These are representative sample records from Science.gov related to your search topic.
For comprehensive and current results, perform a real-time search at Science.gov.
1

When to Start Antiretroviral Therapy  

MedlinePLUS

... circumstances. What factors influence the decision to start ART? The following factors influence the decision to start ... an important factor in deciding when to start ART? A CD4 count measures the number of CD4 ...

2

Agreement between physicians and non-physician clinicians in starting antiretroviral therapy in rural Uganda  

PubMed Central

Background The scarcity of physicians in sub-Saharan Africa – particularly in rural clinics staffed only by non-physician health workers – is constraining access to HIV treatment, as only they are legally allowed to start antiretroviral therapy in the HIV-positive patient. Here we present a pilot study from Uganda assessing agreement between non-physician clinicians (nurses and clinical officers) and physicians in their decisions as to whether to start therapy. Methods We conducted the study at 12 government antiretroviral therapy sites in three regions of Uganda, all of which had staff trained in delivery of antiretroviral therapy using the WHO Integrated Management of Adult and Adolescent Illness guidelines for chronic HIV care. We collected seven key variables to measure patient assessment and the decision as to whether to start antiretroviral therapy, the primary variable of interest being the Final Antiretroviral Therapy Recommendation. Patients saw either a clinical officer or nurse first, and then were screened identically by a blinded physician during the same clinic visit. We measured inter-rater agreement between the decisions of the non-physician health workers and physicians in the antiretroviral therapy assessment variables using simple and weighted Kappa analysis. Results Two hundred fifty-four patients were seen by a nurse and physician, while 267 were seen by a clinical officer and physician. The majority (> 50%) in each arm of the study were in World Health Organization Clinical Stages I and II and therefore not currently eligible for antiretroviral therapy according to national antiretroviral therapy guidelines. Nurses and clinical officers both showed moderate to almost perfect agreement with physicians in their Final Antiretroviral Therapy Recommendation (unweighted ? = 0.59 and ? = 0.91, respectively). Agreement was also substantial for nurses versus physicians for assigning World Health Organization Clinical Stage (weighted ? = 0.65), but moderate for clinical officers versus physicians (? = 0.44). Conclusion Both nurses and clinical officers demonstrated strong agreement with physicians in deciding whether to initiate antiretroviral therapy in the HIV patient. This could lead to immediate benefits with respect to antiretroviral therapy scale-up and decentralization to rural areas in Uganda, as non-physician clinicians – particularly clinical officers – demonstrated the capacity to make correct clinical decisions to start antiretroviral therapy. These preliminary data warrant more detailed and multicountry investigation into decision-making of non-physician clinicians in the management of HIV disease with antiretroviral therapy, and should lead policy-makers to more carefully explore task-shifting as a shorter-term response to addressing the human resource crisis in HIV care and treatment. PMID:19695083

Vasan, Ashwin; Kenya-Mugisha, Nathan; Seung, Kwonjune J; Achieng, Marion; Banura, Patrick; Lule, Frank; Beems, Megan; Todd, Jim; Madraa, Elizabeth

2009-01-01

3

Mortality of HIV-Infected Patients Starting Antiretroviral Therapy in Sub-Saharan Africa: Comparison with HIV-  

E-print Network

active antiretroviral therapy (ART) has declined in sub-Saharan Africa, but it is unclear how mortalityMortality of HIV-Infected Patients Starting Antiretroviral Therapy in Sub-Saharan Africa patients starting ART with non-HIV­related background mortality in four countries in sub- Saharan Africa

Paris-Sud XI, Université de

4

Early loss to program in HIV-infected patients starting potent antiretroviral therapy in lower-income countries  

E-print Network

starting antiretroviral therapy (ART) is important to monitor clinical outcomes and evaluate program combination therapy (ART) has substantially improved the prognosis of HIV-infected patients in industrialized1 Early loss to program in HIV-infected patients starting potent antiretroviral therapy in lower

Paris-Sud XI, Université de

5

Community perspective on the INSIGHT Strategic Timing of AntiRetroviral Treatment (START) trial.  

PubMed

Determining when to start antiretroviral treatment (ART) is vitally important for people living with HIV. Yet the optimal point at which to start to maximize clinical benefit remains unknown. In the absence of randomized studies, current guidelines rely on conflicting observational data and expert opinion, and consequently diverge on this point. In the USA, ART is recommended irrespective of CD4 cell count. The World Health Organization now recommends starting ART at a CD4 cell count of 500?cells/?L, while the threshold for the UK and South Africa remains at 350?cells/?L. The Strategic Timing of AntiRetroviral Treatment (START) study, one of the largest clinical trials on the treatment of HIV infection, will answer this question. START compares two treatment strategies: immediate treatment at a CD4 cell count of 500?cells/?L or higher versus deferring treatment until the CD4 cell count decreases to 350?cells/?L or until AIDS develops. START includes seven substudies, five of which will clarify the relative contributions of HIV and ART in common comorbidities. START is fully enrolled and expected to be completed in 2016. HIV advocates support the study's design and have been involved from inception to enrolment. The trial will produce rigorous data on the benefits and risks of earlier treatment. It will inform policy and treatment advocacy globally, benefitting the health of HIV-positive people. PMID:25711318

Geffen, N; Aagaard, P; Corbelli, Gm; Meulbroek, M; Peavy, D; Rappoport, C; Schwarze, S; Collins, S

2015-04-01

6

The effect of efavirenz versus nevirapine-containing regimens on immunologic, virologic and clinical outcomes in a prospective observational study  

PubMed Central

Objective To compare regimens consisting of either efavirenz or nevirapine and two or more nucleoside reverse transcriptase inhibitors (NRTIs) among HIV-infected, antiretroviral-naive, and AIDS-free individuals with respect to clinical, immunologic, and virologic outcomes. Design Prospective studies of HIV-infected individuals in Europe and the US included in the HIV-CAUSAL Collaboration. Methods Antiretroviral therapy-naive and AIDS-free individuals were followed from the time they started an NRTI, efavirenz or nevirapine, classified as following one or both types of regimens at baseline, and censored when they started an ineligible drug or at 6 months if their regimen was not yet complete. We estimated the ‘intention-to-treat’ effect for nevirapine versus efavirenz regimens on clinical, immunologic, and virologic outcomes. Our models included baseline covariates and adjusted for potential bias introduced by censoring via inverse probability weighting. Results A total of 15 336 individuals initiated an efavirenz regimen (274 deaths, 774 AIDS-defining illnesses) and 8129 individuals initiated a nevirapine regimen (203 deaths, 441 AIDS-defining illnesses). The intention-to-treat hazard ratios [95% confidence interval (CI)] for nevirapine versus efavirenz regimens were 1.59 (1.27, 1.98) for death and 1.28 (1.09, 1.50) for AIDS-defining illness. Individuals on nevirapine regimens experienced a smaller 12-month increase in CD4 cell count by 11.49 cells/?l and were 52% more likely to have virologic failure at 12 months as those on efavirenz regimens. Conclusions Our intention-to-treat estimates are consistent with a lower mortality, a lower incidence of AIDS-defining illness, a larger 12-month increase in CD4 cell count, and a smaller risk of virologic failure at 12 months for efavirenz compared with nevirapine. PMID:22546987

2013-01-01

7

Immunodeficiency at the start of combination antiretroviral therapy in low-, middle- and high-income countries  

PubMed Central

Objectives To describe the CD4 cell count at the start of combination antiretroviral therapy (cART) in low-income (LIC), lower middle-income (LMIC), upper middle-income (UMIC) and high-income (HIC) countries. Methods Patients aged ?16 years starting cART in a clinic participating in a multi-cohort collaboration spanning six continents (International epidemiological Databases to Evaluate AIDS and ART Cohort Collaboration) were eligible. Multi-level linear regression models were adjusted for age, gender and calendar year; missing CD4 counts were imputed. Findings 379,865 patients from nine LIC, four LMIC, four UMIC and six HIC were included. In LIC the median CD4 cell count at cART initiation increased by 83% from 80 to 145 cells/?l between 2002 and 2009. Corresponding increases in LMIC, UMIC and HIC were from 87 to 155 cells/?l (76% increase), 88 to 135 cells/?l (53%) and 209 to 274 cells/?l (31%). In 2009, compared to LIC, median counts were 13 cells/?l (95% CI -56 to +30) lower in LMIC, 22 cells/?l (-62 to +18) lower in UMIC and 112 /?l (+75 to +149) higher in HIC. They were 23 cells/?l (95% CI +18 to +28) higher in women than men. Median counts were 88 cells/?l (95% CI +35 to +141) higher in countries with an estimated national cART coverage >80%, compared to countries with <40% coverage. Conclusions Median CD4 cell counts at start of cART increased 2000-2009 but remained below 200 cells/?l in LIC and MIC and below 300 cells/?l in HIC. Earlier start of cART will require substantial efforts and resources globally. PMID:24419071

2013-01-01

8

Depression and sexual risk behaviour among clients about to start HIV antiretroviral therapy in Uganda.  

