS We conducted a randomized trial of initial therapy with zidovudine and lamivudine plus either nevirapine or ritonavir-boosted lopinavir in HIV-infected children 6 to 36 months of age, in six African countries, who qualified for treatment according to World Health Organization (WHO) criteria. Results are reported for the cohort that included children exposed to single-dose nevirapine prophylaxis. The primary end point was virologic failure or discontinuation of treatment by study week 24. Enrollment in this cohort was terminated early on the recommendation of the data and safety monitoring board. RESULTS A total of 164 children were enrolled. The median percentage of CD4+ lymphocytes was 19%; a total of 56% of the children had WHO stage 3 or 4 disease. More children in the nevirapine group than in the ritonavir-boosted lopinavir group reached a primary end point (39.6% vs. 21.7%; weighted difference, 18.6 percentage-points; 95% confidence interval, 3.7 to 33.6; nominal P = 0.02). Baseline resistance to nevirapine was detected in 18 of 148 children (12%) and was predictive of treatment failure. No significant between-group differences were seen in the rate of adverse events. CONCLUSIONS Among children with prior exposure to single-dose nevirapine for perinatal prevention of HIV transmission, antiretroviral treatment consisting of zidovudine and lamivudine plus ritonavir-boosted lopinavir resulted in better outcomes than did treatment with zidovudine and lamivudine plus nevirapine. Since nevirapine is used for both treatment and perinatal

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

How to improve patient retention in an antiretroviral treatment program in Ethiopia: a mixed-methods study

PubMed Central

2014-01-01

Background Patient retention, defined as continuous engagement of patients in care, is one of the crucial indicators for monitoring and evaluating the performance of antiretroviral treatment (ART) programs. It has been identified that suboptimal patient retention in care is one of the challenges of ART programs in many settings. ART programs have, therefore, been striving hard to identify and implement interventions that improve their suboptimal levels of retention. The objective of this study was to develop a framework for improving patient retention in care based on interventions implemented in health facilities that have achieved higher levels of retention in care. Methods A mixed-methods study, based on the positive deviance approach, was conducted in Ethiopia in 2011/12. Quantitative data were collected to estimate and compare the levels of retention in care in nine health facilities. Key informant interviews and focus group discussions were conducted to identify a package of interventions implemented in the health facilities with relatively higher or improving levels of retention. Results Retention in care in the Ethiopian ART program was found to be variable across health facilities. Among hospitals, the poorest performer had 0.46 (0.35, 0.60) times less retention than the reference; among health centers, the poorest performers had 0.44 (0.28, 0.70) times less retention than the reference. Health facilities with higher and improving patient retention were found to implement a comprehensive package of interventions: (1) retention promoting activities by health facilities, (2) retention promoting activities by community-based organizations, (3) coordination of these activities by case manager(s), and (4) patient information systems by data clerk(s). On the contrary, such interventions were either poorly implemented or did not exist in health facilities with lower retention in care. A framework to improve retention in care was developed based on the evidence

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.

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

[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

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.

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

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.

Trends in antiretroviral treatment use and treatment response in three Australian states in the first decade of combination antiretroviral treatment

PubMed Central

Falster, Kathleen; Gelgor, Linda; Shaik, Ansari; Zablotska, Iryna; Prestage, Garrett; Grierson, Jeffrey; Thorpe, Rachel; Pitts, Marian; Anderson, Jonathon; Chuah, John; Mulhall, Brian; Petoumenos, Kathy; Kelleher, Anthony; Law, Matthew G.

2009-01-01

Objectives To determine if there were any differences in antiretroviral treatment (ART) use across the three eastern states of Australia, New South Wales, Victoria and Queensland, during the period 1997 to 2006. Methods We used data from a clinic-based cohort, the Australian HIV Observational Database (AHOD), to determine the proportion of HIV-infected patients on ART in selected clinics in each state and the proportion of treated patients with an undetectable viral load. Data from the national Highly Specialised Drugs program and AHOD was used to estimate total numbers of individuals on ART and the proportion of individuals living with HIV on ART nationally and by state. Data from the HIV Futures Survey and the Gay Community Periodic Survey (GCPS) were used to determine the proportion of community-based men who have sex with men (MSM) on ART. The proportion of patients with primary HIV infection (PHI) who commenced ART within one year of diagnosis was obtained from the Acute Infection and Early Disease Research Program (AIEDRP) CORE01 protocol and Primary HIV and Early Disease Research: Australian cohort (PHAEDRA) cohorts. Results We estimated that the numbers of individuals on ART increased from 3,181 to 4,553 in NSW, 1,309 to 1,926 in Victoria and 809 to 1615 in Queensland between 2000 and 2006. However, these numbers may reflect a lower proportion of individuals living with HIV on ART in NSW compared to the other states (37% compared to 49 and 55% in 2000). We found similar proportions of HIV-positive MSM participants were on ART in all three states over the study period in the clinic-based AHOD cohort (81-92%) and two large, community based surveys in Australia (69-85% and 49-83%) . Similar proportions of treated patients had an undetectable viral load across the three states, with a consistently increasing trend over time observed in all states. We found that more PHI patients commenced treatment in the first year following HIV diagnosis in NSW compared to

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

Influence of antiretroviral therapy on programmed death-1 (CD279) expression on T cells in lymph nodes of human immunodeficiency virus-infected individuals.

PubMed

Ehrhard, Simone; Wernli, Marion; Dürmüller, Ursula; Battegay, Manuel; Gudat, Fred; Erb, Peter

2009-10-01

Human immunodeficiency virus infection leads to T-cell exhaustion and involution of lymphoid tissue. Recently, the programmed death-1 pathway was found to be crucial for virus-specific T-cell exhaustion during human immunodeficiency virus infection. Programmed death-1 expression was elevated on human immunodeficiency virus-specific peripheral blood CD8+ and CD4+ T cells and correlated with disease severity. During human immunodeficiency infection, lymphoid tissue acts as a major viral reservoir and is an important site for viral replication, but it is also essential for regulatory processes important for immune recovery. We compared programmed death-1 expression in 2 consecutive inguinal lymph nodes of 14 patients, excised before antiretroviral therapy (antiretroviral therapy as of 1997-1999) and 16 to 20 months under antiretroviral therapy. In analogy to lymph nodes of human immunodeficiency virus-negative individuals, in all treated patients, the germinal center area decreased, whereas the number of germinal centers did not significantly change. Programmed death-1 expression was mostly found in germinal centers. The absolute extent of programmed death 1 expression per section was not significantly altered after antiretroviral therapy resulting in a significant-relative increase of programmed death 1 per shrunken germinal center. In colocalization studies, CD45R0+ cells that include helper/inducer T cells strongly expressed programmed death-1 before and during therapy, whereas CD8+ T cells, fewer in numbers, showed a weak expression for programmed death-1. Thus, although antiretroviral therapy seems to reduce the number of programmed death-1-positive CD8+ T lymphocytes within germinal centers, it does not down-regulate programmed death-1 expression on the helper/inducer T-cell subset that may remain exhausted and therefore unable to trigger immune recovery.

Antiretroviral treatment during pregnancy.

PubMed

Keiser, Olivia; Gayet-Ageron, Angèle; Rudin, Christoph; Brinkhof, Martin W G; Gremlich, Erika; Wunder, Dorothea; Drack, Gero; Hirschel, Bernard; de Tejada, Begoña Martinez

2008-11-12

Virologic failure of HIV-positive patients is of special concern during pregnancy. We compared virologic failure and the frequency of treatment changes in pregnant and non-pregnant women of the Swiss HIV Cohort Study. Using data on 372 pregnancies in 324 women we describe antiretroviral therapy during pregnancy. Pregnant women on HAART at conception (n = 131) were matched to 228 non-pregnant women (interindividual comparison) and to a time period of equal length before and after pregnancy (intraindividual comparison). Women starting HAART during pregnancy (n = 145) were compared with 578 non-pregnant women starting HAART. The median age at conception was 31 years, 16% (n = 50) were infected through injecting drug use and the median CD4 cell count was 489 cells/microl. In the majority of pregnancies (n = 220, 59%), women had started ART before conception. When ART was started during pregnancy (n = 145, 39%), it was mainly during the second trimester (n = 100, 69%). Two thirds (n = 26) of 35 women starting in the third trimester were diagnosed with HIV during pregnancy. The risk of virologic failure tended to be lower in pregnant than in non-pregnant women [adjusted odds ratio 0.52 (95% confidence interval 0.25-1.09, P = 0.08)], but was similar in the intraindividual comparison (adjusted odds ratio 1.04, 95% confidence interval 0.48-2.28). Women starting HAART during pregnancy changed the treatment less often than non-pregnant women. Despite the physiological changes occurring during pregnancy, HIV infected pregnant women are not at higher risk of virologic failure.

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

Adherence to Highly Active Antiretroviral Treatment in HIV-Infected Rwandan Women

PubMed Central

Musiime, Stephenson; Muhairwe, Fred; Rutagengwa, Alfred; Mutimura, Eugene; Anastos, Kathryn; Hoover, Donald R.; Qiuhu, Shi; Munyazesa, Elizaphane; Emile, Ivan; Uwineza, Annette; Cowan, Ethan

2011-01-01

Background Scale-up of highly active antiretroviral treatment therapy (HAART) programs in Rwanda has been highly successful but data on adherence is limited. We examined HAART adherence in a large cohort of HIV+ Rwandan women. Methods The Rwanda Women's Interassociation Study Assessment (RWISA) was a prospective cohort study that assessed effectiveness and toxicity of ART. We analyzed patient data 12±3 months after HAART initiation to determine adherence rates in HIV+ women who had initiated HAART. Results Of the 710 HIV+ women at baseline, 490 (87.2%) initiated HAART. Of these, 6 (1.2%) died within 12 months, 15 others (3.0%) discontinued the study and 80 others (19.0%) remained in RWISA but did not have a post-HAART initiation visit that fell within the 12±3 month time points leaving 389 subjects for analysis. Of these 389, 15 women stopped their medications without being advised to do so by their doctors. Of the remaining 374 persons who reported current HAART use 354 completed the adherence assessment. All women, 354/354, reported 100% adherence to HAART at the post-HAART visit. The high self-reported level of adherence is supported by changes in laboratory measures that are influenced by HAART. The median (interquartile range) CD4 cell count measured within 6 months prior to HAART initiation was 185 (128, 253) compared to 264 (182, 380) cells/mm3 at the post-HAART visit. Similarly, the median (interquartile range) MCV within 6 months prior to HAART initiation was 88 (83, 93) fL compared to 104 (98, 110) fL at the 12±3 month visit. Conclusion Self-reported adherence to antiretroviral treatment 12±3 months after initiating therapy was 100% in this cohort of HIV-infected Rwandan women. Future studies should explore country-specific factors that may be contributing to high levels of adherence to HAART in this population. PMID:22114706

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.

A program to provide antiretroviral therapy to residents of an urban slum in Nairobi, Kenya.

PubMed

Marston, Barbara J; Macharia, Doris K; Nga'nga, Lucy; Wangai, Mary; Ilako, Festus; Muhenje, Odylia; Kjaer, Mette; Isavwa, Anthony; Kim, Andrea; Chebet, Kenneth; DeCock, Kevin M; Weidle, Paul J

2007-06-01

To evaluate retention in care and response to therapy for patients enrolled in an antiretroviral treatment program in a severely resource-constrained setting. We evaluated patients enrolled between February 26, 2003, and February 28, 2005, in a community clinic in Kibera, an informal settlement, in Nairobi, Kenya. Midlevel providers offered simplified, standardized antiretroviral therapy (ART) regimens and monitored patients clinically and with basic laboratory tests. Clinical, immunologic, and virologic indicators were used to assess response to ART; adherence was determined by 3-day recall. A total of 283 patients (70% women; median baseline CD4 count, 157 cells/ mm(3); viral load, 5.16 log copies/mL) initiated ART and were followed for a median of 7.1 months (n = 2384 patient-months). At 1 year, the median CD4 count change was +124.5 cells/mm(3) (n = 74; interquartile range, 42 to 180), and 71 (74%) of 96 patients had viral load <400 copies/mL. The proportion of patients reporting 100% adherence over the 3 days before monthly clinic visits was 94% to 100%. As of February 28, 2005, a total of 239 patients (84%) remained in care, 22 (8%) were lost to follow-up, 12 (4%) were known to have died, 5 (2%) had stopped ART, 3 (1%) moved from the area, and 2 (< 1% ) transferred care. Response to ART in this slum population was comparable to that seen in industrialized settings. With government commitment, donor support, and community involvement, it is feasible to implement successful ART programs in extremely challenging social and environmental conditions.

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.

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

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

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

Patterns of geographic mobility predict barriers to engagement in HIV care and antiretroviral treatment adherence.

PubMed

Taylor, Barbara S; Reyes, Emily; Levine, Elizabeth A; Khan, Shah Z; Garduño, L Sergio; Donastorg, Yeycy; Hammer, Scott M; Brudney, Karen; Hirsch, Jennifer S

2014-06-01

Migration and geographic mobility increase risk for HIV infection and may influence engagement in HIV care and adherence to antiretroviral therapy. Our goal is to use the migration-linked communities of Santo Domingo, Dominican Republic, and New York City, New York, to determine the impact of geographic mobility on HIV care engagement and adherence to treatment. In-depth interviews were conducted with HIV+Dominicans receiving antiretroviral therapy, reporting travel or migration in the past 6 months and key informants (n=45). Mobility maps, visual representations of individual migration histories, including lifetime residence(s) and all trips over the past 2 years, were generated for all HIV+ Dominicans. Data from interviews and field observation were iteratively reviewed for themes. Mobility mapping revealed five distinct mobility patterns: travel for care, work-related travel, transnational travel (nuclear family at both sites), frequent long-stay travel, and vacation. Mobility patterns, including distance, duration, and complexity, varied by motivation for travel. There were two dominant barriers to care. First, a fear of HIV-related stigma at the destination led to delays seeking care and poor adherence. Second, longer trips led to treatment interruptions due to limited medication supply (30-day maximum dictated by programs or insurers). There was a notable discordance between what patients and providers perceived as mobility-induced barriers to care and the most common barriers found in the analysis. Interventions to improve HIV care for mobile populations should consider motivation for travel and address structural barriers to engagement in care and adherence.

Patterns of Geographic Mobility Predict Barriers to Engagement in HIV Care and Antiretroviral Treatment Adherence

PubMed Central

Reyes, Emily; Levine, Elizabeth A.; Khan, Shah Z.; Garduño, L. Sergio; Donastorg, Yeycy; Hammer, Scott M.; Brudney, Karen; Hirsch, Jennifer S.

2014-01-01

Abstract Migration and geographic mobility increase risk for HIV infection and may influence engagement in HIV care and adherence to antiretroviral therapy. Our goal is to use the migration-linked communities of Santo Domingo, Dominican Republic, and New York City, New York, to determine the impact of geographic mobility on HIV care engagement and adherence to treatment. In-depth interviews were conducted with HIV+Dominicans receiving antiretroviral therapy, reporting travel or migration in the past 6 months and key informants (n=45). Mobility maps, visual representations of individual migration histories, including lifetime residence(s) and all trips over the past 2 years, were generated for all HIV+ Dominicans. Data from interviews and field observation were iteratively reviewed for themes. Mobility mapping revealed five distinct mobility patterns: travel for care, work-related travel, transnational travel (nuclear family at both sites), frequent long-stay travel, and vacation. Mobility patterns, including distance, duration, and complexity, varied by motivation for travel. There were two dominant barriers to care. First, a fear of HIV-related stigma at the destination led to delays seeking care and poor adherence. Second, longer trips led to treatment interruptions due to limited medication supply (30-day maximum dictated by programs or insurers). There was a notable discordance between what patients and providers perceived as mobility-induced barriers to care and the most common barriers found in the analysis. Interventions to improve HIV care for mobile populations should consider motivation for travel and address structural barriers to engagement in care and adherence. PMID:24839872

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

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

[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.

'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.

Scale-up of national antiretroviral therapy programs: progress and challenges in the Asia Pacific region.

PubMed

Srikantiah, Padmini; Ghidinelli, Massimo; Bachani, Damodar; Chasombat, Sanchai; Daoni, Esorom; Mustikawati, Dyah E; Nhan, Do T; Pathak, Laxmi R; San, Khin O; Vun, Mean C; Zhang, Fujie; Lo, Ying-Ru; Narain, Jai P

2010-09-01

There has been tremendous scale-up of antiretroviral therapy (ART) services in the Asia Pacific region, which is home to an estimated 4.7 million persons living with HIV/AIDS. We examined treatment scale-up, ART program practices, and clinical outcome data in the nine low-and-middle-income countries that share over 95% of the HIV burden in the region. Standardized indicators for ART scale-up and treatment outcomes were examined for Cambodia, China, India, Indonesia, Myanmar, Nepal, Papua New Guinea, Thailand, and Vietnam using data submitted by each country to the WHO/The Joint United Nations Programme on HIV/AIDS (UNAIDS)/UNICEF joint framework tool for monitoring the health sector response to HIV/AIDS. Data on ART program practices were abstracted from National HIV Treatment Guidelines for each country. At the end of 2009, over 700,000 HIV-infected persons were receiving ART in the nine focus countries. Treatment coverage varies widely in the region, ranging from 16 to 93%. All nine countries employ a public health approach to ART services and provide a standardized first-line nonnucleoside reverse transcriptase inhibitor-based regimen. Among patients initiated on first-line ART in these countries, 65-88% remain alive and on treatment 12 months later. Over 50% of mortality occurs in the first 6 months of therapy, and losses to follow-up range from 8 to 16% at 2 years. Impressive ART scale-up efforts in the region have resulted in significant improvements in survival among persons receiving therapy. Continued funding support and political commitment will be essential for further expansion of public sector ART services to those in need. To improve treatment outcomes, national programs should focus on earlier identification of persons requiring ART, decentralization of ART services, and the development of stronger healthcare systems to support the provision of a continuum of HIV care.

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

The costs of HIV antiretroviral therapy adherence programs and impact on health care utilization.

PubMed

Sansom, Stephanie L; Anthony, Monique N; Garland, Wendy H; Squires, Kathleen E; Witt, Mallory D; Kovacs Andrea, A; Larsen, Robert A; Valencia, Rosa; Pals, Sherri L; Hader, Shannon; Weidle, Paul J; Wohl, Amy R

2008-02-01

From a trial comparing interventions to improve adherence to antiretroviral therapy-directly administered antiretroviral therapy (DAART) or an intensive adherence case management (IACM)-to standard of care (SOC), for HIV-infected participants at public HIV clinics in Los Angeles County, California, we examined the cost of adherence programs and associated health care utilization. We assessed differences between DAART, IACM, and SOC in the rate of hospitalizations, hospital days, and outpatient and emergency department visits during an average of 1.7 years from study enrollment, beginning November 2001. We assigned costs to health care utilization and program delivery. We calculated incremental costs of DAART or IACM v SOC, and compared those costs with savings in health care utilization among participants in the adherence programs. IACM participants experienced fewer hospital days compared with SOC (2.3 versus 6.7 days/1000 person-days, incidence rate ratio [IRR]: 0.34, 97.5% confidence interval [CI]: 0.13-0.87). DAART participants had more outpatient visits than SOC (44.2 versus 31.5/1000 person-days, IRR: 1.4; 97.5% CI: 1.01-1.95). Average per-participant health care utilization costs were $13,127, $8,988, and $14,416 for DAART, IACM, and SOC, respectively. Incremental 6-month program costs were $2,120 and $1,653 for DAART and IACM participants, respectively. Subtracting savings in health care utilization from program costs resulted in an average net program cost of $831 per DAART participant; and savings of $3,775 per IACM participant. IACM was associated with a significant decrease in hospital days compared to SOC and was cost saving when program costs were compared to savings in health care utilization.

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

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

Adverse Events among HIV/MDR-TB Co-Infected Patients Receiving Antiretroviral and Second Line Anti-TB Treatment in Mumbai, India

PubMed Central

Isaakidis, Petros; Varghese, Bhanumati; Mansoor, Homa; Cox, Helen S.; Ladomirska, Joanna; Saranchuk, Peter; Da Silva, Esdras; Khan, Samsuddin; Paryani, Roma; Udwadia, Zarir; Migliori, Giovanni Battista; Sotgiu, Giovanni; Reid, Tony

2012-01-01

Background Significant adverse events (AE) have been reported in patients receiving medications for multidrug- and extensively-drug-resistant tuberculosis (MDR-TB & XDR-TB). However, there is little prospective data on AE in MDR- or XDR-TB/HIV co-infected patients on antituberculosis and antiretroviral therapy (ART) in programmatic settings. Methods Médecins Sans Frontières (MSF) is supporting a community-based treatment program for drug-resistant tuberculosis in HIV-infected patients in a slum setting in Mumbai, India since 2007. Patients are being treated for both diseases and the management of AE is done on an outpatient basis whenever possible. Prospective data were analysed to determine the occurrence and nature of AE. Results Between May 2007 and September 2011, 67 HIV/MDR-TB co-infected patients were being treated with anti-TB treatment and ART; 43.3% were female, median age was 35.5 years (Interquartile Range: 30.5–42) and the median duration of anti-TB treatment was 10 months (range 0.5–30). Overall, AE were common in this cohort: 71%, 63% and 40% of patients experienced one or more mild, moderate or severe AE, respectively. However, they were rarely life-threatening or debilitating. AE occurring most frequently included gastrointestinal symptoms (45% of patients), peripheral neuropathy (38%), hypothyroidism (32%), psychiatric symptoms (29%) and hypokalaemia (23%). Eleven patients were hospitalized for AE and one or more suspect drugs had to be permanently discontinued in 27 (40%). No AE led to indefinite suspension of an entire MDR-TB or ART regimen. Conclusions AE occurred frequently in this Mumbai HIV/MDR-TB cohort but not more frequently than in non-HIV patients on similar anti-TB treatment. Most AE can be successfully managed on an outpatient basis through a community-based treatment program, even in a resource-limited setting. Concerns about severe AE in the management of co-infected patients are justified, however, they should not cause delays

[Antiretroviral drug supply in Argentina: National Program to Combat Human Retroviruses, AIDS, and STDs].

PubMed

Colautti, Marisel; Luppi, Irene; Salamano, Mercedes; Traverso, María Luz; Botta, Carina; Palchik, Valeria

2009-01-01

To evaluate the supply cycle of antiretroviral (ARV) drugs, overseen by the National Program to Combat Human Retroviruses, AIDS, and STDs, through its order fulfillment indicators, and to obtain input from supply chain stakeholders. A study was carried out from April-September 2005 in the pharmacies of two hospitals in Rosario, Argentina, involving both a quantitative analysis of indicators and secondary sources and a qualitative evaluation using semistructured interviews. The indicators reveal the impact that interruptions in ARV supply stream from the Program (central level) have and the overstocking that takes place at the pharmacies (local level) to manage the shortages. Changes in ARV treatment account for over 50% of the prescriptions. Fulfillments fall short of the reference value. The interviewees shared possible strategies for overcoming the communication gaps between levels, for building-up stock, for guaranteeing availability, and for shortening waiting times; reached informal agreements to deal with the lack of policies and the shortage of staff; acknowledged the challenges facing the jurisdictions (central, intermediate, and local/community); and recognized local efforts to improve management. These challenges could be the starting point for building teams to work on effectively decentralizing the entire supply chain and allowing the Program to fulfill its much-needed oversight role.

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

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

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

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.

CD4 Counts at Entry to HIV Care in Mexico for Patients under the "Universal Antiretroviral Treatment Program for the Uninsured Population," 2007-2014.

PubMed

Hernández-Romieu, Alfonso C; del Rio, Carlos; Hernández-Ávila, Juan Eugenio; Lopez-Gatell, Hugo; Izazola-Licea, José Antonio; Uribe Zúñiga, Patricia; Hernández-Ávila, Mauricio

2016-01-01

In Mexico, public health services have provided universal access to antiretroviral therapy (ART) since 2004. For individuals receiving HIV care in public healthcare facilities, the data are limited regarding CD4 T-lymphocyte counts (CD4e) at the time of entry into care. Relevant population-based estimates of CD4e are needed to inform strategies to maximize the impact of Mexico's national ART program, and may be applicable to other countries implementing universal HIV treatment programs. For this study, we retrospectively analyzed the CD4e of persons living with HIV and receiving care at state public health facilities from 2007 to 2014, comparing CD4e by demographic characteristics and the marginalization index of the state where treatment was provided, and assessing trends in CD4e over time. Our sample included 66,947 individuals who entered into HIV care between 2007 and 2014, of whom 79% were male. During the study period, the male-to-female ratio increased from 3.0 to 4.3, reflecting the country's HIV epidemic; the median age at entry decreased from 34 years to 32 years. Overall, 48.6% of individuals entered care with a CD4≤200 cells/μl, ranging from 42.2% in states with a very low marginalization index to 52.8% in states with a high marginalization index, and from 38.9% among individuals aged 18-29 to 56.5% among those older than 50. The adjusted geometric mean (95% confidence interval) CD4e increased among males from 135 (131,142) cells/μl in 2007 to 148 (143,155) cells/μl in 2014 (p-value<0.0001); no change was observed among women, with a geometric mean of 178 (171,186) and 171 (165,183) in 2007 and 2014, respectively. There have been important gains in access to HIV care and treatment; however, late entry into care remains an important barrier in achieving optimal outcomes of ART in Mexico. The geographic, socioeconomic, and demographic differences observed reflect important inequities in timely access to HIV prevention, care, and treatment services

Retention of antiretroviral naïve patients registered in HIV care in a program clinic in Pune, India

PubMed Central

Ghate, Manisha V.; Zirpe, Sunil S.; Gurav, Nilam P.; Rewari, Bharat B.; Gangakhedkar, Raman R.; Paranjape, Ramesh S.

2014-01-01

Background: Retention in HIV care ensures delivery of services like secondary prevention, timely initiation of treatment, support, and care on a regular basis. The data on retention in pre antiretroviral therapy (ART) care in India is scanty. Materials and Methods: Antiretroviral naïve HIV-infected adult patients registered between January 2011 and March 2012 in HIV care (pre-ART) were included in the study. The follow-up procedures were done as per the national guidelines. Patients who did not report to the clinic for 1 year were considered as pre-ART lost to follow-up (pre-ART LFU). They were contacted either telephonically or by home visits. Logistic regression analysis was done to find out factors associated with pre-ART loss to follow-up. Results: A total of 689 antiretroviral naïve adult patients were registered in the HIV care. Fourteen (2%) patients died and 76 (11%) were LFU till March 2013. The multivariate analysis showed that baseline CD4 count >350 cells/mm3 (P < 0.01) and illiteracy (P = 0.044) were significantly associated with LFU. Of the total pre-ART LFUs, 35 (46.1%) informed that they would visit the clinic at their convenient time. NGOs that referred 16 female sex workers (FSWs) who were LFU (21.1%) informed that they would make efforts to refer them to the clinic. Conclusion: Higher CD4 count and illiteracy were significantly associated with lower retention in pre-ART care. Developing effective “retention package” for patients and strengthening linkage strategies between key sub-population such as FSWs and ART programming will help to plug the leaky cascade in HIV care. PMID:26396447

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.

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

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.

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.

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

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.

Strengthening healthcare capacity through a responsive, country-specific, training standard: the KITSO AIDS training program's support of Botswana's national antiretroviral therapy rollout.

PubMed

Bussmann, Christine; Rotz, Philip; Ndwapi, Ndwapi; Baxter, Daniel; Bussmann, Hermann; Wester, C William; Ncube, Patricia; Avalos, Ava; Mine, Madisa; Mabe, Elang; Burns, Patricia; Cardiello, Peter; Makhema, Joseph; Marlink, Richard

2008-01-01

In parallel with the rollout of Botswana's national antiretroviral therapy (ART) program, the Botswana Ministry of Health established the KITSO AIDS Training Program by entering into long-term partnerships with the Botswana-Harvard AIDS Institute Partnership for HIV Research and Education and others to provide standardized, country-specific training in HIV/AIDS care. The KITSO training model has strengthened human capacity within Botswana's health sector and been indispensable to successful ART rollout. Through core and advanced training courses and clinical mentoring, different cadres of health care workers have been trained to provide high-quality HIV/AIDS care at all ART sites in the country. Continuous and standardized clinical education will be crucial to sustain the present level of care and successfully address future treatment challenges.

Exploring the population-level impact of antiretroviral treatment: the influence of baseline intervention context.

PubMed

Mishra, Sharmistha; Mountain, Elisa; Pickles, Michael; Vickerman, Peter; Shastri, Suresh; Gilks, Charles; Dhingra, Nandini K; Washington, Reynold; Becker, Marissa L; Blanchard, James F; Alary, Michel; Boily, Marie-Claude

2014-01-01

To compare the potential population-level impact of expanding antiretroviral treatment (ART) in HIV epidemics concentrated among female sex workers (FSWs) and clients, with and without existing condom-based FSW interventions. Mathematical model of heterosexual HIV transmission in south India. We simulated HIV epidemics in three districts to assess the 10-year impact of existing ART programs (ART eligibility at CD4 cell count ≤350) beyond that achieved with high condom use, and the incremental benefit of expanding ART by either increasing ART eligibility, improving access to care, or prioritizing ART expansion to FSWs/clients. Impact was estimated in the total population (including FSWs and clients). In the presence of existing condom-based interventions, existing ART programs (medium-to-good coverage) were predicted to avert 11-28% of remaining HIV infections between 2014 and 2024. Increasing eligibility to all risk groups prevented an incremental 1-15% over existing ART programs, compared with 29-53% when maximizing access to all risk groups. If there was no condom-based intervention, and only poor ART coverage, then expanding ART prevented a larger absolute number but a smaller relative fraction of HIV infections for every additional person-year of ART. Across districts and baseline interventions, for every additional person-year of treatment, prioritizing access to FSWs was most efficient (and resource saving), followed by prioritizing access to FSWs and clients. The relative and absolute benefit of ART expansion depends on baseline condom use, ART coverage, and epidemic size. In south India, maximizing FSWs' access to care, followed by maximizing clients' access are the most efficient ways to expand ART for HIV prevention, across baseline intervention context.

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.

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.

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.

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.

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.

Impact of early treatment programs on HIV epidemics: An immunity-based mathematical model.

PubMed

Rahman, S M Ashrafur; Vaidya, Naveen K; Zou, Xingfu

2016-10-01

While studies on pre-exposure prophylaxis (PrEP) and post-exposure prophylaxis (PEP) have demonstrated substantial advantages in controlling HIV transmission, the overall benefits of the programs with early initiation of antiretroviral therapy (ART) have not been fully understood and are still on debate. Here, we develop an immunity-based (CD4+ T cell count based) mathematical model to study the impacts of early treatment programs on HIV epidemics and the overall community-level immunity. The model is parametrized using the HIV prevalence data from South Africa and fully analyzed for stability of equilibria and infection persistence criteria. Using our model, we evaluate the effects of early treatment on the new infection transmission, disease death, basic reproduction number, HIV prevalence, and the community-level immunity. Our model predicts that the programs with early treatments significantly reduce the new infection transmission and increase the community-level immunity, but the treatments alone may not be enough to eliminate HIV epidemics. These findings, including the community-level immunity, might provide helpful information for proper implementation of HIV treatment programs. Copyright © 2016 Elsevier Inc. All rights reserved.

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

HBV genotypes and drug resistance mutations in antiretroviral treatment-naive and treatment-experienced HBV-HIV-coinfected patients.

PubMed

Archampong, Timothy Na; Boyce, Ceejay L; Lartey, Margaret; Sagoe, Kwamena W; Obo-Akwa, Adjoa; Kenu, Ernest; Blackard, Jason T; Kwara, Awewura

2017-01-01

The presence of HBV resistance mutations upon initiation or during antiretroviral therapy (ART) in HIV-coinfected patients is an important determinant of treatment response. The main objective of the study was to determine the prevalence of HBV resistance mutations in antiretroviral treatment-naive and treatment-experienced HBV-HIV-coinfected Ghanaian patients with detectable HBV viraemia. HBV-HIV-coinfected patients who were ART-naive or had received at least 9 months of lamivudine (3TC)-containing ART were enrolled in a cross-sectional study. Demographic and clinical data were collected and HBV DNA quantified. Partial HBV sequences were amplified by PCR and sequenced bi-directionally to obtain a 2.1-2.2 kb fragment for phylogenetic analysis of HBV genotypes and evaluation of drug resistance mutations. Of the 100 HBV-HIV-coinfected study patients, 75 were successfully PCR-amplified, and 63 were successfully sequenced. Of these 63 patients, 27 (42.9%) were ART-experienced and 58 (92.1%) had HBV genotype E. No resistance mutations were observed in the 36 ART-naive patients, while 21 (77.8%) of 27 treatment-experienced patients had resistance mutations. All patients with resistance mutations had no tenofovir in their regimens, and 80% of them had HIV RNA <40 copies/ml. The 3TC resistance mutations rtL180M and rtM204V were observed in 10 (47.6%) of the 21 patients, while 5 patients (23.8%) had rtV173L, rtL180M and rtM204V mutations. A high proportion of HBV-HIV-coinfected patients with detectable viraemia on 3TC-containing ART had resistance mutations despite good ART adherence as determined by HIV RNA suppression. This study emphasizes the need for dual therapy as part of a fully suppressive ART in all HBV-HIV-coinfected patients in Ghana.

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

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

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.

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.

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.

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...

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.

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

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

[Costs and adherence to antiretroviral treatment].

PubMed

Ventura-Cerdá, J M; Ayago-Flores, D; Vicente-Escrig, E; Mollá-Cantavella, S; Alós-Almiñana, M

2010-01-01

To develop a system of data management that allows us to estimate the comparative effectiveness of the various antiretroviral treatment (ART) regimens. Retrospective observational study in patients infected with HIV with stable ART. Adherence to treatment and unit cost for each patient's treatment was determined. The cost/patient/day was calculated and, multiplying by an adherence factor (fADH), the (cost/patient/day)(ADH). The comparison of both allowed us to obtain the Δcost/patient, which estimates the additional costs caused by lack of adherence. The incremental cost-effectiveness (iCER), grouping the results by the various coformulated drugs ("combos"). A study of the budgetary impact of these combos was carried out. 468 patients were evaluated (62% adherent). Average adherence was 88±18%. The average value of (cost/patient/day) (ADH) was significantly higher than the cost/patient/day (27.3±9.8€ compared to 24.3±7.6€. p<0.001). Just as with the f(ADH), no differences were found in the Δcost/patient between the different ART combinations. The combo with the least deviation from the cost/patient/day due to lack of adherence was that composed of abacavir/zedovudine/lamivudine (ABC/AZT/3TC,Δcost/patient=8.72±14.18%), and that with the greatest deviation AZT/3TC (Δcost/patient=13.52±17.68%). No significant differences were found in the iCER calculated for any combo. The ART that included abacavir/lamivudine (ABC/3TC) obtained the least budgetary impact. The greatest cost and percentage of adherent patients associated with the combos composed of Tenovovir/Emtricitabine(TDF/FTC) and ABC/3TC, and the least cost and effectiveness of those composed of AZT/#TC and ABC/AZT/3TC, does not allow us to identify any option as significantly dominant. The regimens with ABC/3TC were shown to be the most favourable from the combined point of view of cost and adherence. Copyright © 2009 SEFH. Published by Elsevier Espana. All rights reserved.

Barriers to free antiretroviral treatment access for female sex workers in Chennai, India.

PubMed

Chakrapani, Venkatesan; Newman, Peter A; Shunmugam, Murali; Kurian, Abraham K; Dubrow, Robert

2009-11-01

India's National AIDS Control Organization (NACO) provides free first-line antiretroviral treatment (ART) at government centers for people living with HIV. To assist in developing policies and programs to ensure equity in ART access, we explored barriers to ART access among female sex workers (FSWs) living with HIV in Chennai. Between August and November 2007, we conducted three focus group discussions and two key informant interviews. Data were explored using framework analysis to identify categories and derive themes. We found interrelated barriers at the family/social, health care system/programmatic, and individual levels. Major barriers included fear of adverse consequences of disclosure of HIV status due to stigma and discrimination associated with HIV and sex work, lack of family support, negative experiences with health care providers, lack of adequate counseling services at government centers and by outreach workers employed by nongovernmental organizations (NGOs), perceived biased treatment of FSWs who are not referred by NGOs, lack of adequate knowledge about ART, and fatalism. Barriers can be addressed by: creating effective measures to reduce stigma associated with HIV/AIDS and sex work at the familial, societal, and health care system levels; incorporating information about ART into targeted interventions among FSWs; training counselors at government hospitals and NGO outreach workers on treatment issues; improving infrastructure and staffing levels at government centers to allow adequate time and privacy for counseling; and implementing government mass media campaigns on ART availability. Finally, it is crucial that NACO begin monitoring ART coverage of FSWs and other marginalized populations to ensure equitable ART access.

Antiretroviral treatment interruptions induced by the Kenyan postelection crisis are associated with virological failure.

PubMed

Mann, Marita; Diero, Lameck; Kemboi, Emmanuel; Mambo, Fidelis; Rono, Mary; Injera, Wilfred; Delong, Allison; Schreier, Leeann; Kaloustian, Kara W; Sidle, John; Buziba, Nathan; Kantor, Rami

2013-10-01

Antiretroviral treatment interruptions (TIs) cause suboptimal clinical outcomes. Data on TIs during social disruption are limited. We determined effects of unplanned TIs after the 2007-2008 Kenyan postelection violence on virological failure, comparing viral load (VL) outcomes in HIV-infected adults with and without conflict-induced TI. Two hundred and one patients were enrolled, median 2.2 years after conflict and 4.3 years on treatment. Eighty-eight patients experienced conflict-related TIs and 113 received continuous treatment. After adjusting for preconflict CD4, patients with TIs were more likely to have detectable VL, VL >5,000 and VL >10,000. Unplanned conflict-related TIs are associated with increased likelihood of virological failure.

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.

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

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.

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.

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

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.

CD4 Counts at Entry to HIV Care in Mexico for Patients under the “Universal Antiretroviral Treatment Program for the Uninsured Population,” 2007–2014

PubMed Central

Hernández-Romieu, Alfonso C.; del Rio, Carlos; Hernández-Ávila, Juan Eugenio; Lopez-Gatell, Hugo; Izazola-Licea, José Antonio; Uribe Zúñiga, Patricia; Hernández-Ávila, Mauricio

2016-01-01

In Mexico, public health services have provided universal access to antiretroviral therapy (ART) since 2004. For individuals receiving HIV care in public healthcare facilities, the data are limited regarding CD4 T-lymphocyte counts (CD4e) at the time of entry into care. Relevant population-based estimates of CD4e are needed to inform strategies to maximize the impact of Mexico’s national ART program, and may be applicable to other countries implementing universal HIV treatment programs. For this study, we retrospectively analyzed the CD4e of persons living with HIV and receiving care at state public health facilities from 2007 to 2014, comparing CD4e by demographic characteristics and the marginalization index of the state where treatment was provided, and assessing trends in CD4e over time. Our sample included 66,947 individuals who entered into HIV care between 2007 and 2014, of whom 79% were male. During the study period, the male-to-female ratio increased from 3.0 to 4.3, reflecting the country's HIV epidemic; the median age at entry decreased from 34 years to 32 years. Overall, 48.6% of individuals entered care with a CD4≤200 cells/μl, ranging from 42.2% in states with a very low marginalization index to 52.8% in states with a high marginalization index, and from 38.9% among individuals aged 18–29 to 56.5% among those older than 50. The adjusted geometric mean (95% confidence interval) CD4e increased among males from 135 (131,142) cells/μl in 2007 to 148 (143,155) cells/μl in 2014 (p-value<0.0001); no change was observed among women, with a geometric mean of 178 (171,186) and 171 (165,183) in 2007 and 2014, respectively. There have been important gains in access to HIV care and treatment; however, late entry into care remains an important barrier in achieving optimal outcomes of ART in Mexico. The geographic, socioeconomic, and demographic differences observed reflect important inequities in timely access to HIV prevention, care, and treatment

Feasibility of antiretroviral treatment monitoring in the era of decentralized HIV care: a systematic review.

PubMed

Pham, Minh D; Romero, Lorena; Parnell, Bruce; Anderson, David A; Crowe, Suzanne M; Luchters, Stanley

2017-01-19

Regular monitoring of HIV patients who are receiving antiretroviral therapy (ART) is required to ensure patient benefits and the long-term effectiveness and sustainability of ART programs. Prompted by WHO recommendations for expansion and decentralization of HIV treatment and care in low and middle income countries, we conducted a systematic review to assess the feasibility of treatment monitoring in these settings. A comprehensive search strategy was developed using a combination of MeSH and free text terms relevant to HIV treatment and care, health service delivery, health service accessibility, decentralization and other relevant terms. Five electronic databases and two conference websites were searched to identify relevant studies conducted in LMICs, published in English between Jan 2006 and Dec 2015. Outcomes of interest included the proportion of patients who received treatment monitoring and health system factors related to monitoring of patients on ART under decentralized HIV service delivery models. From 5363 records retrieved, twenty studies were included in the review; all but one was conducted in sub-Saharan African countries. The majority of studies (15/20) had relatively short follow-up duration (≤24 months), and only two studies were specifically designed to assess treatment monitoring practices. The most frequently studied follow-up period was 12 months and a wide range of treatment monitoring coverage was observed. The reported proportions of patients on ART who received CD4 monitoring ranged from very low (6%; N = 2145) to very high (95%; N = 488). The median uptake of viral load monitoring was 86% with studies in program settings reporting coverage as low as 14%. Overall, the longer the follow-up period, the lower the proportion of patients who received regular monitoring tests; and programs in rural areas reported low coverage of laboratory monitoring. Moreover, uptake in the context of research had significantly better where monitoring

Antiretroviral Treatment Interruptions Induced by the Kenyan Postelection Crisis Are Associated With Virological Failure

PubMed Central

Kemboi, Emmanuel; Mambo, Fidelis; Rono, Mary; Injera, Wilfred; Delong, Allison; Schreier, Leeann; Kaloustian, Kara W.; Sidle, John; Buziba, Nathan; Kantor, Rami

2014-01-01

Background Antiretroviral treatment interruptions (TIs) cause suboptimal clinical outcomes. Data on TIs during social disruption are limited. Methods We determined effects of unplanned TIs after the 2007–2008 Kenyan postelection violence on virological failure, comparing viral load (VL) outcomes in HIV-infected adults with and without conflict-induced TI. Results Two hundred and one patients were enrolled, median 2.2 years after conflict and 4.3 years on treatment. Eighty-eight patients experienced conflict-related TIs and 113 received continuous treatment. After adjusting for preconflict CD4, patients with TIs were more likely to have detectable VL, VL >5,000 and VL >10,000. Conclusions Unplanned conflict-related TIs are associated with increased likelihood of virological failure. PMID:24047971

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.