PubMed

We investigated depression in relationship to sexual risk behaviour with primary partners among HIV-positive clients in Uganda. Baseline data were analyzed from a cohort of clients starting antiretroviral therapy. The Patient Health Questionnaire (PHQ-9) was used to classify depressive severity (none, minor and major depression) and symptom type (cognitive and somatic). Condom use was assessed over the past six months and during the last episode of sexual intercourse. A total of 386 participants had a primary sex partner, with whom 41.6% always used condoms during sex over the past six months, and 62.4% during last sex. Use of a condom during last sex was associated with having no depression and lower PHQ-9 total and cognitive and somatic subscale scores in bivariate analyses; most of these relationships were marginally significant for intercourse over the past six months. Controlling for demographics, HIV disclosure and partner HIV status, only minor depression was associated with unprotected sex. Depressive symptoms, even if not a clinical disorder, warrant early detection and treatment for promoting HIV prevention among HIV-affected couples. PMID:23970636

Musisi, Seggane; Wagner, Glenn J; Ghosh-Dastidar, Bonnie; Nakasujja, Noeline; Dickens, Akena; Okello, Elialilia

2014-02-01

9

Tuberculosis in HIV-infected Ugandan Children starting on Antiretroviral Therapy  

PubMed Central

Objective To identify the incidence of tuberculosis (TB) in HIV-infected children in a resource-limited setting prior to and after antiretroviral therapy (ART) initiation. A secondary objective was to assess the impact of TB screening by Tuberculin skin testing (TST) and clinical history. Methods A retrospective cohort study of 1806 HIV-infected children and adolescents initiating ART from 2003 through July 1, 2006 in Kampala, Uganda. A TB screening program was instituted clinic-wide in January 2006. Results 311 (17.2%) HIV-infected children had with TB diagnosed among 171 diagnosed pre-ART and among 140 post-ART initiation. During the first 100 days of ART, risk of a new TB diagnosis was 2.7 fold higher compared to the pre-ART period (RR 2.7; 95% CI: 2.1 to 3.5; P<.001). After 100 days of ART, the TB incidence rate decreased below pre-ART levels (RR 0.41; 95% CI: 0.30 to 0.54; P=.002). After TB screening was instituted in 2006, the proportion of new TB cases diagnosed after starting ART decreased by 70% (95% CI: 51 to 82%; P<.001), abating the early excess risk. Conclusions TB is common among African children and adolescents initiating ART in Sub-Saharan Africa. More aggressive screening for active TB prior to starting ART can diminish the rate of TB during immune reconstitution. Future studies are needed to determine optimal screening practice for HIV-infected children. PMID:21740672

Bakeera-Kitaka, Sabrina; Conesa-Botella, Anali; Dhabangi, Aggrey; Maganda, Albert; Kekitiinwa, Addy; Colebunders, Robert; Boulware, David R

2012-01-01

10

Effects of nutritional supplementation for HIV patients starting antiretroviral treatment: randomised controlled trial in Ethiopia  

PubMed Central

Objectives To determine the effects of lipid based nutritional supplements with either whey or soy protein in patients with HIV during the first three months of antiretroviral treatment (ART) and to explore effects of timing by comparing supplementation at the start of ART and after three months delay. Design Randomised controlled trial. Setting Three public ART facilities in Jimma, Oromia region, Ethiopia. Participants Adults with HIV eligible for ART with body mass index (BMI) >16. Intervention Daily supplementation with 200 g (4600 kJ) of supplement containing whey or soy during either the first three or the subsequent three months of ART. Outcome measures Primary: lean body mass assessed with deuterium dilution, grip strength measured with dynamometers, and physical activity measured with accelerometer and heart rate monitors. Secondary: viral load and CD4 counts. Auxiliary: weight and CD3 and CD8 counts. Results Of 318 patients enrolled, 210 (66%) were women, mean age was 33 (SD 9), and mean BMI was 19.5 (SD 2.4). At three months, participants receiving the supplements containing whey or soy had increased their lean body mass by 0.85 kg (95% confidence interval 0.16 kg to 1.53 kg) and 0.97 kg (0.29 kg to 1.64 kg), respectively, more than controls. This was accompanied by an increased gain of grip strength of 0.68 kg (?0.11 kg to 1.46 kg) for the whey supplement group and 0.93 kg (0.16 kg to 1.70 kg) for the soy supplement group. There were no effects on physical activity. Total weight gain increased by 2.05 kg (1.12 kg to 2.99 kg) and 2.06 kg (1.14 kg to 2.97 kg) for the whey and soy groups, respectively. In addition, in the whey supplement group overall CD3 counts improved by 150 cells/µL (24 to 275 cells/µL), of which 112 cells/µL (15 to 209 cells/µL) were CD8 and 25 cells/µL (?2 to 53 cells/µL) were CD4. Effects of the soy containing supplement on immune recovery were not significant. The effects of the two supplements, however, were not significantly different in direct comparison. Exploratory analysis showed that relatively more lean body mass was gained by patients with undetectable viral load at three months. Patients receiving delayed supplementation had higher weight gain but lower gains in functional outcomes. Conclusions Lipid based nutritional supplements improved gain of weight, lean body mass, and grip strength in patients with HIV starting ART. Supplements containing whey were associated with improved immune recovery. Trial registration Controlled-trials.com ISRCTN32453477. PMID:25134117

2014-01-01

11

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

PubMed Central

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 naďve with CD4 count > 500 cells/?L 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/ ?L (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 phase was well underway, and the complexities of conducting the trial in a geographically wide population with diverse regulatory requirements. With the successful completion of the pilot phase, more than 1000 participants from 100 sites in 23 countries have been enrolled. The study will expand to include 237 sites in 36 countries to reach the target accrual of 4000 participants. Conclusions START is addressing one of the most important questions in the clinical management of ART. The randomization provided a platform for the conduct of several substudies aimed at increasing our understanding of HIV disease and the effects of antiretroviral therapy beyond the primary question of the trial. The lessons learned from its design and implementation will hopefully be of use to future publicly funded international trials. PMID:22547421

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

12

Cost-effectiveness analysis of antiretroviral therapy in a cohort of HIV-infected patients starting first-line highly active antiretroviral therapy during 6 years of observation  

PubMed Central

Objectives Costs may play a role in deciding how and when to start highly active antiretroviral therapy (HAART) in a naďve patient. The aim of the present study was to assess the cost- effectiveness of treatment with HAART in a large clinical cohort of naďve adults to determine the potential role of single-tablet regimens in the management of patients with human immunodeficiency virus (HIV). An incremental cost-effectiveness ratio analysis was performed, including a quality-adjusted life year approach. Results In total, 741 patients (females comprising 25.5%) were retrospectively included. The mean age was 39 years, the mean CD4 cell count was 266 cells/?L, and the mean viral load was 192,821 copies/mL. The most commonly used backbone was tenofovir + emtricitabine (77.6%); zidovudine + lamivudine was used in 10%, lamivudine + abacavir in 3%, and other nucleoside reverse transcriptase inhibitor (NRTI) or NRTI-free regimens in 9.4% of patients. NNRTIs were used in 52.8% of cases, boosted protease inhibitors in 44.1%, and unboosted protease inhibitors and integrase inhibitors in 0.7% and 2.4%, respectively. Starting therapy at CD4 >500 cells/?L and CD4 351–500 cells/?L rather than at <201 cells/?L was the more cost-effective approach. The same consideration was not true comparing current indications with the possibility to start HAART at any CD4 value (eg, >500 cells per ?L); in this case, the incremental cost-effectiveness ratio value was €199,130 per quality-adjusted life year gained, a higher value than the one suggested in guidelines. The single-tablet regimen (STR) invariably dominated any other therapeutic approach. Sensitivity analysis was performed, and starting right away with an STR was cost-effective even when compared with therapeutic strategies contemplating STR as simplification. Conclusion By integrating clinical data with economic variables, our study offers an estimate of the cost-effectiveness of the various first-line treatment strategies for patients infected with HIV and provides significant evidence to be used in future prospective pharmacoeconomic evaluations. PMID:25733942

Maggiolo, Franco; Colombo, Giorgio L; Di Matteo, Sergio; Bruno, Giacomo M; Astuti, Noemi; Di Filippo, Elisa; Masini, Giulia; Bernardini, Claudia

2015-01-01

13

Supplementary feeding with either ready-to-use fortified spread or corn-soy blend in wasted adults starting antiretroviral therapy in Malawi: Randomised, Investigator Blinded, Controlled Trial  

Technology Transfer Automated Retrieval System (TEKTRAN)

To investigate the effect of two different food supplements on body mass index (BMI) in wasted Malawian adults with HIV who were starting antiretroviral therapy. A randomised, investigator blinded, controlled trial was used in a large, public clinic associated with a referral hospital in Blantyre, M...