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

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.

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

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

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.

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.

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.

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.

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.

Conjunctival Flora of Human Immunodeficiency Virus Patients on Antiretroviral Treatment.

PubMed

Giles, Kagmeni; Bilong, Yannick; Dohvoma, Andin Viola; Ebana, Steve Robert; Gonsu, Hortance

2017-01-01

To determine the conjunctival flora of human immunodeficiency virus (HIV) patients on antiretroviral treatment (ART). A total of 104 conjunctival swabs from 104 HIV patients on ART underwent microbiological evaluation to describe the flora. There were 71 (68.26%) women and 33 (31.74%) men. The mean age was 42.9 ± 9.77 (range: 22-70) years. Negative cultures were found in 39 (37.50%) cases. Bacterial growth occurred in 65 (62.50%) cases. Coagulase-negative Staphylococcus was found in 59 eyes (90.76%), and coagulase-positive in 3 eyes (4.61%). There was a significant correlation between the duration of ART, the degrees of immunosuppression, and bacterial growth. Knowledge of the conjunctival flora in HIV patients may provide a better guideline in the choice of antibiotic for the management of ocular surface infections.

Evolution of antiretroviral drug costs in Brazil in the context of free and universal access to AIDS treatment.

PubMed

Nunn, Amy S; Fonseca, Elize M; Bastos, Francisco I; Gruskin, Sofia; Salomon, Joshua A

2007-11-13

Little is known about the long-term drug costs associated with treating AIDS in developing countries. Brazil's AIDS treatment program has been cited widely as the developing world's largest and most successful AIDS treatment program. The program guarantees free access to highly active antiretroviral therapy (HAART) for all people living with HIV/AIDS in need of treatment. Brazil produces non-patented generic antiretroviral drugs (ARVs), procures many patented ARVs with negotiated price reductions, and recently issued a compulsory license to import one patented ARV. In this study, we investigate the drivers of recent ARV cost trends in Brazil through analysis of drug-specific prices and expenditures between 2001 and 2005. We compared Brazil's ARV prices to those in other low- and middle-income countries. We analyzed trends in drug expenditures for HAART in Brazil from 2001 to 2005 on the basis of cost data disaggregated by each ARV purchased by the Brazilian program. We decomposed the overall changes in expenditures to compare the relative impacts of changes in drug prices and drug purchase quantities. We also estimated the excess costs attributable to the difference between prices for generics in Brazil and the lowest global prices for these drugs. Finally, we estimated the savings attributable to Brazil's reduced prices for patented drugs. Negotiated drug prices in Brazil are lowest for patented ARVs for which generic competition is emerging. In recent years, the prices for efavirenz and lopinavir-ritonavir (lopinavir/r) have been lower in Brazil than in other middle-income countries. In contrast, the price of tenofovir is US$200 higher per patient per year than that reported in other middle-income countries. Despite precipitous price declines for four patented ARVs, total Brazilian drug expenditures doubled, to reach US$414 million in 2005. We find that the major driver of cost increases was increased purchase quantities of six specific drugs: patented lopinavir

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

[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

Delivery Unit Costs for Antiretroviral Treatment and Prevention of Mother-to-Child-Transmission of HIV

PubMed Central

Galárraga, Omar; Wirtz, Veronika J.; Figueroa-Lara, Alejandro; Santa-Ana-Tellez, Yared; Coulibaly, Ibrahima; Viisainen, Kirsi; Medina-Lara, Antonieta; Korenromp, Eline L.

2013-01-01

Background As antiretroviral treatment (ART) for HIV/AIDS is scaled-up globally, information on per-person costs is critical to improve efficiency in service delivery and maximize coverage and health impact. Objective To review studies on delivery unit costs for adult and pediatric ART provision per-patient-year, and prevention of mother-to-child transmission (PMTCT) interventions per mother-infant pair screened or treated, in low- and middle-income countries. Methods Systematic review of English, French and Spanish publications from 2001 to 2009, reporting empirical costing that accounted for at least antiretroviral (ARV) medicines, laboratory testing and personnel. Expenditures were analyzed by country income level and cost component. All costs were standardized to 2009 US dollars. Results Analyses covered 29 eligible, comprehensive costing studies. In the base case, in low-income countries (LIC), median, ART cost per patient-year was $792 (mean: $839, range: $682-$1089); for lower-middle-income countries (LMIC), the median was $932 (mean: $1246, range: $156-$3904); and for upper-middle-income countries (UMIC) the median was $1454 (mean: $2783, range: $1230-$5667). ARV drugs were largest component of overall ART cost in all settings (62%, 50% and 47% in LIC, LMIC and UMIC respectively). Out of 26 ART studies, 14 report which drug regimes were used, and only one study explicitly reported second line treatment costs. The second cost driver was laboratory cost in LIC and LMIC (14% and 19.5%) whereas it was personnel costs in UMIC (26%). Two studies specified the types of laboratory tests costed, and three studies specifically included above-facility-level personnel costs. Three studies reported detailed PMTCT costs, and two studies reported on pediatric ART. Conclusions There is a paucity of data on the full ART and PMTCT delivery unit costs, in particular for low-and middle-income countries. Heterogeneity in activities costed and insufficient detail regarding

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

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.

Adherence to antiretroviral therapy and treatment outcomes among conflict-affected and forcibly displaced populations: a systematic review

PubMed Central

2012-01-01

Background Optimal adherence to highly active antiretroviral therapy (HAART) is required to promote viral suppression and to prevent disease progression and mortality. Forcibly displaced and conflict-affected populations may face challenges succeeding on HAART. We performed a systematic review of the literature on adherence to HAART and treatment outcomes in these groups, including refugees and internally-displaced persons (IDPs), assessed the quality of the evidence and suggest a future research program. Methods Medline, Embase, and Global Health databases for 1995–2011 were searched using the Ovid platform. A backward citation review of subsequent work that had cited the Ovid results was performed using the Web of Science database. ReliefWeb and Médecins Sans Frontières (MSF) websites were searched for additional grey literature. Results and conclusion We screened 297 records and identified 17 reports covering 15 quantitative and two qualitative studies from 13 countries. Three-quarters (11/15) of the quantitative studies were retrospective studies based on chart review; five studies included <100 clients. Adherence or treatment outcomes were reported in resettled refugees, conflict-affected persons, internally-displaced persons (IDPs), and combinations of refugees, IDPs and other foreign-born persons. The reviewed reports showed promise for conflict-affected and forcibly-displaced populations; the range of optimal adherence prevalence reported was 87–99.5%. Treatment outcomes, measured using virological, immunological and mortality estimates, were good in relation to non-affected groups. Given the diversity of settings where forcibly-displaced and conflict-affected persons access ART, further studies on adherence and treatment outcomes are needed to support scale-up and provide evidence-based justifications for inclusion of these vulnerable groups in national treatment plans. Future studies and program evaluations should focus on systematic monitoring of

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.

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

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.

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.

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

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.

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

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.

Effectiveness of highly active antiretroviral therapy in HIV-positive children: evaluation at 12 months in a routine program in Cambodia.

PubMed

Janssens, Bart; Raleigh, Brian; Soeung, Seithaboth; Akao, Kazumi; Te, Vantha; Gupta, Jitendra; Vun, Mean Chhy; Ford, Nathan; Nouhin, Janin; Nerrienet, Eric

2007-11-01

Increasing access to highly active antiretroviral therapy to reach all those in need in developing countries (scale up) is slowly expanding to HIV-positive children, but documented experience remains limited. We aimed to describe the clinical, immunologic, and virologic outcomes of pediatric patients with >12 months of highly active antiretroviral therapy in 2 routine programs in Cambodia. Between June 2003 and March 2005, 212 children who were younger than 13 years started highly active antiretroviral therapy. Most patients started a standard first-line regimen of lamivudine, stavudine, and nevirapine, using split adult fixed-dosage combinations. CD4 percentage and body weight were monitored routinely. A cross-sectional virologic analysis was conducted in January 2006; genotype resistance testing was performed for patients with a detectable viral load. Mean age of the subjects was 6 years. Median CD4 percentage at baseline was 6. Survival was 92% at 12 months and 91% at 24 months; 13 patients died, and 4 were lost to follow-up. A total of 81% of all patients had an undetectable viral load. Among the patients with a detectable viral load, most mutations were associated with resistance to lamivudine and non-nucleoside reverse-transcriptase inhibitor drugs. Five patients had developed extensive antiretroviral resistance. Being an orphan was found to be a predictor of virologic failure. This study provides additional evidence of the effectiveness of integrating HIV/AIDS care with highly active antiretroviral therapy for children in a routine setting, with good virologic suppression and immunologic recovery achieved by using split adult fixed-dosage combinations. Viral load monitoring and HIV genotyping are valuable tools for the clinical follow-up of the patients. Orphans should receive careful follow-up and extra support.

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

[Implementation and assessment of an HIV treatment training program (2000-2001) for patients in Casablanca (Morocco)].

PubMed

Marchand, Claire; Himmich, Hakima; Maaroufi, Abderahmane; Sohier, Nathalie; Chambon, Jean François; Gagnayre, Rémi

2005-01-01

An educational program to improve the management of HIV patients was introduced in the department of infectious diseases of Ibn Rochd hospital, Casablanca, Morocco in January 2000. The project, funded by the GlaxoSmithKline Foundation, began by training ward physicians as well as volunteers from the ALLOCS (Association de lutte contre le sida) in pedagogy and patient education techniques (four-day course). Other sessions reviewed HIV management and treatment. Treatment training sessions were offered to all patients receiving antiretroviral treatment when the program began. All had been taking medication for at least two months and gave their informed consent to participation in the project. Each patient's sessions took place just after his or her medical consultation, in a room set aside for this purpose in the hospital. During the first session the educator established an educational diagnosis and defined educational objectives according to the individual patient's needs. Objectives were related to patients' knowledge about HIV transmission prevention and treatment management (including problem-solving for mild adverse events, delays, forgetting, vacations etc.). Trainers used several educational tools, including therapeutic planning (planning card with self-adhesive stickers showing the treatment medication); a folder of drawings depicting HIV transmission, prevention, and natural history, as well as the aims of antiretroviral therapy; decks of cards illustrating symptoms and psycho-sociological problems. Each patient had to attend at least 3 educational sessions. The program was evaluated at the end of one year. Patients' attendance, treatment adherence, laboratory test results (CD4 count, viral load), satisfaction about patient-staff relationships and knowledge about HIV disease and treatment were assessed on an on-going basis with various questionnaires and data collection systems. In all, 96 patients attended classes, with a mean of 14 sessions per patient

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.

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

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.

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.

Antiretroviral Therapy Optimisation without Genotype Resistance Testing: A Perspective on Treatment History Based Models

PubMed Central

Prosperi, Mattia C. F.; Rosen-Zvi, Michal; Altmann, André; Zazzi, Maurizio; Di Giambenedetto, Simona; Kaiser, Rolf; Schülter, Eugen; Struck, Daniel; Sloot, Peter; van de Vijver, David A.; Vandamme, Anne-Mieke; Sönnerborg, Anders

2010-01-01

Background Although genotypic resistance testing (GRT) is recommended to guide combination antiretroviral therapy (cART), funding and/or facilities to perform GRT may not be available in low to middle income countries. Since treatment history (TH) impacts response to subsequent therapy, we investigated a set of statistical learning models to optimise cART in the absence of GRT information. Methods and Findings The EuResist database was used to extract 8-week and 24-week treatment change episodes (TCE) with GRT and additional clinical, demographic and TH information. Random Forest (RF) classification was used to predict 8- and 24-week success, defined as undetectable HIV-1 RNA, comparing nested models including (i) GRT+TH and (ii) TH without GRT, using multiple cross-validation and area under the receiver operating characteristic curve (AUC). Virological success was achieved in 68.2% and 68.0% of TCE at 8- and 24-weeks (n = 2,831 and 2,579), respectively. RF (i) and (ii) showed comparable performances, with an average (st.dev.) AUC 0.77 (0.031) vs. 0.757 (0.035) at 8-weeks, 0.834 (0.027) vs. 0.821 (0.025) at 24-weeks. Sensitivity analyses, carried out on a data subset that included antiretroviral regimens commonly used in low to middle income countries, confirmed our findings. Training on subtype B and validation on non-B isolates resulted in a decline of performance for models (i) and (ii). Conclusions Treatment history-based RF prediction models are comparable to GRT-based for classification of virological outcome. These results may be relevant for therapy optimisation in areas where availability of GRT is limited. Further investigations are required in order to account for different demographics, subtypes and different therapy switching strategies. PMID:21060792

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

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

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

Antiretroviral therapy: current drugs.

PubMed

Pau, Alice K; George, Jomy M

2014-09-01

The rapid advances in drug discovery and the development of antiretroviral therapy is unprecedented in the history of modern medicine. The administration of chronic combination antiretroviral therapy targeting different stages of the human immunodeficiency virus' replicative life cycle allows for durable and maximal suppression of plasma viremia. This suppression has resulted in dramatic improvement of patient survival. This article reviews the history of antiretroviral drug development and discusses the clinical pharmacology, efficacy, and toxicities of the antiretroviral agents most commonly used in clinical practice to date. Published by Elsevier Inc.

[Factors predicting lack of adherence to highly active antiretroviral treatment].

PubMed

Martín-Sánchez, Vicente; Ortega-Valín, Luis; Pérez-Simón, María del Rosario; Mostaza-Fernández, José Luis; Ortiz de Urbina-González, Juan José; Rodríguez-María, Miriam; Carro-Fernández, José Antonio; Cuevas-González, María José; Alcoba-Leza, Manuel

2002-12-01

Knowledge of adherence to highly active antiretroviral treatment (HAART) and the variables associated with poor compliance is useful for the follow-up of HIV infected patients. Patients were consecutively recruited from the HIV outpatient clinics of the Hospitals of Leon and El Bierzo from January to June 2000. Patients were considered non-adherent to treatment if they failed to take 10% or more of their prescribed total dose of at least one drug during the 4 days before the interview, or if they had accumulated a delay of more than 9 days over the previous 3 months in picking up their prescribed drugs from the hospital pharmacy. Logistic regression analysis was performed with variables found to be associated with adherence in the univariate analysis. The methods used to determine adherence had a Kappa index of 12.6%. Among the 206 patients interviewed, 108 were considered non-adherent (52.4%; CI 95% 5 45.6-59.2). Multivariate analysis showed that the following factors were associated with poor treatment adherence: cocaine consumption in the previous six months (adjusted OR 5 5.1); patients unsure about the proper way to take prescribed treatment; (adjusted OR 5 2.5); and patients not prescribed the zidovudine-lamivudine combination (adjusted OR 5 1.9). Over one-third of patients with no variable associated with treatment adherence were considered non-compliant. Measurement of medication adherence and its predictive factors involved methodological difficulties. With the criteria used in the present study more than half the patients were considered non-compliant. The variables found to be related to poor adherence can be modified by social, psychological or health care interventions.

Long-Term Antiretroviral Treatment Adherence in HIV-Infected Adolescents and Adults in Uganda: A Qualitative Study

PubMed Central

Inzaule, Seth C.; Hamers, Raph L.; Kityo, Cissy; Rinke de Wit, Tobias F.; Roura, Maria

2016-01-01

Background Long-term success of HIV antiretroviral therapy requires near-perfect adherence, maintained throughout one’s lifetime. However, perceptions towards ART and patterns of adherence may change during the life course. We assessed challenges to long-term adherence in adolescents and adults in three regional HIV treatment centers in Uganda. Methods We conducted 24 in-depth interviews and 2 focus group discussions with a total of 33 health-care providers and expert clients (HIV patients on long-term ART who assist with adherence support of fellow patients). Interview topics included experiences with patients on long-term treatment with either declining adherence or persistent poor adherence. Transcribed texts were coded and analyzed based on the social-ecological framework highlighting differences and commonalities between adolescents and adults. Results The overarching themes in adolescents were unstructured treatment holidays, delays in disclosure of HIV status by caretakers, stigma, which was mainly experienced in boarding schools, and diminishing or lack of clinical support. In particular, there was minimal support for early and gradual disclosure for caretakers to the infected children, diminishing clinical support for young adults during transition to adult-based care and declining peer-to-peer support group activities. The predominating theme in adults was challenges with treatment access among temporary economic migrants. Common themes to adults and adolescents were challenges with disclosure in intimate relationships, treatment related factors including side effects, supply of single tablets in place of fixed-dose combined drugs, supply of drug brands with unfavorable taste and missed opportunities for counseling due to shortage of staff. Conclusion Adherence counseling and support should be adapted differently for adolescents and adults and to the emerging life course challenges in long-term treated patients. Programs should also address constraints

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

Task Shifting for Scale-up of HIV Care: Evaluation of Nurse-Centered Antiretroviral Treatment at Rural Health Centers in Rwanda

PubMed Central

Shumbusho, Fabienne; van Griensven, Johan; Lowrance, David; Turate, Innocent; Weaver, Mark A.; Price, Jessica; Binagwaho, Agnes

2009-01-01

Background The shortage of human resources for health, and in particular physicians, is one of the major barriers to achieve universal access to HIV care and treatment. In September 2005, a pilot program of nurse-centered antiretroviral treatment (ART) prescription was launched in three rural primary health centers in Rwanda. We retrospectively evaluated the feasibility and effectiveness of this task-shifting model using descriptive data. Methods and Findings Medical records of 1,076 patients enrolled in HIV care and treatment services from September 2005 to March 2008 were reviewed to assess: (i) compliance with national guidelines for ART eligibility and prescription, and patient monitoring and (ii) key outcomes, such as retention, body weight, and CD4 cell count change at 6, 12, 18, and 24 mo after ART initiation. Of these, no ineligible patients were started on ART and only one patient received an inappropriate ART prescription. Of the 435 patients who initiated ART, the vast majority had adherence and side effects assessed at each clinic visit (89% and 84%, respectively). By March 2008, 390 (90%) patients were alive on ART, 29 (7%) had died, one (<1%) was lost to follow-up, and none had stopped treatment. Patient retention was about 92% by 12 mo and 91% by 24 mo. Depending on initial stage of disease, mean CD4 cell count increased between 97 and 128 cells/µl in the first 6 mo after treatment initiation and between 79 and 129 cells/µl from 6 to 24 mo of treatment. Mean weight increased significantly in the first 6 mo, between 1.8 and 4.3 kg, with no significant increases from 6 to 24 mo. Conclusions Patient outcomes in our pilot program compared favorably with other ART cohorts in sub-Saharan Africa and with those from a recent evaluation of the national ART program in Rwanda. These findings suggest that nurses can effectively and safely prescribe ART when given adequate training, mentoring, and support. Please see later in the article for the Editors

Scientific Production about the Adherence to Antiretroviral Therapy

PubMed Central

de Oliveira, Regina Célia; de Andrade Moraes, Danielle Chianca; Santos, Cleytiane Stephany Silva; da Silva Monteiro, Gicely Regina Sobral; da Rocha Cabral, Juliana; Beltrão, Roberta Andrade; da Silva, Calos Roberto Lyra

2017-01-01

Objective To identify the elite of authors about the subject adherence to antiretroviral therapy; to identify the journals turned to publishing articles about adherence to antiretroviral therapy; and to identify and analyze the most commonly used words in abstracts of articles about adherence to antiretroviral therapy. Method A bibliometric study conducted through the Scopus base. We used articles published between 1996 and 2014, after application of the eligibility criteria, there were composed the sample with 24 articles. The data were analyzed descriptively. Were used the laws of bibliometric (Lotka, Bradford and Zipf) and the conceptual cloud map of words, through the program Cmap tools. Results Lotka’s Law identified the 5 authors more productive (46% of the total published). Bradford is impaired in this study. Concerning Zipf, 3 zones were determined, 31.47% of the words with in the first zone, 26.46% in the second and 42.06% in the third. In the conceptual map, the words/factors that positively and negatively influence adherence were emphasized, among them the need for more research in the health services. Conclusion There are few publications about the accession to antiretroviral therapy, and the scientific production is in the process of maturation. One can infer that the theme researched is not yet an obsolete topic. It should be noted that the Bibliometric was a relevant statistic tool to generate information about the publications about the antiretroviral therapy. PMID:28979571

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.

Clinical pharmacology quality assurance program: models for longitudinal analysis of antiretroviral proficiency testing for international laboratories.

PubMed

DiFrancesco, Robin; Rosenkranz, Susan L; Taylor, Charlene R; Pande, Poonam G; Siminski, Suzanne M; Jenny, Richard W; Morse, Gene D

2013-10-01

Among National Institutes of Health HIV Research Networks conducting multicenter trials, samples from protocols that span several years are analyzed at multiple clinical pharmacology laboratories (CPLs) for multiple antiretrovirals. Drug assay data are, in turn, entered into study-specific data sets that are used for pharmacokinetic analyses, merged to conduct cross-protocol pharmacokinetic analysis, and integrated with pharmacogenomics research to investigate pharmacokinetic-pharmacogenetic associations. The CPLs participate in a semiannual proficiency testing (PT) program implemented by the Clinical Pharmacology Quality Assurance program. Using results from multiple PT rounds, longitudinal analyses of recovery are reflective of accuracy and precision within/across laboratories. The objectives of this longitudinal analysis of PT across multiple CPLs were to develop and test statistical models that longitudinally: (1) assess the precision and accuracy of concentrations reported by individual CPLs and (2) determine factors associated with round-specific and long-term assay accuracy, precision, and bias using a new regression model. A measure of absolute recovery is explored as a simultaneous measure of accuracy and precision. Overall, the analysis outcomes assured 97% accuracy (±20% of the final target concentration of all (21) drug concentration results reported for clinical trial samples by multiple CPLs). Using the Clinical Laboratory Improvement Act acceptance of meeting criteria for ≥2/3 consecutive rounds, all 10 laboratories that participated in 3 or more rounds per analyte maintained Clinical Laboratory Improvement Act proficiency. Significant associations were present between magnitude of error and CPL (Kruskal-Wallis P < 0.001) and antiretroviral (Kruskal-Wallis P < 0.001).

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

Contrasting Reasons for Discontinuation of Antiretroviral Therapy in Workplace and Public-Sector HIV Programs in South Africa

PubMed Central

Kielmann, Karina; Charalambous, Salome; Karstaedt, Alan S.; Hamilton, Robin; La Grange, Lettie; Fielding, Katherine L.; Churchyard, Gavin J.; Grant, Alison D.

2011-01-01

Abstract We investigated reasons for clinical follow-up and treatment discontinuation among HIV-infected individuals receiving antiretroviral therapy (ART) in a public-sector clinic and in a workplace clinic in South Africa. Participants in a larger cohort study who had discontinued clinical care by the seventh month of treatment were traced using previously provided locator information. Those located were administered a semistructured questionnaire regarding reasons for discontinuing clinical follow-up. Participants who had discontinued antiretroviral therapy were invited to participate in further in-depth qualitative interviews. Fifty-one of 144 (35.4%) in the workplace cohort had discontinued clinical follow-up by the seventh month of treatment. The median age of those who discontinued follow-up was 46 years and median educational level was five years. By contrast, only 16.5% (44/267) of the public-sector cohort had discontinued follow-up. Among them the median age was 37.5 years and median education was 11 years. Qualitative interviews were conducted with 17 workplace participants and 10 public-sector participants. The main reasons for attrition in the workplace were uncertainty about own HIV status and above the value of ART, poor patient–provider relationships and workplace discrimination. In the public sector, these were moving away and having no money for clinic transport. In the workplace, efforts to minimize the time between testing and treatment initiation should be balanced with the need to provide adequate baseline counseling taking into account existing concepts about HIV and ART. In the public sector, earlier diagnosis and ART initiation may help to reduce early mortality, while links to government grants may reduce attrition. PMID:21214378

Meeting the WHO 90% target: antiretroviral treatment efficacy in Poland is associated with baseline clinical patient characteristics

PubMed Central

Parczewski, Milosz; Siwak, Ewa; Leszczyszyn-Pynka, Magdalena; Cielniak, Iwona; Burkacka, Ewa; Pulik, Piotr; Witor, Adam; Muller, Karolina; Zasik, Ewelina; Grzeszczuk, Anna; Jankowska, Maria; Lemańska, Małgorzata; Olczak, Anita; Grąbczewska, Edyta; Szymczak, Aleksandra; Gąsiorowski, Jacek; Szetela, Bartosz; Bociąga-Jasik, Monika; Skwara, Paweł; Witak-Jędra, Magdalena; Jabłonowska, Elżbieta; Wójcik-Cichy, Kamila; Kamerys, Juliusz; Janczarek, Małgorzata; Krankowska, Dagny; Mikuła, Tomasz; Kozieł, Katarzyna; Bielec, Dariusz; Stempkowska, Justyna; Kocbach, Aleksandra; Błudzin, Wiesława; Horban, Andrzej

2017-01-01

Abstract Introduction: Modern combined antiretroviral therapies (cART) allow to effectively suppress HIV-1 viral load, with the 90% virologic success rate, meeting the WHO target in most clinical settings. The aim of this study was to analyse antiretroviral treatment efficacy in Poland and to identify variables associated with virologic suppression. Methods: Cross-sectional data on 5152 (56.92% of the countrywide treated at the time-point of analysis) patients on cART for more than six months with at least one HIV-RNA measurement in 2016 were collected from 14 Polish centres. Patients’ characteristics and treatment type-based outcomes were analysed for the virologic suppression thresholds of <50 and <200 HIV-RNA copies/ml. CART was categorized into two nucleos(t)ide (2NRTI) plus non-nucleoside reverse transcriptase (NNRTI) inhibitors, 2NRTI plus protease (PI) inhibitor, 2NRTI plus integrase (InI) inhibitor, nucleos(t)ide sparing PI/r+InI and three drug class regimens. For statistics Chi-square and U-Mann Whitney tests and adjusted multivariate logistic regression models were used. Results: Virologic suppression rates of <50 copies/mL were observed in 4672 (90.68%) and <200 copies/mL in 4934 (95.77%) individuals. In univariate analyses, for the suppression threshold <50 copies/mL higher efficacy was noted for 2NRTI+NNRTI-based combinations (94.73%) compared to 2NRTI+PI (89.93%), 2NRTI+InI (90.61%), nucleos(t)ide sparing PI/r+InI (82.02%) and three drug class regimens (74.49%) (p < 0.0001), with less pronounced but significant differences for the threshold of 200 copies/mL [2NRTI+NNRTI-97.61%, 2NRTI+PI-95.27%, 2NRTI+InI-96.61%, PI/r+InI- 95.51% and 86.22% for three drug class cART) (p < 0.0001). However, in multivariate model, virologic efficacy for viral load <50 copies/mL was similar across treatment groups with significant influence by history of AIDS [OR:1.48 (95%CI:1.01–2.17) if AIDS diagnosed, p = 0.046], viral load < 5 log copies/mL at care entry [OR

Antiretroviral pill count and clinical outcomes in treatment-naïve patients with HIV infection.

PubMed

Young, J; Smith, C; Teira, R; Reiss, P; Jarrín Vera, I; Crane, H; Miro, J M; D'Arminio Monforte, A; Saag, M; Zangerle, R; Bucher, H C

2018-02-01

Treatment guidelines recommend single-tablet regimens for patients with HIV infection starting antiretroviral therapy. These regimens might be as effective and cost less if taken as separate drugs. We assessed whether the one pill once a day combination of efavirenz, emtricitabine and tenofovir reduces the risk of disease progression compared with multiple-pill formulations of the same regimen. We selected treatment-naïve patients starting one-, two- or three-pill formulations of this regimen in data from the Antiretroviral Therapy Cohort Collaboration. These patients were followed until an AIDS event or death or until they modified their regimen. We analysed these data using Cox regression models, then used our models to predict the potential consequences of exposing a future population to either a one-pill regimen or a three-pill regimen. Among 11 739 treatment-naïve patients starting the regimen, there were 386 AIDS events and 87 deaths. Follow-up often ended when patients switched to the same regimen with fewer pills. After the first month, two pills rather than one was associated with an increase in the risk of AIDS or death [hazard ratio (HR) 1.39; 95% confidence interval (CI) 1.01-1.91], but three pills rather than two did not appreciably add to that increase (HR 1.19; 95% CI 0.84-1.68). We estimate that 77 patients would need to be exposed to a one-pill regimen rather than a three-pill regimen for 1 year to avoid one additional AIDS event or death. This particular single-tablet regimen is associated with a modest decrease in the risk of AIDS or death relative to multiple-pill formulations. © 2017 British HIV Association.

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…

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

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

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.

Longitudinal assessment of associations between food insecurity, antiretroviral adherence and HIV treatment outcomes in rural Uganda.

PubMed

Weiser, Sheri D; Palar, Kartika; Frongillo, Edward A; Tsai, Alexander C; Kumbakumba, Elias; Depee, Saskia; Hunt, Peter W; Ragland, Kathleen; Martin, Jeffrey; Bangsberg, David R

2014-01-02

Food insecurity is a potentially important barrier to the success of antiretroviral therapy (ART) programs in resource-limited settings. We undertook a longitudinal study in rural Uganda to estimate the associations between food insecurity and HIV treatment outcomes. Longitudinal cohort study. Participants were from the Uganda AIDS Rural Treatment Outcomes study and were followed quarterly for blood draws and structured interviews. We measured food insecurity with the validated Household Food Insecurity Access Scale. Our primary outcomes were: ART nonadherence (adherence <90%) measured by visual analog scale; incomplete viral load suppression (>400 copies/ml); and low CD4 T-cell count (<350 cells/μl). We used generalized estimating equations to estimate the associations, adjusting for socio-demographic and clinical variables. We followed 438 participants for a median of 33 months; 78.5% were food insecure at baseline. In adjusted analyses, food insecurity was associated with higher odds of ART nonadherence [adjusted odds ratio (AOR) 1.56, 95% confidence interval (CI) 1.10-2.20, P < 0.05], incomplete viral suppression (AOR 1.52, 95% CI 1.18-1.96, P < 0.01), and CD4 T-cell count less than 350 (AOR 1.47, 95% CI 1.24-1.74, P < 0.01). Adding adherence as a covariate to the latter two models removed the association between food insecurity and viral suppression, but not between food insecurity and CD4 T-cell count. Food insecurity is longitudinally associated with poor HIV outcomes in rural Uganda. Intervention research is needed to determine the extent to which improved food security is causally related to improved HIV outcomes and to identify the most effective policies and programs to improve food security and health.

Exploring 'generative mechanisms' of the antiretroviral adherence club intervention using the realist approach: a scoping review of research-based antiretroviral treatment adherence theories.

PubMed

Mukumbang, Ferdinand C; Van Belle, Sara; Marchal, Bruno; van Wyk, Brian

2017-05-04

Poor retention in care and non-adherence to antiretroviral therapy (ART) continue to undermine the success of HIV treatment and care programmes across the world. There is a growing recognition that multifaceted interventions - application of two or more adherence-enhancing strategies - may be useful to improve ART adherence and retention in care among people living with HIV/AIDS. Empirical evidence shows that multifaceted interventions produce better results than interventions based on a singular perspective. Nevertheless, the bundle of mechanisms by which multifaceted interventions promote ART adherence are poorly understood. In this paper, we reviewed theories on ART adherence to identify candidate/potential mechanisms by which the adherence club intervention works. We searched five electronic databases (PubMed, EBSCOhost, CINAHL, PsycARTICLES and Google Scholar) using Medical Subject Headings (MeSH) terms. A manual search of citations from the reference list of the studies identified from the electronic databases was also done. Twenty-six articles that adopted a theory-guided inquiry of antiretroviral adherence behaviour were included for the review. Eleven cognitive and behavioural theories underpinning these studies were explored. We examined each theory for possible 'generative causality' using the realist evaluation heuristic (Context-Mechanism-Outcome) configuration, then, we selected candidate mechanisms thematically. We identified three major sets of theories: Information-Motivation-Behaviour, Social Action Theory and Health Behaviour Model, which explain ART adherence. Although they show potential in explaining adherence bebahiours, they fall short in explaining exactly why and how the various elements they outline combine to explain positive or negative outcomes. Candidate mechanisms indentified were motivation, self-efficacy, perceived social support, empowerment, perceived threat, perceived benefits and perceived barriers. Although these candidate

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.

Initiation, adherence, and retention in a randomized controlled trial of directly administered antiretroviral therapy.

PubMed

Maru, Duncan Smith-Rohrberg; Bruce, R Douglas; Walton, Mary; Mezger, Jo Anne; Springer, Sandra A; Shield, David; Altice, Frederick L

2008-03-01

Directly administered antiretroviral therapy (DAART) can improve health outcomes among HIV-infected drug users. An understanding of the utilization of DAART-initiation, adherence, and retention-is critical to successful program design. Here, we use the Behavioral Model to assess the enabling, predisposing, and need factors impacting adherence in our randomized, controlled trial of DAART versus self-administered therapy (SAT) among 141 HIV-infected drug users. Of 88 participants randomized to DAART, 74 (84%) initiated treatment, and 51 (69%) of those who initiated were retained in the program throughout the entire six-month period. Mean adherence to directly observed visits was 73%, and the mean overall composite adherence score was 77%. These results were seen despite the finding that 75% of participants indicated that they would prefer to take their own medications. Major causes of DAART discontinuation included hospitalization, incarceration, and entry into drug-treatment programs. The presence of depression and the lack of willingness to travel greater than four blocks to receive DAART predicted time-to-discontinuation.

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

Islamic perspectives on HIV/AIDS and antiretroviral treatment: the case of Nigeria.

PubMed

Balogun, Amusa Saheed

2010-12-01

Some religious reactions to the HIV epidemic in Africa unwittingly contributed to the expansion of the epidemic in its early years. This was because many religious people regarded the emergence of HIV and AIDS as divine punishment for man's sins as a result of people's sexual promiscuity. Some also opposed public promotion of the use of condoms for HIV prevention. However, religious bodies have made positive contributions to HIV/AIDS responses in many African countries in recent times. Though Christian bodies are taking the lead in faith-based responses to HIV and AIDS in Africa, Islamic bodies have also been major partners in HIV/AIDS interventions in several countries. Against this background, this article examines some Islamic perceptions of HIV and AIDS, and especially the impact of antiretroviral treatment (ART) for people living with HIV in Africa, with particular emphasis on Nigeria. In spite of the emergence of antiretroviral (ARV) drugs in Africa, Islam still emphasises the prevention of new infections and care for people living with HIV or AIDS. The article discusses basic issues associated with ARVs, such as health, sickness, life-prolongation and death, from an Islamic viewpoint, as well as some Islamic measures to prevent HIV-risk-taking behaviours in an era of ARVs. It also looks at the nature and extent of Islamic involvement in the national HIV/AIDS response in Nigeria. The paper concludes that while Islam sees HIV and AIDS and other diseases as 'tests' from Allah, the religion is not opposed to ART. Thus, efforts need to be intensified by Islamic bodies and Muslim leaders in Nigeria for an improved response to HIV and AIDS in the country.

Stavudine concentrations in women receiving postpartum antiretroviral treatment and their breastfeeding infants.

PubMed

Fogel, Jessica M; Taha, Taha E; Sun, Jin; Hoover, Donald R; Parsons, Teresa L; Kumwenda, Johnstone J; Mofenson, Lynne M; Fowler, Mary Glenn; Hendrix, Craig W; Kumwenda, Newton I; Eshleman, Susan H; Mirochnick, Mark

2012-08-15

First-line antiretroviral treatment regimens in resource-limited settings used in breastfeeding mothers often include stavudine (d4T). Limited data describing d4T concentrations in breast milk are available. We analyzed d4T concentrations in 52 mother-infant pairs using ultra-performance liquid chromatography-tandem mass spectrometry (lower limit of quantification: 5 ng/mL in plasma, 20 ng/mL in breast milk). Median (interquartile range) d4T concentrations were 86 (36-191) ng/mL in maternal plasma, 151 (48-259) ng/mL in whole milk, 190 (58-296) ng/mL in skim milk, and <5 (<5 to <5) ng/mL in infant plasma. Although d4T is concentrated in breast milk relative to maternal plasma, the infant d4T dose received from breast milk is very small and not clinically significant.

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.

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

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.

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.

Health status, food insecurity, and time allocation patterns of patients with AIDS receiving antiretroviral treatment in South Africa.

PubMed

Bhargava, Alok; Booysen, Frederik Le Roux; Walsh, Corinna M

2018-03-01

For patients with AIDS receiving antiretroviral treatment (ART) in South Africa via public clinics, improvements in nutritional status and economic productivity are likely to depend on adherence to drug regimen and quality of diet reflected in protein and micronutrient intakes. This study randomized 643 patients receiving ART from public clinics in the Free State Province into a Control group, a treatment group receiving adherence support, and a treatment group receiving adherence support and a nutritious food supplement. The data on food insecurity levels and time spent on various activities were analyzed for assessing the impact of the intervention programs. The main results were, first, changes between survey rounds 1 and 3 were significant at the 5% level for outcomes such as food insecurity levels and CD4 cell counts. Moreover, there was a significant reduction in food insecurity levels of patients with BMI less than 25 who received the nutritious food supplement. Second, the estimated parameters from models for patients' food insecurity levels showed that household incomes were significantly associated with lower food insecurity levels. Third, patients' BMI was a significant predictor of time spent on sedentary, moderate and overall activity levels, and it was important to separately evaluate the effects of BMI for under-weight and over-weight patients. Overall, the results indicated the need for reducing food insecurity levels, and for designing different interventions for under-weight and over-weight patients with AIDS for enhancing their labor productivity.

[Antiretroviral treatment adherence for HIV/AIDS in women: a sociocultural perspective].

PubMed

Belmar, Julieta; Stuardo, Valeria

2017-08-01

Adequate adherence to HAART has a high impact on survival of AIDA patients. There is little consensus on the causes of low adherence to treatment in women, who are in a situation of inequality in terms of prevention and related care. To explore and describe the socio-cultural aspects related to the adherence of women to antiretroviral treatment for HIV / AIDS. Qualitative, exploratory-descriptive study. The study population was focused on Chilean women, who are 18 years of age or older, living with HIV/AIDS. The sample size was defined by information saturation. In-depth interviews were conducted with 16 women contacted in seven public care centers for people living with HIV (PLHIV) in 4 regions of the country, and it was take into account the saturation of the information. There are several sociocultural factors that determine the level of adherence that women adopt in relation to HAART. The most relevant ones are the vital satisfaction, the imaginary about HIV, the availability of their networks in front of diagnosis and the availability of information are fundamental. It is necessary to enter into specific interventions considering the sociocultural aspects and satisfying the psychosocial needs of women. It is imperative that public policies and health teams consider these aspects to improve adherence to HAART.

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

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.

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

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.

Diabetes and Hypertension among Patients Receiving Antiretroviral Treatment Since 1998 in Senegal: Prevalence and Associated Factors

PubMed Central

Diouf, Assane; Cournil, Amandine; Ba-Fall, Khadidiatou; Ngom-Guèye, Ndèye Fatou; Eymard-Duvernay, Sabrina; Ndiaye, Ibrahima; Batista, Gilbert; Guèye, Papa Mandoumbé; Bâ, Pape Samba; Taverne, Bernard; Delaporte, Eric; Sow, Papa Salif

2012-01-01

Cardiovascular risk factors in people on antiretroviral treatment (ART) are poorly documented in resource-constrained settings. A cross-sectional study was conducted in 2009 to assess prevalence of diabetes and hypertension in a sample of 242 HIV-infected patients who had initiated ART between 1998 and 2002 in Dakar, Senegal (ANRS 1215 observational cohort). World Health Organization (WHO) criteria were applied to diagnose diabetes and hypertension. Multiple logistic regressions were used to identify factors associated with diabetes and hypertension. Patients had a median age of 46 years and had received ART for a median duration of about 9 years. 14.5% had diabetes and 28.1% had hypertension. Long duration of ART (≥119 months), older age, higher body mass index (BMI), and higher levels of total cholesterol were associated with higher risks of diabetes. Older age, higher BMI at ART initiation, and higher levels of triglycerides were associated with higher risk of hypertension. This study shows that diabetes and hypertension were frequent in these Senegalese HIV patients on ART. It confirms the association between duration of ART and diabetes and highlights the need to implement programs for prevention of cardiovascular risk factors in HIV patients from resource-constrained settings. PMID:24052880

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

Hidden costs of HIV treatment in Spain: inefficiency of the antiretroviral drug packaging.

PubMed

Llibre-Codina, Josep M; Andreu-Crespo, Angels; Cardona-Peitx, Gloria; Sala-Piñol, Ferran; Clotet-Sala, Bonaventura; Bonafont-Pujol, Xavier

2014-01-01

Antiretroviral drugs in Spain are delivered by law only in hospital pharmacies. Commercial packages meet variable quality standards when dispensed drugs are returned due to treatment changes or adherence problems Nearly 20-25% of the initial regimens will be changed at 48 weeks for different reasons. We evaluated the economic impact on public health system of the inability of using returned drugs due to inefficient packaging. We defined socially efficient packaging as the best adapted one to being delivered in unit dose to outpatients and classified: Class A - Drug packed in unit doses with complete info (name of drug, dosage in mg, lot, and expiring date) in each unit, maintaining complete information of the drug if returned when the external package is opened. Class B - packed in blisters with complete info in the blister, but not in unit doses, without special conservation conditions (should be re-packed in unit doses in the pharmacy before its dispensation to assure a class A excellence). Class C - packed in plastic containers with complete info written only on a label over the container, would allow repackaging only before its initial delivery, but not when returned. Class D - drug packed in plastic containers with manufacturer's warning that the product cannot be placed outside of the original package due to special conditions of conservation (fridge, humidity) that doesn't allow a unit dose repackaging or reusing an opened container. We analysed a 12-month period (July 2011-June 2012) in a hospital-based HIV outpatient pharmacy that serves 2413 treated individuals. Patients generated 23,574 visits to pharmacy, and received 48,325 drug packages, with 2.529.137 pills delivered. The patients suffered 1051 treatment changes for any reason. A total amount of 122.945€ in treatment were returned to pharmacy in opened packages during the study period. 47.139.91€ would be totally lost, mainly due to being packaged in class C and D boxes, the equivalent of

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.

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.

Adherence as therapeutic citizenship: impact of the history of access to antiretroviral drugs on adherence to treatment.

PubMed

Nguyen, Vinh-Kim; Ako, Cyriaque Yapo; Niamba, Pascal; Sylla, Aliou; Tiendrébéogo, Issoufou

2007-10-01

A dramatic increase in the use of antiretroviral drugs in Africa has increased focus on adherence to treatment, which has so far been equivalent if not superior to that in northern contexts. The reasons for this exceptional adherence are poorly understood. In this paper, we examine adherence in the historical and ethnographic context of access to treatment in Burkina Faso, Côte d'Ivoire and Mali. Living where there is no social security and minimal, if any, medical care, individuals diagnosed with HIV are faced with the threat of illness, death, ostracism and destitution, and were obliged to negotiate conflicting networks of obligation, reciprocity, and value. HIV and AIDS programmes value efforts to address social, and indeed biological, vulnerability. In contrast, kinship-based social relationships may value individuals in other ways. These conflicting moral economies often intersect in the worlds of people living with HIV. HIV status can be used to claim resources from the public or non-governmental organization programmes. This may interfere with social networks that are the most stable source of material and emotional support. Self-help and empowerment techniques provided effective tools for people living with HIV to fashion themselves into effective advocates. In the early years of the use of antiretroviral therapy (ART), access to treatment was thus mediated by confessional practices and forms of social triage. We introduce the term 'therapeutic citizenship' to describe the way in which people living with HIV appropriate ART as a set of rights and responsibilities to negotiate these at times conflicting moral economies. Exemplary adherence should be viewed through the lens of therapeutic citizenship.

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

“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

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

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.

Combination antiretroviral therapy improves cognitive performance and functional connectivity in treatment-naïve HIV-infected individuals.

PubMed

Zhuang, Yuchuan; Qiu, Xing; Wang, Lu; Ma, Qing; Mapstone, Mark; Luque, Amneris; Weber, Miriam; Tivarus, Madalina; Miller, Eric; Arduino, Roberto C; Zhong, Jianhui; Schifitto, Giovanni

2017-10-01

Our study aimed to investigate the short-term effect of combination antiretroviral therapy (cART) on cognitive performance and functional and structural connectivity and their relationship to plasma levels of antiretroviral (ARV) drugs. Seventeen ARV treatment-naïve HIV-infected individuals (baseline mean CD4 cell count, 479 ± 48 cells/mm 3 ) were age matched with 17 HIV-uninfected individuals. All subjects underwent a detailed neurocognitive and functional assessment and magnetic resonance imaging. HIV-infected subjects were scanned before starting cART and 12 weeks after initiation of treatment. Uninfected subjects were assessed once at baseline. Functional connectivity (FC) was assessed within the default mode network while structural connectivity was assessed by voxel-wise analysis using tract-based spatial statistics (TBSS) and probabilistic tractography within the DMN. Tenofovir and emtricitabine blood concentration were measured at week 12 of cART. Prior to cART, HIV-infected individuals had significantly lower cognitive performance than control subjects as measured by the total Z-score from the neuropsychological tests assessing six cognitive domains (p = 0.020). After 12 weeks of cART treatment, there remained only a weak cognitive difference between HIV-infected and HIV-uninfected subjects (p = 0.057). Mean FC was lower in HIV-infected individuals compared with those uninfected (p = 0.008), but FC differences became non-significant after treatment (p = 0.197). There were no differences in DTI metrics between HIV-infected and HIV-uninfected individuals using the TBSS approach and limited evidence of decreased structural connectivity within the DMN in HIV-infected individuals. Tenofovir and emtricitabine plasma concentrations did not correlate with either cognitive performance or imaging metrics. Twelve weeks of cART improves cognitive performance and functional connectivity in ARV treatment-naïve HIV-infected individuals with relatively

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

Association of HIV diversity and virologic outcomes in early antiretroviral treatment: HPTN 052.

PubMed

Palumbo, Philip J; Wilson, Ethan A; Piwowar-Manning, Estelle; McCauley, Marybeth; Gamble, Theresa; Kumwenda, Newton; Makhema, Joseph; Kumarasamy, Nagalingeswaran; Chariyalertsak, Suwat; Hakim, James G; Hosseinipour, Mina C; Melo, Marineide G; Godbole, Sheela V; Pilotto, Jose H; Grinsztejn, Beatriz; Panchia, Ravindre; Chen, Ying Q; Cohen, Myron S; Eshleman, Susan H; Fogel, Jessica M

2017-01-01

Higher HIV diversity has been associated with virologic outcomes in children on antiretroviral treatment (ART). We examined the association of HIV diversity with virologic outcomes in adults from the HPTN 052 trial who initiated ART at CD4 cell counts of 350-550 cells/mm3. A high resolution melting (HRM) assay was used to analyze baseline (pre-treatment) HIV diversity in six regions in the HIV genome (two in gag, one in pol, and three in env) from 95 participants who failed ART. We analyzed the association of HIV diversity in each genomic region with baseline (pre-treatment) factors and three clinical outcomes: time to virologic suppression after ART initiation, time to ART failure, and emergence of HIV drug resistance at ART failure. After correcting for multiple comparisons, we did not find any association of baseline HIV diversity with demographic, laboratory, or clinical characteristics. For the 18 analyses performed for clinical outcomes evaluated, there was only one significant association: higher baseline HIV diversity in one of the three HIV env regions was associated with longer time to ART failure (p = 0.008). The HRM diversity assay may be useful in future studies exploring the relationship between HIV diversity and clinical outcomes in individuals with HIV infection.

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.

Initiation, Adherence, and Retention in a Randomized Controlled Trial of Directly Administered Antiretroviral Therapy

PubMed Central

Maru, Duncan Smith-Rohrberg; Bruce, R. Douglas; Walton, Mary; Mezger, Jo Anne; Springer, Sandra A.; Shield, David

2009-01-01

Directly administered antiretroviral therapy (DAART) can improve health outcomes among HIV-infected drug users. An understanding of the utilization of DAART—initiation, adherence, and retention—is critical to successful program design. Here, we use the Behavioral Model to assess the enabling, predisposing, and need factors impacting adherence in our randomized, controlled trial of DAART versus self-administered therapy (SAT) among 141 HIV-infected drug users. Of 88 participants randomized to DAART, 74 (84%) initiated treatment, and 51 (69%) of those who initiated were retained in the program throughout the entire six-month period. Mean adherence to directly observed visits was 73%, and the mean overall composite adherence score was 77%. These results were seen despite the finding that 75% of participants indicated that they would prefer to take their own medications. Major causes of DAART discontinuation included hospitalization, incarceration, and entry into drug-treatment programs. The presence of depression and the lack of willingness to travel greater than four blocks to receive DAART predicted time-to-discontinuation. PMID:18085432

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.

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

Costing Analysis of National HIV Treatment and Care Program in Vietnam

PubMed Central

Duong, Anh Thuy; Bales, Sarah; Do, Nhan Thi; Minh Nguyen, Thu Thi; Thanh Cao, Thuy Thi; Nguyen, Long Thanh

2014-01-01

Background: Vietnam achieved rapid scale-up of antiretroviral therapy (ART), although external funds are declining sharply. To achieve and sustain universal access to HIV services, evidence-based planning is essential. To date, there had been limited HIV treatment and care cost data available in Vietnam. Methods: Cost data of outpatient and inpatient HIV care were extracted at 21 sentinel facilities (17 adult and 4 pediatric) that epitomize the national program. Step-down costing for administration costs and bottom-up resource costing for drugs, diagnostics, and labor were used. Records of 1401 adults and 527 pediatric patients were reviewed. Results: Median outpatient care costs per patient-year for pre-ART, first year ART, later year ART, and second-line ART were US $100, US $316, US $303, and US $1557 for adults; and US $171, US $387, US $320, and US $1069 for children, respectively. Median inpatient care cost per episode was US $162 for adults and US $142 for children. Non-antiretroviral (ARV) costs in adults at stand-alone facilities were 44% (first year ART) and 24% (later year ART) higher than those at integrated facilities. Adults who started ART with CD4 count ≤100 cells per cubic millimeter had 47% higher non-ARV costs in the first year ART than those with CD4 count >100 cells per cubic millimeter. Adult ARV drug costs at government sites were from 66% to 85% higher than those at donor-supported sites in the first year ART. Conclusions: The study found that HIV treatment and care costs in Vietnam are economical, yet there is potential to further promote efficiency through strengthening competitive procurement, integrating HIV services, and promoting earlier ART initiation. PMID:23846564

Human resources requirements for highly active antiretroviral therapy scale-up in Malawi.

PubMed

Muula, Adamson S; Chipeta, John; Siziya, Seter; Rudatsikira, Emmanuel; Mataya, Ronald H; Kataika, Edward

2007-12-19

Twelve percent of the adult population in Malawi is estimated to be HIV infected. About 15% to 20% of these are in need of life saving antiretroviral therapy. The country has a public sector-led antiretroviral treatment program both in the private and public health sectors. Estimation of the clinical human resources needs is required to inform the planning and distribution of health professionals. We obtained data on the total number of patients on highly active antiretroviral treatment program from the Malawi National AIDS Commission and Ministry of Health, HIV Unit, and the number of registered health professionals from the relevant regulatory bodies. We also estimated number of health professionals required to deliver highly active antiretroviral therapy (HAART) using estimates of human resources from the literature. We also obtained data from the Ministry of Health on the actual number of nurses, clinical officers and medical doctors providing services in HAART clinics. We then made comparisons between the human resources situation on the ground and the theoretical estimates based on explicit assumptions. There were 610 clinicians (396 clinical officers and 214 physicians), 44 pharmacists and 98 pharmacy technicians and 7264 nurses registered in Malawi. At the end of March 2007 there were 85 clinical officer and physician full-time equivalents (FTEs) and 91 nurse FTEs providing HAART to 95,674 patients. The human resources used for the delivery of HAART comprised 13.9% of all clinical officers and physicians and 1.1% of all nurses. Using the estimated numbers of health professionals from the literature required 15.7-31.4% of all physicians and clinical officers, 66.5-199.3% of all pharmacists and pharmacy technicians and 2.6 to 9.2% of all the available nurses. To provide HAART to all the 170,000 HIV infected persons estimated as clinically eligible would require 4.7% to 16.4% of the total number of nurses, 118.1% to 354.2% of all the available pharmacists and

Considerations in the rationale, design and methods of the Strategic Timing of AntiRetroviral Treatment (START) study

PubMed Central

Babiker, Abdel G; Emery, Sean; Fätkenheuer, Gerd; Gordin, Fred M; Grund, Birgit; Lundgren, Jens D; Neaton, James D; Pett, Sarah L; Phillips, Andrew; Touloumi, Giota; Vjecha, Michael J

2012-01-01

Background Untreated human immunodeficiency virus (HIV) infection is characterized by progressive depletion of CD4+ T lymphocyte (CD4) count leading to the development of opportunistic diseases (acquired immunodeficiency syndrome (AIDS)), and more recent data suggest that HIV is also associated with an increased risk of serious non-AIDS (SNA) diseases including cardiovascular, renal, and liver diseases and non-AIDS-defining cancers. Although combination antiretroviral treatment (ART) has resulted in a substantial decrease in morbidity and mortality in persons with HIV infection, viral eradication is not feasible with currently available drugs. The optimal time to start ART for asymptomatic HIV infection is controversial and remains one of the key unanswered questions in the clinical management of HIV-infected individuals. Purpose In this article, we outline the rationale and methods of the Strategic Timing of AntiRetroviral Treatment (START) study, an ongoing multicenter international trial designed to assess the risks and benefits of initiating ART earlier than is currently practiced. We also describe some of the challenges encountered in the design and implementation of the study and how these challenges were addressed. Methods A total of 4000 study participants who are HIV type 1 (HIV-1) infected, ART naïve with CD4 count > 500 cells/μL are to be randomly allocated in a 1:1 ratio to start ART immediately (early ART) or defer treatment until CD4 count is <350 cells/ μL (deferred ART) and followed for a minimum of 3 years. The primary outcome is time to AIDS, SNA, or death. The study had a pilot phase to establish feasibility of accrual, which was set as the enrollment of at least 900 participants in the first year. Results Challenges encountered in the design and implementation of the study included the limited amount of data on the risk of a major component of the primary endpoint (SNA) in the study population, changes in treatment guidelines when the pilot

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…

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.

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.

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

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

When to Start Antiretroviral Therapy

MedlinePlus

... pregnant should continue taking HIV medicines throughout their pregnancies. When HIV infection is diagnosed during pregnancy, ART should be ... States: Recommendations for Use of Antiretroviral Drugs During Pregnancy: ... with HIV Who Are Currently Receiving Antiretroviral Therapy , and Pregnant ...

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

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.

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

In what ways do communities support optimal antiretroviral treatment in Zimbabwe?

PubMed

Scott, K; Campbell, C; Madanhire, C; Skovdal, M; Nyamukapa, C; Gregson, S

2014-12-01

Little research has been conducted on how pre-existing indigenous community resources, especially social networks, affect the success of externally imposed HIV interventions. Antiretroviral treatment (ART), an externally initiated biomedical intervention, is being rolled out across sub-Saharan Africa. Understanding the ways in which community networks are working to facilitate optimal ART access and adherence will enable policymakers to better engage with and bolster these pre-existing resources. We conducted 67 interviews and eight focus group discussions with 127 people from three key population groups in Manicaland, eastern Zimbabwe: healthcare workers, adults on ART and carers of children on ART. We also observed over 100 h of HIV treatment sites at local clinics and hospitals. Our research sought to determine how indigenous resources were enabling people to achieve optimal ART access and adherence. We analysed data transcripts using thematic network technique, coding references to supportive community networks that enable local people to achieve ART access and adherence. People on ART or carers of children on ART in Zimbabwe report drawing support from a variety of social networks that enable them to overcome many obstacles to adherence. Key support networks include: HIV groups; food and income support networks; home-based care, church and women's groups; family networks; and relationships with healthcare providers. More attention to the community context in which HIV initiatives occur will help ensure that interventions work with and benefit from pre-existing social capital. © The Author (2013). Published by Oxford University Press.

In what ways do communities support optimal antiretroviral treatment in Zimbabwe?

PubMed Central

Scott, K.; Campbell, C.; Madanhire, C.; Skovdal, M.; Nyamukapa, C.; Gregson, S.

2014-01-01

Little research has been conducted on how pre-existing indigenous community resources, especially social networks, affect the success of externally imposed HIV interventions. Antiretroviral treatment (ART), an externally initiated biomedical intervention, is being rolled out across sub-Saharan Africa. Understanding the ways in which community networks are working to facilitate optimal ART access and adherence will enable policymakers to better engage with and bolster these pre-existing resources. We conducted 67 interviews and eight focus group discussions with 127 people from three key population groups in Manicaland, eastern Zimbabwe: healthcare workers, adults on ART and carers of children on ART. We also observed over 100 h of HIV treatment sites at local clinics and hospitals. Our research sought to determine how indigenous resources were enabling people to achieve optimal ART access and adherence. We analysed data transcripts using thematic network technique, coding references to supportive community networks that enable local people to achieve ART access and adherence. People on ART or carers of children on ART in Zimbabwe report drawing support from a variety of social networks that enable them to overcome many obstacles to adherence. Key support networks include: HIV groups; food and income support networks; home-based care, church and women's groups; family networks; and relationships with healthcare providers. More attention to the community context in which HIV initiatives occur will help ensure that interventions work with and benefit from pre-existing social capital. PMID:23503291

The cost of antiretroviral treatment service for patients with HIV/AIDS in a central outpatient clinic in Vietnam.

PubMed

Nguyen, Long Thanh; Tran, Bach Xuan; Tran, Cuong Tuan; Le, Huong Thi; Tran, Son Van

2014-01-01

Antiretroviral treatment (ART) services are estimated to account for 30% of the total resources needed for human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS) control and prevention in Vietnam during the 2011-2020 timeframe. With international funding decreasing, determining the total cost of HIV/AIDS treatment is necessary in order to develop a master plan for the transition of ART services delivery and management. We analyzed the costs of HIV/AIDS treatment paid by both HIV programs and patients in a central outpatient clinic, and we explored factors associated with the capacity of patients to pay for this service. Patients (n=315) receiving ART in the Department of Infectious Diseases at Bach Mai Hospital, Hanoi, Vietnam, were interviewed. Patient records and expenses were reviewed. The total cost of ART per patient was US$611 (75% from health care providers, 25% from patients or their families). The cost of a second-line regimen was found to be 2.7 times higher than the first-line regimen cost. Most outpatients (73.3%) were able to completely pay for all of their ART expenses. Capacity to pay for ART was influenced by five factors, including marital status, distance from house to clinic, patient's monthly income, household economic condition, and health insurance status. Most of the patients (84.8%) would have been willing to pay for health insurance if a copayment scheme for ART were to be introduced. This study provides evidence on payment capacity of HIV/AIDS patients in Vietnam and supplies information on ART costs from both provider and patient perspectives. In particular, results from this study suggest that earlier access to ART after HIV infection could dramatically reduce the overall cost of treatment.

Factors influencing adherence to antiretroviral treatment in Nepal: a mixed-methods study.

PubMed

Wasti, Sharada P; Simkhada, Padam; Randall, Julian; Freeman, Jennifer V; van Teijlingen, Edwin

2012-01-01

Antiretroviral therapy (ART) is a lifesaver for individual patients treated for Human Immunodeficiency Virus (HIV) and Acquired Immune Deficiency Syndrome (AIDS). Maintaining optimal adherence to antiretroviral drugs is essential for HIV infection management. This study aimed to understand the factors influencing adherence amongst ART-prescribed patients and care providers in Nepal. A cross-sectional mixed-methods study surveying 330 ART-prescribed patients and 34 in-depth interviews with three different types of stakeholders: patients, care providers, and key people at policy level. Adherence was assessed through survey self-reporting and during the interviews. A multivariate logistic regression model was used to identify factors associated with adherence, supplemented with a thematic analysis of the interview transcripts. A total of 282 (85.5%) respondents reported complete adherence, i.e. no missed doses in the four-weeks prior to interview. Major factors influencing adherence were: non-disclosure of HIV status (OR = 17.99, p = 0.014); alcohol use (OR = 12.89, p = <0.001), being female (OR = 6.91, p = 0.001), being illiterate (OR = 4.58, p = 0.015), side-effects (OR = 6.04, p = 0.025), ART started ≤24 months (OR = 3.18, p = 0.009), travel time to hospital >1 hour (OR = 2.84, p = 0.035). Similarly, lack of knowledge and negative perception towards ART medications also significantly affected non-adherence. Transport costs (for repeat prescription), followed by pills running out, not wanting others to notice, side-effects, and being busy were the most common reasons for non-adherence. The interviews also revealed religious or ritual obstacles, stigma and discrimination, ART-associated costs, transport problems, lack of support, and side-effects as contributing to non-adherence. Improving adherence requires a supportive environment; accessible treatment; clear instructions about regimens; and regimens

Virologic outcomes in early antiretroviral treatment: HPTN 052

PubMed Central

Eshleman, Susan H.; Wilson, Ethan A.; Zhang, Xinyi C.; Ou, San-San; Piwowar-Manning, Estelle; Eron, Joseph J.; McCauley, Marybeth; Gamble, Theresa; Gallant, Joel E.; Hosseinipour, Mina C.; Kumarasamy, Nagalingeswaran; Hakim, James G.; Kalonga, Ben; Pilotto, Jose H.; Grinsztejn, Beatriz; Godbole, Sheela V.; Chotirosniramit, Nuntisa; Santos, Breno Riegel; Shava, Emily; Mills, Lisa A.; Panchia, Ravindre; Mwelase, Noluthando; Mayer, Kenneth H.; Chen, Ying Q.; Cohen, Myron S.; Fogel, Jessica M.

2017-01-01

INTRODUCTION The HPTN 052 trial demonstrated that early antiretroviral therapy (ART) prevented 93% of HIV transmission events in serodiscordant couples. Some linked infections were observed shortly after ART initiation or after virologic failure. OBJECTIVE To evaluate factors associated with time to viral suppression and virologic failure in participants who initiated ART in HPTN 052. METHODS 1,566 participants who had a viral load (VL) >400 copies/mL at enrollment were included in the analyses. This included 832 in the early ART arm (CD4 350–550 cells/mm3 at ART initiation) and 734 in the delayed ART arm (204 with a CD4 <250 cells/mm3 at ART initiation; 530 with any CD4 at ART initiation). Viral suppression was defined as two consecutive VLs ≤400 copies/mL after ART initiation; virologic failure was defined as two consecutive VLs >1,000 copies/mL >24 weeks after ART initiation. RESULTS Overall, 93% of participants achieved viral suppression by 12 months. The annual incidence of virologic failure was 3.6%. Virologic outcomes were similar in the two study arms. Longer time to viral suppression was associated with younger age, higher VL at ART initiation, and region (Africa vs. Asia). Virologic failure was strongly associated with younger age, lower educational level, and lack of suppression by 3 months; lower VL and higher CD4 at ART initiation were also associated with virologic failure. CONCLUSIONS Several clinical and demographic factors were identified that were associated with longer time to viral suppression and virologic failure. Recognition of these factors may help optimize ART for HIV treatment and prevention. PMID:28385131

Virologic outcomes in early antiretroviral treatment: HPTN 052.

PubMed

Eshleman, Susan H; Wilson, Ethan A; Zhang, Xinyi C; Ou, San-San; Piwowar-Manning, Estelle; Eron, Joseph J; McCauley, Marybeth; Gamble, Theresa; Gallant, Joel E; Hosseinipour, Mina C; Kumarasamy, Nagalingeswaran; Hakim, James G; Kalonga, Ben; Pilotto, Jose H; Grinsztejn, Beatriz; Godbole, Sheela V; Chotirosniramit, Nuntisa; Santos, Breno Riegel; Shava, Emily; Mills, Lisa A; Panchia, Ravindre; Mwelase, Noluthando; Mayer, Kenneth H; Chen, Ying Q; Cohen, Myron S; Fogel, Jessica M

2017-05-01

The HIV Prevention Trials Network (HPTN) 052 trial demonstrated that early antiretroviral therapy (ART) prevented 93% of HIV transmission events in serodiscordant couples. Some linked infections were observed shortly after ART initiation or after virologic failure. To evaluate factors associated with time to viral suppression and virologic failure in participants who initiated ART in HPTN 052. 1566 participants who had a viral load (VL) > 400 copies/mL at enrollment were included in the analyses. This included 832 in the early ART arm (CD4 350-550 cells/mm 3 at ART initiation) and 734 in the delayed ART arm (204 with a CD4 < 250 cells/mm 3 at ART initiation; 530 with any CD4 at ART initiation). Viral suppression was defined as two consecutive VLs ≤ 400 copies/mL after ART initiation; virologic failure was defined as two consecutive VLs > 1000 copies/mL > 24 weeks after ART initiation. Overall, 93% of participants achieved viral suppression by 12 months. The annual incidence of virologic failure was 3.6%. Virologic outcomes were similar in the two study arms. Longer time to viral suppression was associated with younger age, higher VL at ART initiation, and region (Africa vs. Asia). Virologic failure was strongly associated with younger age, lower educational level, and lack of suppression by three months; lower VL and higher CD4 at ART initiation were also associated with virologic failure. Several clinical and demographic factors were identified that were associated with longer time to viral suppression and virologic failure. Recognition of these factors may help optimize ART for HIV treatment and prevention.

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.

Regulatory challenges in developing long-acting antiretrovirals for treatment and prevention of HIV infection.

PubMed

Arya, Vikram; Au, Stanley; Belew, Yodit; Miele, Peter; Struble, Kimberly

2015-07-01

To outline some of the regulatory challenges inherent to the development of long-acting antiretrovirals (ARVs) for the treatment or prevention of HIV infection. Despite advances in drug development that have reduced ARV dosing to once daily, suboptimal drug adherence remains an obstacle to successful HIV treatment. Further, large randomized trials of once daily oral ARVs for preexposure prophylaxis (PrEP) have shown that drug adherence correlates strongly with prophylactic effect and study outcomes. Thus, the prospect of developing long-acting ARVs, which may mitigate drug adherence issues, has attracted considerable attention lately. Because of their pharmacokinetic properties, the development of long-acting ARVs can present novel regulatory challenges. Chief among them is determining the appropriate dosing regimen, the need for an oral lead-in, and whether existing data with an approved oral agent, if available, can be leveraged for a treatment or prevention indication. For PrEP, because validated biomarkers are lacking, additional nonclinical studies and evaluation of tissue concentrations in multiple compartments may be necessary to identify optimal dosages. Study design and choice of controls for registrational trials of new long-acting PrEP agents might also prove challenging following the availability of an oral PrEP drug.

[Non-antiretroviral drugs uses among HIV-infected persons receiving antiretroviral therapy in Senegal: Costs and factors associated with prescription].

PubMed

Diouf, A; Youbong, T J; Maynart, M; Ndoye, M; Diéye, F L; Ndiaye, N A; Koita-Fall, M B; Ndiaye, B; Seydi, M

2017-08-01

In addition to antiretroviral therapy, non-antiretroviral drugs are necessary for the appropriate care of people living with HIV. The costs of such drugs are totally or partially supported by the people living with HIV. We aimed to evaluate the overall costs, the costs supported by the people living with HIV and factors associated with the prescription of non-antiretroviral drugs in people living with HIV on antiretroviral therapy in Senegal. We conducted a retrospective cohort study on 331 people living with HIV who initiated antiretroviral therapy between 2009 and 2011 and followed until March 2012. The costs of non-antiretroviral drugs were those of the national pharmacy for essential drugs; otherwise they were the lowest costs in the private pharmacies. Associated factors were identified through a logistic regression model. The study population was 61 % female. At baseline, 39 % of patients were classified at WHO clinical stage 3 and 40 % at WHO clinical stage 4. Median age, body mass index and CD4 cells count were 41 years, 18kg/m 2  and 93 cells/μL, respectively. After a mean duration of 11.4 months of antiretroviral therapy, 85 % of patients received at least one prescription for a non-antiretroviral drug. Over the entire study period, the most frequently prescribed non-antiretroviral drugs were cotrimoxazole (78.9 % of patients), iron (33.2 %), vitamins (21.1 %) and antibiotics (19.6 %). The mean cost per patient was 34 Euros and the mean cost supported per patient was 14 Euros. The most expensive drugs per treated patient were antihypertensives (168 Euros), anti-ulcer agents (12 Euros), vitamins (8.5 Euros) and antihistamines (7 Euros). The prescription for a non-antiretroviral drug was associated with advanced clinical stage (WHO clinical stage 3/4 versus stage 1/2): OR=2.25; 95 % CI=1.11-4.57 and viral type (HIV-2 versus HIV-1/HIV-1+HIV-2): OR=0.36; 95 % CI=0.14-0.89. Non-antiretroviral drugs are frequently prescribed to

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.

Database-supported teleconferencing: an additional clinical mentoring tool to assist a multinational company HIV/AIDS treatment program in Africa.

PubMed

Clevenbergh, P; Van der Borght, S F M; van Cranenburgh, K; Janssens, V; Kitenge Lubangi, C; Gahimbaza, L; Lange, J M A; Rinke de Wit, T F; Rijckborst, H

2006-01-01

The lack of human resources for health is presently recognized as a major factor limiting scale-up of antiretroviral treatment (ART) programs in resourcelimited settings. The mobilization of public and private partners, the decentralization of care, and the training of non-HIV specialist nurses and general practitioners could help increase the number of HIV-infected patients receiving ART. In addition to other forms of training, scheduled teleconferences (TCs) have been organized to support a comprehensive HIV treatment program delivered by a private company's health team. To describe the role of the TC as an additional tool in mentoring a company's health care workers (HCWs). For this study, all TC reports were retrospectively reviewed and the questions classified by topic. Participating Heineken physicians evaluated the technical quality and scientific relevance of the TCs through an anonymous survey. From October 2001 to December 2003, 10 HCWs working in 14 operating companies in 5 African countries raised 268 problems during 45 TCs. A total of 79 questions (29%) were asked about antiretroviral (ARV) therapy, 53 (20%) about the diagnosis and treatment of opportunistic infection, 43 (16%) about ARV toxicity, 40 (15%) about care organization and policy, 32 (12%) about laboratory or drug supply, and 21 (8%) about biological parameters. The mean TC attendance rate was 70%. The level of satisfaction among local company physicians was 65% for logistics, 89% for scientific relevance, 84% for applicability of advice, and 85% overall. The most common complaints concerned the poor quality of the telephone connection and language problems for francophone participants. Database-supported teleconferencing could be an additional tool to mentor company HCWs in their routine care of HIV-infected workers and family members. The role and costeffectiveness of telemedicine in improving health outcomes should be further studied.

Measuring adherence to antiretroviral treatment: the role of pharmacy records of drug withdrawals.

PubMed

Gutierrez, Eliana Battaggia; Sartori, Ana Marli Christovam; Schmidt, Ana Lucia; Piloto, Bruna Mamprim; França, Bruna Biagi; de Oliveira, Adriana Santos; Pouza, Adriana Rodrigues; Moreno, Roberta Vilela; de Melo Picone, Camila; de Almeida Ribeiro, Manoel Carlos Sampaio

2012-08-01

This study aimed to evaluate adherence to antiretroviral treatment (ART) among HIV + adults, assess its association with HIV viral load (VL) and identify factors associated to adherence. A survey involving a random sample of adults followed at a HIV/AIDS reference center in São Paulo city, Brazil, from 2007 to 2009 was done. A questionnaire was applied and data were retrieved from the pharmacy and medical records. The study involved 292 subjects: 70.2% men; median age: 43 years; median duration of ART: 8 years. 89.3% self-reported taken all prescribed pills in the last 3 days but only 39.3% picked up ≥95% of the prescribed ART from the pharmacy in the last 12 months. At the multivariate analysis having symptoms prior to ART, taking fewer ART pills, and not missing medical appointments were independently associated to higher adherence. Adherence was strongly associated with undetectable HIV VL. Rates of undetectable HIV VL did not differ from 80 to ≥95% of adherence.

The cost-effectiveness of Antiretroviral Treatment in Khayelitsha, South Africa – a primary data analysis

PubMed Central

Cleary, Susan M; McIntyre, Di; Boulle, Andrew M

2006-01-01

Background Given the size of the HIV epidemic in South Africa and other developing countries, scaling up antiretroviral treatment (ART) represents one of the key public health challenges of the next decade. Appropriate priority setting and budgeting can be assisted by economic data on the costs and cost-effectiveness of ART. The objectives of this research were therefore to estimate HIV healthcare utilisation, the unit costs of HIV services and the cost per life year (LY) and quality adjusted life year (QALY) gained of HIV treatment interventions from a provider's perspective. Methods Data on service utilisation, outcomes and costs were collected in the Western Cape Province of South Africa. Utilisation of a full range of HIV healthcare services was estimated from 1,729 patients in the Khayelitsha cohort (1,146 No-ART patient-years, 2,229 ART patient-years) using a before and after study design. Full economic costs of HIV-related services were calculated and were complemented by appropriate secondary data. ART effects (deaths, therapy discontinuation and switching to second-line) were from the same 1,729 patients followed for a maximum of 4 years on ART. No-ART outcomes were estimated from a local natural history cohort. Health-related quality of life was assessed on a sub-sample of 95 patients. Markov modelling was used to calculate lifetime costs, LYs and QALYs and uncertainty was assessed through probabilistic sensitivity analysis on all utilisation and outcome variables. An alternative scenario was constructed to enhance generalizability. Results Discounted lifetime costs for No-ART and ART were US$2,743 and US$9,435 over 2 and 8 QALYs respectively. The incremental cost-effectiveness ratio through the use of ART versus No-ART was US$1,102 (95% CI 1,043-1,210) per QALY and US$984 (95% CI 913-1,078) per life year gained. In an alternative scenario where adjustments were made across cost, outcome and utilisation parameters, costs and outcomes were lower, but the

[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.

Clinic Attendance for Antiretroviral Pills Pick-Up among HIV-Positive People in Nepal: Roles of Perceived Family Support and Associated Factors.

PubMed

Ayer, Rakesh; Kikuchi, Kimiyo; Ghimire, Mamata; Shibanuma, Akira; Pant, Madhab Raj; Poudel, Krishna C; Jimba, Masamine

2016-01-01

HIV-positive people's clinic attendance for medication pick-up is critical for successful HIV treatment. However, limited evidence exists on it especially in low-income settings such as Nepal. Moreover, the role of family support in clinic attendance remains under-explored. Therefore, this study was conducted to examine the association between perceived family support and regular clinic attendance and to assess factors associated with regular clinic attendance for antiretroviral pills pick-up among HIV-positive individuals in Nepal. A cross-sectional study was conducted among 423 HIV-positive people in three districts of Nepal. Clinic attendance was assessed retrospectively for the period of 12 months. To assess the factors associated, an interview survey was conducted using a semi-structured questionnaire from July to August, 2015. Multiple logistic regression models were used to assess the factors associated with regular clinic attendance. Of 423 HIV-positive people, only 32.6% attended the clinics regularly. They were more likely to attend them regularly when they received high family support (AOR = 3.98, 95% CI = 2.29, 6.92), participated in support programs (AOR = 1.68, 95% CI = 1.00, 2.82), and had knowledge on the benefits of antiretroviral therapy (AOR = 2.62, 95% CI = 1.15, 5.99). In contrast, they were less likely to attend them regularly when they commuted more than 60 minutes to the clinics (AOR = 0.53, 95% CI = 0.30, 0.93), when they self-rated their health status as being very good (AOR = 0.13, 95% CI = 0.04, 0.44), good (AOR = 0.14, 95% CI = 0.04, 0.46), and fair (AOR = 0.21, 95% CI = 0.06, 0.70). HIV-positive individuals are more likely to attend the clinics regularly when they receive high family support, know the benefits of antiretroviral therapy, and participate in support programs. To improve clinic attendance, family support should be incorporated with HIV care programs in resource limited settings. Service providers should also consider

Clinic Attendance for Antiretroviral Pills Pick-Up among HIV-Positive People in Nepal: Roles of Perceived Family Support and Associated Factors

PubMed Central

Kikuchi, Kimiyo; Ghimire, Mamata; Shibanuma, Akira; Pant, Madhab Raj; Poudel, Krishna C.; Jimba, Masamine

2016-01-01

Introduction HIV-positive people’s clinic attendance for medication pick-up is critical for successful HIV treatment. However, limited evidence exists on it especially in low-income settings such as Nepal. Moreover, the role of family support in clinic attendance remains under-explored. Therefore, this study was conducted to examine the association between perceived family support and regular clinic attendance and to assess factors associated with regular clinic attendance for antiretroviral pills pick-up among HIV-positive individuals in Nepal. Methods A cross-sectional study was conducted among 423 HIV-positive people in three districts of Nepal. Clinic attendance was assessed retrospectively for the period of 12 months. To assess the factors associated, an interview survey was conducted using a semi-structured questionnaire from July to August, 2015. Multiple logistic regression models were used to assess the factors associated with regular clinic attendance. Results Of 423 HIV-positive people, only 32.6% attended the clinics regularly. They were more likely to attend them regularly when they received high family support (AOR = 3.98, 95% CI = 2.29, 6.92), participated in support programs (AOR = 1.68, 95% CI = 1.00, 2.82), and had knowledge on the benefits of antiretroviral therapy (AOR = 2.62, 95% CI = 1.15, 5.99). In contrast, they were less likely to attend them regularly when they commuted more than 60 minutes to the clinics (AOR = 0.53, 95% CI = 0.30, 0.93), when they self-rated their health status as being very good (AOR = 0.13, 95% CI = 0.04, 0.44), good (AOR = 0.14, 95% CI = 0.04, 0.46), and fair (AOR = 0.21, 95% CI = 0.06, 0.70). Conclusion HIV-positive individuals are more likely to attend the clinics regularly when they receive high family support, know the benefits of antiretroviral therapy, and participate in support programs. To improve clinic attendance, family support should be incorporated with HIV care programs in resource limited settings

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 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.

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.

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

Calculating the affordability of antiretrovirals in St Lucia.

PubMed

Reddock, J R; Grignon, M

2013-01-01

The cost of antiretrovirals is borne by donors in many low- and middle-income countries, including St Lucia. Although donor involvement has facilitated access to antiretrovirals, donor engagement in HIV/AIDS has changed over the years. This paper assesses the affordability of antiretrovirals at the individual level if donors were no longer available to fund the cost of first and second-line antiretrovirals and a prospective third-line regimen. Various conceptions of affordability are reviewed using different assumptions of what is required to maintain a standard of living that would avoid individuals descending into poverty as a result of antiretroviral purchases. These concepts of affordability are operationalized using data from the Household Budgeting Survey conducted in St Lucia in 2005/2006. While there is a range of results for the affordability of first and second-line antiretrovirals depending on which standard of affordability is used, third-line antiretrovirals are unaffordable to more than 80% of the population across the four standards of affordability used - the national poverty line, 50% of median annual consumption, 10% of annual consumption and a proposed reasonable minimum standard.

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

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

Disclosure History Among Persons Initiating Antiretroviral Treatment at Six HIV Clinics in Oromia, Ethiopia, 2012-2013.

PubMed

Gadisa, Tsigereda; Tymejczyk, Olga; Kulkarni, Sarah Gorrell; Hoffman, Susie; Lahuerta, Maria; Remien, Robert H; Yigzaw, Muluneh; Daba, Shalo; Elul, Batya; Nash, Denis; Melaku, Zenebe

2017-01-01

HIV status disclosure can help patients obtain support which may influence treatment adherence and subsequent healthcare needs. We examined the extent of disclosure and correlates of non-disclosure among 1180 adults newly initiating antiretroviral treatment (ART). While 91 % of those in a relationship shared their status with their partners, 14 % of the overall sample had not disclosed to anyone. Non-disclosure was positively associated with older age; control over household resources; and concerns about unintended disclosure, life disruptions, and family reactions. Knowing other HIV-positive people and longer time since diagnosis were associated with lower odds of non-disclosure. Most respondents reporting disclosure experienced supportive responses, frequently including decision to get an HIV test by confidants who had not known their own status. Although HIV status disclosure prior to ART initiation was high, some individuals cited concerns about unintended disclosure, gossip, and partner violence, and may benefit from additional disclosure support.

[Successful treatment of HIV-associated chronic inflammatory demyelinating polyneuropathy by early initiation of highly active anti-retroviral therapy].

PubMed

Kume, Kodai; Ikeda, Kazuyo; Kamada, Masaki; Touge, Tetsuo; Deguchi, Kazushi; Masaki, Tsutomu

2013-01-01

A 47-year-old man with HIV infection presented with lower leg dominant dysesthesia, muscle weakness and sensory ataxia of 3 month's duration. Nerve conduction studies (NCS) showed demyelination change in the median and tibial nerves and sensory nerve action potential (SNAP) in the sural nerve was not evoked. Somatosensory evoked potential (SEP) showed the delayed N9 latency. Diagnose of HIV-associated chronic inflammatory demyelinating polyneuropathy (CIDP) was made. Although the CD4 lymphocyte counts were relatively preserved (466/μl), highly active anti-retroviral therapy (HAART) was started according to a new guideline for the use of antiretroviral agents in HIV-1-infected adults and adolescents recommending early initiation of treatment. After six months, HIV1-RNA was not detected and the CD4 lymphocyte counts showed a recovering trend (585/μl). His symptoms had disappeared, except for dysesthesia in the tip of a toe. Repeated NCS demonstrated full recovery from the demyelination and appearance of SNAP in the sural nerve. The improvement of his symptoms and NCS findings has been maintained for two years. Although effectiveness of immunotherapies such as oral prednisone, high-dose immunoglobulins and plasmapheresis have been reported in HIV-associated CIDP, early initiation of HAART may be also important for favorable prognosis in HIV-associated CIDP.

"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…

Antiretroviral treatment sequencing strategies to overcome HIV type 1 drug resistance in adolescents and adults in low-middle-income countries.

PubMed

De Luca, Andrea; Hamers, Raphael L; Schapiro, Jonathan M

2013-06-15

Antiretroviral treatment (ART) is expanding to human immunodeficiency virus type 1 (HIV-1)-infected persons in low-middle income countries, thanks to a public health approach. With 3 available drug classes, 2 ART sequencing lines are programmatically foreseen. The emergence and transmission of viral drug resistance represents a challenge to the efficacy of ART. Knowledge of HIV-1 drug resistance selection associated with specific drugs and regimens and the consequent activity of residual drug options are essential in programming ART sequencing options aimed at preserving ART efficacy for as long as possible. This article determines optimal ART sequencing options for overcoming HIV-1 drug resistance in resource-limited settings, using currently available drugs and treatment monitoring opportunities. From the perspective of drug resistance and on the basis of limited virologic monitoring data, optimal sequencing seems to involve use of a tenofovir-containing nonnucleoside reverse-transcriptase inhibitor-based first-line regimen, followed by a zidovudine-containing, protease inhibitor (PI)-based second-line regimen. Other options and their consequences are explored by considering within-class and between-class sequencing opportunities, including boosted PI monotherapies and future options with integrase inhibitors. Nucleoside reverse-transcriptase inhibitor resistance pathways in HIV-1 subtype C suggest an additional reason for accelerating stavudine phase out. Viral load monitoring avoids the accumulation of resistance mutations that significantly reduce the activity of next-line options. Rational use of resources, including broader access to viral load monitoring, will help ensure 3 lines of fully active treatment options, thereby increasing the duration of ART success.

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

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

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

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 treatment facility (DEWATS);

[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.

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.

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.

Antiretroviral Therapy Program Expansion in Zambézia Province, Mozambique: Geospatial Mapping of Community-Based and Health Facility Data for Integrated Health Planning

PubMed Central

Moon, Troy D.; Ossemane, Ezequiel B.; Green, Ann F.; Ndatimana, Elisée; José, Eurico; Buehler, Charlotte P.; Wester, C. William; Vermund, Sten H.; Olupona, Omo

2014-01-01

Objective To generate maps reflecting the intersection of community-based Voluntary Counseling and Testing (VCT) delivery points with facility-based HIV program demographic information collected at the district level in three districts (Ile, Maganja da Costa and Chinde) of Zambézia Province, Mozambique; in order to guide planning decisions about antiretroviral therapy (ART) program expansion. Methods Program information was harvested from two separate open source databases maintained for community-based VCT and facility-based HIV care and treatment monitoring from October 2011 to September 2012. Maps were created using ArcGIS 10.1. Travel distance by foot within a 10 km radius is generally considered a tolerable distance in Mozambique for purposes of adherence and retention planning. Results Community-based VCT activities in each of three districts were clustered within geographic proximity to clinics providing ART, within communities with easier transportation access, and/or near the homes of VCT volunteers. Community HIV testing results yielded HIV seropositivity rates in some regions that were incongruent with the Ministry of Health’s estimates for the entire district (2–13% vs. 2% in Ile, 2–54% vs. 11.5% in Maganja da Costa, and 23–43% vs. 14.4% in Chinde). All 3 districts revealed gaps in regional disbursement of community-based VCT activities as well as access to clinics offering ART. Conclusions Use of geospatial mapping in the context of program planning and monitoring allowed for characterizing the location and size of each district’s HIV population. In extremely resource limited and logistically challenging settings, maps are valuable tools for informing evidence-based decisions in planning program expansion, including ART. PMID:25329169

Outcomes of Patients Lost to Follow-up in African Antiretroviral Therapy Programs: Individual Patient Data Meta-analysis.