14

Is long term virological response related to CCR 5 32 deletion in HIV infected patients started on highly active antiretroviral therapy?  

E-print Network

Is long term virological response related to CCR 5 32 deletion in HIV infected patients started, antiretroviral therapy, CCR5 32 deletion, virological response Corresponding author : Dr. Jean to have a sustained virological response if all plasma HIV-RNA measurements between month 4 and years 3

Boyer, Edmond

15

Laboratory adverse events and discontinuation of therapy according to CD4+ cell count at the start of antiretroviral therapy  

PubMed Central

Objective: Few data describe antiretroviral treatment (ART)-related adverse events when treatment is initiated at CD4+ cell counts more than 350?cells/?l. We compared rates of laboratory-defined adverse events (LDAEs) according to CD4+ cell count at ART initiation. Design: Analysis of on-going cohort study. Methods: ART-naive persons initiating ART from 2000 to 2010 were included. Chi-square, analysis of variance (ANOVA) and Kruskal–Wallis tests compared characteristics among those starting ART with a CD4+ cell count of 350 or less, 351–499 and at least 500?cells/?l. Time-updated Poisson regression compared rates of LDAE in the three CD4+ cell strata. Cox proportional hazard models compared risk of ART discontinuation. Results: Nine thousand, four hundred and six individuals were included: median age 37 years, 61% white, 80% men, median viral load 4.8?log copies/ml. Four hundred and forty-seven (4.9%) and 1099 (11.7%) started ART with a CD4+ cell count at least 500 and 351–499?cells/?l, respectively. One thousand, two hundred and eighty-three (13.6%) patients experienced at least one LDAE. The rate of LDAE did not differ between those starting ART with a CD4+ cell count 351–499 and less than 350?cells/?l [relative rate 0.90, 95% confidence interval (CI) 0.74–1.09)], but an increased risk of ART discontinuation was observed (hazard ratio 1.58, 95% CI 1.10–2.27). Those starting ART at CD4+ cell count at least 500?cells/?l had an increased rate of LDAE (relative rate 1.44, 95% CI 1.13–1.82) but were not more likely to discontinue ART (hazard ratio 1.15, 95% CI 0.64–2.09). Conclusion: This study demonstrates the need to consider ART-related toxicities when initiating therapy at CD4+ cell counts at least 500?cells/?l. Whilst evidence from randomized controlled trials is awaited, the timing of ART initiation in terms of benefits and risks of ART remains an important question. PMID:24583670

Jose, Sophie; Quinn, Killian; Hill, Teresa; Leen, Clifford; Walsh, John; Hay, Phillip; Fisher, Martin; Post, Frank; Nelson, Mark; Gompels, Mark; Johnson, Margaret; Chadwick, David; Gilson, Richard; Sabin, Caroline; Fidler, Sarah

2014-01-01

16

Supplementary feeding with either ready-to-use fortified spread or corn-soy blend in wasted adults starting antiretroviral therapy in Malawi: randomised, investigator blinded, controlled trial  

Microsoft Academic Search

Objective To investigate the effect of two different food supplements on body mass index (BMI) in wasted Malawian adults with HIV who were starting antiretroviral therapy.Design Randomised, investigator blinded, controlled trial.Setting Large, public clinic associated with a referral hospital in Blantyre, Malawi.Participants 491 adults with BMI <18.5.Interventions Ready-to-use fortified spread (n=245) or corn-soy blend (n=246).Main outcome measures Primary outcomes: changes

MacDonald J Ndekha; Joep J G van Oosterhout; Eduard E Zijlstra; Micah Manary; Haroon Saloojee; Mark J Manary

2009-01-01

17

Gender Differences in Survival among Adult Patients Starting Antiretroviral Therapy in South Africa: A Multicentre Cohort Study  

PubMed Central

Background Increased mortality among men on antiretroviral therapy (ART) has been documented but remains poorly understood. We examined the magnitude of and risk factors for gender differences in mortality on ART. Methods and Findings Analyses included 46,201 ART-naďve adults starting ART between January 2002 and December 2009 in eight ART programmes across South Africa (SA). Patients were followed from initiation of ART to outcome or analysis closure. The primary outcome was mortality; secondary outcomes were loss to follow-up (LTF), virologic suppression, and CD4+ cell count responses. Survival analyses were used to examine the hazard of death on ART by gender. Sensitivity analyses were limited to patients who were virologically suppressed and patients whose CD4+ cell count reached >200 cells/µl. We compared gender differences in mortality among HIV+ patients on ART with mortality in an age-standardised HIV-negative population. Among 46,201 adults (65% female, median age 35 years), during 77,578 person-years of follow-up, men had lower median CD4+ cell counts than women (85 versus 110 cells/µl, p<0.001), were more likely to be classified WHO stage III/IV (86 versus 77%, p<0.001), and had higher mortality in crude (8.5 versus 5.7 deaths/100 person-years, p<0.001) and adjusted analyses (adjusted hazard ratio [AHR] 1.31, 95% CI 1.22–1.41). After 36 months on ART, men were more likely than women to be truly LTF (AHR 1.20, 95% CI 1.12–1.28) but not to die after LTF (AHR 1.04, 95% CI 0.86–1.25). Findings were consistent across all eight programmes. Virologic suppression was similar by gender; women had slightly better immunologic responses than men. Notably, the observed gender differences in mortality on ART were smaller than gender differences in age-standardised death rates in the HIV-negative South African population. Over time, non-HIV mortality appeared to account for an increasing proportion of observed mortality. The analysis was limited by missing data on baseline HIV disease characteristics, and we did not observe directly mortality in HIV-negative populations where the participating cohorts were located. Conclusions HIV-infected men have higher mortality on ART than women in South African programmes, but these differences are only partly explained by more advanced HIV disease at the time of ART initiation, differential LTF and subsequent mortality, and differences in responses to treatment. The observed differences in mortality on ART may be best explained by background differences in mortality between men and women in the South African population unrelated to the HIV/AIDS epidemic. Please see later in the article for the Editors' Summary. PMID:22973181

Cornell, Morna; Schomaker, Michael; Garone, Daniela Belen; Giddy, Janet; Hoffmann, Christopher J.; Lessells, Richard; Maskew, Mhairi; Prozesky, Hans; Wood, Robin; Johnson, Leigh F.; Egger, Matthias; Boulle, Andrew; Myer, Landon

2012-01-01

18

Supplementary feeding with either ready-to-use fortified spread or corn-soy blend in wasted adults starting antiretroviral therapy in Malawi: randomised, investigator blinded, controlled trial  

PubMed Central

Objective To investigate the effect of two different food supplements on body mass index (BMI) in wasted Malawian adults with HIV who were starting antiretroviral therapy. Design Randomised, investigator blinded, controlled trial. Setting Large, public clinic associated with a referral hospital in Blantyre, Malawi. Participants 491 adults with BMI <18.5. Interventions Ready-to-use fortified spread (n=245) or corn-soy blend (n=246). Main outcome measures Primary outcomes: changes in BMI and fat-free body mass after 3.5 months. Secondary outcomes: survival, CD4 count, HIV viral load, quality of life, and adherence to antiretroviral therapy. Results The mean BMI at enrolment was 16.5. After 14 weeks, patients receiving fortified spread had a greater increase in BMI and fat-free body mass than those receiving corn-soy blend: 2.2 (SD 1.9) v 1.7 (SD 1.6) (difference 0.5, 95% confidence interval 0.2 to 0.8), and 2.9 (SD 3.2) v 2.2 (SD 3.0) kg (difference 0.7 kg, 0.2 to 1.2 kg), respectively. The mortality rate was 27% for those receiving fortified spread and 26% for those receiving corn-soy blend. No significant differences in the CD4 count, HIV viral load, assessment of quality of life, or adherence to antiretroviral therapy were noted between the two groups. Conclusion Supplementary feeding with fortified spread resulted in a greater increase in BMI and lean body mass than feeding with corn-soy blend. Trial registration Current Controlled Trials ISRCTN67515515. PMID:19465470

2009-01-01

19

Metabolic Disorders and Cardiovascular Risk in Treatment-Naive HIV-Infected Patients of Sub-Saharan Origin Starting Antiretrovirals: Impact of Westernized Lifestyle.  