PubMed

Chammartin, Frédérique; Zürcher, Kathrin; Keiser, Olivia; Weigel, Ralf; Chu, Kathryn; Kiragga, Agnes N; Ardura-Garcia, Cristina; Anderegg, Nanina; Laurent, Christian; Cornell, Morna; Tweya, Hannock; Haas, Andreas D; Rice, Brian D; Geng, Elvin H; Fox, Matthew P; Hargreaves, James R; Egger, Matthias

2018-06-08

Low retention on combination antiretroviral therapy (cART) has emerged as a threat to the Joint United Nations Programme on human immunodeficiency virus (HIV)/AIDS (UNAIDS) 90-90-90 targets. We examined outcomes of patients who started cART but were subsequently lost to follow-up (LTFU) in African treatment programs. This was a systematic review and individual patient data meta-analysis of studies that traced patients who were LTFU. Outcomes were analyzed using cumulative incidence functions and proportional hazards models for the competing risks of (i) death, (ii) alive but stopped cART, (iii) silent transfer to other clinics, and (iv) retention on cART. Nine studies contributed data on 7377 patients who started cART and were subsequently LTFU in sub-Saharan Africa. The median CD4 count at the start of cART was 129 cells/μL. At 4 years after the last clinic visit, 21.8% (95% confidence interval [CI], 20.8%-22.7%) were known to have died, 22.6% (95% CI, 21.6%-23.6%) were alive but had stopped cART, 14.8% (95% CI, 14.0%-15.6%) had transferred to another clinic, 9.2% (95% CI, 8.5%-9.8%) were retained on cART, and 31.6% (95% CI, 30.6%-32.7%) could not been found. Mortality was associated with male sex, more advanced disease, and shorter cART duration; stopping cART with less advanced disease andlonger cART duration; and silent transfer with female sex and less advanced disease. Mortality in patients LTFU must be considered for unbiased assessments of program outcomes and UNAIDS targets in sub-Saharan Africa. Immediate start of cART and early tracing of patients LTFU should be priorities.

2007 costs and coverage of antiretrovirals under Medicare Part D for people with HIV/AIDS living in North Carolina.

PubMed

Sengupta, Sohini

2008-01-01

Effective January 1, 2006 Medicare Part D became a new source of prescription drug coverage for people with HIV/AIDS in the United States. The implementation of Part D has affected access to antiretrovirals for people with HIV/AIDS. In North Carolina, access can be difficult because of the state's struggling safety net programs and the growing HIV-infected populations among Blacks and in poor rural counties. This analysis examines Medicare Part D antiretroviral coverage in 2007 for beneficiaries with HIV/AIDS in North Carolina, particularly those who did not qualify as dual eligibles or for a full low-income subsidy. Data describing program coverage were obtained from the Web site www.medicare.gov and descriptive analyses were performed to assess changes in antiretroviral coverage in Part D prescription drug plans in North Carolina. Most of the 26 antiretrovirals are covered in some way by 76 North Carolina prescription drug plans. There may be variability in coverage however associated with (a) antiretroviral classification within formularies; (b) drug premiums; (c) whether premiums can be waived; (d) annual deductibles; and (e) whether coverage is provided in the "doughnut hole." The data may not reflect actual patterns of drug use and realized access to the drugs. The findings are limited to antiretroviral coverage in North Carolina's Part D offerings but could be generalized to other states with similar prescription drug plan costs and coverage. These concerns continue to pose significant challenges to accessing antiretrovirals for Part D beneficiaries with HIV/AIDS in North Carolina. Variability demonstrated within prescription drug plans will continue, and beneficiaries with HIV/AIDS who do not qualify as dual eligibles or for low-income subsidies will need to evaluate these issues when selecting a prescription drug plan in future enrollment periods.

When masculinity interferes with women's treatment of HIV infection: a qualitative study about adherence to antiretroviral therapy in Zimbabwe.

PubMed

Skovdal, Morten; Campbell, Catherine; Nyamukapa, Constance; Gregson, Simon

2011-06-09

Social constructions of masculinity have been shown to serve as an obstacle to men's access and adherence to antiretroviral therapies (ART). In the light of women's relative lack of power in many aspects of interpersonal relationships with men in many African settings, our objective is to explore how male denial of HIV/AIDS impacts on their female partners' ability to access and adhere to ART. We conducted a qualitative case study involving thematic analysis of 37 individual interviews and five focus groups with a total of 53 male and female antiretroviral drug users and 25 healthcare providers in rural eastern Zimbabwe. Rooted in hegemonic notions of masculinity, men saw HIV/AIDS as a threat to their manhood and dignity and exhibited a profound fear of the disease. In the process of denying and avoiding their association with AIDS, many men undermine their wives' efforts to access and adhere to ART. Many women felt unable to disclose their HIV status to their husbands, forcing them to take their medication in secret, and act without a supportive treatment partner, which is widely accepted to be vitally important for adherence success. Some husbands, when discovering that their wives are on ART, deny them permission to take the drugs, or indeed steal the drugs for their own treatment. Men's avoidance of HIV also leaves many HIV-positive women feeling vulnerable to re-infection as their husbands, in an attempt to demonstrate their manhood, are believed to continue engaging in HIV-risky behaviours. Hegemonic notions of masculinity can interfere with women's adherence to ART. It is important that those concerned with promoting effective treatment services recognise the gender and household dynamics that may prevent some women from successfully adhering to ART, and explore ways to work with both women and men to identify couples-based strategies to increase adherence to ART.

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

Replication-Competent Simian Immunodeficiency Virus (SIV) Gag Escape Mutations Archived in Latent Reservoirs during Antiretroviral Treatment of SIV-Infected Macaques▿

PubMed Central

Queen, Suzanne E.; Mears, Brian M.; Kelly, Kathleen M.; Dorsey, Jamie L.; Liao, Zhaohao; Dinoso, Jason B.; Gama, Lucio; Adams, Robert J.; Zink, M. Christine; Clements, Janice E.; Kent, Stephen J.; Mankowski, Joseph L.

2011-01-01

In response to pressure exerted by major histocompatibility complex (MHC) class I-mediated CD8+ T cell control, human immunodeficiency virus (HIV) escape mutations often arise in immunodominant epitopes recognized by MHC class I alleles. While the current standard of care for HIV-infected patients is treatment with highly active antiretroviral therapy (HAART), suppression of viral replication in these patients is not absolute and latently infected cells persist as lifelong reservoirs. To determine whether HIV escape from MHC class I-restricted CD8+ T cell control develops during HAART treatment and then enters latent reservoirs in the periphery and central nervous system (CNS), with the potential to emerge as replication-competent virus, we tracked the longitudinal development of the simian immunodeficiency virus (SIV) Gag escape mutation K165R in HAART-treated SIV-infected pigtailed macaques. Key findings of these studies included: (i) SIV Gag K165R escape mutations emerged in both plasma and cerebrospinal fluid (CSF) during the decaying phase of viremia after HAART initiation before suppression of viral replication, (ii) SIV K165R Gag escape mutations were archived in latent proviral DNA reservoirs, including the brain in animals receiving HAART that suppressed viral replication, and (iii) replication-competent SIV Gag K165R escape mutations were present in the resting CD4+ T cell reservoir in HAART-treated SIV-infected macaques. Despite early administration of aggressive antiretroviral treatment, HIV immune escape from CD8+ T cell control can still develop during the decaying phases of viremia and then persist in latent reservoirs, including the brain, with the potential to emerge if HAART therapy is interrupted. PMID:21715484

Factors Influencing Adherence to Antiretroviral Treatment in Nepal: A Mixed-Methods Study

PubMed Central

Wasti, Sharada P.; Simkhada, Padam; Randall, Julian; Freeman, Jennifer V.; van Teijlingen, Edwin

2012-01-01

Background Antiretroviral therapy (ART) is a lifesaver for individual patients treated for Human Immunodeficiency Virus (HIV) and Acquired Immune Deficiency Syndrome (AIDS). Maintaining optimal adherence to antiretroviral drugs is essential for HIV infection management. This study aimed to understand the factors influencing adherence amongst ART-prescribed patients and care providers in Nepal. Methods A cross-sectional mixed-methods study surveying 330 ART-prescribed patients and 34 in-depth interviews with three different types of stakeholders: patients, care providers, and key people at policy level. Adherence was assessed through survey self-reporting and during the interviews. A multivariate logistic regression model was used to identify factors associated with adherence, supplemented with a thematic analysis of the interview transcripts. Results A total of 282 (85.5%) respondents reported complete adherence, i.e. no missed doses in the four-weeks prior to interview. Major factors influencing adherence were: non-disclosure of HIV status (OR = 17.99, p =  0.014); alcohol use (OR = 12.89, p = <0.001), being female (OR = 6.91, p = 0.001), being illiterate (OR = 4.58, p = 0.015), side-effects (OR = 6.04, p = 0.025), ART started ≤24 months (OR = 3.18, p = 0.009), travel time to hospital >1 hour (OR = 2.84, p = 0.035). Similarly, lack of knowledge and negative perception towards ART medications also significantly affected non-adherence. Transport costs (for repeat prescription), followed by pills running out, not wanting others to notice, side-effects, and being busy were the most common reasons for non-adherence. The interviews also revealed religious or ritual obstacles, stigma and discrimination, ART-associated costs, transport problems, lack of support, and side-effects as contributing to non-adherence. Conclusion Improving adherence requires a supportive environment; accessible treatment; clear

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

Impact of Stewardship Interventions on Antiretroviral Medication Errors in an Urban Medical Center: A 3-Year, Multiphase Study.

PubMed

Zucker, Jason; Mittal, Jaimie; Jen, Shin-Pung; Cheng, Lucy; Cennimo, David

2016-03-01

There is a high prevalence of HIV infection in Newark, New Jersey, with University Hospital admitting approximately 600 HIV-infected patients per year. Medication errors involving antiretroviral therapy (ART) could significantly affect treatment outcomes. The goal of this study was to evaluate the effectiveness of various stewardship interventions in reducing the prevalence of prescribing errors involving ART. This was a retrospective review of all inpatients receiving ART for HIV treatment during three distinct 6-month intervals over a 3-year period. During the first year, the baseline prevalence of medication errors was determined. During the second year, physician and pharmacist education was provided, and a computerized order entry system with drug information resources and prescribing recommendations was implemented. Prospective audit of ART orders with feedback was conducted in the third year. Analyses and comparisons were made across the three phases of this study. Of the 334 patients with HIV admitted in the first year, 45% had at least one antiretroviral medication error and 38% had uncorrected errors at the time of discharge. After education and computerized order entry, significant reductions in medication error rates were observed compared to baseline rates; 36% of 315 admissions had at least one error and 31% had uncorrected errors at discharge. While the prevalence of antiretroviral errors in year 3 was similar to that of year 2 (37% of 276 admissions), there was a significant decrease in the prevalence of uncorrected errors at discharge (12%) with the use of prospective review and intervention. Interventions, such as education and guideline development, can aid in reducing ART medication errors, but a committed stewardship program is necessary to elicit the greatest impact. © 2016 Pharmacotherapy Publications, Inc.

Dyslipidemia, Diet and Physical Exercise in Children on Treatment With Antiretroviral Medication in El Salvador: A Cross-sectional Study.

PubMed

Sonego, Michela; Sagrado, Maria José; Escobar, Gustavo; Lazzerini, Marzia; Rivas, Estefanie; Martín-Cañavate, Rocio; Pérez de López, Elsy; Ayala, Sandra; Castaneda, Luis; Aparicio, Pilar; Custodio, Estefanía

2016-10-01

Dyslipidemias are common in HIV-infected children, especially if treated with protease inhibitors, but there are few data on how to treat dyslipidemias in this population. We estimated the dyslipidemia prevalence and its association with treatment, diet and physical exercise in children on antiretroviral treatment at the El Salvador reference center for pediatric HIV care (CENID). Information was gathered regarding socio-demographic characteristics, treatment, diet and physical activity of 173 children aged 5-18 years and receiving antiretroviral therapy. Triglycerides, total cholesterol, low-density lipoprotein (LDL-C), high-density lipoprotein (HDL-C), viral load and CD4 T-lymphocytes were measured. Abnormal concentrations were defined as triglycerides ≥130 mg/dL in 10- to 18-year olds and ≥100 mg/dL in <10-year olds; total cholesterol ≥200 mg/dL; LDL-C ≥130 mg/dL and HDL-C ≤35 mg/dL. We adjusted 4 different multivariate models to assess the independent association of each type of dyslipidemia with protease inhibitors, diet and physical exercise. Of the 173 children, 83 (48%) had hypertriglyceridemia and 25 (14.5%) hypercholesterolemia. High LDL-C concentrations were observed in 17 children (9.8%) and low HDL-C in 38 (22%). Treatment with protease inhibitors was significantly associated with hypertriglyceridemia [prevalence ratio (PR) 2.8; 95% confidence interval (CI): 2.0-3.8] and hypercholesterolemia (PR 9.0; 95% CI: 3.6-22.2). Higher adherence to a "high fat/sugar diet" was associated with hypercholesterolemia (PR 1.6; 95% CI: 1.1-2.3) and high LDL-C (PR 1.7; 95% CI: 1.0-2.9). Compared with those exercising <3 times/week, children exercising ≥7 times were less likely to have low HDL-C (PR = 0.4; 95% CI: 0.2-0.7). These results suggest that a healthy diet and exercise habits can contribute to controlling some aspects of the lipid profile in this population.

Redeeming Lost Mothers: Adolescent Antiretroviral Treatment and the Making of Home in South Africa.

PubMed

Vale, Beth; Thabeng, Mildred

2016-01-01

In this article, we explore how adolescent antiretroviral treatment (ART) might be signified to repair sociality in Eastern Cape homes that have been ruptured by HIV/AIDS and maternal loss. The post-apartheid period has exposed these families to new forms of social fragmentation, propelled by the disintegration of wage labor, declining marriage rates, and a rampant HIV/AIDS epidemic. Drawing on eight months of ethnographic fieldwork (August 2013-April 2014), we show that in the homes of some adolescents born with HIV, these present-day domestic ruptures were discursively connected to the past shortcomings of their dead and absent mothers. In some familial narratives lost mothers were accused of disobeying their elders, neglecting their children, and flouting custom; their social transgressions were made manifest in their child's inherited HIV. By signifying adolescent ART-taking as an enactment of the discipline and care purportedly absent in their mothers, these families might also attempt to imbue ART, beyond its biomedical function, as a means of social repair.

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.

Metabolic disorders and cardiovascular risk in people living with HIV/AIDS without the use of antiretroviral therapy.

PubMed

Raposo, Mariana Amaral; Armiliato, Geyza Nogueira de Almeida; Guimarães, Nathalia Sernizon; Caram, Camila Abrahão; Silveira, Raíssa Domingues de Simoni; Tupinambás, Unaí

2017-01-01

Metabolic disorders in people living with HIV/AIDS (PLH) have been described even before the introduction of antiretroviral (ARV) drugs in the treatment of HIV infection and are risk factors for cardiovascular diseases. Based on this, the purpose of this study was to assess metabolic disorders and cardiovascular risk in PLH before the initiation of antiretroviral treatment (ART). This was a cross-sectional descriptive study of 87 PLH without the use of ART, which was carried out between January and September 2012 at a specialized infectious diseases center in Minas Gerais, Brazil. The main metabolic disorders in the population were low serum levels of HDL-cholesterol, hypertriglyceridemia and abdominal obesity. Dyslipidemia was prevalent in 62.6% of the study population, whereas metabolic syndrome (MS) was prevalent in 11.5% of patients assessed by the International Diabetes Federation (IDF) criteria and 10.8% assessed by the National Cholesterol Education Program-Adult Treatment Panel (NCEP-ATPIII) criteria. Regarding cardiovascular risk, 89.7% of the population presented a low coronary risk according to the Framingham Risk Score. A greater proportion of patients diagnosed with MS presented low cardiovascular risk (80% assessed by IDF criteria and 77.8% assessed by NCEP-ATPIII criteria). Metabolic disorders in this population may be due to HIV infection or lifestyle (smoking, sedentary lifestyle and inadequate diet). The introduction of ART can enhance dyslipidemia, increasing cardiovascular risk, especially among those who have classic risks of cardiovascular disease.

HIV, antiretroviral treatment, hypertension, and stroke in Malawian adults

PubMed Central

Corbett, Elizabeth L.; Connor, Myles D.; Mzinganjira, Henry; Kampondeni, Sam; Choko, Augustine; Hopkins, Mark; Emsley, Hedley C.A.; Bryer, Alan; Faragher, Brian; Heyderman, Robert S.; Allain, Theresa J.; Solomon, Tom

2016-01-01

Objective: To investigate HIV, its treatment, and hypertension as stroke risk factors in Malawian adults. Methods: We performed a case-control study of 222 adults with acute stroke, confirmed by MRI in 86%, and 503 population controls, frequency-matched for age, sex, and place of residence, using Global Positioning System for random selection. Multivariate logistic regression models were used for case-control comparisons. Results: HIV infection (population attributable fraction [PAF] 15%) and hypertension (PAF 46%) were strongly linked to stroke. HIV was the predominant risk factor for young stroke (≤45 years), with a prevalence of 67% and an adjusted odds ratio (aOR) (95% confidence interval) of 5.57 (2.43–12.8) (PAF 42%). There was an increased risk of a stroke in patients with untreated HIV infection (aOR 4.48 [2.44–8.24], p < 0.001), but the highest risk was in the first 6 months after starting antiretroviral therapy (ART) (aOR 15.6 [4.21–46.6], p < 0.001); this group had a lower median CD4+ T-lymphocyte count (92 vs 375 cells/mm3, p = 0.004). In older participants (HIV prevalence 17%), HIV was associated with stroke, but with a lower PAF than hypertension (5% vs 68%). There was no interaction between HIV and hypertension on stroke risk. Conclusions: In a population with high HIV prevalence, where stroke incidence is increasing, we have shown that HIV is an important risk factor. Early ART use in immunosuppressed patients poses an additional and potentially treatable stroke risk. Immune reconstitution inflammatory syndrome may be contributing to the disease mechanisms. PMID:26683649

Effect of treatment course of comprehensive intervention with Traditional Chinese Medicine on mortality of acquired immunodeficiency syndrome patients treated with combined antiretroviral therapy.

PubMed

Guo, Huijun; Wang, Jian; Li, Zhengwei; Jiang, Ziqiang; Xu, Qianlei; Xu, Liran

2016-08-01

To investigate the effect of a treatment course of comprehensive intervention with Traditional Chinese Medicine (TCM) on the mortality of patients with acquired immunodeficiency syndrome (AIDS) treated with combined antiretroviral therapy (cART). AIDS patients who had taken cART in a national TCM human immunodeficiency virus treatment trial program (NTCMTP) before 2009 were enrolled in this study and followed for 36 months from November 2009. Patients enrolled in the NTCMTP in 2004 were taken as the first group, those enrolled in 2006 as the second group, and those enrolled in 2009 as the third group. Cumulative survival rates were calculated by the life table method. Survival curves for subgroups were compared by the log-rank test. Hazard ratios were calculated with a Cox proportional hazards model. A total of 1443 AIDS patients were followed for 3 years (4198 person-years). During this period, 91 (6.3%) patients died and 13 (0.9%) were lost to follow-up. The total mortality rate was 2.17/ 100 person-years. The mortality rate of patients enrolled in the NTCMTP in 2004 was 1.49/100 person- years, which was lower than that of patients enrolled in 2006 (2.23/100 person-years) and 2009 (3.48/100 person-years). After adjusting for other factors, a shorter time of treatment with TCM, male sex, older age, lower CD4 + T-cell counts, and long-term treatment with cART were risk factors of mortality. Long-term treatment with TCM decreased the mortality risk of AIDS patients. Factors such as being male, older age, CD4 + T-cell counts, and time of treatment with TCM and cART were correlated with mortality.

Disclosure History Among Persons Initiating Antiretroviral Treatment at Six HIV Clinics in Oromia, Ethiopia, 2012–2013

PubMed Central

Gadisa, Tsigereda; Kulkarni, Sarah Gorrell; Hoffman, Susie; Lahuerta, Maria; Remien, Robert H.; Yigzaw, Muluneh; Daba, Shalo; Elul, Batya; Nash, Denis; Melaku, Zenebe

2016-01-01

HIV status disclosure can help patients obtain support which may influence treatment adherence and subsequent healthcare needs. We examined the extent of disclosure and correlates of non-disclosure among 1180 adults newly initiating antiretroviral treatment (ART). While 91 % of those in a relationship shared their status with their partners, 14 % of the overall sample had not disclosed to anyone. Non- disclosure was positively associated with older age; control over household resources; and concerns about unintended disclosure, life disruptions, and family reactions. Knowing other HIV-positive people and longer time since diagnosis were associated with lower odds of non-disclosure. Most respondents reporting disclosure experienced supportive responses, frequently including decision to get an HIV test by confidants who had not known their own status. Although HIV status disclosure prior to ART initiation was high, some individuals cited concerns about unintended disclosure, gossip, and partner violence, and may benefit from additional disclosure support. PMID:26781869

Concurrent Anemia and Elevated C-Reactive Protein Predicts HIV Clinical Treatment Failure, Including Tuberculosis, After Antiretroviral Therapy Initiation.

PubMed

Shivakoti, Rupak; Yang, Wei-Teng; Gupte, Nikhil; Berendes, Sima; Rosa, Alberto La; Cardoso, Sandra W; Mwelase, Noluthando; Kanyama, Cecilia; Pillay, Sandy; Samaneka, Wadzanai; Riviere, Cynthia; Sugandhavesa, Patcharaphan; Santos, Brento; Poongulali, Selvamuthu; Tripathy, Srikanth; Bollinger, Robert C; Currier, Judith S; Tang, Alice M; Semba, Richard D; Christian, Parul; Campbell, Thomas B; Gupta, Amita

2015-07-01

Anemia is a known risk factor for clinical failure following antiretroviral therapy (ART). Notably, anemia and inflammation are interrelated, and recent studies have associated elevated C-reactive protein (CRP), an inflammation marker, with adverse human immunodeficiency virus (HIV) treatment outcomes, yet their joint effect is not known. The objective of this study was to assess prevalence and risk factors of anemia in HIV infection and to determine whether anemia and elevated CRP jointly predict clinical failure post-ART. A case-cohort study (N = 470 [236 cases, 234 controls]) was nested within a multinational randomized trial of ART efficacy (Prospective Evaluation of Antiretrovirals in Resource Limited Settings [PEARLS]). Cases were incident World Health Organization stage 3, 4, or death by 96 weeks of ART treatment (clinical failure). Multivariable logistic regression was used to determine risk factors for pre-ART (baseline) anemia (females: hemoglobin <12.0 g/dL; males: hemoglobin <13.0 g/dL). Association of anemia as well as concurrent baseline anemia and inflammation (CRP ≥ 10 mg/L) with clinical failure were assessed using multivariable Cox models. Baseline anemia prevalence was 51% with 15% prevalence of concurrent anemia and inflammation. In analysis of clinical failure, multivariate-adjusted hazard ratios were 6.41 (95% confidence interval [CI], 2.82-14.57) for concurrent anemia and inflammation, 0.77 (95% CI, .37-1.58) for anemia without inflammation, and 0.45 (95% CI, .11-1.80) for inflammation without anemia compared to those without anemia and inflammation. ART-naive, HIV-infected individuals with concurrent anemia and inflammation are at particularly high risk of failing treatment, and understanding the pathogenesis could lead to new interventions. Reducing inflammation and anemia will likely improve HIV disease outcomes. Alternatively, concurrent anemia and inflammation could represent individuals with occult opportunistic infections in need of

Concurrent Anemia and Elevated C-Reactive Protein Predicts HIV Clinical Treatment Failure, Including Tuberculosis, After Antiretroviral Therapy Initiation

PubMed Central

Shivakoti, Rupak; Yang, Wei-Teng; Gupte, Nikhil; Berendes, Sima; Rosa, Alberto La; Cardoso, Sandra W.; Mwelase, Noluthando; Kanyama, Cecilia; Pillay, Sandy; Samaneka, Wadzanai; Riviere, Cynthia; Sugandhavesa, Patcharaphan; Santos, Brento; Poongulali, Selvamuthu; Tripathy, Srikanth; Bollinger, Robert C.; Currier, Judith S.; Tang, Alice M.; Semba, Richard D.; Christian, Parul; Campbell, Thomas B.; Gupta, Amita

2015-01-01

Background. Anemia is a known risk factor for clinical failure following antiretroviral therapy (ART). Notably, anemia and inflammation are interrelated, and recent studies have associated elevated C-reactive protein (CRP), an inflammation marker, with adverse human immunodeficiency virus (HIV) treatment outcomes, yet their joint effect is not known. The objective of this study was to assess prevalence and risk factors of anemia in HIV infection and to determine whether anemia and elevated CRP jointly predict clinical failure post-ART. Methods. A case-cohort study (N = 470 [236 cases, 234 controls]) was nested within a multinational randomized trial of ART efficacy (Prospective Evaluation of Antiretrovirals in Resource Limited Settings [PEARLS]). Cases were incident World Health Organization stage 3, 4, or death by 96 weeks of ART treatment (clinical failure). Multivariable logistic regression was used to determine risk factors for pre-ART (baseline) anemia (females: hemoglobin <12.0 g/dL; males: hemoglobin <13.0 g/dL). Association of anemia as well as concurrent baseline anemia and inflammation (CRP ≥10 mg/L) with clinical failure were assessed using multivariable Cox models. Results. Baseline anemia prevalence was 51% with 15% prevalence of concurrent anemia and inflammation. In analysis of clinical failure, multivariate-adjusted hazard ratios were 6.41 (95% confidence interval [CI], 2.82–14.57) for concurrent anemia and inflammation, 0.77 (95% CI, .37–1.58) for anemia without inflammation, and 0.45 (95% CI, .11–1.80) for inflammation without anemia compared to those without anemia and inflammation. Conclusions. ART-naive, HIV-infected individuals with concurrent anemia and inflammation are at particularly high risk of failing treatment, and understanding the pathogenesis could lead to new interventions. Reducing inflammation and anemia will likely improve HIV disease outcomes. Alternatively, concurrent anemia and inflammation could represent

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.

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

The Macroeconomic Consequences of Renouncing to Universal Access to Antiretroviral Treatment for HIV in Africa: A Micro-Simulation Model

PubMed Central

Ventelou, Bruno; Arrighi, Yves; Greener, Robert; Lamontagne, Erik; Carrieri, Patrizia; Moatti, Jean-Paul

2012-01-01

Aim Previous economic literature on the cost-effectiveness of antiretroviral treatment (ART) programs has been mainly focused on the microeconomic consequences of alternative use of resources devoted to the fight against the HIV pandemic. We rather aim at forecasting the consequences of alternative scenarios for the macroeconomic performance of countries. Methods We used a micro-simulation model based on individuals aged 15–49 selected from nationally representative surveys (DHS for Cameroon, Tanzania and Swaziland) to compare alternative scenarios : 1-freezing of ART programs to current levels of access, 2- universal access (scaling up to 100% coverage by 2015, with two variants defining ART eligibility according to previous or current WHO guidelines). We introduced an “artificial” ageing process by programming methods. Individuals could evolve through different health states: HIV negative, HIV positive (with different stages of the syndrome). Scenarios of ART procurement determine this dynamics. The macroeconomic impact is obtained using sample weights that take into account the resulting age-structure of the population in each scenario and modeling of the consequences on total growth of the economy. Results Increased levels of ART coverage result in decreasing HIV incidence and related mortality. Universal access to ART has a positive impact on workers' productivity; the evaluations performed for Swaziland and Cameroon show that universal access would imply net cost-savings at the scale of the society, when the full macroeconomic consequences are introduced in the calculations. In Tanzania, ART access programs imply a net cost for the economy, but 70% of costs are covered by GDP gains at the 2034 horizon, even in the extended coverage option promoted by WHO guidelines initiating ART at levels of 350 cc/mm3 CD4 cell counts. Conclusion Universal Access ART scaling-up strategies, which are more costly in the short term, remain the best economic choice in the

The macroeconomic consequences of renouncing to universal access to antiretroviral treatment for HIV in Africa: a micro-simulation model.

PubMed

Ventelou, Bruno; Arrighi, Yves; Greener, Robert; Lamontagne, Erik; Carrieri, Patrizia; Moatti, Jean-Paul

2012-01-01

Previous economic literature on the cost-effectiveness of antiretroviral treatment (ART) programs has been mainly focused on the microeconomic consequences of alternative use of resources devoted to the fight against the HIV pandemic. We rather aim at forecasting the consequences of alternative scenarios for the macroeconomic performance of countries. We used a micro-simulation model based on individuals aged 15-49 selected from nationally representative surveys (DHS for Cameroon, Tanzania and Swaziland) to compare alternative scenarios : 1-freezing of ART programs to current levels of access, 2- universal access (scaling up to 100% coverage by 2015, with two variants defining ART eligibility according to previous or current WHO guidelines). We introduced an "artificial" ageing process by programming methods. Individuals could evolve through different health states: HIV negative, HIV positive (with different stages of the syndrome). Scenarios of ART procurement determine this dynamics. The macroeconomic impact is obtained using sample weights that take into account the resulting age-structure of the population in each scenario and modeling of the consequences on total growth of the economy. Increased levels of ART coverage result in decreasing HIV incidence and related mortality. Universal access to ART has a positive impact on workers' productivity; the evaluations performed for Swaziland and Cameroon show that universal access would imply net cost-savings at the scale of the society, when the full macroeconomic consequences are introduced in the calculations. In Tanzania, ART access programs imply a net cost for the economy, but 70% of costs are covered by GDP gains at the 2034 horizon, even in the extended coverage option promoted by WHO guidelines initiating ART at levels of 350 cc/mm(3) CD4 cell counts. Universal Access ART scaling-up strategies, which are more costly in the short term, remain the best economic choice in the long term. Renouncing or

Relationship Between Time to Initiation of Antiretroviral Therapy and Treatment Outcomes: A Cohort Analysis of ART Eligible Adolescents in Zimbabwe.

PubMed

Vogt, Florian; Rehman, Andrea M; Kranzer, Katharina; Nyathi, Mary; Van Griensven, Johan; Dixon, Mark; Ndebele, Wedu; Gunguwo, Hilary; Colebunders, Robert; Ndlovu, Mbongeni; Apollo, Tsitsi; Ferrand, Rashida A

2017-04-01

Age-specific retention challenges make antiretroviral therapy (ART) initiation in adolescents difficult, often requiring a lengthy preparation process. This needs to be balanced against the benefits of starting treatment quickly. The optimal time to initiation duration in adolescents is currently unknown. To assess the effect of time to ART initiation on mortality and loss to follow-up (LTFU) among treatment eligible adolescents. We conducted a retrospective cohort analysis among 1499 ART eligible adolescents aged ≥10 to <19 years registered in a public sector HIV program in Bulawayo, Zimbabwe, between 2004 and 2011. Hazard ratios (HR) for mortality and LTFU were calculated for different time to ART durations using multivariate Cox regression models. Median follow-up duration was 1.6 years. Mortality HRs of patients who initiated at 0 to ≤7 days, >14 days to ≤1 month, >1 to ≤2 months, >2 months, and before initiation were 1.59, 1.19, 1.56, 1.08, and 0.94, respectively, compared with the reference group of >7 to ≤14 days. LTFU HRs were 1.02, 1.07, 0.85, 0.97, and 3.96, respectively. Among patients not on ART, 88% of deaths and 85% of LTFU occurred during the first 3 months after becoming ART eligible, but only 37% and 29% among adolescents on ART, respectively. Neither mortality or LTFU was associated with varying time to ART. The initiation process can be tailored to the adolescents' needs and individual life situations without risking to increase poor treatment outcomes. Early mortality was high despite rapid ART initiation, calling for earlier rather than faster initiation through HIV testing scale-up.

Relationship Between Time to Initiation of Antiretroviral Therapy and Treatment Outcomes: A Cohort Analysis of ART Eligible Adolescents in Zimbabwe

PubMed Central

Rehman, Andrea M.; Kranzer, Katharina; Nyathi, Mary; Van Griensven, Johan; Dixon, Mark; Ndebele, Wedu; Gunguwo, Hilary; Colebunders, Robert; Ndlovu, Mbongeni; Apollo, Tsitsi; Ferrand, Rashida A.

2017-01-01

Background: Age-specific retention challenges make antiretroviral therapy (ART) initiation in adolescents difficult, often requiring a lengthy preparation process. This needs to be balanced against the benefits of starting treatment quickly. The optimal time to initiation duration in adolescents is currently unknown. Objective: To assess the effect of time to ART initiation on mortality and loss to follow-up (LTFU) among treatment eligible adolescents. Methods: We conducted a retrospective cohort analysis among 1499 ART eligible adolescents aged ≥10 to <19 years registered in a public sector HIV program in Bulawayo, Zimbabwe, between 2004 and 2011. Hazard ratios (HR) for mortality and LTFU were calculated for different time to ART durations using multivariate Cox regression models. Results: Median follow-up duration was 1.6 years. Mortality HRs of patients who initiated at 0 to ≤7 days, >14 days to ≤1 month, >1 to ≤2 months, >2 months, and before initiation were 1.59, 1.19, 1.56, 1.08, and 0.94, respectively, compared with the reference group of >7 to ≤14 days. LTFU HRs were 1.02, 1.07, 0.85, 0.97, and 3.96, respectively. Among patients not on ART, 88% of deaths and 85% of LTFU occurred during the first 3 months after becoming ART eligible, but only 37% and 29% among adolescents on ART, respectively. Conclusions: Neither mortality or LTFU was associated with varying time to ART. The initiation process can be tailored to the adolescents' needs and individual life situations without risking to increase poor treatment outcomes. Early mortality was high despite rapid ART initiation, calling for earlier rather than faster initiation through HIV testing scale-up. PMID:28002183

Pooled nucleic acid testing to identify antiretroviral treatment failure during HIV infection.

PubMed

May, Susanne; Gamst, Anthony; Haubrich, Richard; Benson, Constance; Smith, Davey M

2010-02-01

Pooling strategies have been used to reduce the costs of polymerase chain reaction-based screening for acute HIV infection in populations in which the prevalence of acute infection is low (less than 1%). Only limited research has been done for conditions in which the prevalence of screening positivity is higher (greater than 1%). We present data on a variety of pooling strategies that incorporate the use of polymerase chain reaction-based quantitative measures to monitor for virologic failure among HIV-infected patients receiving antiretroviral therapy. For a prevalence of virologic failure between 1% and 25%, we demonstrate relative efficiency and accuracy of various strategies. These results could be used to choose the best strategy based on the requirements of individual laboratory and clinical settings such as required turnaround time of results and availability of resources. Virologic monitoring during antiretroviral therapy is not currently being performed in many resource-constrained settings largely because of costs. The presented pooling strategies may be used to significantly reduce the cost compared with individual testing, make such monitoring feasible, and limit the development and transmission of HIV drug resistance in resource-constrained settings. They may also be used to design efficient pooling strategies for other settings with quantitative screening measures.

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.

Antiretroviral treatment-induced dyslipidemia in HIV-infected patients is influenced by the APOC3-related rs10892151 polymorphism.

PubMed

Aragonès, Gerard; Alonso-Villaverde, Carlos; Pardo-Reche, Pedro; Rull, Anna; Beltrán-Debón, Raúl; Rodríguez-Gallego, Esther; Fernández-Sender, Laura; Camps, Jordi; Joven, Jorge

2011-09-22

The recently observed association between the APOC3-related rs10892151 polymorphism and serum triglyceride levels has prompted us the possibility to explore whether this genetic variant may play a major role in human immunodeficiency virus (HIV)/antiretroviral therapy-induced dyslipidemia. We determined the rs10892151 genotype distribution and serum apolipoprotein (apo) C-III concentration in a group of HIV-infected patients (n = 208) and in a group of age and sex-matched healthy volunteers (n = 200). Circulating lipid and lipoprotein levels were followed for 12 months after antiretroviral treatment initiation in the HIV-infected group. There were no significant variations in the frequency of the A allele between the healthy and HIV-infected groups (7.5 vs. 8.6%, respectively; p = 0.7); additionally, the A allele was not related to serum apo C-III concentration. However, among patients receiving protease inhibitor (PI) treatment, carriers of the A allele had significantly increased serum triglyceride (5.76 ± 2.54 mmol/L) and total cholesterol (6.63 ± 2.85 mmol/L) concentrations together with depressed levels of HDL-cholesterol (0.75 ± 0.3 mmol/L) when compared with patients not carrying the allele (2.43 ± 1.32, 5.2 ± 2.17 and 1.24 ± 0.4 mmol/L, respectively) at the end of the study. This effect was only evident for HDL-cholesterol concentration when patients were treated with non-nucleoside reverse transcriptase inhibitors (1.05 ± 0.4 vs. 1.28 ± 0.4 mmol/L). The A allelic variant of the rs10892151 polymorphism is not associated with serum apo C-III concentration, but predisposes HIV-infected patients to less favorable lipid profile, particularly in those patients treated with PIs.

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.

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

Assessment, Diagnosis, and Treatment of HIV-Associated Neurocognitive Disorder: A Consensus Report of the Mind Exchange Program

PubMed Central

Antinori, Andrea; Arendt, Gabriele; Grant, Igor; Letendre, Scott; Chair; Muñoz-Moreno, Jose A.; Eggers, Christian; Brew, Bruce; Brouillette, Marie-Josée; Bernal-Cano, Francisco; Carvalhal, Adriana; Christo, Paulo Pereira; Cinque, Paola; Cysique, Lucette; Ellis, Ronald; Everall, Ian; Gasnault, Jacques; Husstedt, Ingo; Korten, Volkan; Machala, Ladislav; Obermann, Mark; Ouakinin, Silvia; Podzamczer, Daniel; Portegies, Peter; Rackstraw, Simon; Rourke, Sean; Sherr, Lorraine; Streinu-Cercel, Adrian; Winston, Alan; Wojna, Valerie; Yazdanpannah, Yazdan; Arbess, Gordon; Baril, Jean-Guy; Begovac, Josip; Bergin, Colm; Bonfanti, Paolo; Bonora, Stefano; Brinkman, Kees; Canestri, Ana; Cholewińska-Szymańska, Graźyna; Chowers, Michal; Cooney, John; Corti, Marcelo; Doherty, Colin; Elbirt, Daniel; Esser, Stefan; Florence, Eric; Force, Gilles; Gill, John; Goffard, Jean-Christophe; Harrer, Thomas; Li, Patrick; de Kerckhove, Linos Van; Knecht, Gaby; Matsushita, Shuzo; Matulionyte, Raimonda; McConkey, Sam; Mouglignier, Antoine; Oka, Shinichi; Penalva, Augusto; Riesenberg, Klaris; Sambatakou, Helen; Tozzi, Valerio; Vassallo, Matteo; Wetterberg, Peter; Drapato, Alicia Wiercińska

2013-01-01

Many practical clinical questions regarding the management of human immunodeficiency virus (HIV)–associated neurocognitive disorder (HAND) remain unanswered. We sought to identify and develop practical answers to key clinical questions in HAND management. Sixty-six specialists from 30 countries provided input into the program, which was overseen by a steering committee. Fourteen questions were rated as being of greatest clinical importance. Answers were drafted by an expert group based on a comprehensive literature review. Sixty-three experts convened to determine consensus and level of evidence for the answers. Consensus was reached on all answers. For instance, good practice suggests that all HIV patients should be screened for HAND early in disease using standardized tools. Follow-up frequency depends on whether HAND is already present or whether clinical data suggest risk for developing HAND. Worsening neurocognitive impairment may trigger consideration of antiretroviral modification when other causes have been excluded. The Mind Exchange program provides practical guidance in the diagnosis, monitoring, and treatment of HAND. PMID:23175555

Coconut Oil Extract Mitigates Testicular Injury Following Adjuvant Treatment with Antiretroviral Drugs

PubMed Central

Ogedengbe, Oluwatosin O; Jegede, Ayoola I; Onanuga, Ismail O; Offor, Ugochukwu; Naidu, Edwin CS; Peter, Aniekan I; Azu, Onyemaechi O

2016-01-01

Increased access to highly active antiretroviral therapy (HAART) has made the management of drug toxicities an increasingly crucial component of HIV. This study investigated the effects of adjuvant use of coconut oil and HAART on testicular morphology and seminal parameters in Sprague- Dawley rats. Twelve adult male Sprague-Dawley rats, weighing 153~169 g were distributed into four groups (A–D) and treated as follows: A served as control (distilled water); B (HAART cocktail- Zidovudine, Lamivudine and Nevirapine); C (HAART + Virgin coconut oil 10 mL/kg) and D (Virgin coconut oil 10 mL/kg). After 56 days of treatment, animals were killed and laparotomy to exercise the epididymis for seminal fluid analyses done whilst testicular tissues were processed for histomorphometric studies. Result showed a significant decline in sperm motility (P < 0.05) and count (P < 0.0001) in HAART-treated animals while there was insignificant changes in other parameters in groups C and D except count that was reduced (P < 0.0001) when compared with controls. Histomorphological studies showed HAART caused disorders in seminiferous tubular architecture with significant (P < 0.01) decline in epithelial height closely mirrored by extensive reticulin framework and positive PAS cells. Adjuvant Virgin coconut oil + HAART resulted in significant decrease in seminiferous tubular diameter (P < 0.05), but other morphometric and histological parameters were similar to control or Virgin coconut oil alone (which showed normal histoarchitecture levels). While derangements in testicular and seminal fluid parameters occurred following HAART, adjuvant treatment with Virgin coconut oil restored the distortions emanating thereof. PMID:27818734

Coconut Oil Extract Mitigates Testicular Injury Following Adjuvant Treatment with Antiretroviral Drugs.