PubMed

In a cohort of HIV-infected patients of sub-Saharan origin we describe the incidence of metabolic syndrome, insulin resistance, and lipodystrophy after 3 years of combined antiretroviral therapy, and model the 10-year risk of cardiovascular diseases, while taking into account environmental factors. This is a multinational, prospective cohort study conducted in HIV outpatient clinics from four tertiary care centers set in France and Côte d'Ivoire. The participants were HIV-infected, treatment-naive patients eligible to start antiretroviral treatment and were of sub-Saharan African origin. The main outcome measures were the incidence of metabolic syndrome, insulin resistance, and lipodystrophy, and the assessment of the 10-year risk of cardiovascular diseases using Framingham risk prediction, D.A.D. Cardiovascular Disease Risk, and WHO/ISH prediction charts. Of 245 patients followed for up to 3 years, the incidence of metabolic syndrome, insulin resistance, and lipodystrophy was 5.5, 8.5, and 6.8 per 100 person-years of follow-up (cumulative incidence: 14.4%, 19.2%, and 18.1%, respectively). Living in France as well as female gender and being overweight were risk factors for metabolic disorders as whole and only first generation protease inhibitors were marginally associated with metabolic syndrome. Cardiovascular risk as modeled through the three equations was high in all patients with the synergistic and deleterious effect of living in France compared to Côte d'Ivoire. This cohort study shows how the synergy between HIV, antiretroviral (ARV) exposure, and westernization of life style in a cohort of HIV-infected patients of sub-Saharan origin leads to a progressive increase in the risk of lipodystrophy, as well as metabolic syndrome and insulin resistance, all associated with increased cardiovascular risk. PMID:25707418

Eholié, Serge Paul; Lacombe, Karine; Krain, Alysa; Diallo, Zelica; Ouiminga, Mariama; Campa, Pauline; Bouchaud, Olivier; Bissagnene, Emmanuel; Girard, Pierre-Marie

2015-04-01

20

One-year outcomes of women started on antiretroviral therapy during pregnancy before and after the implementation of Option B+ in Malawi: A retrospective chart review  

PubMed Central

Objective To compare one-year outcomes of women started on antiretroviral therapy (ART) during pregnancy in the pre-Option B+ era to those in the Option B+ era. Methods A retrospective chart review was performed at three sites in Malawi. Women were included in the ‘pre-Option B+’ cohort if they started ART during pregnancy for a CD4 count < 350 cells/mm3 or WHO 3/4 condition and in the ‘Option B+’ cohort if they started ART during pregnancy regardless of CD4 count or clinical stage. One-year outcomes were compared using Fisher's exact and ANOVA F-tests. Results A higher proportion of women in the pre-Option B+ cohort started ART at WHO stage 3/4 (11.9% versus 1.1%, P < 0.001), switched ART regimens (5.9% versus 0%, P = 0.002), or died in the first year after starting treatment (3.9% versus .5%, P = 0.05). While more women in the Option B+ cohort had poor adherence or defaulted, these differences were not significant. Conclusions At our study sites, the transition to Option B+ has been associated with ART initiation in women with less advanced HIV infection, improved medication tolerability, and lower mortality. Further research is needed to better understand outcomes of Option B+.

Kamuyango, Alfred A.; Hirschhorn, Lisa R; Wang, Wenjia; Jansen, Perry; Hoffman, Risa M.

2015-01-01

21

Toxicity-related antiretroviral drug treatment modifications in individuals starting therapy: A cohort analysis of time patterns, sex, and other risk factors  

PubMed Central

Background Modifications to combination antiretroviral drug therapy (CART) regimens can occur for a number of reasons, including adverse drug effects. We investigated the frequency of and reasons for antiretroviral drug modifications (ADM) during the first 3 years after initiation of CART, in a closed cohort of CART-naďve adult patients who started treatment in the period 1998–2007 in Croatia. Material/Methods We calculated differential toxicity rates by the Poisson method. In multivariable analysis, we used a discrete-time regression model for repeated events for the outcome of modification due to drug toxicity. Results Of 321 patients who started CART, median age was 40 years, 19% were women, baseline CD4 was <200 cells/mm3 in 71%, and viral load was ?100 000 copies/mL in 69%. Overall, 220 (68.5%) patients had an ADM; 124 (56%) of these had ?1 ADM for toxicity reasons. Only 12.7% of individuals starting CART in the period 1998–2002 and 39.4% in the period 2003–2007 remained on the same regimen after 3 years. The following toxicities caused ADM most often: lipoatrophy (22%), gastrointestinal symptoms (20%), and neuropathy (18%). Only 5% of drug changes were due to virologic failure. Female sex (hazard ratio [HR], 2.42 95%; confidence intervals, 1.39–4.24) and older age (HR, 1.42 per every 10 years) were associated with toxicity-related ADM in the first 3 months of a particular CART regimen, but after 3 months of CART they were not. Conclusions Less toxic and better-tolerated HIV treatment options should be available and used more frequently in Croatia. PMID:23787803

Mihanovi?, Marta Perovi?; Haque, Najm S.; Rutherford, George W.; Zekan, Šime; Begovac, Josip

2013-01-01

22

Quality of Life Among Individuals with HIV Starting Antiretroviral Therapy in Diverse Resource-Limited Areas of the World  

PubMed Central

As Antiretroviral Therapy (ART) is scaled up in low- and middle-income countries, it is important to understand Quality of Life (QOL) correlates including disease severity and person characteristics and to determine the extent of between-country differences among those with HIV. QOL and medical data were collected from 1,563 of the 1,571 participants at entry into a randomized clinical trial of ART conducted in the U.S. (n = 203) and 8 resource-limited countries (n = 1,360) in the Caribbean, South America, Asia, and Africa. Participants were interviewed prior to initiation of ART using a modified version of the ACTG SF-21, a health-related QOL measure including 8 subscales: general health perception, physical functioning, role functioning, social functioning, cognitive functioning, pain, mental health, and energy/fatigue. Other measures included demographics, CD4+ lymphocyte count, plasma HIV-1 RNA viral load. Higher quality of life in each of the 8 QOL subscales was associated with higher CD4+ lymphocyte category. General health perception, physical functioning, role functioning, and energy/fatigue varied by plasma HIV-1 RNA viral load categories. Each QOL subscale included significant variation by country. Only the social functioning subscale varied by sex, with men having greater impairments than women, and only the physical functioning subscale varied by age category. This was the first large-scale international ART trial to conduct a standardized assessment of QOL in diverse international settings, thus demonstrating that implementation of the behavioral assessment was feasible. QOL indicators at study entry varied with disease severity, demographics, and country. The relationship of these measures to treatment outcomes can and should be examined in clinical trials of ART in resource-limited settings using similar methodologies. PMID:21499794

Hendriksen, Ellen S.; Smeaton, Laura; Celentano, David D.; Hosseinipour, Mina C.; Barnett, Ronald; Guanira, Juan; Flanigan, Timothy; Kumarasamy, N.; Klingman, Karin; Campbell, Thomas

2011-01-01

23

Predicting Patterns of Long-Term CD4 Reconstitution in HIV-Infected Children Starting Antiretroviral Therapy in Sub-Saharan Africa: A Cohort-Based Modelling Study  