PubMed

Ogedengbe, Oluwatosin O; Jegede, Ayoola I; Onanuga, Ismail O; Offor, Ugochukwu; Naidu, Edwin Cs; Peter, Aniekan I; Azu, Onyemaechi O

2016-10-01

Increased access to highly active antiretroviral therapy (HAART) has made the management of drug toxicities an increasingly crucial component of HIV. This study investigated the effects of adjuvant use of coconut oil and HAART on testicular morphology and seminal parameters in Sprague- Dawley rats. Twelve adult male Sprague-Dawley rats, weighing 153~169 g were distributed into four groups (A-D) and treated as follows: A served as control (distilled water); B (HAART cocktail- Zidovudine, Lamivudine and Nevirapine); C (HAART + Virgin coconut oil 10 mL/kg) and D (Virgin coconut oil 10 mL/kg). After 56 days of treatment, animals were killed and laparotomy to exercise the epididymis for seminal fluid analyses done whilst testicular tissues were processed for histomorphometric studies. Result showed a significant decline in sperm motility ( P < 0.05) and count ( P < 0.0001) in HAART-treated animals while there was insignificant changes in other parameters in groups C and D except count that was reduced ( P < 0.0001) when compared with controls. Histomorphological studies showed HAART caused disorders in seminiferous tubular architecture with significant ( P < 0.01) decline in epithelial height closely mirrored by extensive reticulin framework and positive PAS cells. Adjuvant Virgin coconut oil + HAART resulted in significant decrease in seminiferous tubular diameter ( P < 0.05), but other morphometric and histological parameters were similar to control or Virgin coconut oil alone (which showed normal histoarchitecture levels). While derangements in testicular and seminal fluid parameters occurred following HAART, adjuvant treatment with Virgin coconut oil restored the distortions emanating thereof.

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

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

78 FR 31563 - Ryan White HIV/AIDS Program Core Medical Services Waiver; Application Requirements

Federal Register 2010, 2011, 2012, 2013, 2014

2013-05-24

... HIV/AIDS Program Core Medical Services Waiver; Application Requirements AGENCY: Health Resources and... Public Health Service Act, as amended by the Ryan White HIV/AIDS Treatment Extension Act of 2009 (Ryan... medical services, including antiretroviral drugs, for individuals with HIV/AIDS identified and eligible...

'Time is costly': modelling the macroeconomic impact of scaling-up antiretroviral treatment in sub-Saharan Africa.

PubMed

Ventelou, Bruno; Moatti, Jean-Paul; Videau, Yann; Kazatchkine, Michel

2008-01-02

Macroeconomic policy requirements may limit the capacity of national and international policy-makers to allocate sufficient resources for scaling-up access to HIV care and treatment in developing countries. An endogenous growth model, which takes into account the evolution of society's human capital, was used to assess the macroeconomic impact of policies aimed at scaling-up access to HIV/AIDS treatment in six African countries (Angola, Benin, Cameroon, Central African Republic, Ivory Coast and Zimbabwe). The model results showed that scaling-up access to treatment in the affected population would limit gross domestic product losses due to AIDS although differently from country to country. In our simulated scenarios of access to antiretroviral therapy, only 10.3% of the AIDS shock is counterbalanced in Zimbabwe, against 85.2% in Angola and even 100.0% in Benin (a total recovery). For four out of the six countries (Angola, Benin, Cameroon, Ivory Coast), the macro-economic gains of scaling-up would become potentially superior to its associated costs in 2010. Despite the variability of HIV prevalence rates between countries, macro-economic estimates strongly suggest that a massive investment in scaling-up access to HIV treatment may efficiently counteract the detrimental long-term impact of the HIV pandemic on economic growth, to the extent that the AIDS shock has not already driven the economy beyond an irreversible 'no-development epidemiological trap'.

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.

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.

Stavudine (d4T) concentrations in women receiving post-partum antiretroviral treatment and their breastfeeding infants

PubMed Central

Fogel, Jessica M.; Taha, Taha E.; Sun, Jin; Hoover, Donald R.; Parsons, Teresa L.; Kumwenda, Johnstone J.; Mofenson, Lynne M.; Fowler, Mary Glenn; Hendrix, Craig W.; Kumwenda, Newton I.; Eshleman, Susan H.; Mirochnick, Mark

2012-01-01

First-line antiretroviral treatment regimens in resource-limited settings used in breastfeeding mothers often include stavudine (d4T). Limited data describing d4T concentrations in breast milk are available. We analyzed d4T concentrations in 52 mother-infant pairs using ultra-performance liquid chromatography-tandem mass spectrometry (lower limit of quantification: 5 ng/ml in plasma, 20 ng/ml in breast milk). Median (interquartile range) d4T concentrations were 86 (36–191) ng/ml in maternal plasma, 151 (48–259) ng/ml in whole milk, 190 (58–296) ng/ml in skim milk, and <5 (<5-<5) ng/ml in infant plasma. While d4T is concentrated in breast milk relative to maternal plasma, the infant d4T dose received from breast milk is very small and not clinically significant. PMID:22614899

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

[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].

Existing capacity to manage pharmaceuticals and related commodities in East Africa: an assessment with specific reference to antiretroviral therapy

PubMed Central

Waako, Paul J; Odoi-adome, Richard; Obua, Celestino; Owino, Erisa; Tumwikirize, Winnie; Ogwal-okeng, Jasper; Anokbonggo, Willy W; Matowe, Lloyd; Aupont, Onesky

2009-01-01

Background East African countries have in the recent past experienced a tremendous increase in the volume of antiretroviral drugs. Capacity to manage these medicines in the region remains limited. Makerere University, with technical assistance from the USAID supported Rational Pharmaceutical Management Plus (RPM Plus) Program of Management Sciences for Health (MSH) established a network of academic institutions to build capacity for pharmaceutical management in the East African region. The initiative includes institutions from Uganda, Tanzania, Kenya and Rwanda and aims to improve access to safe, effective and quality-assured medicines for the treatment of HIV/AIDS, TB and Malaria through spearheading in-country capacity. The initiative conducted a regional assessment to determine the existing capacity for the management of antiretroviral drugs and related commodities. Methods Heads and implementing workers of fifty HIV/AIDS programs and institutions accredited to offer antiretroviral services in Uganda, Kenya, Tanzania and Rwanda were key informants in face-to-face interviews guided by structured questionnaires. The assessment explored categories of health workers involved in the management of ARVs, their knowledge and practices in selection, quantification, distribution and use of ARVs, nature of existing training programs, training preferences and resources for capacity building. Results Inadequate human resource capacity including, inability to select, quantify and distribute ARVs and related commodities, and irrational prescribing and dispensing were some of the problems identified. A competence gap existed in all the four countries with a variety of healthcare professionals involved in the supply and distribution of ARVs. Training opportunities and resources for capacity development were limited particularly for workers in remote facilities. On-the-job training and short courses were the preferred modes of training. Conclusion There is inadequate capacity for

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

The influence of patient beliefs and treatment satisfaction on the discontinuation of current first-line antiretroviral regimens.

PubMed

Casado, J L; Marín, A; Romero, V; Bañón, S; Moreno, A; Perez-Elías, M J; Moreno, S; Rodriguez-Sagrado, M A

2016-01-01

Large cohort studies have shown a high rate of first-line combination antiretroviral therapy (cART) regimen discontinuation in HIV-infected patients, attributed to characteristics of the cART regimen or toxicity. A cohort study of 274 patients receiving a first-line regimen was carried out. Patients' perceptions and beliefs prior to initiation were assessed using an attitude towards medication scale (0-15 points), and their satisfaction during therapy was assessed using an HIV treatment satisfaction questionnaire (HIVTSQ). Treatment discontinuation was defined as any switch in the cART regimen. During 474.8 person-years of follow-up, 63 (23%) patients changed their cART regimen, mainly because of toxicity/intolerance (42; 67%). The overall rate of change was 13.2 per 100 patient-years [95% confidence interval (CI) 11.1-16.4 per 100 patient-years]. An efavirenz (EFV)-based single tablet regimen showed the highest rate of adverse events (27%), but the lowest rate of change (16%; 7.44 per 100 patient-years). Cox regression revealed a decreased hazard of first regimen termination with better initial attitude towards drugs [hazard ratio (HR) 0.76; 95% CI 0.62-0.93; P < 0.01] and higher satisfaction (HR 0.94; 95% CI 0.89-0.99; P = 0.01), and an increased hazard of termination with the presence of adverse events (HR 7.7; 95% CI 2.4-11.6; P < 0.01). One-third of patients (18 of 59; 31%) with mild/moderate adverse events (which were mainly central nervous system symptoms) continued the regimen; these patients, compared with those discontinuing therapy, showed better perception of therapy (mean score 14.4 versus 12.1, respectively; P = 0.05) and greater satisfaction during therapy (mean score 50.6 versus 44.6, respectively; P = 0.04). Patients' beliefs and satisfaction with therapy influence the durability of the first antiretroviral regimen. These patient-related factors modulate the impact of mild adverse events, and could explain differences in the

Effect of analytical treatment interruption and reinitiation of antiretroviral therapy on HIV reservoirs and immunologic parameters in infected individuals.

PubMed

Clarridge, Katherine E; Blazkova, Jana; Einkauf, Kevin; Petrone, Mary; Refsland, Eric W; Justement, J Shawn; Shi, Victoria; Huiting, Erin D; Seamon, Catherine A; Lee, Guinevere Q; Yu, Xu G; Moir, Susan; Sneller, Michael C; Lichterfeld, Mathias; Chun, Tae-Wook

2018-01-01

Therapeutic strategies aimed at achieving antiretroviral therapy (ART)-free HIV remission in infected individuals are under active investigation. Considering the vast majority of HIV-infected individuals experience plasma viral rebound upon cessation of therapy, clinical trials evaluating the efficacy of curative strategies would likely require inclusion of ART interruption. However, it is unclear what impact short-term analytical treatment interruption (ATI) and subsequent reinitiation of ART have on immunologic and virologic parameters of HIV-infected individuals. Here, we show a significant increase of HIV burden in the CD4+ T cells of infected individuals during ATI that was correlated with the level of plasma viral rebound. However, the size of the HIV reservoirs as well as immune parameters, including markers of exhaustion and activation, returned to pre-ATI levels 6-12 months after the study participants resumed ART. Of note, the proportions of near full-length, genome-intact and structurally defective HIV proviral DNA sequences were similar prior to ATI and following reinitiation of ART. In addition, there was no evidence of emergence of antiretroviral drug resistance mutations within intact HIV proviral DNA sequences following reinitiation of ART. These data demonstrate that short-term ATI does not necessarily lead to expansion of the persistent HIV reservoir nor irreparable damages to the immune system in the peripheral blood, warranting the inclusion of ATI in future clinical trials evaluating curative strategies.

When masculinity interferes with women's treatment of HIV infection: a qualitative study about adherence to antiretroviral therapy in Zimbabwe

PubMed Central

2011-01-01

Background Social constructions of masculinity have been shown to serve as an obstacle to men's access and adherence to antiretroviral therapies (ART). In the light of women's relative lack of power in many aspects of interpersonal relationships with men in many African settings, our objective is to explore how male denial of HIV/AIDS impacts on their female partners' ability to access and adhere to ART. Methods We conducted a qualitative case study involving thematic analysis of 37 individual interviews and five focus groups with a total of 53 male and female antiretroviral drug users and 25 healthcare providers in rural eastern Zimbabwe. Results Rooted in hegemonic notions of masculinity, men saw HIV/AIDS as a threat to their manhood and dignity and exhibited a profound fear of the disease. In the process of denying and avoiding their association with AIDS, many men undermine their wives' efforts to access and adhere to ART. Many women felt unable to disclose their HIV status to their husbands, forcing them to take their medication in secret, and act without a supportive treatment partner, which is widely accepted to be vitally important for adherence success. Some husbands, when discovering that their wives are on ART, deny them permission to take the drugs, or indeed steal the drugs for their own treatment. Men's avoidance of HIV also leave many HIV-positive women feeling vulnerable to re-infection as their husbands, in an attempt to demonstrate their manhood, are believed to continue engaging in HIV-risky behaviours. Conclusions Hegemonic notions of masculinity can interfere with women's adherence to ART. It is important that those concerned with promoting effective treatment services recognise the gender and household dynamics that may prevent some women from successfully adhering to ART, and explore ways to work with both women and men to identify couples-based strategies to increase adherence to ART PMID:21658260

Program closure and change among VA substance abuse treatment programs.

PubMed

Floyd, A S

1999-10-01

The population of Veterans Affairs (VA) substance abuse treatment programs in 1990 and 1994 was examined to determine which factors-program legitimacy or cost-accounted for program closure and change. Legitimacy is a concept in institutional theory that organizations tend to take on a form appropriate to the environment. The study had two competing hypotheses. The first was that if external pressures push programs to produce high-quality and efficient treatment, then those that are initially closer to the legitimate form should be less likely to close later, and among surviving programs they should be less likely to experience change. The second hypothesis was that cost is the primary factor in program closure and change. The study used data from administrative surveys of all VA programs (273 in 1990 and 389 in 1994). Program legitimacy variables measured whether programs offered the prevalent type of treatment, such as 12-step groups or behavioral treatment, and had the prevalent type of staff. Program costs did not explain closure or change. For inpatient programs, the risk of closure increased in facilities with more than one substance abuse treatment program. The risk of closure increased for outpatient programs offering the prevalent type of treatment, contrary to what was predicted by the legitimacy hypothesis. Inpatient programs that offered the prevalent treatment were less likely to change the type of treatment offered. Patterns of change differed over time for inpatient and outpatient programs. Legitimacy factors, rather than cost, seem to play a role in program closure and change, although the picture is clearer for inpatient programs than for outpatient programs.

The need for anal dysplasia screening and treatment programs for HIV-infected men who have sex with men: a review of the literature.

PubMed

Roark, Randall

2011-01-01

Anal cancer rates, which were higher for men who have sex with men (MSM) compared to the general population before HIV, increased dramatically after the HIV epidemic began and continue to increase in HIV-infected MSM despite the advent of antiretroviral therapy and associated immune reconstitution. Because of the similarity to cervical cancer and an established link to human papillomavirus infection, many experts have called for widespread implementation of anal cytological screening and treatment programs, especially for HIV-infected MSM. However, other experts argue that it is too early for widespread implementation of such programs for reasons including lack of clear evidence that anal dysplasia is a precursor to anal cancer, or that detecting and treating anal dysplasia reduces the risk for developing anal cancer; lack of effective treatments for anal dysplasia when it is discovered; and lack of resources. This paper reviews current literature regarding these issues. Copyright © 2011 Association of Nurses in AIDS Care. Published by Elsevier Inc. All rights reserved.

Marital sex among people living with HIV receiving antiretroviral treatment in northern Thailand.

PubMed

Le Coeur, Sophie; Bozon, Michel; Lelièvre, Eva; Sirijitraporn, Preecha; Pipustanawong, Narongdate; Cowatcharagul, Worawut; Pattanapornpun, Nopporn

2014-01-01

Before the advent of effective antiretroviral treatment (ART), the sexuality of people living with HIV was mostly discussed in terms of risk. To assess the extent to which ART allows people living with HIV to regain a regular sexual life, we surveyed all HIV-infected people treated in four hospitals in Northern Thailand and a control group from the general population matched by sex, age and residence. Data included socio-demographic and health characteristics, frequency of sexual intercourse in the last month and condom use. Our findings indicate that people living with HIV less often live in steady partnership (50% of the HIV-infected people versus 79% of the controls). After adjusting for factors known to influence sexuality, their probability of being sexually active was estimated to be about half that of the controls. When sexually active, men had a reduced sexual activity compared to controls (2.8 intercourse in the last month versus 4.0), while levels of reported sexual activity were similar among women (2.2 versus 2.8, respectively). Consistent condom use was high among people living with HIV (66% for women and 70% for men).

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…

Comparative efficacy and safety of first-line antiretroviral therapy for the treatment of HIV infection: a systematic review and network meta-analysis.

PubMed

Kanters, Steve; Vitoria, Marco; Doherty, Meg; Socias, Maria Eugenia; Ford, Nathan; Forrest, Jamie I; Popoff, Evan; Bansback, Nick; Nsanzimana, Sabin; Thorlund, Kristian; Mills, Edward J

2016-11-01

New antiretroviral therapy (ART) regimens for HIV could improve clinical outcomes for patients. To inform global guidelines, we aimed to assess the comparative effectiveness of recommended ART regimens for HIV in ART-naive patients. For this systematic review and network meta-analysis, we searched for randomised clinical trials published up to July 5, 2015, comparing recommended antiretroviral regimens in treatment-naive adults and adolescents (aged 12 years or older) with HIV. We extracted data on trial and patient characteristics, and the following primary outcomes: viral suppression, mortality, AIDS defining illnesses, discontinuations, discontinuations due to adverse events, and serious adverse events. We synthesised data using network meta-analyses in a Bayesian framework and included older treatments, such as indinavir, to serve as connecting nodes. We defined network nodes in terms of specific antivirals rather than specific ART regimens. We categorised backbone regimens and adjusted for them through group-specific meta-regression. We used the GRADE framework to interpret the strength of inference. We identified 5865 citations through database searches and other sources, of which, 126 articles related to 71 unique trials were included in the network analysis, including 34 032 patients randomly assigned to 161 treatment groups. For viral suppression at 48 weeks, compared with efavirenz, the odds ratio (OR) for viral suppression was 1·87 (95% credible interval [CrI] 1·34-2·64) with dolutegravir and 1·40 (1·02-1·96) with raltegravir; with respect to viral suppression, low-dose efavirenz was similar to all other treatments. Both low-dose efavirenz and integrase strand transfer inhibitors tended to be protective of discontinuations due to adverse events relative to normal-dose efavirenz. The most protective effect relative to efavirenz in network meta-analyses was that of dolutegravir (OR 0·26, 95% CrI 0·14-0·47), followed by low-dose efavirenz (0·39

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

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.

Dosing antiretroviral medication when crossing time zones: a review

PubMed Central

Lewis, Joseph M.; Volny-Anne, Alain; Waitt, Catriona; Boffito, Marta; Khoo, Saye

2016-01-01

International tourism continues to increase worldwide, and people living with HIV and their clinicians are increasingly confronted with the problem of how to dose antiretroviral therapy during transmeridian air travel across time zones. No guidance on this topic currently exists. This review is a response to requests from patient groups for clear, practical and evidence-based guidance for travelling on antiretroviral therapy; we present currently available data on the pharmacokinetic forgiveness and toxicity of various antiretroviral regimens, and synthesize this data to provide guidelines on how to safely dose antiretrovirals when travelling across time zones. PMID:26684823

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.

Pharmacokinetics of Antiretrovirals in Mucosal Tissue

PubMed Central

Cottrell, M.L.; Srinivas, N.; Kashuba, A.D.M.

2015-01-01

Introduction In the absence of an HIV vaccine or cure, antiretroviral (ARV) based prevention strategies are being investigated to reduce HIV incidence. These prevention strategies depend on achieving effective drug concentrations at the site HIV exposure which is most commonly the mucosal tissues of the lower gastrointestinal tract and the female genital tract. Areas covered This article collates all known data regarding drug exposure in these vulnerable mucosal tissues, and reviews important mechanisms of ARV drug distribution. Research papers and abstracts describing antiretroviral pharmacokinetics in the female genital tract and lower gastrointestinal mucosal tissues available in MEDLINE® or presented at scientific conferences prior to December 2014 are reviewed in detail. Important influences on ARV mucosal tissue distribution, including protein binding, active drug transport, and endogenous hormones, are also reviewed. Expert opinion ARVs exhibit highly variable pharmacokinetics in mucosal tissues. In general, antiretroviral exposure is higher in the lower gastrointestinal tract compared to the female genital tract, but concentrations required for protective efficacy are largely unknown. The expected site of HIV exposure represents an important consideration when designing and optimizing antiretroviral based prevention strategies. PMID:25797064

Generalized psychological distress among HIV-infected patients enrolled in antiretroviral treatment in Dilla University Hospital, Gedeo zone, Ethiopia

PubMed Central

Tesfaye, Solomon H.; Bune, Girma T.

2014-01-01

Background Psychological disorders like depression and anxiety are potentially dangerous conditions. In the context of HIV/AIDS, this can influence health-seeking behavior or uptake of diagnosis and treatment for HIV/AIDS, add to the burden of disease for HIV patients, create difficulty in adherence to treatment, and increase the risk of mortality and morbidity. The objective of this study was to assess the prevalence and correlates of generalized psychological distress among HIV-infected subjects on antiretroviral treatment (ART). Design An institution-based cross-sectional study was conducted. Interviews were conducted with 500 patients initiating ART at Dilla Referral Hospital. Generalized psychological distress was measured using the Hospital Anxiety and Depression Scale (HADS). A cutoff score ≥19 was used to identify possible cases of patients with generalized psychological distress. Multivariable logistic regression analysis using SPSS Version 20 was performed to identify factors associated with psychological distress. Results The prevalence of generalized psychological distress among the population of this study was 11.2% (HADS≥19). Factors independently associated with generalized psychological distress were moderate stress (OR=6.87, 95% CI 2.27–20.81), low social support (OR=10.17, 95% CI 2.85–36.29), number of negative life events of six and above (OR=3.99, 95% CI 1.77–8.99), not disclosing HIV status (OR=5.24, 95% CI 1.33–20.62), and CD4 cell count of <200 cells/mm3 (OR=1.98, 95% CI 0.45–0.83) and 200–499 cells/mm3 (OR=3.53, 95% CI 1.62–7.73). Conclusions This study provides prevalence of psychological distress lower than the prevalence of common mental disorders in Ethiopia and comparable to some other studies in sub-Saharan Africa. The findings are important in terms of their relevance to identifying high-risk groups for generalized psychological distress and preventing distress through integrating mental health services with HIV

Generalized psychological distress among HIV-infected patients enrolled in antiretroviral treatment in Dilla University Hospital, Gedeo zone, Ethiopia.

PubMed

Tesfaye, Solomon H; Bune, Girma T

2014-01-01

Psychological disorders like depression and anxiety are potentially dangerous conditions. In the context of HIV/AIDS, this can influence health-seeking behavior or uptake of diagnosis and treatment for HIV/AIDS, add to the burden of disease for HIV patients, create difficulty in adherence to treatment, and increase the risk of mortality and morbidity. The objective of this study was to assess the prevalence and correlates of generalized psychological distress among HIV-infected subjects on antiretroviral treatment (ART). An institution-based cross-sectional study was conducted. Interviews were conducted with 500 patients initiating ART at Dilla Referral Hospital. Generalized psychological distress was measured using the Hospital Anxiety and Depression Scale (HADS). A cutoff score ≥19 was used to identify possible cases of patients with generalized psychological distress. Multivariable logistic regression analysis using SPSS Version 20 was performed to identify factors associated with psychological distress. The prevalence of generalized psychological distress among the population of this study was 11.2% (HADS≥19). Factors independently associated with generalized psychological distress were moderate stress (OR=6.87, 95% CI 2.27-20.81), low social support (OR=10.17, 95% CI 2.85-36.29), number of negative life events of six and above (OR=3.99, 95% CI 1.77-8.99), not disclosing HIV status (OR=5.24, 95% CI 1.33-20.62), and CD4 cell count of <200 cells/mm(3) (OR=1.98, 95% CI 0.45-0.83) and 200-499 cells/mm(3) (OR=3.53, 95% CI 1.62-7.73). This study provides prevalence of psychological distress lower than the prevalence of common mental disorders in Ethiopia and comparable to some other studies in sub-Saharan Africa. The findings are important in terms of their relevance to identifying high-risk groups for generalized psychological distress and preventing distress through integrating mental health services with HIV/AIDS care and support program.

CROI 2017: Advances in Antiretroviral Therapy

PubMed Central

Jones, Joyce; Taylor, Barbara S.; Tieu, Hong-Van; Wilkin, Timothy J.

2017-01-01

The 2017 Conference on Retroviruses and Opportunistic Infections (CROI) featured exciting preclinical data on investigational antiretroviral agents with good in vitro efficacy and long half-lives. Investigational medications, including bictegravir, demonstrated excellent efficacy and tolerability, as did dual-agent therapy with dolutegravir paired with rilpivirine or with lamivudine. Dolutegravir monotherapy proved inadvisable due to virologic failure and resistance. The gap between high- and low-income settings along the HIV care continuum is narrowing, with Zimbabwe, Malawi, and Zambia approaching the 90-90-90 targets established by the joint United Nations Programme on HIV/AIDS (UNAIDS), whereas communities in the Southern United States are falling behind. Innovative strategies to improve outcomes include 2-way text messaging, home-based HIV testing, peer navigation, and New York City's realignment of services into comprehensive sexual health programs. A high prevalence of resistance was documented in low- and middle-income settings and policy considerations were modeled to address increasing resistance rates. Novel resistance mutations to integrase strand transfer inhibitors and nucleoside analogue reserve transcriptase inhibitors were identified, but the clinical implications are unclear and require further investigation. Several studies provided insights on dosing and safety of antiretroviral therapy to prevent mother-to-child transmission through pharmacokinetic analysis. A special session devoted to Zika virus included a study of its effects on the central nervous system and a promising animal study of a Zika vaccine. PMID:28598790

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

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

An overview of the antiretroviral market.

PubMed

Camponeschi, Geannan; Fast, Jessica; Gauval, Marianne; Guerra, Katherine; Moore, Meredith; Ravinutala, Siddharth; Ripin, David; Shepel, Vadim

2013-11-01

An understanding of the current state of the antiretroviral marketplace is an important context in which to consider drug optimization work. The antiretroviral marketplace has undergone a remarkable evolution over the past 11 years, expanding from serving less than 300 000 patients in low and middle-income countries in 2002 to almost 10 million patients today. In addition to dramatic growth, a steady and rapid improvement in the drugs and drug regimens used to treat patients has characterized a rapidly changing market. The antiretroviral marketplace has been characterized by rapid growth and a succession of improving drugs and regimens over the past 11 years. The dynamic and innovative marketplace provides a strong platform from which to introduce new, optimized drugs and regimens to better serve patients' health needs.

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

Predictors of unstructured antiretroviral treatment interruption and resumption among HIV-positive individuals in Canada.

PubMed

Samji, H; Taha, T E; Moore, D; Burchell, A N; Cescon, A; Cooper, C; Raboud, J M; Klein, M B; Loutfy, M R; Machouf, N; Tsoukas, C M; Montaner, J S G; Hogg, R S

2015-02-01

Sustained optimal use of combination antiretroviral therapy (cART) has been shown to decrease morbidity, mortality and HIV transmission. However, incomplete adherence and treatment interruption (TI) remain challenges to the full realization of the promise of cART. We estimated trends and predictors of treatment interruption and resumption among individuals in the Canadian Observational Cohort (CANOC) collaboration. cART-naïve individuals ≥ 18 years of age who initiated cART between 2000 and 2011 were included in the study. We defined TIs as ≥ 90 consecutive days off cART. We used descriptive analyses to study TI trends over time and Cox regression to identify factors predicting time to first TI and time to treatment resumption after a first TI. A total of 7633 participants were eligible for inclusion in the study, of whom 1860 (24.5%) experienced a TI. The prevalence of TI in the first calendar year of cART decreased by half over the study period. Our analyses highlighted a higher risk of TI among women [adjusted hazard ratio (aHR) 1.59; 95% confidence interval (CI) 1.33-1.92], younger individuals (aHR 1.27; 95% CI 1.15-1.37 per decade increase), earlier treatment initiators (CD4 count ≥ 350 vs. <200 cells/μL: aHR 1.46; 95% CI 1.17-1.81), Aboriginal participants (aHR 1.67; 95% CI 1.27-2.20), injecting drug users (aHR 1.43; 95% CI 1.09-1.89) and users of zidovudine vs. tenofovir in the initial cART regimen (aHR 2.47; 95% CI 1.92-3.20). Conversely, factors predicting treatment resumption were male sex, older age, and a CD4 cell count <200 cells/μL at cART initiation. Despite significant improvements in cART since its advent, our results demonstrate that TIs remain relatively prevalent. Strategies to support continuous HIV treatment are needed to maximize the benefits of cART. © 2014 British HIV Association.

[Assessment of factors associated with patients' comprehension of treatment at the start of antiretroviral therapy].

PubMed

Braga Ceccato, Maria das Graças; Acurcio, Francisco de Assis; Vallano, Antonio; Comini César, Cibele; Crosland Guimarães, Mark Drew

2009-01-01

The aim of this study was to evaluate factors associated with patients' comprehension of antiretroviral therapy (ART). Cross-sectional analysis in which patients at 2 HIV/AIDS public referral centers (Belo Horizonte, Brazil) were interviewed after initiating ART. Information was recorded on variables related to the patient's characteristics, the treatment prescribed, and the healthcare professional involved. A score indicating the patients' level of comprehension regarding the medications prescribed was obtained using a latent trait model estimated by the item response theory. A total of 406 patients were interviewed. Mean (SD) age was 35 (10) years, 227 were men (56%), 302 of Afro-American ethnicity (77%), and 213 had <8 years of education (53%). The regression model determined that 52.25% of the variability of comprehension was explained by the individual's characteristics. Variables associated (P<0.05) with poorest understanding about ART were lower education (<8 years), lack of knowledge about treatment duration and clinical severity, inadequate information provided by physicians, inability to understand pharmaceutical information, daily number of tablets, and the ART regimen prescribed. Comprehension of information about the ART regimen prescribed varies considerably between individuals. Nonetheless, several factors were found to be associated with the level of understanding: characteristics of the patient (education, clinical severity), characteristics of treatment (daily number of tablets, ART regimen prescribed), and contribution of healthcare professionals (information from physicians and pharmacists). Strategies to reinforce information about ART should be a priority for patients with a low level of understanding.

[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%.

Antiretroviral Treatment in HIV-1-Positive Mothers: Neurological Implications in Virus-Free Children

PubMed Central

Coelho, Antonio Victor Campos; Tricarico, Paola Maura; Celsi, Fulvio; Crovella, Sergio

2017-01-01

Since the worldwide introduction of antiretroviral therapy (ART) in human immunodeficiency virus type 1, HIV-1-positive mothers, together with HIV-1 testing prior to pregnancy, caesarian birth and breastfeeding cessation with replacement feeding, a reduction of HIV-1 mother-to-child transmission (MTCT) has been observed in the last few years. As such, an increasing number of children are being exposed in utero to ART. Several questions have arisen concerning the neurological effects of ART exposure in utero, considering the potential effect of antiretroviral drugs on the central nervous system, a structure which is in continuous development in the fetus and characterized by great plasticity. This review aims at discussing the possible neurological impairment of children exposed to ART in utero, focusing attention on the drugs commonly used for HIV-1 MTCT prevention, clinical reports of ART neurotoxicity in children born to HIV-1-positive mothers, and neurologic effects of protease inhibitors (PIs), especially ritonavir-“boosted” lopinavir (LPV/r) in cell and animal central nervous system models evaluating the potential neurotoxic effect of ART. Finally, we present the findings of a meta-analysis to assess the effects on the neurodevelopment of children exposed to ART in utero. PMID:28212307

HIV Treatment as Prevention: Modelling the Cost of Antiretroviral Treatment—State of the Art and Future Directions

PubMed Central

Meyer-Rath, Gesine; Over, Mead

2012-01-01

Policy discussions about the feasibility of massively scaling up antiretroviral therapy (ART) to reduce HIV transmission and incidence hinge on accurately projecting the cost of such scale-up in comparison to the benefits from reduced HIV incidence and mortality. We review the available literature on modelled estimates of the cost of providing ART to different populations around the world, and suggest alternative methods of characterising cost when modelling several decades into the future. In past economic analyses of ART provision, costs were often assumed to vary by disease stage and treatment regimen, but for treatment as prevention, in particular, most analyses assume a uniform cost per patient. This approach disregards variables that can affect unit cost, such as differences in factor prices (i.e., the prices of supplies and services) and the scale and scope of operations (i.e., the sizes and types of facilities providing ART). We discuss several of these variables, and then present a worked example of a flexible cost function used to determine the effect of scale on the cost of a proposed scale-up of treatment as prevention in South Africa. Adjusting previously estimated costs of universal testing and treatment in South Africa for diseconomies of small scale, i.e., more patients being treated in smaller facilities, adds 42% to the expected future cost of the intervention. PMID:22802731

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.

Development of a National Campaign Addressing South African Men's Fears About HIV Counseling and Testing and Antiretroviral Treatment

PubMed Central

Orr, Neil; Myers, Laura; Makhubele, Mzamani Benjamin; Matekane, Tselisehang; Delate, Richard; Mahlasela, Lusanda; Goldblatt, Brenda

2017-01-01

Introduction: South African men are less likely to get tested for HIV than women and are more likely to commence antiretroviral treatment (ART) at later stages of disease, default on treatment, and to die from AIDS compared with women. The purpose of this study was to conduct formative research into the ideational and behavioral factors that enable or create obstacles to mens' uptake of HIV counseling and testing (HCT) and ART. The study consulted men with a goal of developing a communication campaign aimed at improving the uptake of HIV testing and ART initiation among men. Methods: Eleven focus groups and 9 in-depth interviews were conducted with 97 male participants in 6 priority districts in 4 South African provinces in rural, peri-urban, and urban localities. Results: Fears of compromised masculine pride and reputation, potential community rejection, and fear of loss of emotional control (“the stress of knowing”) dominated men's rationales for avoiding HIV testing and treatment initiation. Conclusions: A communication campaign was developed based on the findings. Creative treatments aimed at redefining a ‘strong’ man as someone who faces his fears and knows his HIV status. The resultant campaign concept was: “positive or negative—you are still the same person.” PMID:27930614

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.

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

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.

Antiretroviral prophylaxis for HIV prevention in heterosexual men and women.

PubMed

Baeten, Jared M; Donnell, Deborah; Ndase, Patrick; Mugo, Nelly R; Campbell, James D; Wangisi, Jonathan; Tappero, Jordan W; Bukusi, Elizabeth A; Cohen, Craig R; Katabira, Elly; Ronald, Allan; Tumwesigye, Elioda; Were, Edwin; Fife, Kenneth H; Kiarie, James; Farquhar, Carey; John-Stewart, Grace; Kakia, Aloysious; Odoyo, Josephine; Mucunguzi, Akasiima; Nakku-Joloba, Edith; Twesigye, Rogers; Ngure, Kenneth; Apaka, Cosmas; Tamooh, Harrison; Gabona, Fridah; Mujugira, Andrew; Panteleeff, Dana; Thomas, Katherine K; Kidoguchi, Lara; Krows, Meighan; Revall, Jennifer; Morrison, Susan; Haugen, Harald; Emmanuel-Ogier, Mira; Ondrejcek, Lisa; Coombs, Robert W; Frenkel, Lisa; Hendrix, Craig; Bumpus, Namandjé N; Bangsberg, David; Haberer, Jessica E; Stevens, Wendy S; Lingappa, Jairam R; Celum, Connie

2012-08-02

Antiretroviral preexposure prophylaxis is a promising approach for preventing human immunodeficiency virus type 1 (HIV-1) infection in heterosexual populations. We conducted a randomized trial of oral antiretroviral therapy for use as preexposure prophylaxis among HIV-1-serodiscordant heterosexual couples from Kenya and Uganda. The HIV-1-seronegative partner in each couple was randomly assigned to one of three study regimens--once-daily tenofovir (TDF), combination tenofovir-emtricitabine (TDF-FTC), or matching placebo--and followed monthly for up to 36 months. At enrollment, the HIV-1-seropositive partners were not eligible for antiretroviral therapy, according to national guidelines. All couples received standard HIV-1 treatment and prevention services. We enrolled 4758 couples, of whom 4747 were followed: 1584 randomly assigned to TDF, 1579 to TDF-FTC, and 1584 to placebo. For 62% of the couples followed, the HIV-1-seronegative partner was male. Among HIV-1-seropositive participants, the median CD4 count was 495 cells per cubic millimeter (interquartile range, 375 to 662). A total of 82 HIV-1 infections occurred in seronegative participants during the study, 17 in the TDF group (incidence, 0.65 per 100 person-years), 13 in the TDF-FTC group (incidence, 0.50 per 100 person-years), and 52 in the placebo group (incidence, 1.99 per 100 person-years), indicating a relative reduction of 67% in the incidence of HIV-1 with TDF (95% confidence interval [CI], 44 to 81; P<0.001) and of 75% with TDF-FTC (95% CI, 55 to 87; P<0.001). Protective effects of TDF-FTC and TDF alone against HIV-1 were not significantly different (P=0.23), and both study medications significantly reduced the HIV-1 incidence among both men and women. The rate of serious adverse events was similar across the study groups. Eight participants receiving active treatment were found to have been infected with HIV-1 at baseline, and among these eight, antiretroviral resistance developed in two during the

Taking Antiretroviral Therapy for HIV Infection

PubMed Central

Laws, M Barton; Wilson, Ira B; Bowser, Diana M; Kerr, Sarah E

2000-01-01

OBJECTIVE To describe how people with HIV understand and experience the problem of adhering to antiretroviral medication regimens. DESIGN We performed a qualitative study based on interviews with HIV-infected patients, including 46 clients of AIDS service organizations, who were sampled according to age, ethnicity, and injection drug use history, and a convenience sample of 15 patients. Interviews were conducted in English or Spanish and were audiotaped and transcribed. PARTICIPANTS Of 52 respondents who had prescriptions for antiretroviral therapy, 25 were randomly selected for in-depth analysis. Of these, 5 reported having an AIDS diagnosis, 15 reported symptoms they attributed to HIV, and 5 reported having no symptoms of HIV disease. MEASUREMENTS AND MAIN RESULTS Investigators prepared structured abstracts of interviews to extract adherence-related data. One investigator compared the abstracts with the original transcripts to confirm the interpretations, and used the abstracts to organize and classify the findings. Most subjects (84%) reported recent nonadherent behavior, including ceasing treatment, medication “holidays,” sleeping through doses, forgetting doses, skipping doses due to side effects, and following highly asymmetric schedules. Initially, most reported that they were not significantly nonadherent, and many did not consider their behavior nonadherent. Only a minority clearly understood the possible consequences of missing doses. Most said they had not discussed their nonadherence with their physicians. CONCLUSIONS Many people rationalize their difficulty in adhering to HIV treatment by deciding that the standard of adherence they can readily achieve is appropriate. Physicians should inquire about adherence-related behavior in specific detail, and ensure that patients understand the consequences of not meeting an appropriate standard. PMID:11119181

Relationship between medication synchronization and antiretroviral adherence.

PubMed

Ghassemi, Emily; Smith, Jennifer; Owens, Laura; Herring, Charles; Holland, Melissa

2018-06-12

To compare antiretroviral adherence (measured as the proportion of days covered [PDC]) and change in viral load in insured, HIV-infected, adult outpatients enrolled and not enrolled in a medication synchronization program. This was a multicenter, retrospective, pilot cohort study. Fifty-eight insured, HIV-infected, outpatients at least 18 years of age receiving antiretroviral therapy (ART) for at least 3 months as of August 2015 were included. PDC, viral load, PDC dichotomized into adherent or nonadherent, and viral load dichotomized into detectable or undetectable were collected for each patient. Study data were compared in those with (enrolled) and without (not enrolled or control) medication synchronization. The study end points were analyzed between the 2 groups retrospectively after 3 months. PDC in patients undergoing medication synchronization was significantly higher than in control patients: mean ± SD 96 ± 9% versus 71 ± 27%, respectively (P < 0.0001). The medication synchronization group was also more likely to be adherent to ART than the control group (odds ratio 10.67, 95% confidence interval 2.63-43.31). In the medication synchronization group, 75.9% of patients had an undetectable baseline viral load, and 83.3% had an undetectable viral load at study completion. In the control group, 62.1% and 64.7% had an undetectable viral load at baseline and completion, respectively. No statistically significant change in viral load was observed between groups (P = 0.34). In insured, HIV-infected, adult outpatients, implementation of a medication synchronization program was associated with improved ART adherence. Future studies are needed to better assess the impact of medication synchronization on clinical outcomes. Copyright © 2018 American Pharmacists Association®. All rights reserved.

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.

Effect of improved access to antiretroviral therapy on clinical characteristics of patients enrolled in the HIV care and treatment clinic, at Muhimbili National Hospital (MNH), Dar es Salaam, Tanzania.

PubMed

Mugusi, Sabina F; Mwita, Julius C; Francis, Joel M; Aboud, Said; Bakari, Muhammad; Aris, Eric A; Swai, Andrew B; Mugusi, Ferdinand M; Pallangyo, Kisali; Sandstrom, Eric

2010-05-28

Sub-Saharan Africa has been severely affected by the HIV and AIDS pandemic. Global efforts at improving care and treatment has included scaling up use of antiretroviral therapy (ART). In Tanzania, HIV care and treatment program, including the provision of free ART started in 2004 with a pilot program at Muhimbili National Hospital in Dar es Salaam. This study describes the socio-demographic and clinical features of patients enrolled at the care and treatment clinic at MNH, Dar es Salaam, Tanzania. A cross-sectional study looking at baseline characteristics of patients enrolled at the HIV clinic at MNH between June 2004-Dec 2005 compared to those enrolled between 2006 and September 2008. Of all enrolled patients, 2408 (58.5%) were used for analysis. More females than males were attending the clinic. Their baseline median CD4 cell count was low (136 cells/microl) with 65.7% having below 200 cells/microl. Females had higher CD4 cell counts (150 cells/microl) than males (109 cells/microl) p < 0.001). The most common presenting features were skin rash and/or itching (51.6%); progressive weight loss (32.7%) and fever (23.4). Patients enrolled earlier at the clinic (2004-5) were significantly more symptomatic and had significantly lower CD4 cell count (127 cells/microl) compared to CD4 of 167 cells/microl in those seen later (2006-8) (p < 0.001). Patients enrolled to the MNH HIV clinic were predominantly females, and presented with advanced immune-deficiency. Improved access to HIV care and treatment services seems to be associated with patients' early presentation to the clinics in the course of HIV disease.

Impact of a massive earthquake on adherence to antiretroviral therapy, mental health, and treatment failure among people living with HIV in Nepal

PubMed Central

Nakazawa, Minato; Kotaki, Tomohiro; Bastola, Anup; Kameoka, Masanori

2018-01-01

Introduction The April 2015 Nepal earthquake resulted in more than 8,700 deaths and 22,000 casualties including damage to health facilities. The impact of this situation on chronic conditions such as human immunodeficiency virus infection and acquired immune deficiency syndrome (HIV/AIDS) may become a long-lasting public health threat. Therefore, the objectives of this study were i) to assess the association of antiretroviral therapy (ART) adherence with mental health problems, and social behaviors, ii) to examine factors affecting treatment failure, and iii) to investigate changes in ART adherence and post-traumatic stress disorder (PTSD) among people living with HIV 6 and 12 months after the disaster. Methods Study was conducted 6 months after the earthquake in 2015 with a sample size of 305 earthquake victims with HIV and followed after 12 months of the earthquake. A logistic regression analysis was used to examine relationships, while a paired t-test analysis was conducted to assess changes in adherence to ART and PTSD level at 6 months and 12 months after earthquake. Results In the earthquake, 5.2% of the participants lost their family member. Approximately 44% of participants had earthquake-PTSD symptoms and 50% experienced HIV stigma. PTSD and HIV status disclosure were significantly associated with adherence to ART, while HIV stigma and religion were associated with treatment failure. PTSD and adherence levels to ART were significantly improved over the 6-month period. Conclusion Awareness programs for general public to eliminate HIV stigma; promote psychosocial counseling to earthquake victims living with HIV in order to reduce PTSD will contribute to maintaining optimal ART adherence and to prevent treatment failure. PMID:29889840

Tuberculosis Incidence and Risk Factors Among Human Immunodeficiency Virus (HIV)-Infected Adults Receiving Antiretroviral Therapy in a Large HIV Program in Nigeria

PubMed Central

Chang, Charlotte A.; Meloni, Seema Thakore; Eisen, Geoffrey; Chaplin, Beth; Akande, Patrick; Okonkwo, Prosper; Rawizza, Holly E.; Tchetgen Tchetgen, Eric; Kanki, Phyllis J.

2015-01-01

Background. Despite the benefits of antiretroviral therapy (ART), tuberculosis (TB) is the leading cause of mortality among human immunodeficiency virus (HIV)-infected persons in Africa. Nigeria bears the highest TB burden in Africa and second highest HIV burden globally. This long-term multicenter study aimed to determine the incidence rate and predictors of TB in adults in the Harvard/AIDS Prevention Initiative in Nigeria (APIN) and President's Emergency Plan for AIDS Relief (PEPFAR) Nigeria ART program. Methods. This retrospective evaluation used data collected from 2004 to 2012 through the Harvard/APIN PEPFAR program. Risk factors for incident TB were determined using multivariate Cox proportional hazards regression with time-dependent covariates. Results. Of 50 320 adults enrolled from 2005 to 2010, 11 092 (22%) had laboratory-confirmed active TB disease at ART initiation, and 2021 (4%) developed active TB after commencing ART. During 78 228 total person-years (PY) of follow-up, the TB incidence rate was 25.8 cases per 1000 PY (95% confidence interval [CI], 24.7–27.0) overall, and it decreased significantly both with duration on ART and calendar year. Risk factors at ART initiation for incident TB included the following: earlier ART enrollment year, tenofovir-containing initial ART regimen, and World Health Organization clinical stage above 1. Time-updated risk factors included the following: low body mass index, low CD4+ cell count, unsuppressed viral load, anemia, and ART adherence below 80%. Conclusions. The rate of incident TB decreased with longer duration on ART and over the program years. The strongest TB risk factors were time-updated clinical markers, reinforcing the importance of consistent clinical and laboratory monitoring of ART patients in prompt diagnosis and treatment of TB and other coinfections. PMID:26613097

Effect of analytical treatment interruption and reinitiation of antiretroviral therapy on HIV reservoirs and immunologic parameters in infected individuals

PubMed Central

Petrone, Mary; Justement, J. Shawn; Shi, Victoria; Huiting, Erin D.; Yu, Xu G.; Moir, Susan; Sneller, Michael C.; Lichterfeld, Mathias

2018-01-01

Therapeutic strategies aimed at achieving antiretroviral therapy (ART)-free HIV remission in infected individuals are under active investigation. Considering the vast majority of HIV-infected individuals experience plasma viral rebound upon cessation of therapy, clinical trials evaluating the efficacy of curative strategies would likely require inclusion of ART interruption. However, it is unclear what impact short-term analytical treatment interruption (ATI) and subsequent reinitiation of ART have on immunologic and virologic parameters of HIV-infected individuals. Here, we show a significant increase of HIV burden in the CD4+ T cells of infected individuals during ATI that was correlated with the level of plasma viral rebound. However, the size of the HIV reservoirs as well as immune parameters, including markers of exhaustion and activation, returned to pre-ATI levels 6–12 months after the study participants resumed ART. Of note, the proportions of near full-length, genome-intact and structurally defective HIV proviral DNA sequences were similar prior to ATI and following reinitiation of ART. In addition, there was no evidence of emergence of antiretroviral drug resistance mutations within intact HIV proviral DNA sequences following reinitiation of ART. These data demonstrate that short-term ATI does not necessarily lead to expansion of the persistent HIV reservoir nor irreparable damages to the immune system in the peripheral blood, warranting the inclusion of ATI in future clinical trials evaluating curative strategies. PMID:29324842

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.

Mortality among people living with HIV on antiretroviral treatment in Bali, Indonesia: incidence and predictors.

PubMed

Utami, Sri; Sawitri, Anak Agung Sagung; Wulandari, Luh Putu Lila; Artawan Eka Putra, I Wayan Gede; Astuti, Putu Ayu Swandewi; Wirawan, Dewa Nyoman; Causer, Louise; Mathers, Bradley

2017-10-01

Indonesia has the third highest number of people living with HIV/AIDS (PLWH) and the greatest increase in proportion of AIDS-related mortality in the Asia Pacific region between 2005 and 2013. Longitudinal mortality data among PLWH in Indonesia are limited. We conducted a retrospective cohort study from medical records of antiretroviral treatment (ART) recipients attending Badung General Hospital (BGH) and Bali Medica Clinic (BMC) between 2006 and 2014. We explored incidence of mortality by Kaplan-Meier analysis and identified predictors using a Cox proportional hazard model. In total, 575 patients were included in the analysis; the majority were male. The overall mortality rate was 10% per year. Multivariate analysis suggested that being male (adjusted hazard ratio [aHR]: 2.74; 95% confidence interval [CI]: 1.34-5.59), having a lower education (aHR: 2.17; 95%CI: 1.31-3.61), having heterosexual (aHR: 7.40; 95% CI: 2.61-21.00) or injecting drug use (aHR: 13.20; 95% CI: 3.17-55.00) as the likely transmission risk category, starting treatment with low CD4 cell counts (aHR: 3.18; 95% CI: 1.16-8.69), and not having a treatment supervisor (aHR: 4.02; 95% CI: 2.44-6.65) were independent predictors of mortality. The mortality was high, particularly in the first three months after initiating ART. These findings highlight the need to encourage HIV testing and early diagnosis and prompt treatment. Applying aspects of BMCs targeted HIV services model in more generalised services such as BGH may be beneficial. Providing adherence support as part of ART services is key to promoting adherence to ART.

Predictors and treatment strategies of HIV-related fatigue in the combined antiretroviral therapy era.

PubMed

Jong, Eefje; Oudhoff, Lisanne A; Epskamp, Cynthia; Wagener, Marlies N; van Duijn, Miranda; Fischer, Steven; van Gorp, Eric Cm

2010-06-19

To assess predictors and reported treatment strategies of HIV-related fatigue in the combined antiretroviral (cART) era. Five databases were searched and reference lists of pertinent articles were checked. Studies published since 1996 on predictors or therapy of HIV-related fatigue measured by a validated instrument were selected. A total of 42 studies met the inclusion criteria. The reported HIV-related fatigue prevalence in the selected studies varied from 33 to 88%. The strongest predictors for sociodemographic variables were unemployment and inadequate income. Concerning HIV-associated factors, the use of cART was the strongest predictor. Comorbidity and sleeping difficulties were important factors when assessing physiological influences. Laboratory parameters were not predictive of fatigue. The strongest and most uniform associations were observed between fatigue and psychological factors such as depression and anxiety. Reported therapeutic interventions for HIV-related fatigue include testosterone, psycho-stimulants (dextroamphetamine, methylphenidate hydrochloride, pemoline, modafinil), dehydroepiandrosterone, fluoxetine and cognitive behavioural or relaxation therapy. HIV-related fatigue has a high prevalence and is strongly associated with psychological factors such as depression and anxiety. A validated instrument should be used to measure intensity and consequences of fatigue in HIV-infected individuals. In the case of fatigue, clinicians should not only search for physical mechanisms, but should question depression and anxiety in detail. There is a need for intervention studies comparing the effect of medication (antidepressants, anxiolytics) and behavioural interventions (cognitive-behavioural therapy, relaxation therapy, graded exercise therapy) to direct the best treatment strategy. Treatment of HIV-related fatigue is important in the care for HIV-infected patients and requires a multidisciplinary approach.

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.

Modified Directly Observed Antiretroviral Therapy Compared with Self-Administered Therapy in Treatment-Naïve HIV-1 Infected Patients: A Randomized Trial

PubMed Central

Gross, Robert; Tierney, Camlin; Andrade, Adriana; Lalama, Christina; Rosenkranz, Susan; Eshleman, Susan H.; Flanigan, Timothy; Santana, Jorge; Salomon, Nadim; Reisler, Ronald; Wiggins, Ilene; Hogg, Evelyn; Flexner, Charles; Mildvan, Donna

2009-01-01

Context Success of antiretroviral therapy depends on high rates of adherence, but few interventions are effective. Objective Determine if modified directly observed therapy (mDOT) improves initial antiretroviral success. Design Open-label randomized trial comparing mDOT and self-administered therapy with lopinavir/ritonavir soft gel capsules 800 mg/200 mg, emtricitabine 200 mg, and either extended release stavudine 100 mg or tenofovir 300 mg, all once daily. Setting 23 U.S. AIDS Clinical Trials Group (ACTG) sites and one in South Africa between October 2002 and January 2006. Participants Plasma HIV RNA ≥2000 copies/ml and antiretroviral-naïve. 82 participants received mDOT and 161 self-administration. Participants were predominantly male (79%), median age 38 years, with 84 Latinos (35%), 74 non-Latino blacks (30%), and 79 non-Latino whites (33%). Intervention mDOT Monday through Friday for 24 weeks. Main Outcome Measure(s) Primary outcome was week 24 virologic success and secondary outcomes were week 48 virologic success, clinical progression, and adherence. Results mDOT had greater virologic success over 24 weeks [0.91 (95% CI: 0.81, 0.95)] than self-administered therapy [0.84 (95% CI: 0.77, 0.89)], but the difference [0.07 (lower bound 95% CI: −0.01)] did not reach the pre-specified threshold of 0.075. Over 48 weeks, virologic success was not significantly different between mDOT [0.72 (95% CI: 0.61, 0.81)] and self-administered therapy [0.78 (95% CI: 0.70, 0.84)], [−0.06 (95% CI: −0.18, 0.07); p=0.19)]. Conclusions The potential benefit of mDOT was marginal and not sustained after mDOT was discontinued. mDOT should not be incorporated routinely for care of treatment naïve HIV-1 infected patients. PMID:19597072

Relationship between alcohol consumption, whether linked to other substance use or not, and antiretroviral treatment adherence in HIV+ patients.

PubMed

González-Álvarez, Sara; Madoz-Gúrpide, Agustín; Parro-Torres, Carlos; Hernández-Huerta, Daniel; Ochoa Mangado, Enriqueta

2017-07-14

Hazardous alcohol consumption is a common diagnosis among people living with HIV infection. The relationship between alcohol consumption and poor adherence to antiretroviral therapy has been highlighted in different studies, yet few of them performed a parallel analysis of other substance use. In Spain, alcohol consumption is frequently associated with other substance use, mainly cannabis and cocaine. The aim of this study is to assess the influence of hazardous alcohol consumption both combined with other substances (cocaine, heroin, methadone and/or cannabis) or alone on antiretroviral therapy adherence in our social environment. We performed an observational case-control study including 119 HIV+ individuals. We recruited 40 non-adherent patients, defined by less than 90% compliance according to hospital pharmacy refill data, and corroborated by the Simplified Medication Adherence Questionnaire (SMAQ) and referring professional's opinion. Control cases (n=79) were defined as those patients with similar characteristics but considered adherent according to the same parameters. Data collection took place between May 2013 and September 2015. Statistical analysis was performed using a binary logistic regression model. Our results indicate that alcohol consumption decreases adherence to antiretroviral therapy. The use of methadone represents a statistically significant increased risk of poor adherence. No significant differences were found between adherent and non-adherent groups regarding cocaine, heroin or cannabis use in this study. In summary, the detection of substance use and especially alcohol consumption in HIV+ patients can improve the effectiveness of antiretroviral therapy by identifying and treating at-risk individuals for a poor therapeutic adherence.

Persistent Genital Tract HIV-1 RNA Shedding After Change in Treatment Regimens in Antiretroviral-Experienced Women with Detectable Plasma Viral Load

PubMed Central

DeLong, Allison K.; Kantor, Rami; Chapman, Stacey; Ingersoll, Jessica; Kurpewski, Jaclynn; De Pasquale, Maria Pia; D'Aquila, Richard; Caliendo, Angela M.; Cu-Uvin, Susan

2013-01-01

Abstract Objective To longitudinally assess the association between plasma viral load (PVL) and genital tract human immunodeficiency virus (GT HIV) RNA among HIV-1 infected women changing highly active antiretroviral therapy (HAART) because of detectable PVL on current treatment. Methods Women were eligible for the study if they had detectable PVL (defined as two consecutive samples with PVL>1000 copies/mL) and intended to change their current HAART regimen at the time of enrollment. Paired plasma and GT HIV-1 RNA were measured prospectively over 3 years. Longitudinal analyses examined rates of GT HIV-1 RNA shedding and the association with PVL. Results Sixteen women were followed for a median of 11 visits contributing a total of 205 study visits. At study enrollment, all had detectable PVL and 69% had detectable GT HIV-1 RNA. Half of the women changed to a new HAART regimen with ≥3 active antiretroviral drugs. The probability of having detectable PVL ≥30 days after changing HAART was 0.56 (95% CI: 0.37 to 0.74). Fourteen women (88%) had detectable PVL on a follow-up visit ≥30 or 60 days after changing HAART; and 12 women (75%) had detectable GT HIV-1 RNA on a follow-up visit ≥30 or 60 days after changing HAART. When PVL was undetectable, GT shedding occurred at 11% of visits, and when PVL was detectable, GT shedding occurred at 47% of visits. Conclusions Some treatment-experienced HIV-infected women continue to have detectable virus in both the plasma and GT following a change in HAART, highlighting the difficulty of viral suppression in this patient population. PMID:23531097

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.

Effects of a mobile phone short message service on antiretroviral treatment adherence in Kenya (WelTel Kenya1): a randomised trial.

PubMed

Lester, Richard T; Ritvo, Paul; Mills, Edward J; Kariri, Antony; Karanja, Sarah; Chung, Michael H; Jack, William; Habyarimana, James; Sadatsafavi, Mohsen; Najafzadeh, Mehdi; Marra, Carlo A; Estambale, Benson; Ngugi, Elizabeth; Ball, T Blake; Thabane, Lehana; Gelmon, Lawrence J; Kimani, Joshua; Ackers, Marta; Plummer, Francis A

2010-11-27

Mobile (cell) phone communication has been suggested as a method to improve delivery of health services. However, data on the effects of mobile health technology on patient outcomes in resource-limited settings are limited. We aimed to assess whether mobile phone communication between health-care workers and patients starting antiretroviral therapy in Kenya improved drug adherence and suppression of plasma HIV-1 RNA load. WelTel Kenya1 was a multisite randomised clinical trial of HIV-infected adults initiating antiretroviral therapy (ART) in three clinics in Kenya. Patients were randomised (1:1) by simple randomisation with a random number generating program to a mobile phone short message service (SMS) intervention or standard care. Patients in the intervention group received weekly SMS messages from a clinic nurse and were required to respond within 48 h. Randomisation, laboratory assays, and analyses were done by investigators masked to treatment allocation; however, study participants and clinic staff were not masked to treatment. Primary outcomes were self-reported ART adherence (>95% of prescribed doses in the past 30 days at both 6 and 12 month follow-up visits) and plasma HIV-1 viral RNA load suppression (<400 copies per mL) at 12 months. The primary analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, NCT00830622. Between May, 2007, and October, 2008, we randomly assigned 538 participants to the SMS intervention (n=273) or to standard care (n=265). Adherence to ART was reported in 168 of 273 patients receiving the SMS intervention compared with 132 of 265 in the control group (relative risk [RR] for non-adherence 0·81, 95% CI 0·69-0·94; p=0·006). Suppressed viral loads were reported in 156 of 273 patients in the SMS group and 128 of 265 in the control group, (RR for virologic failure 0·84, 95% CI 0·71-0·99; p=0·04). The number needed to treat (NNT) to achieve greater than 95% adherence was nine (95% CI 5·0-29·5

Effects of treatment with suppressive combination antiretroviral drug therapy and the histone deacetylase inhibitor suberoylanilide hydroxamic acid; (SAHA) on SIV-infected Chinese rhesus macaques.

PubMed

Ling, Binhua; Piatak, Michael; Rogers, Linda; Johnson, Ann-Marie; Russell-Lodrigue, Kasi; Hazuda, Daria J; Lifson, Jeffrey D; Veazey, Ronald S

2014-01-01

Viral reservoirs-persistent residual virus despite combination antiretroviral therapy (cART)-remain an obstacle to cure of HIV-1 infection. Difficulty studying reservoirs in patients underscores the need for animal models that mimics HIV infected humans on cART. We studied SIV-infected Chinese-origin rhesus macaques (Ch-RM) treated with intensive combination antiretroviral therapy (cART) and 3 weeks of treatment with the histone deacetyalse inhibitor, suberoylanilide hydroxamic acid (SAHA). SIVmac251 infected Ch-RM received reverse transcriptase inhibitors PMPA and FTC and integrase inhibitor L-870812 beginning 7 weeks post infection. Integrase inhibitor L-900564 and boosted protease inhibitor treatment with Darunavir and Ritonavir were added later. cART was continued for 45 weeks, with daily SAHA administered for the last 3 weeks, followed by euthanasia/necropsy. Plasma viral RNA and cell/tissue-associated SIV gag RNA and DNA were quantified by qRT-PCR/qPCR, with flow cytometry monitoring changes in immune cell populations. Upon cART initiation, plasma viremia declined, remaining <30 SIV RNA copy Eq/ml during cART, with occasional blips. Decreased viral replication was associated with decreased immune activation and partial restoration of intestinal CD4+ T cells. SAHA was well tolerated but did not result in demonstrable treatment-associated changes in plasma or cell associated viral parameters. The ability to achieve and sustain virological suppression makes cART-suppressed, SIV-infected Ch-RM a potentially useful model to evaluate interventions targeting residual virus. However, despite intensive cART over one year, persistent viral DNA and RNA remained in tissues of all three animals. While well tolerated, three weeks of SAHA treatment did not demonstrably impact viral RNA levels in plasma or tissues; perhaps reflecting dosing, sampling and assay limitations.

Determinants of weight evolution among HIV-positive patients initiating antiretroviral treatment in low resource settings

PubMed Central

Huis in ‘t Veld, D.; Balestre, E.; Buyze, J; Menten, J.; Jaquet, A.; Cooper, D.A.; Dabis, F.; Yiannoutsos, C. T.; Diero, L.; Mutevedzi, P.; Fox, M.P.; Messou, E.; Hoffmann, C.J.; Prozesky, H.W.; Egger, M.; Hemingway-Foday, J.J.; Colebunders, R.

2015-01-01

Background In resource limited settings clinical parameters, including body weight changes, are used to monitor clinical response. Therefore we studied body weight changes in patients on antiretroviral treatment (ART) in different regions of the world. Methods Data were extracted from the “International Epidemiologic Databases to Evaluate AIDS”, a network of ART programmes that prospectively collects routine clinical data. Adults on ART from the Southern-, East-, West- and Central African and the Asia-Pacific regions were selected from the database if baseline data on body weight, gender, ART regimen and CD4 count were available. Body weight change over the first two years and the probability of body weight loss in the second year were modelled using linear mixed models and logistic regression respectively. Results Data from 205,571 patients were analysed. Mean adjusted body weight change in the first 12 months was higher in patients started on tenofovir and/or efavirenz; in patients from Central, West and East Africa, in men, and in patients with a poorer clinical status. In the second year of ART it was greater in patients initiated on tenofovir and/or nevirapine, and for patients not on stavudine, in women, in Southern Africa and in patients with a better clinical status at initiation. Stavudine in the initial regimen was associated with a lower mean adjusted body weight change and with weight loss in the second treatment year. Conclusion Different ART regimens have different effects on body weight change. Body weight loss after one year of treatment in patients on stavudine might be associated with lipoatrophy. PMID:26375465

Health and federal budgetary effects of increasing access to antiretroviral medications for HIV by expanding Medicaid.

PubMed

Kahn, J G; Haile, B; Kates, J; Chang, S

2001-09-01

OBJECTIVES. This study modeled the health and federal fiscal effects of expanding Medicaid for HIV-infected people to improve access to highly active antiretroviral therapy. A disease state model of the US HIV epidemic, with and without Medicaid expansion, was used. Eligibility required a CD4 cell count less than 500/mm3 or viral load greater than 10,000, absent or inadequate medication insurance, and annual income less than $10,000. Two benefits were modeled, "full" and "limited" (medications, outpatient care). Federal spending for Medicaid, Medicare, AIDS Drug Assistance Program, Supplemental Security Income, and Social Security Disability Insurance were assessed. An estimated 38,000 individuals would enroll in a Medicaid HIV expansion. Over 5 years, expansion would prevent an estimated 13,000 AIDS diagnoses and 2600 deaths and add 5,816 years of life. Net federal costs for all programs are $739 million (full benefits) and $480 million (limited benefits); for Medicaid alone, the costs are $1.43 and $1.17 billion, respectively. Results were sensitive to awareness of serostatus, highly active antiretroviral therapy cost, and participation rate. Strategies for federal cost neutrality include Medicaid HIV drug price reductions as low as 9% and private insurance buy-ins. Expansion of the Medicaid eligibility to increase access to antiretroviral therapy would have substantial health benefits at affordable costs.

Outcomes and factors associated with survival of patients with HIV/AIDS initiating antiretroviral treatment in Liangshan Prefecture, southwest of China

PubMed Central

Zhang, Guang; Gong, Yuhan; Wang, Qixing; Deng, Ling; Zhang, Shize; Liao, Qiang; Yu, Gang; Wang, Ke; Wang, Ju; Ye, Shaodong; Liu, Zhongfu

2016-01-01

Abstract Human immunodeficiency virus (HIV)–positive cases have been reported among people who injected drugs in Liangshan Prefecture in southwest of China since 1995 and Liangshan has become one of the most seriously affected epidemic areas in China. In 2004, several patients with HIV/acquired immunodeficiency syndrome (AIDS) initiated antiretroviral treatment (ART) at the Central Hospital of Liangshan Prefecture. From 2005 to 2013, the number of patients receiving ART dramatically increased. We conducted a retrospective cohort study to analyze the long-term survival time and associated factors among patients with HIV/AIDS who received ART in Liangshan Prefecture for the first time. Data were collected from the Chinese AIDS Antiretroviral Therapy DATAFax Information System. A life table and the Kaplan–Meier and Cox proportion hazard regression were used to calculate the survival time and its associated factors, respectively. Among 8310 ART-naïve patients with HIV/AIDS who initiated ART, 436 patients died of AIDS-related diseases, and their median time of receiving ART was 15.0 ± 12.3 months, whereas 28.7% of them died within the first 6 months after treatment. The cumulative survival rates of those receiving ART in 1, 2, 3, 4, and 5 years were 97.1%, 93.4%, 90.6%, 88.8%, and 86.0%, respectively. Multivariate Cox regression analysis showed that male patients on ART were at a higher risk of death from AIDS-related diseases (adjusted hazard ratio [AHR] = 1.5, 95% confidence interval [CI]: 1.1–2.1) than female patients. Patients infected with HIV through injection drug use (IDU) were at a higher risk of death (AHR = 1.6, 95% CI: 1.2–2.2) than those infected through heterosexual transmission. Patients with a baseline CD4 cell count <50/mm3 (AHR = 9.8, 95% CI: 6.0–15.9), 50–199/mm3 (AHR = 3.3, 95% CI: 2.3–4.6), and 200–349/mm3 (AHR = 1.7, 95% CI: 1.2–2.3) were at a higher risk of death than those with a CD4 cell count ≥350/mm3. ART prolonged

The Impact of Non-Antiretroviral Polypharmacy on the Continuity of Antiretroviral Therapy (ART) Among HIV Patients.

PubMed

Krentz, Hartmut B; Gill, M John

2016-01-01

Improved survival achieved by many patients with HIV/AIDS has complicated their medical care as increasing numbers of co-morbidities leads to polypharmacy, increased pill burdens, and greater risks of drug-drug interactions potentially compromising antiretroviral treatment (ART). We examined the impact of non-antiretroviral polypharmacy on ART for all adults followed at the Southern Alberta Clinic, Calgary, Canada. Polypharmacy was defined as ≥5 daily medications. We compared the impact of polypharmacy on continuous (i.e., remaining on same ART for ≥6 months) vs. non-continuous (i.e., discontinuing or switching ART) ART dosing frequency, number of ART pills, number of non-ART medications, and age. Of 1190 (89.5%) patients on ART, 95% were on three-drug regimens, 63.9% on QD ART, and 62% ≥3 ART pills daily; 32.2% were experiencing polypharmacy. Polypharmacy was associated with lower CD4, AIDS, >180 months living with HIV, higher numbers of ART pills, and older age (all p < 0.01); 32.1% stopped or switched ART. Polypharmacy increased the risk for non-continuous ART (36.8% vs. 30.0%; p < 0.01). Non-continuous ART increased with daily ART pill count but not increased age. Non-adherence and adverse effects accounted for the majority of non-continuous ART. We found a strong association between polypharmacy and non-continuous ART, potentially leading to effective ART being compromised. Collaborative approaches are needed to anticipate the negative impacts of polypharmacy.

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.

Tinea Capitis in the form of Concentric Rings in an HIV Positive Adult on Antiretroviral Treatment

PubMed Central

Narang, Kirti; Pahwa, Manish; Ramesh, V

2012-01-01

Dermatophyte infection may present in the form of concentric rings caused by Trichophyton concentricum, known as Tinea Imbricata. In immunosuppressed patients, there are reports of lesions in the form of concentric rings caused by dermatophytes other than Trichophyton concentricum too, mostly by Trichophyton tonsurans, known as Tinea indesiciva or Tinea pseudoimbricata. We report a case of tinea capitis in a HIV-positive adult woman on antiretroviral therapy, who presented with concentric rings of papules and pustules with slight scaling on the scalp along with diffuse thinning of hair. Both Potassium hydroxide mount and culture showed the presence of Dermatophytes. Tinea capitis is considered rare in adults, but new cases are being reported in immunocompromised as well as in immunocompetent patients. The pertinent features of this case are: HIV-positive adult female on antiretroviral therapy, presenting with tinea capitis in the form of concentric rings; culture from the lesion grew Microsporum audouinii; responding to oral Terbinafine. PMID:22837564

EFFECT OF HIV PREVENTION AND TREATMENT PROGRAM ON HIV AND HCV TRANSMISSION AND HIV MORTALITY AT AN INDONESIAN NARCOTIC PRISON.

PubMed

Nelwan, Erni J; Indrati, Agnes K; Isa, Ahmad; Triani, Nurlita; Alam, Nisaa Nur; Herlan, Maria S; Husen, Wahid; Pohan, Herdiman T; Alisjahbana, Bachti; Meheus, Andre; Van Crevel, Reinout; van der Ven, Andre Jam

2015-09-01

Validated data regarding HIV-transmission in prisons in developing countries is scarce. We examined sexual and injecting drug use behavior and HIV and HCV transmission in an Indonesian narcotic prison during the implementation of an HIV prevention and treatment program during 2004-2007 when the Banceuy Narcotic Prison in Indonesia conducted an HIV transmission prevention program to provide 1) HIV education, 2) voluntary HIV testing and counseling, 3) condom supply, 4) prevention of rape and sexual violence, 5) antiretroviral treatment for HIV-positive prisoners and 6) methadone maintenance treatment. During a first survey that was conducted between 2007 and 2009, new prisoners entered Banceuy Narcotics Prison were voluntary tested for HIV and HCV-infection after written informed consent was obtained. Information regarding sexual and injecting risk behavior and physical status were also recorded at admission to the prison. Participants who tested negative for both HIV and HCV during the first survey were included in a second survey conducted during 2008-2011. During both surveys, data on mortality among HIV-seropositive patients were also recorded. All HIV-seropositive participants receive treatment for HIV. HIV/ AIDS-related deaths decreased: 43% in 2006, 18% in 2007, 9% in 2008 and 0% in 2009. No HIV and HCV seroconversion inside Banceuy Narcotic Prison were found after a median of 23 months imprisonment (maximum follow-up: 38 months). Total of 484.8 person-years observation was done. Participants reported HIV transmission risk-behavior in Banceuy Prison during the second survey was low. After implementation of HIV prevention and treatment program, no new HIV or HCV cases were detected and HIV-related mortality decreased.

Evaluation of three sampling methods to monitor outcomes of antiretroviral treatment programmes in low- and middle-income countries.

PubMed

Tassie, Jean-Michel; Malateste, Karen; Pujades-Rodríguez, Mar; Poulet, Elisabeth; Bennett, Diane; Harries, Anthony; Mahy, Mary; Schechter, Mauro; Souteyrand, Yves; Dabis, François

2010-11-10

Retention of patients on antiretroviral therapy (ART) over time is a proxy for quality of care and an outcome indicator to monitor ART programs. Using existing databases (Antiretroviral in Lower Income Countries of the International Databases to Evaluate AIDS and Médecins Sans Frontières), we evaluated three sampling approaches to simplify the generation of outcome indicators. We used individual patient data from 27 ART sites and included 27,201 ART-naive adults (≥15 years) who initiated ART in 2005. For each site, we generated two outcome indicators at 12 months, retention on ART and proportion of patients lost to follow-up (LFU), first using all patient data and then within a smaller group of patients selected using three sampling methods (random, systematic and consecutive sampling). For each method and each site, 500 samples were generated, and the average result was compared with the unsampled value. The 95% sampling distribution (SD) was expressed as the 2.5(th) and 97.5(th) percentile values from the 500 samples. Overall, retention on ART was 76.5% (range 58.9-88.6) and the proportion of patients LFU, 13.5% (range 0.8-31.9). Estimates of retention from sampling (n = 5696) were 76.5% (SD 75.4-77.7) for random, 76.5% (75.3-77.5) for systematic and 76.0% (74.1-78.2) for the consecutive method. Estimates for the proportion of patients LFU were 13.5% (12.6-14.5), 13.5% (12.6-14.3) and 14.0% (12.5-15.5), respectively. With consecutive sampling, 50% of sites had SD within ±5% of the unsampled site value. Our results suggest that random, systematic or consecutive sampling methods are feasible for monitoring ART indicators at national level. However, sampling may not produce precise estimates in some sites.

Early loss to follow-up and mortality of HIV-infected patients diagnosed after the era of antiretroviral treatment scale up: a call for re-invigorating the response in Iran.

PubMed

Badie, Banafsheh Moradmand; Nabaei, Ghaemeh; Rasoolinejad, Mehrnaz; Mirzazadeh, Ali; McFarland, Willi

2013-12-01

In Iran, the HIV/AIDS epidemic is growing during an era of scaling up the national surveillance system and antiretroviral therapy programs. We examined the early loss to follow-up and mortality rates in a retrospective cohort of 1495 HIV-infected patients by survival proportional hazard Cox model. We also conducted a data abstraction sub-study in a systematic random sample of 147 patients to assess the association between mortality and predictor factors. Overall, 17.3% patients were not seen after their first visit and 17.4% more were lost by 6 months. The overall mortality rate was 7.0 (95% CI 6.1-8.1) per 100 person-years. Moreover, crude mortality rate was higher in men (8.6) than in women (1.7), with an age-adjusted hazard ratio for men compared to women of 4.55 (95% CI 2.31-8.93). Lastly, history of tuberculosis and not being on antiretroviral therapy were significantly associated with higher mortality in the patient sub-sample.

Effect of Improved access to Antiretroviral Therapy on clinical characteristics of patients enrolled in the HIV care and treatment clinic, at Muhimbili National Hospital (MNH), Dar es Salaam, Tanzania

PubMed Central

2010-01-01

Background Sub-Saharan Africa has been severely affected by the HIV and AIDS pandemic. Global efforts at improving care and treatment has included scaling up use of antiretroviral therapy (ART). In Tanzania, HIV care and treatment program, including the provision of free ART started in 2004 with a pilot program at Muhimbili National Hospital in Dar es Salaam. This study describes the socio-demographic and clinical features of patients enrolled at the care and treatment clinic at MNH, Dar es Salaam, Tanzania. Methods A cross-sectional study looking at baseline characteristics of patients enrolled at the HIV clinic at MNH between June 2004 - Dec 2005 compared to those enrolled between 2006 and September 2008. Results Of all enrolled patients, 2408 (58.5%) were used for analysis. More females than males were attending the clinic. Their baseline median CD4 cell count was low (136 cells/μl) with 65.7% having below 200 cells/μl. Females had higher CD4 cell counts (150 cells/μl) than males (109 cells/μl) p < 0.001). The most common presenting features were skin rash and/or itching (51.6%); progressive weight loss (32.7%) and fever (23.4). Patients enrolled earlier at the clinic (2004-5) were significantly more symptomatic and had significantly lower CD4 cell count (127 cells/μl) compared to CD4 of 167 cells/μl in those seen later (2006-8) (p < 0.001). Conclusion Patients enrolled to the MNH HIV clinic were predominantly females, and presented with advanced immune-deficiency. Improved access to HIV care and treatment services seems to be associated with patients' early presentation to the clinics in the course of HIV disease. PMID:20509892

Adherence to and effectiveness of highly active antiretroviral treatment for HIV infection: assessing the bidirectional relationship.

PubMed

Lamiraud, Karine; Moatti, Jean-Paul; Raffi, François; Carrieri, Maria-Patrizia; Protopopescu, Camelia; Michelet, Christian; Schneider, Luminita; Collin, Fideline; Leport, Catherine; Spire, Bruno

2012-05-01

It is well established that high adherence to HIV-infected patients on highly active antiretroviral treatment (HAART) is a major determinant of virological and immunologic success. Furthermore, psychosocial research has identified a wide range of adherence factors including patients' subjective beliefs about the effectiveness of HAART. Current statistical approaches, mainly based on the separate identification either of factors associated with treatment effectiveness or of those associated with adherence, fail to properly explore the true relationship between adherence and treatment effectiveness. Adherence behavior may be influenced not only by perceived benefits-which are usually the focus of related studies-but also by objective treatment benefits reflected in biological outcomes. Our objective was to assess the bidirectional relationship between adherence and response to treatment among patients enrolled in the ANRS CO8 APROCO-COPILOTE study. We compared a conventional statistical approach based on the separate estimations of an adherence and an effectiveness equation to an econometric approach using a 2-equation simultaneous system based on the same 2 equations. Our results highlight a reciprocal relationship between adherence and treatment effectiveness. After controlling for endogeneity, adherence was positively associated with treatment effectiveness. Furthermore, CD4 count gain after baseline was found to have a positive significant effect on adherence at each observation period. This immunologic parameter was not significant when the adherence equation was estimated separately. In the 2-equation model, the covariances between disturbances of both equations were found to be significant, thus confirming the statistical appropriacy of studying adherence and treatment effectiveness jointly. Our results, which suggest that positive biological results arising as a result of high adherence levels, in turn reinforce continued adherence and strengthen the argument

Understanding reasons for and outcomes of patients lost to follow-up in antiretroviral therapy programs in Africa through a sampling-based approach.

PubMed

Geng, Elvin H; Bangsberg, David R; Musinguzi, Nicolas; Emenyonu, Nneka; Bwana, Mwebesa Bosco; Yiannoutsos, Constantin T; Glidden, David V; Deeks, Steven G; Martin, Jeffrey N

2010-03-01

Losses to follow-up after initiation of antiretroviral therapy (ART) are common in Africa and are a considerable obstacle to understanding the effectiveness of nascent treatment programs. We sought to characterize, through a sampling-based approach, reasons for and outcomes of patients who become lost to follow-up. Cohort study. We searched for and interviewed a representative sample of lost patients or close informants in the community to determine reasons for and outcomes among lost patients. Three thousand six hundred twenty-eight HIV-infected adults initiated ART between January 1, 2004 and September 30, 2007 in Mbarara, Uganda. Eight hundred twenty-nine became lost to follow-up (cumulative incidence at 1, 2, and 3 years of 16%, 30%, and 39%). We sought a representative sample of 128 lost patients in the community and ascertained vital status in 111 (87%). Top reasons for loss included lack of transportation or money and work/child care responsibilities. Among the 111 lost patients who had their vital status ascertained through tracking, 32 deaths occurred (cumulative 1-year incidence 36%); mortality was highest shortly after the last clinic visit. Lower pre-ART CD4 T-cell count, older age, low blood pressure, and a central nervous system syndrome at the last clinic visit predicted deaths. Of patients directly interviewed, 83% were in care at another clinic and 71% were still using ART. Sociostructural factors are the primary reasons for loss to follow-up. Outcomes among the lost are heterogeneous: both deaths and transfers to other clinics were common. Tracking a sample of lost patients is an efficient means for programs to understand site-specific reasons for and outcomes among patients lost to follow-up.

Treatment retention in a prison-based residential sex offender treatment program.

PubMed

Pelissier, Bernadette

2007-12-01

This study assessed the role of static factors, a dynamic factor (motivation to change sexually deviant behavior), and an administrative factor in predicting treatment retention within a prison-based sex offender treatment program. The analyses also included assessing differences in initial levels of motivation and differences in beginning-versus end-of-treatment motivation scores for various types of program discharges. The sample consisted of 251 individuals who were admitted to a residential prison-based sex offender treatment program where 46% completed the program. Paired comparison t-tests showed higher motivation scores at the end of treatment only among treatment completers. Multivariate analyses showed that treatment retention was associated with higher initial motivation scores, higher levels of education and admission to treatment within 3 months of initial commitment to prison. Implications for motivational enhancement programming as well as for changes in admission criteria are discussed.

Methods Development for Blood Borne Macrophage Carriage of Nanoformulated Antiretroviral Drugs

PubMed Central

Roy, Upal; Martinez-Skinner, Andrea; McMillan, JoEllyn; Gendelman, Howard E.

2010-01-01

Nanoformulated drugs can improve pharmacodynamics and bioavailability while serving also to reduce drug toxicities for antiretroviral (ART) medicines. To this end, our laboratory has applied the principles of nanomedicine to simplify ART regimens and as such reduce toxicities while improving compliance and drug pharmacokinetics. Simple and reliable methods for manufacturing nanoformulated ART (nanoART) are shown. Particles of pure drug are encapsulated by a thin layer of surfactant lipid coating and produced by fractionating larger drug crystals into smaller ones by either wet milling or high-pressure homogenization. In an alternative method free drug is suspended in a droplet of a polymer. Herein, drug is dissolved within a polymer then agitated by ultrasonication until individual nanosized droplets are formed. Dynamic light scattering and microscopic examination characterize the physical properties of the particles (particle size, charge and shape). Their biologic properties (cell uptake and retention, cytotoxicity and antiretroviral efficacy) are determined with human monocyte-derived macrophages (MDM). MDM are derived from human peripheral blood monocytes isolated from leukopacks using centrifugal elutriation for purification. Such blood-borne macrophages may be used as cellular transporters for nanoART distribution to human immunodeficiency virus (HIV) infected organs. We posit that the repackaging of clinically available antiretroviral medications into nanoparticles for HIV-1 treatments may improve compliance and positively affect disease outcomes. PMID:21178968

Integrating community pharmacy into community based anti-retroviral therapy program: A pilot implementation in Abuja, Nigeria.

PubMed

Avong, Yohanna Kambai; Aliyu, Gambo Gumel; Jatau, Bolajoko; Gurumnaan, Ritmwa; Danat, Nanfwang; Kayode, Gbenga Ayodele; Adekanmbi, Victor; Dakum, Patrick

2018-01-01

The landscape of Human Immunodeficiency Virus (HIV) epidemic control is shifting with the United Nations Programme on HIV/AIDS (UNAIDS) 90-90-90 benchmarks for epidemic control. Community-based Antiretroviral Therapy (CART) models have improved treatment uptake and demonstrated good clinical outcomes. We assessed the feasibility of integrating community pharmacy as a task shift structure for differentiated community ART in Abuja-Nigeria. Stable patients on first line ART regimens from public health facilities were referred to community pharmacies in different locations within the Federal Capital Territory, Abuja for prescription refills and treatment maintenance. Bio-demographic and clinical data were collected from February 25, 2016 to May 31st, 2017 and descriptive statistics analysis applied. The outcomes of measure were prescription refill and patient retention in care at the community pharmacy. Almost 10% of stable patients on treatment were successfully devolved from eight health facilities to ten community pharmacies. Median age of the participants was 35 years [interquartile range (IQR); 30, 41] with married women in the majority. Prescription refill was 100% and almost all the participants (99.3%) were retained in care after they were devolved to the community pharmacies. Only one participant was lost-to-follow-up as a result of death. Excellent prescription refill and high retention in care with very low loss-to-follow-up were associated with the community pharmacy model. The use of community pharmacy for community ART is feasible in Nigeria. We recommend the scale up of the model in all the 36 states of Nigeria.