PubMed Central

Background Long-term immune reconstitution on antiretroviral therapy (ART) has important implications for HIV-infected children, who increasingly survive into adulthood. Children's response to ART differs from adults', and better descriptive and predictive models of reconstitution are needed to guide policy and direct research. We present statistical models characterising, qualitatively and quantitatively, patterns of long-term CD4 recovery. Methods and Findings CD4 counts every 12 wk over a median (interquartile range) of 4.0 (3.7, 4.4) y in 1,206 HIV-infected children, aged 0.4–17.6 y, starting ART in the Antiretroviral Research for Watoto trial (ISRCTN 24791884) were analysed in an exploratory analysis supplementary to the trial's pre-specified outcomes. Most (n?=?914; 76%) children's CD4 counts rose quickly on ART to a constant age-corrected level. Using nonlinear mixed-effects models, higher long-term CD4 counts were predicted for children starting ART younger, and with higher CD4 counts (p<0.001). These results suggest that current World Health Organization–recommended CD4 thresholds for starting ART in children ?5 y will result in lower CD4 counts in older children when they become adults, such that vertically infected children who remain ART-naďve beyond 10 y of age are unlikely ever to normalise CD4 count, regardless of CD4 count at ART initiation. CD4 profiles with four qualitatively distinct reconstitution patterns were seen in the remaining 292 (24%) children. Study limitations included incomplete viral load data, and that the uncertainty in allocating children to distinct reconstitution groups was not modelled. Conclusions Although younger ART-naďve children are at high risk of disease progression, they have good potential for achieving high CD4 counts on ART in later life provided ART is initiated following current World Health Organization (WHO), Paediatric European Network for Treatment of AIDS, or US Centers for Disease Control and Prevention guidelines. In contrast, to maximise CD4 reconstitution in treatment-naďve children >10 y, ART should ideally be considered even if there is a low risk of immediate disease progression. Further exploration of the immunological mechanisms for these CD4 recovery profiles should help guide management of paediatric HIV infection and optimise children's immunological development. Please see later in the article for the Editors' Summary PMID:24204216

Musiime, Victor; Prendergast, Andrew; Nathoo, Kusum; Kekitiinwa, Addy; Nahirya Ntege, Patricia; Gibb, Diana M.; Thiebaut, Rodolphe; Walker, A. Sarah; Klein, Nigel; Callard, Robin

2013-01-01

24

Nevirapine-related adverse events among children switched from efavirenz to nevirapine as compared to children who were started on nevirapine-based antiretroviral therapy directly.  

PubMed

In this retrospective study, incidence of nevirapine (NVP) toxicity in children who were switched from efavirenz (EFV) to NVP (treatment experienced [TE] group) was compared with that of children who had started NVP-based antiretroviral therapy directly (treatment naďve [TN] group). This study also identified risk factors associated with development of NVP toxicity in children. The incidence and risk of developing NVP toxicities were significantly higher in TE when compared to TN group. Median duration of onset of NVP toxicity from the initiation was 2.14 and 3.84 weeks in TE and TN children, respectively. Mean CD4 count was found to be significantly higher in children who developed toxicity (577 ± 81 cells/µL) as compared to the children who did not develop toxicity (403 ± 29 cells/µL). Similarly, children in TE group who developed NVP toxicity had higher mean CD4 cell count than children in TN with NVP toxicity. The risk factors for the development of NVP toxicity include female gender with CD4 count >250 cells/?L and TE children especially girls with CD4% >15% and boys with CD4 count >400 cells/?L. To conclude, the higher incidence of NVP toxicity among TE group warrants a cautious approach while switching the NVP- from EFV-based therapy. PMID:25517472

Sanjeeva, G N; Sukanya, V; Pavithra, H B; Dodderi, S K; Rewari, B B; Govindaraj, M; Shivananda, S; Premalatha, R

2015-05-01

25

Mortality in Patients with HIV-1 Infection Starting Antiretroviral Therapy in South Africa, Europe, or North America: A Collaborative Analysis of Prospective Studies  

PubMed Central

Background High early mortality in patients with HIV-1 starting antiretroviral therapy (ART) in sub-Saharan Africa, compared to Europe and North America, is well documented. Longer-term comparisons between settings have been limited by poor ascertainment of mortality in high burden African settings. This study aimed to compare mortality up to four years on ART between South Africa, Europe, and North America. Methods and Findings Data from four South African cohorts in which patients lost to follow-up (LTF) could be linked to the national population register to determine vital status were combined with data from Europe and North America. Cumulative mortality, crude and adjusted (for characteristics at ART initiation) mortality rate ratios (relative to South Africa), and predicted mortality rates were described by region at 0–3, 3–6, 6–12, 12–24, and 24–48 months on ART for the period 2001–2010. Of the adults included (30,467 [South Africa], 29,727 [Europe], and 7,160 [North America]), 20,306 (67%), 9,961 (34%), and 824 (12%) were women. Patients began treatment with markedly more advanced disease in South Africa (median CD4 count 102, 213, and 172 cells/µl in South Africa, Europe, and North America, respectively). High early mortality after starting ART in South Africa occurred mainly in patients starting ART with CD4 count <50 cells/µl. Cumulative mortality at 4 years was 16.6%, 4.7%, and 15.3% in South Africa, Europe, and North America, respectively. Mortality was initially much lower in Europe and North America than South Africa, but the differences were reduced or reversed (North America) at longer durations on ART (adjusted rate ratios 0.46, 95% CI 0.37–0.58, and 1.62, 95% CI 1.27–2.05 between 24 and 48 months on ART comparing Europe and North America to South Africa). While bias due to under-ascertainment of mortality was minimised through death registry linkage, residual bias could still be present due to differing approaches to and frequency of linkage. Conclusions After accounting for under-ascertainment of mortality, with increasing duration on ART, the mortality rate on HIV treatment in South Africa declines to levels comparable to or below those described in participating North American cohorts, while substantially narrowing the differential with the European cohorts. Please see later in the article for the Editors' Summary PMID:25203931

Boulle, Andrew; Schomaker, Michael; May, Margaret T.; Hogg, Robert S.; Shepherd, Bryan E.; Monge, Susana; Keiser, Olivia; Lampe, Fiona C.; Giddy, Janet; Ndirangu, James; Garone, Daniela; Fox, Matthew; Ingle, Suzanne M.; Reiss, Peter; Dabis, Francois; Costagliola, Dominique; Castagna, Antonella; Ehren, Kathrin; Campbell, Colin; Gill, M. John; Saag, Michael; Justice, Amy C.; Guest, Jodie; Crane, Heidi M.; Egger, Matthias; Sterne, Jonathan A. C.

2014-01-01

26

Estimating the cost-effectiveness of nutrition supplementation for malnourished, HIV-infected adults starting antiretroviral therapy in a resource-constrained setting  

PubMed Central

Background Low body mass index (BMI) individuals starting antiretroviral therapy (ART) for HIV infection in sub-Saharan Africa have high rates of death and loss to follow-up in the first 6 months of treatment. Nutritional supplementation may improve health outcomes in this population, but the anticipated benefit of any intervention should be commensurate with the cost given resource limitations and the need to expand access to ART in the region. Methods We used Markov models incorporating historical data and program-wide estimates of treatment costs and health benefits from the Zambian national ART program to estimate the improvements in 6-month survival and program retention among malnourished adults necessary for a combined nutrition support and ART treatment program to maintain cost-effectiveness parity with ART treatment alone. Patients were stratified according to World Health Organization criteria for severe (BMI <16.0 kg/m2), moderate (16.00-16.99 kg/m2), and mild (17.00-18.49 kg/m2) malnutrition categories. Results 19,247 patients contributed data between May 2004 and October 2010. Quarterly survival and retention were lowest in the BMI <16.0 kg/m2 category compared to higher BMI levels, and there was less variation in both measures across BMI strata after 180 days. ART treatment was estimated to cost $556 per year and averted 7.3 disability-adjusted life years. To maintain cost-effectiveness parity with ART alone, a supplement needed to cost $10.99 per quarter and confer a 20% reduction in both 6-month mortality and loss to follow-up among BMI <16.0 kg/m2 patients. Among BMI 17.00-18.49 kg/m2 patients, supplement costs accompanying a 20% reduction in mortality and loss to follow-up could not exceed $5.18 per quarter. In sensitivity analyses, the maximum permitted supplement cost increased if the ART program cost rose, and fell if patients classified as lost to follow-up at 6 months subsequently returned to care. Conclusions Low BMI adults starting ART in sub-Saharan Africa are at high risk of early mortality and loss to follow-up. The expense of providing nutrition supplementation would require only modest improvements in survival and program retention to be cost-effective for the most severely malnourished individuals starting ART, but interventions are unlikely to be cost-effective among those in higher BMI strata. PMID:24839400

2014-01-01

27

The presence of CXCR4-using HIV-1 prior to start of antiretroviral therapy is an independent predictor of delayed viral suppression.  