Impact of Socioeconomic Inequality on Access, Adherence, and Outcomes of Antiretroviral Treatment Services for People Living with HIV/AIDS in Vietnam

PubMed Central

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

Background 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. Methods 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. Results 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 Conclusion 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. PMID:28005937

The Functional Status of Patients with AIDS Attending Antiretroviral Treatment Center

PubMed Central

Thejus, TJ; Jeeja, MC; Jayakrishnan, T

2009-01-01

Aims: To assess the functional status of patients with Acquired immunodeficiency syndrome (AIDS) registered in the Anti-Retroviral Treatment (ART) center. Materials and Methods: Design: Descriptive study. Study setting: ART center in Calicut Medical College, Kerala, India. Subjects: Cohorts of AIDS patients attending the ART center during the year 2007. Data collection: Done prospectively from the secondary data available from the center. Outcome measures: The demographic, morbidity, functional status and laboratory parameters were collected. Data processing was done using Excel datasheet and analysis were done using Epi info 2003. Results: One hundred and ninety-five patients received care during this period; 69% were males. The mean age was 38±9 years; 80% of them were married and in 50% of their spouses also tested positive for HIV. The mean CD4 count was 127 cells/microliter. The majority (90%) were categorized as WHO Stage 3 or 4 of HIV. Only 52% of them were able to perform their usual work in or outside their house; the rest were not able to lead an economically productive life. Thirty-six per cent were only able to perform activities of daily living; 12% were bedridden. The functional status of the patients positively correlated with WHO disease stage (P = < 0-0001), and CD4 count and hemoglobin levels negatively correlated with staging (P = <0.001). 62% are having any of the opportunistic infections. Conclusion: Fifty per cent of the AIDS patients are disabled and need support and care. As AIDS is a growing problem, community-based palliative care for AIDS patients should be strengthened in India. PMID:20606857

Attrition from antiretroviral treatment services among pregnant and non-pregnant patients following adoption of Option B+ in Haiti.

PubMed

Domercant, Jean Wysler; Puttkammer, Nancy; Young, Paul; Yuhas, Krista; François, Kesner; Grand'Pierre, Reynold; Lowrance, David; Adler, Michelle

2017-01-01

Access to antiretroviral therapy (ART) has expanded in Haiti because of the adoption of Option B+ and the revision of treatment guidelines. Retention in care and treatment varies greatly and few studies have examined retention rates, particularly among women enrolled in Option B+. To assess attrition among pregnant and non-pregnant patients initiating ART following adoption of Option B+ in Haiti. Longitudinal data of adult patients initiated on ART from October 2012 through August 2014 at 73 health facilities across Haiti were analyzed using a survival analysis framework to determine levels of attrition. The Kaplan-Meier method and Cox proportional hazards regression were used to examine risk factors associated with attrition. Among 17,059 patients who initiated ART, 7627 (44.7%) were non-pregnant women, 5899 (34.6%) were men, and 3533 (20.7%) were Option B+ clients. Attrition from the ART program was 36.7% at 12 months (95% CI: 35.9-37.5%). Option B+ patients had the highest level of attrition at 50.4% at 12 months (95% CI: 48.6-52.3%). While early HIV disease stage at ART initiation was protective among non-pregnant women and men, it was a strong risk factor among Option B+ clients. In adjusted analyses, key protective factors were older age (p < 0.0001), living near the health facility (p = 0.04), having another known HIV-positive household member (p < 0.0001), having greater body mass index (BMI) (p < 0.0001), pre-ART counseling (p < 0.0001), and Cotrimoxazole prophylaxis during baseline (p < 0.01). Higher attrition was associated with rapidly starting ART after enrollment (p < 0.0001), anemia (p < 0.0001), and regimen tenofovir+lamivudine+nevirapine (TDF+3TC+NVP) (p < 0.001). ART attrition in Haiti is high among adults, especially among Option B+ patients. Identifying newly initiated patients most at risk for attrition and providing appropriate interventions could help reduce ART attrition.

Changing Antiretroviral Eligibility Criteria: Impact on the Number and Proportion of Adults Requiring Treatment in Swaziland.

PubMed

Bock, Naomi N; Emerson, Ruth C; Reed, Jason B; Nkambule, Rejoice; Donnell, Deborah J; Bicego, George T; Okello, Velephi; Philip, Neena M; Ehrenkranz, Peter D; Duong, Yen T; Moore, Janet S; Justman, Jessica E

2016-03-01

Early initiation of antiretroviral treatment (ART) at CD4 cell count ≥ 500 cells per microliter reduces morbidity and mortality in HIV-infected adults. We determined the proportion of HIV-infected people with high viral load (VL) for whom transmission prevention would be an additional benefit of early treatment. A randomly selected subset of a nationally representative sample of HIV-infected adults in Swaziland in 2012. Eight to 12 months after a national survey to determine adult HIV prevalence, 1067 of 5802 individuals identified as HIV-infected were asked to participate in a follow-up cross-sectional assessment. CD4 cell enumeration, VL measurements, and ART status were obtained to estimate the proportion of currently untreated adults and of the entire HIV-infected population with high VL (≥ 1000 copies/mL) whose treatment under a test-and-treat or VL threshold eligibility strategy would reduce HIV transmission. Of the 927 (87% of 1067) participants enrolled, 466 (50%) reported no ART use. Among them, 424 (91%) had VL ≥ 1000 copies per milliliter; of these, 148 (35%) were eligible for ART at the then existing CD4 count threshold of <350 cells per microliter; an additional 107 (25%) were eligible with expanded CD4 criterion of <500 cells per microliter; and 169 (40%) remained ART ineligible. Thus, 36% of the 466 currently untreated and 18% of the total 927 had high VL yet remained ART ineligible under a CD4 criterion of <500 cells per microliter. A test-and-treat or VL threshold for treatment eligibility is necessary to maximize the HIV transmission prevention benefits of ART.

Interruption of antiretroviral therapy is associated with increased plasma cystatin C.

PubMed

Mocroft, Amanda; Wyatt, Christina; Szczech, Lynda; Neuhaus, Jacquie; El-Sadr, Wafaa; Tracy, Russell; Kuller, Lewis; Shlipak, Michael; Angus, Brian; Klinker, Harting; Ross, Michael

2009-01-02

Cystatin C has been proposed as an alternative marker of renal function. We sought to determine whether participants randomized to episodic use of antiretroviral therapy guided by CD4 cell count (drug conservation) had altered cystatin C levels compared with those randomized to continuous antiretroviral therapy (viral suppression) in the Strategies for Management of Antiretroviral Therapy trial, and to identify factors associated with increased cystatin C. Cystatin C was measured in plasma collected at randomization, 1, 2, 4, 8 and 12 months after randomization in a random sample of 249 and 250 participants in the drug conservation and viral suppression groups, respectively. Logistic regression was used to model the odds of at least 0.15 mg/dl increase in cystatin C (1 SD) in the first month after randomization, adjusting for demographic and clinical characteristics. At randomization, mean (SD) cystatin C level was 0.99 (0.26 mg/dl) and 1.01 (0.28 mg/dl) in the drug conservation and viral suppression arms, respectively (P = 0.29). In the first month after randomization, 21.8 and 10.6% had at least 0.15 mg/dl increase in cystatin C in the drug conservation and viral suppression arms, respectively (P = 0.0008). The difference in cystatin C between the treatment arms was maintained through 1 year after randomization. After adjustment, participants in the viral suppression arm had significantly reduced odds of at least 0.15 mg/dl increase in cystatin C in the first month (odds ratio 0.42; 95% confidence interval 0.23-0.74, P = 0.0023). These results demonstrate that interruption of antiretroviral therapy is associated with an increase in cystatin C, which may reflect worsened renal function.

Results of antiretroviral treatment interruption and intensification in advanced multi-drug resistant HIV infection from the OPTIMA trial.

PubMed

Holodniy, Mark; Brown, Sheldon T; Cameron, D William; Kyriakides, Tassos C; Angus, Brian; Babiker, Abdel; Singer, Joel; Owens, Douglas K; Anis, Aslam; Goodall, Ruth; Hudson, Fleur; Piaseczny, Mirek; Russo, John; Schechter, Martin; Deyton, Lawrence; Darbyshire, Janet

2011-03-31

Guidance is needed on best medical management for advanced HIV disease with multidrug resistance (MDR) and limited retreatment options. We assessed two novel antiretroviral (ARV) treatment approaches in this setting. We conducted a 2×2 factorial randomized open label controlled trial in patients with a CD4 count≤300 cells/µl who had ARV treatment (ART) failure requiring retreatment, to two options (a) re-treatment with either standard (≤4 ARVs) or intensive (≥5 ARVs) ART and b) either treatment starting immediately or after a 12-week monitored ART interruption. Primary outcome was time to developing a first AIDS-defining event (ADE) or death from any cause. Analysis was by intention to treat. From 2001 to 2006, 368 patients were randomized. At baseline, mean age was 48 years, 2% were women, median CD4 count was 106/µl, mean viral load was 4.74 log(10) copies/ml, and 59% had a prior AIDS diagnosis. Median follow-up was 4.0 years in 1249 person-years of observation. There were no statistically significant differences in the primary composite outcome of ADE or death between re-treatment options of standard versus intensive ART (hazard ratio 1.17; CI 0.86-1.59), or between immediate retreatment initiation versus interruption before re-treatment (hazard ratio 0.93; CI 0.68-1.30), or in the rate of non-HIV associated serious adverse events between re-treatment options. We did not observe clinical benefit or harm assessed by the primary outcome in this largest and longest trial exploring both ART interruption and intensification in advanced MDR HIV infection with poor retreatment options. Clinicaltrials.gov NCT00050089.

Funding antiretroviral treatment for HIV-positive temporary residents in Australia prevents transmission and is inexpensive.

PubMed

Gray, Richard T; Watson, Jo; Cogle, Aaron J; Smith, Don E; Hoy, Jennifer F; Bastian, Lisa A; Finlayson, Robert; Drummond, Fraser M; Whittaker, Bill; Law, Matthew G; Petoumenos, Kathy

2018-02-01

Background The aim of this study is to estimate the reduction in new HIV infections and resultant cost outcomes of providing antiretroviral treatment (ART) through Australia's 'universal access' health scheme to all temporary residents with HIV infection living legally in Australia, but currently deemed ineligible to access subsidised ART via this scheme. A mathematical model to estimate the number of new HIV infections averted and the associated lifetime costs over 5 years if all HIV-positive temporary residents in Australia had access to ART and subsidised medical care was developed. Input data came from a cohort of 180 HIV-positive temporary residents living in Australia who are receiving free ART donated by pharmaceutical companies for up to 4 years. Expanding ART access to an estimated total 450 HIV+ temporary residents in Australia for 5 years could avert 80 new infections. The model estimated the total median discounted (5%) cost for ART and associated care to be A$36million, while the total savings in lifetime-discounted costs for the new infections averted was A$22million. It is estimated that expanded access to ART for all HIV-positive temporary residents in Australia will substantially reduce HIV transmission to their sexual partners at little additional cost. In the context of Australia's National HIV strategy and Australia's endorsement of global goals to provide universal access to ART for all people with HIV, this is an important measure to remove inequities in the provision of HIV-related treatment and care.

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

Retained in HIV Care But Not on Antiretroviral Treatment: A Qualitative Patient-Provider Dyadic Study.

PubMed

Christopoulos, Katerina A; Olender, Susan; Lopez, Andrea M; Lekas, Helen-Maria; Jaiswal, Jessica; Mellman, Will; Geng, Elvin; Koester, Kimberly A

2015-08-01

Patients retained in HIV care but not on antiretroviral therapy (ART) represent an important part of the HIV care cascade in the United States. Even in an era of more tolerable and efficacious ART, decision making in regards to ART offer and uptake remains complex and calls for exploration of both patient and provider perspectives. We sought to understand reasons for lack of ART usage in patients meeting the Health Resources Services Administration definition of retention as well as what motivated HIV primary care appointment attendance in the absence of ART. We conducted a qualitative study consisting of 70 in-depth interviews with ART-naïve and ART-experienced patients off ART and their primary care providers in two urban safety-net HIV clinics in San Francisco and New York. Twenty patients and their providers were interviewed separately at baseline, and 15 dyads were interviewed again after at least 3 mo and another clinic visit in order to understand any ART use in the interim. We applied dyadic analysis to our data. Nearly all patients were willing to consider ART, and 40% of the sample went on ART, citing education on newer antiretroviral drugs, acceptance of HIV diagnosis, social support, and increased confidence in their ability to adhere as facilitators. However, the strength of the provider recommendation of ART played an important role. Many patients had internalized messages from providers that their health was too good to warrant ART. In addition, providers, while demonstrating patient-centered care through sensitivity to patients experiencing psychosocial instability, frequently muted the offer of ART, at times unintentionally. In the absence of ART, lab monitoring, provider relationships, access to social services, opiate pain medications, and acute symptoms motivated care. The main limitations of this study were that treatment as prevention was not explored in depth and that participants were recruited from academic HIV clinics in the US, making

Retained in HIV Care But Not on Antiretroviral Treatment: A Qualitative Patient-Provider Dyadic Study

PubMed Central

Christopoulos, Katerina A.; Olender, Susan; Lopez, Andrea M.; Lekas, Helen-Maria; Jaiswal, Jessica; Mellman, Will; Geng, Elvin; Koester, Kimberly A.

2015-01-01

Background Patients retained in HIV care but not on antiretroviral therapy (ART) represent an important part of the HIV care cascade in the United States. Even in an era of more tolerable and efficacious ART, decision making in regards to ART offer and uptake remains complex and calls for exploration of both patient and provider perspectives. We sought to understand reasons for lack of ART usage in patients meeting the Health Resources Services Administration definition of retention as well as what motivated HIV primary care appointment attendance in the absence of ART. Methods and Findings We conducted a qualitative study consisting of 70 in-depth interviews with ART-naïve and ART-experienced patients off ART and their primary care providers in two urban safety-net HIV clinics in San Francisco and New York. Twenty patients and their providers were interviewed separately at baseline, and 15 dyads were interviewed again after at least 3 mo and another clinic visit in order to understand any ART use in the interim. We applied dyadic analysis to our data. Nearly all patients were willing to consider ART, and 40% of the sample went on ART, citing education on newer antiretroviral drugs, acceptance of HIV diagnosis, social support, and increased confidence in their ability to adhere as facilitators. However, the strength of the provider recommendation of ART played an important role. Many patients had internalized messages from providers that their health was too good to warrant ART. In addition, providers, while demonstrating patient-centered care through sensitivity to patients experiencing psychosocial instability, frequently muted the offer of ART, at times unintentionally. In the absence of ART, lab monitoring, provider relationships, access to social services, opiate pain medications, and acute symptoms motivated care. The main limitations of this study were that treatment as prevention was not explored in depth and that participants were recruited from academic

The Effect of Antiretroviral Treatment on Health Care Utilization in Rural South Africa: A Population-Based Cohort Study

PubMed Central

Tanser, Frank C.; Naidu, Kevindra K.; Pillay, Deenan; Bärnighausen, Till

2016-01-01

Background The effect of the rapid scale-up of vertical antiretroviral treatment (ART) programs for HIV in sub-Saharan Africa on the overall health system is under intense debate. Some have argued that these programs have reduced access for people suffering from diseases unrelated to HIV because ART programs have drained human and physical resources from other parts of the health system; others have claimed that the investments through ART programs have strengthened the general health system and the population health impacts of ART have freed up health care capacity for the treatment of diseases that are not related to HIV. To establish the population-level impact of ART programs on health care utilization in the public-sector health system, we compared trends in health care utilization among HIV-infected people receiving and not receiving ART with HIV-uninfected people during a period of rapid ART scale-up. Methods and Findings We used data from the Wellcome Trust Africa Centre for Population Health, which annually elicited information on health care utilization from all surveillance participants over the period 2009–2012 (N = 32,319). We determined trends in hospitalization, and public-sector and private-sector primary health care (PHC) clinic visits for HIV-infected and -uninfected people over a time period of rapid ART scale-up (2009–2012) in this community. We regressed health care utilization on HIV status and ART status in different calendar years, controlling for sex, age, and area of residence. The proportion of people who reported to have visited a public-sector primary health care (PHC) clinic in the last 6 months increased significantly over the period 2009–2012, for both HIV-infected people (from 59% to 67%; p<0.001), and HIV-uninfected people (from 41% to 47%; p<0.001). In contrast, the proportion of HIV-infected people visiting a private-sector PHC clinic declined from 22% to 12% (p<0.001) and hospitalization rates declined from 128 to 82 per

The Effect of Antiretroviral Treatment on Health Care Utilization in Rural South Africa: A Population-Based Cohort Study.

PubMed

Hontelez, Jan A C; Tanser, Frank C; Naidu, Kevindra K; Pillay, Deenan; Bärnighausen, Till

2016-01-01

The effect of the rapid scale-up of vertical antiretroviral treatment (ART) programs for HIV in sub-Saharan Africa on the overall health system is under intense debate. Some have argued that these programs have reduced access for people suffering from diseases unrelated to HIV because ART programs have drained human and physical resources from other parts of the health system; others have claimed that the investments through ART programs have strengthened the general health system and the population health impacts of ART have freed up health care capacity for the treatment of diseases that are not related to HIV. To establish the population-level impact of ART programs on health care utilization in the public-sector health system, we compared trends in health care utilization among HIV-infected people receiving and not receiving ART with HIV-uninfected people during a period of rapid ART scale-up. We used data from the Wellcome Trust Africa Centre for Population Health, which annually elicited information on health care utilization from all surveillance participants over the period 2009-2012 (N = 32,319). We determined trends in hospitalization, and public-sector and private-sector primary health care (PHC) clinic visits for HIV-infected and -uninfected people over a time period of rapid ART scale-up (2009-2012) in this community. We regressed health care utilization on HIV status and ART status in different calendar years, controlling for sex, age, and area of residence. The proportion of people who reported to have visited a public-sector primary health care (PHC) clinic in the last 6 months increased significantly over the period 2009-2012, for both HIV-infected people (from 59% to 67%; p<0.001), and HIV-uninfected people (from 41% to 47%; p<0.001). In contrast, the proportion of HIV-infected people visiting a private-sector PHC clinic declined from 22% to 12% (p<0.001) and hospitalization rates declined from 128 to 82 per 1000 PY (p<0.001). For HIV

An appeal for large scale production of antiretroviral drugs in Africa

PubMed Central

Martial, Nkamedjie Pete Patrick; Sieleunou, Isidore

2016-01-01

The Acquired Immuno Deficiency Syndrome (AIDS) remains a major global public health challenge especially in Africa. The deadline set for the Millennium Development Goals (MDGs) has elapsed, meanwhile most low and middle income countries did not reach the targets. With regards to the fight against HIV / AIDS, many African countries show slow progress in implementing efficient and effective strategies to counter this pandemic. The fact that most HIV/AIDS programs in Sub-Saharan African countries are still very dependent on external funding to carry out their activities, including the supply of Antiretroviral Treatment (ART), highlights the concern of sustainability. So far, solutions that have been proposed are mainly symptomatic, claiming more budget commitment from government. Without rejecting this view, we call for the implementation of sustainable solutions to deal with the long term ART challenges. A way forward is to promote the establishment of an effective machinery for the manufacturing and large scale distribution of ART. In addition to the health gains, we argue that such an initiative would have a three-dimensional impact: (i) political, (ii) economic and (iii) social. PMID:28154710

Otitis media in Brazilian human immunodeficiency virus infected children undergoing antiretroviral therapy.

PubMed

Miziara, I D; Weber, R; Araújo Filho, B Cunha; Pinheiro Neto, C Diógenes

2007-11-01

To assess changes in the prevalence of otitis media, associated with the use of highly active antiretroviral therapy, in Brazilian human immunodeficiency virus (HIV) infected children. Division of otorhinolaryngology, Hospital das Clínicas, Sao Paulo University Medical School, Brazil. A cohort of 459 HIV-infected children aged below 13 years. The prevalence of otitis media and the serum cluster of differentiation four glycoprotein T lymphocyte count were compared for children receiving highly active antiretroviral therapy (with protease inhibitors) and those receiving standard antiretroviral therapy (without protease inhibitors). Otitis media was present in 33.1 per cent of the children. Children aged from zero years to five years 11 months receiving highly active antiretroviral therapy had a higher prevalence of acute otitis media (p=0.02) and a lower prevalence of chronic otitis media (p=0.02). Children who were receiving highly active antiretroviral therapy had a mean serum cluster of differentiation four glycoprotein T lymphocyte count greater than that of those who were receiving standard antiretroviral therapy (p<0.001). The use of highly active antiretroviral therapy in Brazilian HIV-infected children was associated with a lower prevalence of chronic otitis media.

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.

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.

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

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.

Survival of people on antiretroviral treatment in Zambia: a retrospective cohort analysis of HIV clients on ART.

PubMed

Amanzi, Patrick; Michelo, Charles; Simoonga, Christopher; Dambe, Rosalia; Chongwe, Gershom

2016-01-01

Provision of free anti-retroviral therapy in Zambia started in June 2004. There were only 15,000 people on treatment as at December that year, mainly due to lack of access. This number rose to 580,000 people as at December 2013. The general objective of this study was to determine survival of people on ART and to examine associated predictors for survival. The study included ART patients enrolled between the year 2002 and 2013 (n=10,395) in 285 health facilities in Zambia. Patient files were analyzed retrospectively. The study used Kaplan Meier and Cox-proportional hazard models to describe the relationship between lost to follow up and age, sex, baseline CD4 cell count and weight. Results showed that lost to follow up accounted for 90% of the clients that had dropped out, while 10% was to deaths. Low baseline CD4 count (p-value 0.001, HR 0.9994, (95% CI 0.9993, 0.9996) at initiation was associated with lost to follow up together with weight at initiation (p-value 0.031, HR 0.9987 at 95% CI (0.9975, 0.9998)) of ART. This study has demonstrated that lost to follow up is a substantial contributing factor to drop outs among HIV patients on treatment. Strengthening of community treatment supporters especially immediate family members in emphasizing to the client the need to continue treatment is necessary. The health facility could do more in emphasizing the importance of treatment especially in the initial stages. Further, in order to reduce opportunistic infections and probable deaths during treatment, cotrimoxazole prophylaxis should be maintained so as to raise the CD4 levels. Improved nutritional assessment and counseling to boost the nutritional status of the clients throughout should be encouraged.

Estimating the resources required in the roll-out of universal access to antiretroviral treatment in Zimbabwe.

PubMed

Hallett, T B; Gregson, S; Dube, S; Mapfeka, E S; Mugurungi, O; Garnett, G P

2011-12-01

To develop projections of the resources required (person-years of drug supply and healthcare worker time) for universal access to antiretroviral treatment (ART) in Zimbabwe. A stochastic mathematical model of disease progression, diagnosis, clinical monitoring and survival in HIV infected individuals. The number of patients receiving ART is determined by many factors, including the strategy of the ART programme (method of initiation, frequency of patient monitoring, ability to include patients diagnosed before ART became available), other healthcare services (referral rates from antenatal clinics, uptake of HIV testing), demographic and epidemiological conditions (past and future trends in incidence rates and population growth) as well as the medical impact of ART (average survival and the relationship with CD4 count when initiated). The variations in these factors lead to substantial differences in long-term projections; with universal access by 2010 and no further prevention interventions, between 370 000 and almost 2 million patients could be receiving treatment in 2030-a fivefold difference. Under universal access, by 2010 each doctor will initiate ART for up to two patients every day and the case-load for nurses will at least triple as more patients enter care and start treatment. The resources required by ART programmes are great and depend on the healthcare systems and the demographic/epidemiological context. This leads to considerable uncertainty in long-term projections and large variation in the resources required in different countries and over time. Understanding how current practices relate to future resource requirements can help optimise ART programmes and inform long-term public health planning.

Impact of an antiretroviral stewardship strategy on medication error rates.

PubMed

Shea, Katherine M; Hobbs, Athena Lv; Shumake, Jason D; Templet, Derek J; Padilla-Tolentino, Eimeira; Mondy, Kristin E

2018-05-02

The impact of an antiretroviral stewardship strategy on medication error rates was evaluated. This single-center, retrospective, comparative cohort study included patients at least 18 years of age infected with human immunodeficiency virus (HIV) who were receiving antiretrovirals and admitted to the hospital. A multicomponent approach was developed and implemented and included modifications to the order-entry and verification system, pharmacist education, and a pharmacist-led antiretroviral therapy checklist. Pharmacists performed prospective audits using the checklist at the time of order verification. To assess the impact of the intervention, a retrospective review was performed before and after implementation to assess antiretroviral errors. Totals of 208 and 24 errors were identified before and after the intervention, respectively, resulting in a significant reduction in the overall error rate ( p < 0.001). In the postintervention group, significantly lower medication error rates were found in both patient admissions containing at least 1 medication error ( p < 0.001) and those with 2 or more errors ( p < 0.001). Significant reductions were also identified in each error type, including incorrect/incomplete medication regimen, incorrect dosing regimen, incorrect renal dose adjustment, incorrect administration, and the presence of a major drug-drug interaction. A regression tree selected ritonavir as the only specific medication that best predicted more errors preintervention ( p < 0.001); however, no antiretrovirals reliably predicted errors postintervention. An antiretroviral stewardship strategy for hospitalized HIV patients including prospective audit by staff pharmacists through use of an antiretroviral medication therapy checklist at the time of order verification decreased error rates. Copyright © 2018 by the American Society of Health-System Pharmacists, Inc. All rights reserved.

Delivery of antiretroviral treatment services in India: Estimated costs incurred under the National AIDS Control Programme.

PubMed

Agarwal, Reshu; Rewari, Bharat Bhushan; Shastri, Suresh; Nagaraja, Sharath Burugina; Rathore, Abhilakh Singh

2017-04-01

Competing domestic health priorities and shrinking financial support from external agencies necessitates that India's National AIDS Control Programme (NACP) brings in cost efficiencies to sustain the programme. In addition, current plans to expand the criteria for eligibility for antiretroviral therapy (ART) in India will have significant financial implications in the near future. ART centres in India provide comprehensive services to people living with HIV (PLHIV): those fulfilling national eligibility criteria and receiving ART and those on pre-ART care, i.e. not on ART. ART centres are financially supported (i) directly by the NACP; and (ii) indirectly by general health systems. This study was conducted to determine (i) the cost incurred per patient per year of pre-ART and ART services at ART centres; and (ii) the proportion of this cost incurred by the NACP and by general health systems. The study used national data from April 2013 to March 2014, on ART costs and non-ART costs (human resources, laboratory tests, training, prophylaxis and management of opportunistic infections, hospitalization, operational, and programme management). Data were extracted from procurement records and reports, statements of expenditure at national and state level, records and reports from ART centres, databases of the National AIDS Control Organisation, and reports on use of antiretroviral drugs. The analysis estimates the cost for ART services as US$ 133.89 (?8032) per patient per year, of which 66% (US$ 88.66, ?5320) is for antiretroviral drugs and 34% (US$ 45.23, ?2712) is for non-ART recurrent expenditure, while the cost for pre-ART care is US$ 33.05 (?1983) per patient per year. The low costs incurred for patients in ART and pre-ART care services can be attributed mainly to the low costs of generic drugs. However, further integration with general health systems may facilitate additional cost saving, such as in human resources.

Assessing the quality of data aggregated by antiretroviral treatment clinics in Malawi.

PubMed

Makombe, Simon D; Hochgesang, Mindy; Jahn, Andreas; Tweya, Hannock; Hedt, Bethany; Chuka, Stuart; Yu, Joseph Kwong-Leung; Aberle-Grasse, John; Pasulani, Olesi; Bailey, Christopher; Kamoto, Kelita; Schouten, Erik J; Harries, Anthony D

2008-04-01

As national antiretroviral treatment (ART) programmes scale-up, it is essential that information is complete, timely and accurate for site monitoring and national planning. The accuracy and completeness of reports independently compiled by ART facilities, however, is often not known. This study assessed the quality of quarterly aggregate summary data for April to June 2006 compiled and reported by ART facilities ("site report") as compared to the "gold standard" facility summary data compiled independently by the Ministry of Health supervision team ("supervision report"). Completeness and accuracy of key case registration and outcome variables were compared. Data were considered inaccurate if variables from the site reports were missing or differed by more than 5% from the supervision reports. Additionally, we compared the national summaries obtained from the two data sources. Monitoring and evaluation of Malawi's national ART programme is based on WHO's recommended tools for ART monitoring. It includes one master card for each ART patient and one patient register at each ART facility. Each quarter, sites complete cumulative cohort analyses and teams from the Ministry of Health conduct supervisory visits to all public sector ART sites to ensure the quality of reported data. Most sites had complete case registration and outcome data; however many sites did not report accurate data for several critical data fields, including reason for starting, outcome and regimen. The national summary using the site reports resulted in a 12% undercount in the national total number of persons on first-line treatment. Several facility-level characteristics were associated with data quality. While many sites are able to generate complete data summaries, the accuracy of facility reports is not yet adequate for national monitoring. The Ministry of Health and its partners should continue to identify and support interventions such as supportive supervision to build sites' capacity to

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 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.

Patient-Reported Symptoms on the Antiretroviral Regimen Efavirenz/Emtricitabine/Tenofovir

PubMed Central

Gordon, Kirsha; Rodriguez-Barradas, Maria C.; Justice, Amy C.

2012-01-01

Abstract Most patients (80–90%) newly diagnosed with HIV are started on the antiretroviral regimen efavirenz, emtricitabine, and tenofovir (EFV/FTC/TDF). Existing studies of patient tolerability, however, are limited. We compared symptom experiences of patients on EFV/FTC/TDF, and the subsequent impact on health-related quality of life, with those of patients on other combination antiretroviral therapy (cART). We conducted a cross-sectional analysis of the Veterans Aging Cohort Study from February 2008 to August 2009 to compare the symptom experiences of patients on EFV/FTC/TDF vs. other cART, unadjusted and then adjusted for treatment characteristics, and comorbid disease severity. We then assessed the association between EFV/FTC/TDF use and health-related quality of life. Among the 1,759 patients in our analytic sample, EFV/FTC/TDF use was associated with fewer symptoms than was other cART. The use of EFV/FTC/TDF was independently associated with health-related quality of life, and this association was at least partially explained by symptom burden. PMID:22612469

Despite Access to Antiretrovirals for Prevention and Treatment, High Rates of Mortality Persist Among HIV-infected Infants and Young Children.

PubMed

Abrams, Elaine J; Woldesenbet, Selamawit; Soares Silva, Juliana; Coovadia, Ashraf; Black, Viviane; Technau, Karl-Günter; Kuhn, Louise

2017-06-01

Outcomes of HIV-infected children before widespread use of antiretroviral therapy (ART) for treatment and prevention of mother-to-child transmission (PMTCT) have been well characterized but less is known about children who acquire HIV infection in the context of good ART access. We enrolled newly diagnosed HIV-infected children ≤24 months of age at 3 hospitals and 2 clinics in Johannesburg, South Africa. We report ART initiation and mortality rates during 6 months from enrollment and factors associated with mortality. Of 272 children enrolled, median age 6.1 months, 69.5% were diagnosed during hospitalization. By 6 months postenrollment, 53 (19.5%) died and 73 (26.8%) were lost-to-follow-up. Using Kaplan-Meier analysis, the probability of death by 6 months after enrollment was 23.5%. The median age of death was 9.1 months [95% confidence interval (CI): 8.6-12.0]. Overall, 226 (83%) children initiated ART which was associated with a 71% reduction in risk of death [hazard ratio (HR) = 0.29 (95% CI: 0.15-0.58)]. In multivariable analysis of infant factors, weight-for-age Z score < -2 standard deviation (SD) [HR = 2.43 (95% CI: 1.03-5.73)], CD4 <20% [HR = 3.29 (95% CI: 1.60-6.76)] and identification during hospitalization [HR = 2.89 (95% CI: 1.16-7.25)] were independently associated with mortality. In multivariable analysis of maternal factors, CD4 ≤350/no maternal ART was associated with increased mortality risk [HR = 2.57 (95% CI: 1.19-5.59)] versus CD4 >350/no maternal ART; exposure to maternal/infant antiretrovirals for PMTCT was associated with reduced mortality risk [HR = 0.53 (95% CI: 0.28-0.99)] versus no PMTCT. ART initiation is highly protective against death in young children. However, despite improved access to ART, young children remain at risk for early death; innovative approaches to rapidly diagnose and initiate treatment as early in life as possible are needed.

Assessing the population health impact of market interventions to improve access to antiretroviral treatment

PubMed Central

Bärnighausen, Till; Kyle, Margaret; Salomon, Joshua A; Waning, Brenda

2012-01-01

Despite extraordinary global progress in increasing coverage of antiretroviral treatment (ART), the majority of people needing ART currently are not receiving treatment. Both the number of people needing ART and the average ART price per patient-year are expected to increase in coming years, which will dramatically raise funding needs for ART. Several international organizations are using interventions in ART markets to decrease ART price or to improve ART quality, delivery and innovation, with the ultimate goal of improving population health. These organizations need to select those market interventions that are most likely to substantially affect population health outcomes (ex ante assessment) and to evaluate whether implemented interventions have improved health outcomes (ex post assessment). We develop a framework to structure ex ante and ex post assessment of the population health impact of market interventions, which is transmitted through effects in markets and health systems. Ex ante assessment should include evaluation of the safety and efficacy of the ART products whose markets will be affected by the intervention; theoretical consideration of the mechanisms through which the intervention will affect population health; and predictive modelling to estimate the potential population health impact of the intervention. For ex post assessment, analysts need to consider which outcomes to estimate empirically and which to model based on empirical findings and understanding of the economic and biological mechanisms along the causal pathway from market intervention to population health. We discuss methods for ex post assessment and analyse assessment issues (unintended intervention effects, interaction effects between different interventions, and assessment impartiality and cost). We offer seven recommendations for ex ante and ex post assessment of population health impact of market interventions. PMID:21914713

Improving care for patients on antiretroviral therapy through a gap analysis framework.

PubMed

Massoud, M Rashad; Shakir, Fazila; Livesley, Nigel; Muhire, Martin; Nabwire, Juliana; Ottosson, Amanda; Jean-Baptiste, Rachel; Megere, Humphrey; Karamagi-Nkolo, Esther; Gaudreault, Suzanne; Marks, Pamela; Jennings, Larissa

2015-07-01

To improve quality of care through decreasing existing gaps in the areas of coverage, retention, and wellness of patients receiving HIV care and treatment. The antiretroviral therapy (ART) Framework utilizes improvement methods and the Chronic Care Model to address the coverage, retention, and wellness gaps in HIV care and treatment. This is a time-series study. The ART Framework was applied in five health centers in Buikwe District, Uganda. Quality improvement teams, consisting of healthcare workers and expert patients, were established in each of the five healthcare facilities. The intervention period was October 2010 to September 2012. It consisted of quality improvement teams analyzing their facility and systems of care from the perspective of the Chronic Care Model to identify areas of improvement. They implemented the ART Framework, collected data and assessed outcomes, focused on self-management support for patients, to improve coverage, retention, and wellness gaps in HIV care and treatment. Coverage was defined as every patient who needs ART in the catchment area, receives it. Retention was defined as every patient who receives ART stays on ART, and wellness defined as having a positive clinical, immunological, and/or virological response to treatment without intolerable or unmanageable side-effects. Results from Buikwe show the gaps in coverage, retention, and wellness greatly decreased a gap in coverage of 44-19%, gap in retention of 49-24%, and gap in wellness of 53-14% during a 2-year intervention period. The ART Framework is an innovative and practical tool for HIV program managers to improve HIV care and treatment.

Durability of Adherence to Antiretroviral Therapy on Initial and Subsequent Regimens

PubMed Central

GARDNER, EDWARD M.; BURMAN, WILLIAM J.; MARAVI, MOISES E.; DAVIDSON, ARTHUR J.

2007-01-01

There is uncertainty regarding the durability of adherence to antiretroviral therapy. This study is a retrospective review of previously antiretroviral naïve patients initiating therapy between 1997 and 2002. Antiretroviral adherence was calculated using prescription refill data and was analyzed over time on an initial regimen and on sequential antiretroviral regimens. Three hundred forty-four patients were included. The median lengths of the first, second, and third regimens were stable at 1.7 years, 1.2 years, and 1.5 years, respectively (p = 0.10). In multivariate analysis the factor most significantly associated with earlier initial regimen termination was poor adherence. On an initial regimen, adherence decreased over time and declined most rapidly in patients with the shortest regimens (4 to <16 months, −43% per year), followed by patients with intermediate regimen duration (16 to <28 months, −19% per year), and then patients with longer regimens (≥28 months, −5% per year). In patients progressing to a third regimen, there was a trend toward decreasing adherence over successive regimens. In conclusion, sequential antiretroviral regimens are of similar lengths, with adherence being highly associated with first regimen duration. Adherence decreases during an initial regimen and on sequential antiretroviral regimens. Effective and durable interventions to prevent declining adherence are needed. PMID:16987049

Results of Antiretroviral Treatment Interruption and Intensification in Advanced Multi-Drug Resistant HIV Infection from the OPTIMA Trial

PubMed Central

Holodniy, Mark; Brown, Sheldon T.; Cameron, D. William; Kyriakides, Tassos C.; Angus, Brian; Babiker, Abdel; Singer, Joel; Owens, Douglas K.; Anis, Aslam; Goodall, Ruth; Hudson, Fleur; Piaseczny, Mirek; Russo, John; Schechter, Martin; Deyton, Lawrence; Darbyshire, Janet

2011-01-01

Background Guidance is needed on best medical management for advanced HIV disease with multidrug resistance (MDR) and limited retreatment options. We assessed two novel antiretroviral (ARV) treatment approaches in this setting. Methods and Findings We conducted a 2×2 factorial randomized open label controlled trial in patients with a CD4 count ≤300 cells/µl who had ARV treatment (ART) failure requiring retreatment, to two options (a) re-treatment with either standard (≤4 ARVs) or intensive (≥5 ARVs) ART and b) either treatment starting immediately or after a 12-week monitored ART interruption. Primary outcome was time to developing a first AIDS-defining event (ADE) or death from any cause. Analysis was by intention to treat. From 2001 to 2006, 368 patients were randomized. At baseline, mean age was 48 years, 2% were women, median CD4 count was 106/µl, mean viral load was 4.74 log10 copies/ml, and 59% had a prior AIDS diagnosis. Median follow-up was 4.0 years in 1249 person-years of observation. There were no statistically significant differences in the primary composite outcome of ADE or death between re-treatment options of standard versus intensive ART (hazard ratio 1.17; CI 0.86–1.59), or between immediate retreatment initiation versus interruption before re-treatment (hazard ratio 0.93; CI 0.68–1.30), or in the rate of non-HIV associated serious adverse events between re-treatment options. Conclusions We did not observe clinical benefit or harm assessed by the primary outcome in this largest and longest trial exploring both ART interruption and intensification in advanced MDR HIV infection with poor retreatment options. Trial Registration Clinicaltrials.gov NCT00050089 PMID:21483491

Incidence and risk factors of antiretroviral treatment failure in treatment-naïve HIV-infected patients at Chiang Mai University Hospital, Thailand

PubMed Central

2011-01-01

Background The use of combination antiretroviral therapy (cART) has become a standard of care for the treatment of HIV infection. However, cost and resistance to cART are major obstacles for access to treatment especially in resource-limited settings. In this study, we aimed to determine the incidence and risk factors of treatment failure in a cohort of treatment-naïve Thai HIV-infected patients. Methods A retrospective cohort study was conducted among HIV-infected patients initiating their first cART at Chiang Mai University Hospital, Thailand. Results From January 2002 to December 2008, 788 patients were enrolled; 365 were male (46.3%), and the mean age was 37.9 ± 8.6 years. The median baseline CD4 count was 57.7 cells/mm3 (IQR 22, 127). GPO-VIR® (a fixed-dose combination of lamivudine, stavudine, and nevirapine) was the most common prescribed cART (657 patients, 83.4%). Seventy-six patients developed virological failure given the cumulative incidence of 9.6%. The incidence of virological failure was 2.79 (95% CI 2.47, 3.14) cases per 100 person years. Poor adherence was the strongest predictor for virological failure. Of 535 immunologically evaluable patients, 179 (33.5%) patients developed immunological failure. A low CD4 cell count at baseline (< 100 cells/mm3) and the increment of CD4 cell count of < 50 cell/mm3 after 6 months of cART were the predictors for immunological failure (p < 0.001). Conclusions This study demonstrated that even in resource-limited settings, the high rate of success could be expected in the cohort with good and sustainable drug adherence. Poor adherence, older age, and low baseline CD4 cell count are the predictors for unfavorable outcome of cART. PMID:22060823

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.

Treatment Programs in the National Drug Abuse Treatment Clinical Trials Network

PubMed Central

McCarty, Dennis; Fuller, Bret; Kaskutas, Lee Ann; Wendt, William W.; Nunes, Edward V.; Miller, Michael; Forman, Robert; Magruder, Kathryn M.; Arfken, Cynthia; Copersino, Marc; Floyd, Anthony; Sindelar, Jody; Edmundson, Eldon

2008-01-01

Drug abuse treatment programs and university-based research centers collaborate to test emerging therapies for alcohol and drug disorders in the National Drug Abuse Treatment Clinical Trials Network (CTN). Programs participating in the CTN completed organizational (n = 106 of 112; 95% response rate) and treatment unit surveys (n = 348 of 384; 91% response rate) to describe the levels of care, ancillary services, patient demographics, patient drug use and co-occurring conditions. Analyses describe the corporations participating in the CTN and provide an exploratory assessment of variation in treatment philosophies. A diversity of treatment centers participate in the CTN; not for profit organizations with a primary mission of treating alcohol and drug disorders dominate. Compared to N-SSATS (National Survey of Substance Abuse Treatment Services), programs located in medical settings are over-represented and centers that are mental health clinics are under-represented. Outpatient, methadone, long-term residential and inpatient treatment units differed on patients served and services proved. Larger programs with higher counselor caseloads in residential settings reported more social model characteristics. Programs with higher social model scores were more likely to offer self-help meetings, vocational services and specialized services for women. Conversely, programs with accreditation had less social model influence. The CTN is an ambitious effort to engage community-based treatment organizations into research and more fully integrate research and practice. PMID:17875368

Adipocytes Impair Efficacy of Antiretroviral Therapy

PubMed Central

Couturier, Jacob; Winchester, Lee C.; Suliburk, James W.; Wilkerson, Gregory K.; Podany, Anthony T.; Agarwal, Neeti; Chua, Corrine Ying Xuan; Nehete, Pramod N.; Nehete, Bharti P.; Grattoni, Alessandro; Sastry, K. Jagannadha; Fletcher, Courtney V.; Lake, Jordan E.; Balasubramanyan, Ashok; Lewis, Dorothy E.