PubMed

The emergence of CXCR4-using HIV variants (X4-HIV) is associated with accelerated disease progression in the absence of antiretroviral therapy. However, the effect of X4-HIV variants on the treatment response remains unclear. Here we determined whether the presence of X4-HIV variants influenced the time to undetectable viral load and CD4+ T cell reconstitution after initiation of cART in 732 patients. The presence of X4-HIV variants was determined by MT-2 assay prior to cART initiation and viral load and CD4+ T cell counts were analyzed every 3 to 6 months during a three year follow-up period. Kaplan-Meier and Cox proportional hazard analyses were performed to compare time to viral suppression and the absolute CD4+ T cell counts and increases in CD4+ T cell counts during follow-up were compared for patients with and without X4-HIV at start of cART. Patients harboring X4-HIV variants at baseline showed a delay in time to achieve viral suppression below the viral load detection limit. This delay in viral suppression was independently associated with high viral load and the presence of X4-HIV variants. Furthermore, the absolute CD4+ T cell counts were significantly lower in patients harboring X4-HIV variants at all time points during follow-up. However, no differences were observed in the increase in absolute CD4+ T cell numbers after treatment initiation, indicating that the reconstitution of CD4+ T cells is independent of the presence of X4-HIV variants. The emergence of X4-HIV has been associated with an accelerated CD4+ T cell decline during the natural course of infection and therefore, patients who develop X4-HIV variants may benefit from earlier treatment initiation in order to obtain faster reconstitution of the CD4+ T cell population to normal levels. PMID:24098454

Gijsbers, Esther F; van Sighem, Ard; Harskamp, Agnes M; Welkers, Matthijs R A; de Wolf, Frank; Brinkman, Kees; Prins, Jan M; Schuitemaker, Hanneke; van 't Wout, Angélique B; Kootstra, Neeltje A

2013-01-01

28

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

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. PMID:22544188

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

2012-05-01

29

Impact of nutritional supplementation on immune response, body mass index and bioelectrical impedance in HIV-positive patients starting antiretroviral therapy  

PubMed Central

Background Challenges to HIV care in resource limited settings (RLS) include malnutrition. Limited evidence supports the benefit of nutritional supplementation when starting antiretroviral therapy (ART) in RLS. Methods Randomized controlled pilot study. HIV-positive ART-naive adults with self-reported weight loss were randomized to receive ART plus FutureLife porridge® nutritional supplement (NS) (388 kcal/day) or ART alone (Controls) for 6 months. Patients returned for monthly assessments and blood was drawn at enrolment and 6 months on ART. Differences in body composition, biochemical and laboratory parameters were estimated at 6 months on treatment. Results Of the 36 randomized patients, 26 completed the 6 month follow-up (11 NS vs 15 Controls). At enrolment, groups were similar in terms of age, gender, body mass index (BMI) and bioelectrical impedance. NS patients had a lower median CD4 count (60 cells/mm3 [IQR 12–105 vs 107 cells/mm3 [IQR 63–165]; p?=?0.149) and hemoglobin (10.3 g/dL [IQR 9.0-11.3] vs 13.1 g/dL [IQR 11.1-14.7]; p?=?0.001). At 6 months, NS patients increased their median CD4 count by 151 cells/mm3 [IQR 120–174) vs 77 cells/mm3 [IQR 33–145] in the Controls. NS patients had higher mean percentage change in body weight (12.7% vs 4.9%; p?=?0.047), BMI (7.8% vs 5.5%; p?=?0.007), absolute CD4 count (83.0% vs 46.4%, p?=?0.002) and hemoglobin (9.5% vs 1.0%; p?=?0.026). Patients in the NS arm had a higher mean percentage fat-free mass (16.7% vs ?3.5%, p?=?0.036), total body water (13.0% vs ?1.9%, p?=?0.026), intracellular water (16.1% vs ?4.1%, p?=?0.010) and basal metabolic rate (5.3% vs ?0.2%, p?=?0.014) compared to Controls. Patients in the NS arm also showed an improvement in physical activity at 6 months post-ART initiation compared to Controls (p?=?0.037). Conclusion Preliminary results are encouraging and suggest that NS taken concurrently with ART can promote weight gain, improve immune response and improve physical activity in HIV-positive patients that present at ART initiation with weight loss. PMID:23919622

2013-01-01

30

When to Start Antiretroviral Therapy in Children Aged 2–5 Years: A Collaborative Causal Modelling Analysis of Cohort Studies from Southern Africa  

PubMed Central

Background There is limited evidence on the optimal timing of antiretroviral therapy (ART) initiation in children 2–5 y of age. We conducted a causal modelling analysis using the International Epidemiologic Databases to Evaluate AIDS–Southern Africa (IeDEA-SA) collaborative dataset to determine the difference in mortality when starting ART in children aged 2–5 y immediately (irrespective of CD4 criteria), as recommended in the World Health Organization (WHO) 2013 guidelines, compared to deferring to lower CD4 thresholds, for example, the WHO 2010 recommended threshold of CD4 count <750 cells/mm3 or CD4 percentage (CD4%) <25%. Methods and Findings ART-naďve children enrolling in HIV care at IeDEA-SA sites who were between 24 and 59 mo of age at first visit and with ?1 visit prior to ART initiation and ?1 follow-up visit were included. We estimated mortality for ART initiation at different CD4 thresholds for up to 3 y using g-computation, adjusting for measured time-dependent confounding of CD4 percent, CD4 count, and weight-for-age z-score. Confidence intervals were constructed using bootstrapping. The median (first; third quartile) age at first visit of 2,934 children (51% male) included in the analysis was 3.3 y (2.6; 4.1), with a median (first; third quartile) CD4 count of 592 cells/mm3 (356; 895) and median (first; third quartile) CD4% of 16% (10%; 23%). The estimated cumulative mortality after 3 y for ART initiation at different CD4 thresholds ranged from 3.4% (95% CI: 2.1–6.5) (no ART) to 2.1% (95% CI: 1.3%–3.5%) (ART irrespective of CD4 value). Estimated mortality was overall higher when initiating ART at lower CD4 values or not at all. There was no mortality difference between starting ART immediately, irrespective of CD4 value, and ART initiation at the WHO 2010 recommended threshold of CD4 count <750 cells/mm3 or CD4% <25%, with mortality estimates of 2.1% (95% CI: 1.3%–3.5%) and 2.2% (95% CI: 1.4%–3.5%) after 3 y, respectively. The analysis was limited by loss to follow-up and the unavailability of WHO staging data. Conclusions The results indicate no mortality difference for up to 3 y between ART initiation irrespective of CD4 value and ART initiation at a threshold of CD4 count <750 cells/mm3 or CD4% <25%, but there are overall higher point estimates for mortality when ART is initiated at lower CD4 values. Please see later in the article for the Editors' Summary PMID:24260029

Schomaker, Michael; Egger, Matthias; Ndirangu, James; Phiri, Sam; Moultrie, Harry; Technau, Karl; Cox, Vivian; Giddy, Janet; Chimbetete, Cleophas; Wood, Robin; Gsponer, Thomas; Bolton Moore, Carolyn; Rabie, Helena; Eley, Brian; Muhe, Lulu; Penazzato, Martina; Essajee, Shaffiq; Keiser, Olivia; Davies, Mary-Ann

2013-01-01

31

Initiation of antiretroviral therapy  

PubMed Central

With the widespread availability of antiretroviral therapy, there is a dramatic decline in HIV related morbidity and mortality in both developed and developing countries. Further, the current antiretroviral drug combinations are safer and the availability of newer monitoring assays and guidelines has vastly improved the patient management. The clinician needs to evaluate several key issues prior to institution of antiretroviral regimen including the correct stage of starting the treatment and the kind of regimen to initiate. In addition to various disease related factors, it is also critical to assess the patient's general condition including nutritional status, presence of co-morbidities and mental preparedness prior to starting the therapy. The patients need to develop an overall understanding of the treatment and its benefits and the importance of lifelong adherence to the drugs. The presence of special situations like pediatric age, older patients, pregnancy, lactation and presence of opportunistic infections also require modification of the therapy. This review briefly summarizes issues relevant to the clinician prior to the initiation of antiretroviral therapy. PMID:24958979

Pandhi, Deepika; Ailawadi, Pallavi

2014-01-01

32

Pharmacogenetics of antiretrovirals.  