2018-01-01

Adequate distribution of antiretroviral drugs to infected cells in HIV patients is critical for viral suppression. In humans and primates, HIV- and SIV-infected CD4 T cells in adipose tissues have recently been identified as reservoirs for infectious virus. To better characterize adipose tissue as a pharmacological sanctuary for HIV-infected cells, in vitro experiments were conducted to assess antiretroviral drug efficacy in the presence of adipocytes, and drug penetration in adipose tissue cells (stromal-vascular-fraction cells and mature adipocytes) was examined in treated humans and monkeys. Co-culture experiments between HIV-1-infected CD4 T cells and primary human adipocytes showed that adipocytes consistently reduced the antiviral efficacy of the nucleotide reverse transcriptase inhibitor tenofovir and its prodrug forms tenofovir disoproxil fumarate (TDF) and tenofovir alafenamide (TAF). In HIV-infected persons, LC-MS/MS analysis of intracellular lysates derived from adipose tissue stromal-vascular-fraction cells or mature adipocytes suggested that integrase inhibitors penetrate adipose tissue, whereas penetration of nucleoside/nucleotide reverse transcriptase inhibitors such as TDF, emtricitabine, abacavir, and lamivudine is restricted. The limited distribution and functions of key antiretroviral drugs within fat depots may contribute to viral persistence in adipose tissue. PMID:29630975

Efavirenz or nevirapine in three-drug combination therapy with two nucleoside-reverse transcriptase inhibitors for initial treatment of HIV infection in antiretroviral-naïve individuals.

PubMed

Mbuagbaw, Lawrence Ce; Irlam, James H; Spaulding, Alicen; Rutherford, George W; Siegfried, Nandi

2010-12-08

The advent of highly active antiretroviral therapy (HAART) has reduced the morbidity and mortality due to HIV. The World Health Organisation (WHO) antiretroviral treatment (ART) guidelines focus on three classes of antiretroviral drugs, namely: nucleoside/nucleotide reverse transcriptase inhibitors (NRTI), non-nucleoside reverse transcriptase inhibitors (NNRTI) and protease inhibitors (PI). Two of the most common medications given in first-line treatment are the NNRTIs, efavirenz (EFV) and nevirapine (NVP). It is unclear which NNRTI is more efficacious for initial therapy. To determine which NNRTI, EFV or NVP, is more efficacious when given in combination with two NRTIs as part of initial ART for HIV infection in adults and children. We used a comprehensive and exhaustive strategy in an attempt to identify all relevant studies, regardless of language or publication status, in electronic databases and conference proceedings from 1996 to 2009. All randomised controlled trials comparing EFV to NVP in HIV-infected individuals without prior exposure to ART, irrespective of the dosage or NRTI backbone.The primary outcome of interest was virologic response to ART. Other primary outcomes included mortality, clinical progression, severe adverse events, and discontinuation of therapy for any reason. Secondary outcomes were immunologic response to ART, treatment failure, development of ART drug resistance, and prevention of sexual transmission of HIV. Two authors assessed each reference for inclusion and exclusion criteria established a priori. Data were abstracted independently using a standardised abstraction form. Data were analysed on an intention-to-treat basis and reported as per dosage of NVP. We identified seven randomised controlled trials that met our inclusion criteria.The trials were pooled as per dosage of NVP. None of these trials included children.The seven trials enrolled 1,688 participants and found no critical differences between EFV and NVP, except for

Relationship between characteristics of volunteer community health workers and antiretroviral treatment outcomes in a community-based treatment programme in Uganda.

PubMed

Alibhai, Arif; Kipp, Walter; Saunders, L Duncan; Rubaale, Tom; Mill, Judy; Konde-Lule, Joseph

2017-09-01

Community health workers (CHWs) can help to redress the shortages of health human resources needed to scale up antiretroviral treatment (ART). However, the selection of CHWs could influence the effectiveness of a CHW programme. The purpose of this observational study was to assess whether sociodemographic characteristics and geographic proximity to patients of volunteer CHWs were predictors of clinical outcomes in a community-based ART (CBART) programme in Kabarole, Uganda. Data from CHW surveys for 41 CHWs and clinic charts for 185 patients in the CBART programme were analysed using multivariable logistic and Cox regression models. Time to travel to patients was the only statistically significant characteristic of CHWs associated with ART outcomes. Patients whose CHWs had to travel one or more hours had a 71% lower odds of virologic suppression (adjusted OR = 0.29, 95% CI = 0.13-0.65, p = .002) and a 4.52 times higher mortality hazard rate (adjusted HR = 4.52, 95% CI = 1.20-17.09, p = .026) compared to patients whose CHWs had to travel less than one hour. The findings show that the sociodemographic characteristics of CHWs were not as important as the geographic distance they had to travel to patients.

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

[Pulmonary hypertension in human immunodeficiency virus-infected patients: the role of antiretroviral therapy].

PubMed

Olalla, Julián; Urdiales, Daniel; Pombo, Marta; del Arco, Alfonso; de la Torre, Javier; Prada, José Luis

2014-03-20

Pulmonary arterial hypertension (PAH) is a serious disorder, more prevalent in patients infected with human immunodeficiency virus (HIV). It is not entirely clear what role is played by highly active antiretroviral therapy (HAART) in PAH development or course. Our aim was to describe PAH prevalence in a series of HIV-infected patients and identify possible links with cumulative and current use of different antiretrovirals. Cross-sectional study of a cohort of HIV-infected patients attending a hospital in southern Spain. Demographic data, data on HIV infection status and on cumulative and recent antiretroviral treatment were recorded. Transthoracic echocardiography was performed in all study participants. PAH was defined as pulmonary artery systolic pressure of 36mmHg or more. A total of 400 patients participated in the study; 178 presented with tricuspid regurgitation and 22 of these presented with PAH (5.5%). No differences were encountered in age, sex, CD4 lymphocytes, proportion of naive patients or patients with AIDS. No differences were encountered in cumulative use of antiretrovirals. However, recent use of lamivudine was associated with a greater presence of PAH, whereas recent use of tenofovir and emtricitabine was associated with a lower presence of PAH. Logistic regression analysis was performed including the use of lamivudine, emtricitabine and tenofovir. Only recent use of tenofovir was associated with a lower presence of PAH (odds ratio 0.31; 95% confidence interval: 0.17-0.84). PAH prevalence in our study was similar to others series. Current use of tenofovir may be associated with lower PAH prevalence. Copyright © 2012 Elsevier España, S.L. All rights reserved.

Comparison of survival in adult antiretroviral treatment naïve patients treated in primary health care centers versus those treated in hospitals: retrospective cohort study; Oromia region, Ethiopia.

PubMed

Megerso, Abebe; Garoma, Sileshi

2016-10-18

Antiretroviral treatment (ART) service scaling up has been practiced in the Ethiopia since 2006. Regardless of increasing number of primary health care centers providing the service, the existing hospitals are still overcrowded with ART service seeking patients may be because of the common belief that treatment outcome is better for hospital patients than those treated at the primary health centers. However, documented evidence comparing the treatment outcome for the two categories of health facilities is scarce in the study setting. The purpose of the current study was to compare major treatment outcomes among new patients treated at the two health facility categories. Retrospective cohort study was implemented using secondary data from medical records collected between October 2010 and January 2014 in the selected health facilities. All patients (1895) who started the treatment in the facilities during the period were included in the study. Univariate analyses were made using descriptive methods such as frequency distributions and measures of central tendency. Bivariate and multivariate analyses were made using Kaplan Meier and Cox regression models respectively to compare the mean survival time between the two facility categories. P-value less than 0.05 was considered as statistically significant. A total of 1895 patient records were followed for 27,990 person-months. Risks of unwanted treatment outcomes (death and lose-to-follow-up) were the same for both categories of patients. The median survival probability was similar to the facility categories (P-value = 0.11). Baseline performance scale III/IV (AHR, 2.4; 95 % CI: 2.0, 3.0), baseline WHO clinical stages III/IV (AHR, 2.8; 95 % CI: 2.3, 3.4), and low adherence (<95 %) to ART drugs (AHR, 3.4; 95 % CI: 2.8, 5.2) were the independent predictors of the unwanted treatment outcomes. Antiretroviral treatment service delivery at primary health care facilities did not compromise the treatment outcomes among

Changes in Cardiovascular Disease Risk Factors With Immediate Versus Deferred Antiretroviral Therapy Initiation Among HIV-Positive Participants in the START (Strategic Timing of Antiretroviral Treatment) Trial.

PubMed

Baker, Jason V; Sharma, Shweta; Achhra, Amit C; Bernardino, Jose Ignacio; Bogner, Johannes R; Duprez, Daniel; Emery, Sean; Gazzard, Brian; Gordin, Jonathan; Grandits, Greg; Phillips, Andrew N; Schwarze, Siegfried; Soliman, Elsayed Z; Spector, Stephen A; Tambussi, Giuseppe; Lundgren, Jens

2017-05-22

HIV infection and certain antiretroviral therapy (ART) medications increase atherosclerotic cardiovascular disease risk, mediated, in part, through traditional cardiovascular disease risk factors. We studied cardiovascular disease risk factor changes in the START (Strategic Timing of Antiretroviral Treatment) trial, a randomized study of immediate versus deferred ART initiation among HIV-positive persons with CD4 + cell counts >500 cells/mm 3 . Mean change from baseline in risk factors and the incidence of comorbid conditions were compared between groups. The characteristics among 4685 HIV-positive START trial participants include a median age of 36 years, a CD4 cell count of 651 cells/mm 3 , an HIV viral load of 12 759 copies/mL, a current smoking status of 32%, a median systolic/diastolic blood pressure of 120/76 mm Hg, and median levels of total cholesterol of 168 mg/dL, low-density lipoprotein cholesterol of 102 mg/dL, and high-density lipoprotein cholesterol of 41 mg/dL. Mean follow-up was 3.0 years. The immediate and deferred ART groups spent 94% and 28% of follow-up time taking ART, respectively. Compared with patients in the deferral group, patients in the immediate ART group had increased total cholesterol and low-density lipoprotein cholesterol and higher use of lipid-lowering therapy (1.2%; 95% CI, 0.1-2.2). Concurrent increases in high-density lipoprotein cholesterol with immediate ART resulted in a 0.1 lower total cholesterol to high-density lipoprotein cholesterol ratio (95% CI, 0.1-0.2). Immediate ART resulted in 2.3% less BP-lowering therapy use (95% CI, 0.9-3.6), but there were no differences in new-onset hypertension or diabetes mellitus. Among HIV-positive persons with preserved immunity, immediate ART led to increases in total cholesterol and low-density lipoprotein cholesterol but also concurrent increases in high-density lipoprotein cholesterol and decreased use of blood pressure medications. These opposing effects suggest that, in

[Current situation related to antiretroviral therapy and related influential factors on HIV infected injection drug users in the methadone maintenance treatment clinics].

PubMed

Cheng, Xiao-Qing; Pang, Lin; Cao, Xiao-Bin; Wang, Chang-He; Luo, Wei; Zhang, Bo; Wang, Hua; Li, Rong-Jian; Rou, Ke-Ming; Wu, Zun-You

2013-08-01

To find out the current coverage of antiretroviral therapy (ART) among HIV positive subjects and to identify the major influential factors associated with the participation in ART among them. 291 HIV positive subjects from 6 methadone maintenance treatment (MMT) clinics in Guangxi and Yunnan province were surveyed by questionnaires. 217 males (74.6%) and 74 females (25.4%) were under investigation, with the average age of 38.4 +/- 5.9. Most of them received less than senior high school education, married and unemployed. Results from the single factor logistic regression analysis showed that: working status, living alone, self-reported history of drinking alcohol in the last month, negative attitude towards MMT among family members,poor self-reported compliance to MMT in the last month,lack of incentives in the MMT clinics, reluctance on disclosure of their own HIV status, good self-perception on their health status, lack of communication on ART related topics among family members in the last 6 months, lack of correct attitude and knowledge on ART etc. appeared as the main factors that influencing the participation in ART program among the patients. Data from the multivariate logistic regression analysis showed that factors as: living alone, unwilling to tell others about the status of HIV infection, poor self-perception on HIV infection, lack of discussion of ART related topics within family members in the last 6 months and poor awareness towards ART among the family members etc., were associated with the low participation rate of ART. Conclusion Strengthening the publicity and education programs on HIV positive patients and their family members at the MMT clinics seemed to be effective in extending the ART coverage. Attention should also be paid to increase the family support to the patients.

[Sustainability of Brazilian policy for access to antiretroviral drugs].

PubMed

Grangeiro, Alexandre; Teixeira, Luciana; Bastos, Francisco I; Teixeira, Paulo

2006-04-01

The expense of acquiring antiretroviral drugs in Brazil has given rise to debate about the sustainability of the policy of universal access to AIDS medications, despite the evident benefits. The objective of this study was to analyze the evolution of the Ministry of Health's spending on acquiring antiretroviral drugs from 1998 to 2005, the determining factors and the medium-term sustainability of this policy (2006-2008). The study on the evolution of spending on antiretrovirals included analysis of their prices, the year-by-year expenditure, the number of patients utilizing the medication, the mean expenditure per patient and the strategies for reducing the prices maintained during this period. To analyze the sustainability of the policy for access to antiretrovirals, the cost of acquiring the drugs over the period from 2006 to 2008 was estimated, along with the proportion of gross domestic product and federal health expenditure represented by this spending. The data were collected from the Ministry of Health, the Brazilian Institute for Geography and Statistics (IBGE) and the Ministry of Planning. The expenditure on antiretrovirals increased by 66% in 2005, breaking the declining trend observed over the period from 2000 to 2004. The main factors associated with this increase were the weakening of the national generics industry and the unsatisfactory results from the process of negotiating with pharmaceutical companies. The Brazilian policy for universal access is unsustainable at the present growth rates of the gross domestic product, unless the country compromises its investments in other fields.

Non-linear mixed effects modeling of antiretroviral drug response after administration of lopinavir, atazanavir and efavirenz containing regimens to treatment-naïve HIV-1 infected patients.

PubMed

Röshammar, Daniel; Simonsson, Ulrika S H; Ekvall, Håkan; Flamholc, Leo; Ormaasen, Vidar; Vesterbacka, Jan; Wallmark, Eva; Ashton, Michael; Gisslén, Magnus

2011-12-01

The objective of this analysis was to compare three methods of handling HIV-RNA data below the limit of quantification (LOQ) when describing the time-course of antiretroviral drug response using a drug-disease model. Treatment naïve Scandinavian HIV-positive patients (n = 242) were randomized to one of three study arms. Two nucleoside reverse transcriptase inhibitors were administrated in combination with 400/100 mg lopinavir/ritonavir twice daily, 300/100 mg atazanavir/ritonavir once a day or 600 mg efavirenz once a day. The viral response was monitored at screening, baseline and at 1, 2, 3, 4, 12, 24, 48, 96, 120, and 144 weeks after study initiation. Data up to 400 days was fitted using a viral dynamics non-linear mixed effects drug-disease model in NONMEM. HIV-RNA data below LOQ of 50 copies/ml plasma (39%) was omitted, replaced by LOQ/2 or included in the analysis using a likelihood-based method (M3 method). Including data below LOQ using the M3 method substantially improved the model fit. The drug response parameter expressing the fractional inhibition of viral replication was on average (95% CI) estimated to 0.787 (0.721-0.864) for lopinavir and atazanavir treatment arms and 0.868 (0.796-0.923) for the efavirenz containing regimen. At 400 days after treatment initiation 90% (76-100) of the lopinavir and atazanavir treated patients were predicted to have undetectable viral levels and 96% (89-100%) for the efavirenz containing treatment. Including viral data below the LOQ rather than omitting or replacing data provides advantages such as better model predictions and less biased parameter estimates which are of importance when quantifying antiretroviral drug response.

Antiretroviral Therapy Reduces HIV Transmission in Discordant Couples in Rural Yunnan, China

PubMed Central

He, Na; Duan, Song; Ding, Yingying; Rou, Keming; McGoogan, Jennifer M.; Jia, Manhong; Yang, Yuecheng; Wang, Jibao; Montaner, Julio S. G.; Wu, Zunyou

2013-01-01

Background Although HIV treatment as prevention (TasP) via early antiretroviral therapy (ART) has proven to reduce transmissions among HIV-serodiscordant couples, its full implementation in developing countries remains a challenge. In this study, we determine whether China's current HIV treatment program prevents new HIV infections among discordant couples in rural China. Methods A prospective, longitudinal cohort study was conducted from June 2009 to March 2011, in rural Yunnan. A total of 1,618 HIV-discordant couples were eligible, 1,101 were enrolled, and 813 were followed for an average of 1.4 person-years (PY). Routine ART was prescribed to HIV-positive spouses according to eligibility (CD4<350 cells/µl). Seroconversion was used to determine HIV incidence. Results A total of 17 seroconversions were documented within 1,127 PY of follow-up, for an overall incidence of 1.5 per 100 PY. Epidemiological and genetic evidence confirmed that all 17 seroconverters were infected via marital secondary sexual transmission. Having an ART-experienced HIV-positive partner was associated with a lower rate of seroconvertion compared with having an ART-naïve HIV-positive partner (0.8 per 100 PY vs. 2.4 per 100 PY, HR = 0.34, 95%CI = 0.12–0.97, p = 0.0436). While we found that ART successfully suppressed plasma viral load to <400 copies/ml in the majority of cases (85.0% vs. 19.5%, p<0.0001 at baseline), we did document five seroconversions among ART-experienced subgroup. Conclusions ART is associated with a 66% reduction in HIV incidence among discordant couples in our sample, demonstrating the effectiveness of China's HIV treatment program at preventing new infections, and providing support for earlier ART initiation and TasP implementation in this region. PMID:24236010

Longitudinal relationships between antiretroviral treatment adherence and discrimination due to HIV-serostatus, race, and sexual orientation among African-American men with HIV.

PubMed

Bogart, Laura M; Wagner, Glenn J; Galvan, Frank H; Klein, David J

2010-10-01

African-Americans show worse HIV disease outcomes compared to Whites. Health disparities may be aggravated by discrimination, which is associated with worse health and maladaptive health behaviors. We examined longitudinal effects of discrimination on antiretroviral treatment adherence among 152 HIV-positive Black men who have sex with men. We measured adherence and discrimination due to HIV-serostatus, race/ethnicity, and sexual orientation at baseline and monthly for 6 months. Hierarchical repeated-measures models tested longitudinal effects of each discrimination type on adherence. Over 6 months, participants took 60% of prescribed medications on average; substantial percentages experienced discrimination (HIV-serostatus, 38%; race/ethnicity, 40%; and sexual orientation, 33%). Greater discrimination due to all three characteristics was significantly bivariately associated with lower adherence (all p's < 0.05). In the multivariate model, only racial discrimination was significant (p < 0.05). Efforts to improve HIV treatment adherence should consider the context of multiple stigmas, especially racism.

Improving data quality and supervision of antiretroviral therapy sites in Malawi: an application of Lot Quality Assurance Sampling

PubMed Central

2012-01-01

Background High quality program data is critical for managing, monitoring, and evaluating national HIV treatment programs. By 2009, the Malawi Ministry of Health had initiated more than 270,000 patients on HIV treatment at 377 sites. Quarterly supervision of these antiretroviral therapy (ART) sites ensures high quality care, but the time currently dedicated to exhaustive record review and data cleaning detracts from other critical components. The exhaustive record review is unlikely to be sustainable long term because of the resources required and increasing number of patients on ART. This study quantifies the current levels of data quality and evaluates Lot Quality Assurance Sampling (LQAS) as a tool to prioritize sites with low data quality, thus lowering costs while maintaining sufficient quality for program monitoring and patient care. Methods In January 2010, a study team joined supervision teams at 19 sites purposely selected to reflect the variety of ART sites. During the exhaustive data review, the time allocated to data cleaning and data discrepancies were documented. The team then randomly sampled 76 records from each site, recording secondary outcomes and the time required for sampling. Results At the 19 sites, only 1.2% of records had discrepancies in patient outcomes and 0.4% in treatment regimen. However, data cleaning took 28.5 hours in total, suggesting that data cleaning for all 377 ART sites would require over 350 supervision-hours quarterly. The LQAS tool accurately identified the sites with the low data quality, reduced the time for data cleaning by 70%, and allowed for reporting on secondary outcomes. Conclusions Most sites maintained high quality records. In spite of this, data cleaning required significant amounts of time with little effect on program estimates of patient outcomes. LQAS conserves resources while maintaining sufficient data quality for program assessment and management to allow for quality patient care. PMID:22776745

Improving data quality and supervision of antiretroviral therapy sites in Malawi: an application of Lot Quality Assurance Sampling.

PubMed

Hedt-Gauthier, Bethany L; Tenthani, Lyson; Mitchell, Shira; Chimbwandira, Frank M; Makombe, Simon; Chirwa, Zengani; Schouten, Erik J; Pagano, Marcello; Jahn, Andreas

2012-07-09

High quality program data is critical for managing, monitoring, and evaluating national HIV treatment programs. By 2009, the Malawi Ministry of Health had initiated more than 270,000 patients on HIV treatment at 377 sites. Quarterly supervision of these antiretroviral therapy (ART) sites ensures high quality care, but the time currently dedicated to exhaustive record review and data cleaning detracts from other critical components. The exhaustive record review is unlikely to be sustainable long term because of the resources required and increasing number of patients on ART. This study quantifies the current levels of data quality and evaluates Lot Quality Assurance Sampling (LQAS) as a tool to prioritize sites with low data quality, thus lowering costs while maintaining sufficient quality for program monitoring and patient care. In January 2010, a study team joined supervision teams at 19 sites purposely selected to reflect the variety of ART sites. During the exhaustive data review, the time allocated to data cleaning and data discrepancies were documented. The team then randomly sampled 76 records from each site, recording secondary outcomes and the time required for sampling. At the 19 sites, only 1.2% of records had discrepancies in patient outcomes and 0.4% in treatment regimen. However, data cleaning took 28.5 hours in total, suggesting that data cleaning for all 377 ART sites would require over 350 supervision-hours quarterly. The LQAS tool accurately identified the sites with the low data quality, reduced the time for data cleaning by 70%, and allowed for reporting on secondary outcomes. Most sites maintained high quality records. In spite of this, data cleaning required significant amounts of time with little effect on program estimates of patient outcomes. LQAS conserves resources while maintaining sufficient data quality for program assessment and management to allow for quality patient care.

A 'one-stop shop' approach in antenatal care: does this improve antiretroviral treatment uptake in Zimbabwe?

PubMed

Gunguwo, H; Zachariah, R; Bissell, K; Ndebele, W; Moyo, J; Mutasa-Apollo, T

2013-12-21

Prevention of mother-to-child transmission (PMTCT) programme, Mpilo Hospital antenatal clinic, Zimbabwe. Before and after the introduction of a one-stop shop approach and task-shifting of antiretroviral treatment (ART) to midwives in the PMTCT programme, 1) to compare ART uptake and 2) to determine socio-demographic and other characteristics associated with non-initiation of ART post integration. Before and after cohort study. A total of 285 women were eligible for ART before the introduction of the one-stop approach and 280 after. Of the 285, 163 (57%) initiated ART before integration; this increased to 244/280 (87%) after integration (RR 1.5, 95% CI 1.4-1.7, P < 0.001). A total of 36 (13%) women did not initiate ART after integration; this was significantly associated with cotrimoxazole uptake (P = 0.03). Integrating ART into antenatal care along with task-shifting to midwives considerably increased the uptake of ART. This provides further evidence for scaling up integration rapidly to other facilities in Zimbabwe, and is in line with the vision of a world where no child will be born with the human immunodeficiency virus by 2015.

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

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.

Sexual practices of HIV-positive individuals attending antiretroviral treatment (ART) in Addis Ababa public hospitals: findings from in-depth interview.

PubMed

Dessie, Yadeta; Deresa, Merga

2012-01-01

The rollout of Antiretroviral Treatment (ART) and improved health care services contributed in recuperating the quality of life and the functional status of HIV-positive people. These clinical effects of the treatment and cares are believed to bring a change on their sexual practices. The objective of this study was to explore the sexual practices of the HIV-positive people who were getting ART in selected Addis Ababa public hospitals. A qualitative in-depth interview was conducted. The interviews were made by trained nurse counselors of the same sex and were tape recorded. Verbatim transcription was made before the analysis. Thematic categorizations were made to present the findings. Most participants expressed regained sexual desires with initiation of ART while some others didn't appreciate the regains. Not using condoms or inconsistently using them was identified risky sexual practices. Sero-discordances and sero-status non-disclosure were common issues among the partners. Sero-status non-disclosure, non-use of condom and inconsistent using them were common sexual issues. These hinder the efforts that are being made to reduce new HIV infections and re-infections. Interventions against these problems can be made when clients come for their ART treatment and clinical care follow up.

Strengthening Healthcare Capacity Through a Responsive, Country-Specific, Training Standard: The KITSO AIDS Training Program’s Sup-port of Botswana’s National Antiretroviral Therapy Rollout

PubMed Central

Bussmann, Christine; Rotz, Philip; Ndwapi, Ndwapi; Baxter, Daniel; Bussmann, Hermann; Wester, C. William; Ncube, Patricia; Avalos, Ava; Mine, Madisa; Mabe, Elang; Burns, Patricia; Cardiello, Peter; Makhema, Joseph; Marlink, Richard

2008-01-01

In parallel with the rollout of Botswana’s national antiretroviral therapy (ART) program, the Botswana Ministry of Health established the KITSO AIDS Training Program by entering into long-term partnerships with the Botswana–Harvard AIDS Institute Partnership for HIV Research and Education and others to provide standardized, country-specific training in HIV/AIDS care. The KITSO training model has strengthened human capacity within Botswana’s health sector and been indispensable to successful ART rollout. Through core and advanced training courses and clinical mentoring, different cadres of health care workers have been trained to provide high-quality HIV/AIDS care at all ART sites in the country. Continuous and standardized clinical education will be crucial to sustain the present level of care and successfully address future treatment challenges. PMID:18923699

Laboratory Innovation Towards Quality Program Sustainability.

PubMed

Abimiku, Alash'le; Timperi, Ralph; Blattner, William

2016-08-01

Laboratory innovation significantly affects program sustainability of HIV programs in low and middle income countries (LMICs) far beyond its immediate sphere of impact. Innovation in rapid development of diagnostic technologies, improved quality management systems, strengthened laboratory management, affordable external quality assurance and accreditation schemes, and building local capacity have reduced costs, brought quality improvement to point-of-care testing, increased access to testing services, reduced treatment and prevention costs and opened the door to the real possibility of ending the AIDS epidemic. However, for effectively implemented laboratory innovation to contribute to HIV quality program sustainability, it must be implemented within the overall context of the national strategic plan and HIV treatment programs. The high quality of HIV rapid diagnostic test was a breakthrough that made it possible for more persons to learn their HIV status, receive counseling, and if infected to receive treatment. Likewise, the use of dried blood spots made the shipment of samples easier for the assessment of different variables of HIV infection-molecular diagnosis, CD4+ cell counts, HIV antibodies, drug resistance surveillance, and even antiretroviral drug level measurements. Such advancement is critical for to reaching the UNAIDS target of 90-90-90 and for bringing the AIDS epidemic to an end, especially in LMICs.

Predictors of early mortality in a cohort of HIV-infected children receiving high active antiretroviral treatment in public hospitals in Ethiopia.

PubMed

Ebissa, Getachew; Deyessa, Negusse; Biadgilign, Sibhatu

2015-01-01

Highly active antiretroviral therapy (HAART) is the breakthrough in care and treatment of people living with HIV, leading to a reduction in mortality and an improvement in the quality of life. Without antiretroviral treatment, most HIV-infected children die before their fifth birthday. So the objective of this study is to determine the mortality and associated factors in a cohort of HIV-infected children receiving ART in Ethiopia. A multicentre facility-based retrospective cohort study was done in selected pediatric ART units in hospitals found in Addis Ababa, Ethiopia. The probability of survival was estimated using the Kaplan-Meier method, and multivariate analysis by Cox proportional hazards regression models was conducted to determine the independent predictor of survival. A total of 556 children were included in this study. Of the total children, 10.4% were died in the overall cohort. More deaths (70%) occurred in the first 6 months of ART initiation, and the remaining others were still on follow-up at different hospitals. Underweight (moderate and severe; HR: 10.10; 95% CI: 2.08, 28.00; P = 0.004; and HR: 46.69; 95% CI: 9.26, 200.45; P < 0.01, respectively), advanced disease stage (WHO clinical stages III and IV; HR: 10.13: 95% CI: 2.25, 45.58; P = 0.003), poor ART adherence (HR: 11.72; 95% CI: 1.60, 48.44; P = 0.015), and hemoglobin level less than 7 g/dl (HR: 4.08: 95% CI: 1.33, 12.56; P = 0.014) were confirmed as significant independent predictors of death after controlling for other factors. Underweight, advanced disease stage, poor adherence to ART, and anemia appear to be independent predictor of survival in HIV-infected children receiving HAART at the pediatric units of public hospitals in Ethiopia. Nutritional supplementations, early initiation of HAART, close supervision, and monitoring of patients during the first 6 months, the follow up period is recommended.

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.

Adipocytes impair efficacy of antiretroviral therapy.

PubMed

Couturier, Jacob; Winchester, Lee C; Suliburk, James W; Wilkerson, Gregory K; Podany, Anthony T; Agarwal, Neeti; Xuan Chua, Corrine Ying; Nehete, Pramod N; Nehete, Bharti P; Grattoni, Alessandro; Sastry, K Jagannadha; Fletcher, Courtney V; Lake, Jordan E; Balasubramanyam, Ashok; Lewis, Dorothy E

2018-06-01

Adequate distribution of antiretroviral drugs to infected cells in HIV patients is critical for viral suppression. In humans and primates, HIV- and SIV-infected CD4 T cells in adipose tissues have recently been identified as reservoirs for infectious virus. To better characterize adipose tissue as a pharmacological sanctuary for HIV-infected cells, in vitro experiments were conducted to assess antiretroviral drug efficacy in the presence of adipocytes, and drug penetration in adipose tissue cells (stromal-vascular-fraction cells and mature adipocytes) was examined in treated humans and monkeys. Co-culture experiments between HIV-1-infected CD4 T cells and primary human adipocytes showed that adipocytes consistently reduced the antiviral efficacy of the nucleotide reverse transcriptase inhibitor tenofovir and its prodrug forms tenofovir disoproxil fumarate (TDF) and tenofovir alafenamide (TAF). In HIV-infected persons, LC-MS/MS analysis of intracellular lysates derived from adipose tissue stromal-vascular-fraction cells or mature adipocytes suggested that integrase inhibitors penetrate adipose tissue, whereas penetration of nucleoside/nucleotide reverse transcriptase inhibitors such as TDF, emtricitabine, abacavir, and lamivudine is restricted. The limited distribution and functions of key antiretroviral drugs within fat depots may contribute to viral persistence in adipose tissue. Copyright © 2018 Elsevier B.V. All rights reserved.

Antiretroviral drug regimens to prevent mother-to-child transmission of HIV: a review of scientific, program, and policy advances for sub-Saharan Africa.

PubMed

Chi, Benjamin H; Stringer, Jeffrey S A; Moodley, Dhayendre

2013-06-01

Considerable advances have been made in the effort to prevent mother-to-child HIV transmission (PMTCT) in sub-Saharan Africa. Clinical trials have demonstrated the efficacy of antiretroviral regimens to interrupt HIV transmission through the antenatal, intrapartum, and postnatal periods. Scientific discoveries have been rapidly translated into health policy, bolstered by substantial investment in health infrastructure capable of delivering increasingly complex services. A new scientific agenda is also emerging, one that is focused on the challenges of effective and sustainable program implementation. Finally, global campaigns to "virtually eliminate" pediatric HIV and dramatically reduce HIV-related maternal mortality have mobilized new resources and renewed political will. Each of these developments marks a major step in regional PMTCT efforts; their convergence signals a time of rapid progress in the field, characterized by an increased interdependency between clinical research, program implementation, and policy. In this review, we take stock of recent advances across each of these areas, highlighting the challenges--and opportunities--of improving health services for HIV-infected mothers and their children across the region.

Intellectual property rights, market competition and access to affordable antiretrovirals.

PubMed

Pascual, Fernando

2014-01-01

The number of patients receiving antiretroviral therapy (ART) has increased from around half a million in 2003 to almost 10 million in only 10 years, and will continue to increase in the coming years. Over 16 million more are eligible to start ART according to the last World Health Organization (WHO) guidelines. The demand is also switching from the less expensive antiretrovirals (ARVs) that allowed such scale-up to newer more expensive ones with fewer side effects or those that can be used by people who have developed resistance to first-line treatment. However, patents on these new drugs can delay robust generic competition and, consequently, price reduction made possible by economies of scale. Various ways to address this issue have been envisaged or implemented, including the use of the flexibilities available under the Agreement on Trade-Related Aspects of Intellectual Property Rights (TRIPS), systematic widespread voluntary licensing, of which the Medicines Patent Pool (MPP) is an example, and the application of different prices in different countries, called tiered pricing. This paper helps explain the impact of patents on market competition for ARVs and analyses various approaches available today to minimize this impact.

Improving antiretroviral therapy scale-up and effectiveness through service integration and decentralization.

PubMed

Suthar, Amitabh B; Rutherford, George W; Horvath, Tara; Doherty, Meg C; Negussie, Eyerusalem K

2014-03-01

Current service delivery systems do not reach all people in need of antiretroviral therapy (ART). In order to inform the operational and service delivery section of the WHO 2013 consolidated antiretroviral guidelines, our objective was to summarize systematic reviews on integrating ART delivery into maternal, newborn, and child health (MNCH) care settings in countries with generalized epidemics, tuberculosis (TB) treatment settings in which the burden of HIV and TB is high, and settings providing opiate substitution therapy (OST); and decentralizing ART into primary health facilities and communities. A summary of systematic reviews. The reviewers searched PubMed, Embase, PsycINFO, Web of Science, CENTRAL, and the WHO Index Medicus databases. Randomized controlled trials and observational cohort studies were included if they compared ART coverage, retention in HIV care, and/or mortality in MNCH, TB, or OST facilities providing ART with MNCH, TB, or OST facilities providing ART services separately; or primary health facilities or communities providing ART with hospitals providing ART. The reviewers identified 28 studies on integration and decentralization. Antiretroviral therapy integration into MNCH facilities improved ART coverage (relative risk [RR] 1.37, 95% confidence interval [CI] 1.05-1.79) and led to comparable retention in care. ART integration into TB treatment settings improved ART coverage (RR 1.83, 95% CI 1.48-2.23) and led to a nonsignificant reduction in mortality (RR 0.55, 95% CI 0.29-1.05). The limited data on ART integration into OST services indicated comparable rates of ART coverage, retention, and mortality. Partial decentralization into primary health facilities improved retention (RR 1.05, 95% CI 1.01-1.09) and reduced mortality (RR 0.34, 95% CI 0.13-0.87). Full decentralization improved retention (RR 1.12, 95% CI 1.08-1.17) and led to comparable mortality. Community-based ART led to comparable rates of retention and mortality. Integrating ART

Attrition from antiretroviral treatment services among pregnant and non-pregnant patients following adoption of Option B+ in Haiti

PubMed Central

Domercant, Jean Wysler; Puttkammer, Nancy; Young, Paul; Yuhas, Krista; François, Kesner; Grand’Pierre, Reynold; Lowrance, David; Adler, Michelle

2017-01-01

ABSTRACT Background: Access to antiretroviral therapy (ART) has expanded in Haiti because of the adoption of Option B+ and the revision of treatment guidelines. Retention in care and treatment varies greatly and few studies have examined retention rates, particularly among women enrolled in Option B+. Objective: To assess attrition among pregnant and non-pregnant patients initiating ART following adoption of Option B+ in Haiti. Methods: Longitudinal data of adult patients initiated on ART from October 2012 through August 2014 at 73 health facilities across Haiti were analyzed using a survival analysis framework to determine levels of attrition. The Kaplan–Meier method and Cox proportional hazards regression were used to examine risk factors associated with attrition. Results: Among 17,059 patients who initiated ART, 7627 (44.7%) were non-pregnant women, 5899 (34.6%) were men, and 3533 (20.7%) were Option B+ clients. Attrition from the ART program was 36.7% at 12 months (95% CI: 35.9–37.5%). Option B+ patients had the highest level of attrition at 50.4% at 12 months (95% CI: 48.6–52.3%). While early HIV disease stage at ART initiation was protective among non-pregnant women and men, it was a strong risk factor among Option B+ clients. In adjusted analyses, key protective factors were older age (p < 0.0001), living near the health facility (p = 0.04), having another known HIV-positive household member (p < 0.0001), having greater body mass index (BMI) (p < 0.0001), pre-ART counseling (p < 0.0001), and Cotrimoxazole prophylaxis during baseline (p < 0.01). Higher attrition was associated with rapidly starting ART after enrollment (p < 0.0001), anemia (p < 0.0001), and regimen tenofovir+lamivudine+nevirapine (TDF+3TC+NVP) (p < 0.001). Conclusions: ART attrition in Haiti is high among adults, especially among Option B+ patients. Identifying newly initiated patients most at risk for attrition and providing appropriate interventions could help

Does short-term virologic failure translate to clinical events in antiretroviral-naïve patients initiating antiretroviral therapy in clinical practice?

PubMed

Mugavero, Michael J; May, Margaret; Harris, Ross; Saag, Michael S; Costagliola, Dominique; Egger, Matthias; Phillips, Andrew; Günthard, Huldrych F; Dabis, Francois; Hogg, Robert; de Wolf, Frank; Fatkenheuer, Gerd; Gill, M John; Justice, Amy; D'Arminio Monforte, Antonella; Lampe, Fiona; Miró, Jose M; Staszewski, Schlomo; Sterne, Jonathan A C

2008-11-30

To determine whether differences in short-term virologic failure among commonly used antiretroviral therapy (ART) regimens translate to differences in clinical events in antiretroviral-naïve patients initiating ART. Observational cohort study of patients initiating ART between January 2000 and December 2005. The Antiretroviral Therapy Cohort Collaboration (ART-CC) is a collaboration of 15 HIV cohort studies from Canada, Europe, and the United States. A total of 13 546 antiretroviral-naïve HIV-positive patients initiating ART with efavirenz, nevirapine, lopinavir/ritonavir, nelfinavir, or abacavir as third drugs in combination with a zidovudine and lamivudine nucleoside reverse transcriptase inhibitor backbone. Short-term (24-week) virologic failure (>500 copies/ml) and clinical events within 2 years of ART initiation (incident AIDS-defining event, death, and a composite measure of these two outcomes). Compared with efavirenz as initial third drug, short-term virologic failure was more common with all other third drugs evaluated; nevirapine (adjusted odds ratio = 1.87, 95% confidence interval (CI) = 1.58-2.22), lopinavir/ritonavir (1.32, 95% CI = 1.12-1.57), nelfinavir (3.20, 95% CI = 2.74-3.74), and abacavir (2.13, 95% CI = 1.82-2.50). However, the rate of clinical events within 2 years of ART initiation appeared higher only with nevirapine (adjusted hazard ratio for composite outcome measure 1.27, 95% CI = 1.04-1.56) and abacavir (1.22, 95% CI = 1.00-1.48). Among antiretroviral-naïve patients initiating therapy, between-ART regimen, differences in short-term virologic failure do not necessarily translate to differences in clinical outcomes. Our results should be interpreted with caution because of the possibility of residual confounding by indication.

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.

Factors influencing antiretroviral treatment suboptimal adherence among perinatally HIV-infected adolescents in Thailand

PubMed Central

Munir, Kerim; Kanabkaew, Cheeraya; Le Coeur, Sophie

2017-01-01

Background Existing studies have suggested decreased adherence and rebound in mortality in perinatally HIV-infected adolescents receiving antiretroviral therapy (ART) as compared to adults and young children. Methods We used both quantitative and qualitative approaches to identify factors influencing adherence among perinatally infected adolescents in Thailand. We analyzed data from 568 pairs of perinatally infected adolescents (aged 12–19) and their primary caregivers in the Teens Living With Antiretrovirals (TEEWA) study, a cross-sectional survey conducted in 2010–2012. We also conducted 12 in-depth interviews in 2014 with infected adolescents or their primary caregivers to elicit experiences of living with long-term ART. Results From the quantitative analysis, a total of 275 (48.4%) adolescents had evidence of suboptimal adherence based on this composite outcome: adolescents self-reported missing doses in the past 7 days, caregiver rating of overall adherence as suboptimal, or latest HIV-RNA viral load ≥1000 copies/ml. In multivariate logistic regression analysis, younger age, having grandparents or extended family members as the primary caregiver, caregiver-assessed poor intellectual ability, having a boy/girlfriend, frequent online chatting, self-reported unhappiness and easiness in asking doctors questions were significantly associated with suboptimal adherence. From the in-depth interviews, tensed relationships with caregivers, forgetfulness due to busy schedules, and fear of disclosing HIV status to others, especially boy/girlfriends, were important contributors to suboptimal adherence. Social and emotional support and counseling from peer group was consistently reported as a strong adherence-promoting factor. Conclusion Our findings highlight unique barriers of ART adherence among the perinatally infected adolescents. Future interventions should be targeted at helping adolescents to improve interpersonal relationships and build adaptive skills in

Understanding reasons for treatment interruption amongst patients on antiretroviral therapy – A qualitative study at the Lighthouse Clinic, Lilongwe, Malawi

PubMed Central

Tabatabai, Julia; Namakhoma, Ireen; Tweya, Hannock; Phiri, Sam; Schnitzler, Paul; Neuhann, Florian

2014-01-01

Background In recent years, scaling up of antiretroviral therapy (ART) in resource-limited settings moved impressively towards universal access. Along with these achievements, public health HIV programs are facing a number of challenges including the support of patients on lifelong therapy and the prevention of temporary/permanent loss of patients in care. Understanding reasons for treatment interruption (TI) can inform strategies for improving drug adherence and retention in care. Objective To evaluate key characteristics of patients resuming ART after TI at the Lighthouse Clinic in Lilongwe, Malawi, and to identify their reasons for interrupting ART. Design This study uses a mixed methods design to evaluate patients resuming ART after TI. We analysed an assessment form for patients with TI using pre-defined categories and a comments field to identify frequently stated reasons for TI. Additionally, we conducted 26 in-depth interviews to deepen our understanding of common reasons for TI. In-depth interviews also included the patients’ knowledge about ART and presence of social support systems. Qualitative data analysis was based on a thematic framework approach. Results A total of 347 patients (58.2% female, average age 35.1±11.3 years) with TI were identified. Despite the presence of social support and sufficient knowledge of possible consequences of TI, all patients experienced situations that resulted in TI. Analysis of in-depth interviews led to new and distinct categories for TI. The most common reason for TI was travel (54.5%, n=80/147), which further differentiated into work- or family-related travel. Patients also stated transport costs and health-care-provider-related reasons, which included perceived/enacted discrimination by health care workers. Other drivers of TI were treatment fatigue/forgetfulness, the patients’ health status, adverse drug effects, pregnancy/delivery, religious belief or perceived/enacted stigma. Conclusions To adequately