PubMed

The introduction of highly active antiretroviral therapy (HAART) as standard of care has changed the natural history of HIV infection into a manageable chronic disease requiring long-term antiretroviral (ARV) treatment. However, response to HAART is often limited by the occurrence of toxicity or by the emergence of drug resistance. Antiretroviral treatment is characterized by differing rates of adverse events and responses. Genetic variations between human beings account for a relevant proportion of this variability. A relevant number of associations between human genetic variants and predisposition to adverse events have been described and for some antiretroviral drugs a clear and casual genotype-phenotype correlation has already been established. The strong association between abacavir hypersensitivity reaction and HLA-B*5701 has been demonstrated in both observational and blinded randomized clinical trials in racially diverse populations and represents the best example of the clinical utility of pharmacogenetic screening in HIV medicine. Genotyping for HLA-B*5701 before prescribing an abacavir containing regimen has been introduced into routine clinical practice as the standard of care for all patients. Other well-established associations include CYP2B6 alleles and efavirenz central nervous system side effects, UGT1A1 alleles and atazanavir-associated hyperbilirubinemia and HLA class II allele HLA-DRB*0101 and nevirapine-associated hypersensitivity. Despite genetic associations having been described for peripheral neuropathy, lipodystrophy, hyperlipidaemia, pancreatitis and renal proximal tubulopathy, numerous barriers exist to the successful introduction of widespread genetic testing to the clinic. Future prospects point in the direction of individualization of antiretroviral therapy through insights from host genetics. The present paper is aimed to provide a comprehensive review of the published literature and to summarize the state of research in this area. 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. PMID:19744523

Tozzi, Valerio

2010-01-01

33

AIDS and Non-AIDS Morbidity and Mortality Across the Spectrum of CD4 Cell Counts in HIV-Infected Adults Before Starting Antiretroviral Therapy in Côte d’Ivoire  

PubMed Central

Background.?In Western Europe, North America, and Australia, large cohort collaborations have been able to estimate the short-term CD4 cell count–specific risk of AIDS or death in untreated human immunodeficiency virus (HIV)–infected adults with high CD4 cell counts. In sub–Saharan Africa, these CD4 cell count–specific estimates are scarce. Methods.?From 1996 through 2006, we followed up 2 research cohorts of HIV-infected adults in Côte d’Ivoire. This included follow-up off antiretroviral therapy (ART) across the entire spectrum of CD4 cell counts before the ART era, and only in patients with CD4 cell counts >200?cells/?L once ART became available. Data were censored at ART initiation. We modeled the CD4 cell count decrease using an adjusted linear mixed model. CD4 cell count–specific rates of events were obtained by dividing the number of first events occurring in a given CD4 cell count stratum by the time spent in that stratum. Results.?Eight hundred sixty patients were followed off ART over 2789 person-years (PY). In the ?650, 500–649, 350–499, 200–349, 100–199, 50–99, and 0–49?cells/?L CD4 cell count strata, the rates of AIDS or death were 0.9, 1.7, 3.7, 10.4, 30.9, 60.8, and 99.9 events per 100 PY, respectively. In patients with CD4 cell counts ?200 CD4?cells/?L, the most frequent AIDS-defining disease was tuberculosis (decreasing from 4.0 to 0.6 events per 100 PY for 200–349 and ?650 cells/?L, respectively), and the most frequent HIV non-AIDS severe diseases were visceral bacterial diseases (decreasing from 9.1 to 3.6 events per 100 PY). Conclusions.?Rates of AIDS or death, tuberculosis, and invasive bacterial diseases are substantial in patients with CD4 cell counts ?200 cells/?L. Tuberculosis and bacterial diseases should be the most important outcomes in future trials of early ART in sub–Saharan Africa. PMID:22173233

Minga, Albert; Gabillard, Delphine; Ouassa, Timothée; Messou, Eugene; Morris, Brandon; Traore, Moussa; Coulibaly, Ali; Freedberg, Kenneth A.; Lewden, Charlotte; Ménan, Hervé; Abo, Yao; Dakoury-Dogbo, Nicole; Toure, Siaka; Seyler, Catherine

2012-01-01

34

Community outreach with weekly delivery of anti-retroviral drugs compared to cognitive-behavioural health care team-based approach to improve adherence among indigent women newly starting HAART  

Microsoft Academic Search

Sustained virological suppression requires adherence to >95% of doses of therapy. Overall there is paucity of data on adherence interventions among women and post-intervention outcomes. In this pilot study, we evaluated a novel strategy of weekly delivery of medications (Directly Delivered Therapy: DDT) for six months using an outreach worker (ORW), among ARV naďve indigent women starting HAART and compared

F. Visnegarwala; M. C. Rodriguez-Barradass; E. A. Graviss; M. Caprio; M. Nykyforchyn; L. Laufman

2006-01-01

35

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

PubMed Central

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 Frontičres-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

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

2006-01-01

36

Variable impact on mortality of AIDS-defining events diagnosed during combination antiretroviral therapy: not all AIDS-defining conditions are created equal  

Microsoft Academic Search

BACKGROUND: The extent to which mortality differs following individual acquired immunodeficiency syndrome (AIDS)-defining events (ADEs) has not been assessed among patients initiating combination antiretroviral therapy. METHODS: We analyzed data from 31,620 patients with no prior ADEs who started combination antiretroviral therapy. Cox proportional hazards models were used to estimate mortality hazard ratios for each ADE that occurred in >50 patients,

A. Mocroft; J. A. Sterne; M. Egger; M. May; S. Grabar; H. Furrer; C. Sabin; G. Fatkenheuer; A. Justice; P. Reiss; A. d' Arminio Monforte; J. Gill; R. Hogg; F. Bonnet; M. Kitahata; S. Staszewski; J. Casabona; R. Harris; M. Saag; P. P. Koopmans; R. van Crevel; R. de Groot; M. Keuter; F. Post; A. J. A. M. van der Ven; A. Warris

2009-01-01

37

Complications of Antiretroviral Therapy Initiation in Hospitalised Patients with HIV-Associated Tuberculosis  

PubMed Central

Background HIV-associated tuberculosis is a common coinfection in Sub-Saharan Africa, which causes high morbidity and mortality. A sub-set of HIV-associated tuberculosis patients require prolonged hospital admission, during which antiretroviral therapy initiation may be required. The aim of this study was to document the causes of clinical deterioration of hospitalised patients with HIV-associated tuberculosis starting antiretroviral therapy in order to inform healthcare practice in low- to middle-income countries. Methods Prospective, observational cohort study of adult inpatients with HIV-associated tuberculosis starting antiretroviral therapy in a dedicated tuberculosis hospital in Cape Town, South Africa. Causes of clinical deterioration and outcome were recorded in the first 12 weeks of antiretroviral therapy. Patients with rifampicin-resistant tuberculosis were excluded. Results Between May 2009 and November 2010, 112 patients (60% female), with a median age of 32 years were enrolled. At baseline the median CD4 count was 55 cells/mm3 (IQR 31–106) and HIV viral load 5.6 log copies/mL. All patients had significant comorbidity: 82% were bed-bound, 65% had disseminated tuberculosis and 27% had central nervous system tuberculosis. Seventy six patients (68%) developed 144 clinical events after starting antiretroviral therapy. TB-IRIS, hospital-acquired infections and significant drug toxicities occurred in 42%, 20.5% and 15% of patients respectively. A new opportunistic disease occurred in 15% of patients and a thromboembolic event in 8%. Mortality during the 12 week period was 10.6%. Conclusions High rates of TB-IRIS, hospital-acquired infections and drug toxicities complicate the course of patients with HIV-associated tuberculosis starting antiretroviral therapy in hospital. Despite the high morbidity, mortality was relatively low. Careful clinical management and adequate resources are needed in hospitalised HIV-TB patients in the 1st three months following ART initiation. PMID:23408935

van der Plas, Helen; Meintjes, Graeme; Schutz, Charlotte; Goliath, Rene; Myer, Landon; Baatjie, Dorothea; Wilkinson, Robert J.; Maartens, Gary; Mendelson, Marc

2013-01-01

38

Epidemiology of antiretroviral multiclass resistance.  

PubMed

Given the recent evolution of therapeutic trends, the frequency and determinants of multiclass-resistant HIV infection in the modern combination highly active antiretroviral therapy (HAART) era are less well understood. In this study, the authors characterize the epidemiology of antiretroviral multiclass resistance among HAART-naďve patients enrolled in a province-wide HAART distribution program in British Columbia, Canada. HAART and resistance testing are free to eligible individuals in British Columbia. This study was based on patients who initiated naďve on HAART and were followed during January 1, 2000-June 30, 2007. Explanatory logistic and survival models were built to identify those factors most influential in the emergence of multiclass resistance. Among the 1,820 individuals in our study, 833 (46%) were tested for antiretroviral resistance at least once during their follow-up. Multiclass resistance was observed in 142 individuals (n = 833; 17%) during a median follow-up of 14 months (interquartile range, 3-34 months) (incidence rate, 0.8 cases/1,000 person-months). The authors found that initial nonnucleoside reverse transcriptase inhibitor-based HAART was the main determinant of multiclass resistance. Given that these inhibitors are still widely used, priority should be given to make resistance testing and viral load monitoring a standard part of human immunodeficiency virus care to maximize the long-term efficacy and efficiency of HAART. PMID:20667931

Lima, Viviane D; Harrigan, P Richard; Sénécal, Martin; Yip, Benita; Druyts, Eric; Hogg, Robert S; Montaner, Julio S G

2010-08-15

39

Combination antiretroviral therapy in population affected by conflict: outcomes from large cohort in northern Uganda  

PubMed Central

Objective To measure the clinical and immunological outcomes of HIV positive adult patients receiving combination antiretroviral therapy in conflict affected northern Uganda. Design Prospective cohort study. Setting Gulu District, northern Uganda. Participants 1625 adults (aged over 14 years) receiving combination antiretroviral therapy. Main outcome measures Primary outcome: all cause mortality. Secondary outcomes: impact of covariates (sex, age, CD4 count at start, adherence, tuberculosis at start, duration of treatment, and internally displaced person status) on mortality. Results Sixty nine (4.2%) patients died during follow-up. The mortality incidence rate was 3.48 (95% confidence interval 2.66 to 4.31) per 100 person years. Patients started treatment with a median CD4 count of 157 (interquartile range 90-220) cells/?l; most (1009; 63%) had World Health Organization stage 2 defined illness. Sixty two patients had pulmonary tuberculosis at the start of treatment. Of the 1521 patients with adherence data, 118 (7.8%) had adherence of less than 95% and 1403 (92.2%) had adherence of 95% or above. Conclusion Patients receiving combination antiretroviral therapy in conflict affected northern Uganda had a mortality comparable to that of patients in peaceful, low income settings and better adherence than patients in higher income settings. These favourable findings highlight the need to expand access to combination antiretroviral therapy in populations affected by armed conflict. PMID:19223338

2009-01-01

40

Brief report Tuberculosis following initiation of antiretroviral therapy  

E-print Network

-income countries Running title: Tuberculosis on antiretroviral therapy The ART-LINC Collaboration The Antiretroviral Therapy in Low-Income Countries (ART-LINC) Collaboration is a network of antiretroviral treatment1 Brief report Tuberculosis following initiation of antiretroviral therapy in low-income and high

Paris-Sud XI, Université de

41

Start Young!  

ERIC Educational Resources Information Center

Discusses the importance of early interest in science and how effective it is on career choice in adult stages of life. Recommends starting mathematics and science activities in preschool and kindergarten. Describes how to create a career-oriented learning center in the classroom with examples of kitchen chemistry, nutrition/botany, zoology,…

Rubin, Penni

2002-01-01

42

Getting Started  

NSDL National Science Digital Library

Before starting any of the activities in this guide, we strongly recommend that you read the information in this section. Here we cover the critically important issues of how to handle amphibians and reptiles, and safety issues concerning these animals and field activities in general. We also discuss permits and regulations relating to the collecting, handling, and raising of herps. This free selection also includes the Table of Contents, Preface, and Introduction.

Marianne E. Krasny

2001-01-01

43

Press Start  

NASA Astrophysics Data System (ADS)

This level sets the stage for the design philosophy called “Triadic Game Design” (TGD). This design philosophy can be summarized with the following sentence: it takes two to tango, but it takes three to design a meaningful game or a game with a purpose. Before the philosophy is further explained, this level will first delve into what is meant by a meaningful game or a game with a purpose. Many terms and definitions have seen the light and in this book I will specifically orient at digital games that aim to have an effect beyond the context of the game itself. Subsequently, a historical overview is given of the usage of games with a serious purpose which starts from the moment we human beings started to walk on our feet till our contemporary society. It turns out that we have been using games for all kinds of non-entertainment purposes for already quite a long time. With this introductory material in the back of our minds, I will explain the concept of TGD by means of a puzzle. After that, the protagonist of this book, the game Levee Patroller, is introduced. Based on the development of this game, the idea of TGD, which stresses to balance three different worlds, the worlds of Reality, Meaning, and Play, came into being. Interested? Then I suggest to quickly “press start!”

Harteveld, Casper

44

Antiretroviral Pharmacology in Mucosal Tissues  

PubMed Central

Strategies to prevent HIV infection using pre-exposure prophylaxis (PrEP) are required to curtail the HIV pandemic. The mucosal tissues of the genital and rectal tracts play a critical role in HIV acquisition, but antiretroviral (ARV) disposition and correlates of efficacy within these tissues are not well understood. Pre-clinical and clinical strategies to describe ARV pharmacokinetic-pharmacodynamic relationships (PK/PD) within mucosal tissues are currently being investigated. In this review, we summarize the physiochemical and biologic factors influencing ARV tissue exposure. Further, we discuss the necessary steps to generate relevant PK/PD data and the challenges associated with this process. Finally, we suggest how pre-clinical and clinical data might be practically translated into optimal PrEP dosing strategies for clinical trials testing using mathematical modeling and simulation. PMID:23764642

Thompson, Corbin G.; Cohen, Myron S.; Kashuba, Angela D.M.

2014-01-01

45

Start Young!  

NSDL National Science Digital Library

A person, place, or thing is what usually sparks those first memorable childhood impressions. Of course, we often do not study our newfound interests from the time of our personal enlightenment to adulthood, but early childhood interests are strong and they can have a powerful hold on us. Children usually show interest in many areas, though one interest usually resurfaces as they get older. Often, it seems this interest--usually one from childhood--is the one that leads to a profession. This free selection from Start Young! Early Childhood Science Activities also includes a Contents, Introduction, and Index section, along with a Quick Reference Chart.

Penni Rubin

2006-01-01

46

New Antiretroviral Therapies for Pediatric HIV Infection  

PubMed Central

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

Morris, Jennifer L.; Kraus, Donna M.

2005-01-01

47

Accelerated suppression of primary Epstein-Barr virus infection in HIV-infected infants initiating lopinavir/ritonavir-based versus nevirapine-based combination antiretroviral therapy.  

PubMed

We compared primary Epstein-Barr virus (EBV) infection and suppression between Kenyan human immunodeficiency virus-infected infants starting nevirapine-based vs lopinavir/ritonavir-based antiretroviral regimens. Although the rate of EBV infection was similar between groups, infants receiving lopinavir/ritonavir suppressed EBV more rapidly. Our findings suggest that specific antiretrovirals may potentially impact the risk of future EBV-associated malignancies. PMID:24550373

Slyker, Jennifer A; Casper, Corey; Tapia, Kenneth; Richardson, Barbra; Bunts, Lisa; Huang, Meei-Li; Wamalwa, Dalton; Benki-Nugent, Sarah; John-Stewart, Grace

2014-05-01

48

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

PubMed

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. PMID:25309984

Pascual, Fernando

2014-01-01

49

World Health Organization surveys to monitor HIV drug resistance prevention and associated factors in sentinel antiretroviral treatment sites  

Microsoft Academic Search

The World Health Organization (WHO) estimates that >2 million people will have started antiretroviral therapy (ART) by the end of 2006. As the development of some HIV drug resistance (HIVDR) is inevitable in populations taking ART, the emergence of HIVDR must be balanced against the benefits of providing ART, including improved health outcomes and decreased HIV\\/AIDS-associated morbidity and mortality. ART

Michael R Jordan; Diane E Bennett; Silvia Bertagnolio; Charles F Gilks; Donald Sutherland

2008-01-01

50

“Risk factors associated with virologic failure in HIV-infected patients receiving antiretroviral therapy at a public hospital in Peru”  

PubMed Central

OBJECTIVE To describe clinical and biological characteristics of subjects with virologic failure who participated in the sexually transmitted diseases HIV/AIDS National Program from a Peruvian public hospital. MATERIALS AND METHODS An exploratory descriptive study was performed with data from subjects older than 18 who started high activity antiretroviral therapy (HAART) between May 2004 and December 2009 and who had a viral load control after 24 weeks of HAART. Virologic failure was defined as a viral load value above 1000 copies/mL on follow up after 24 weeks on HAART. RESULTS Of 1 478 records of patients on HAART analized, the median age was 35 years [IQR, 29-41] and 69.6% were male. Also, virologic failure occurred in 24% and 3.7% died. Of subjects with virologic failure, 9.5% died. On multivariate analysis, age, history of antiretroviral use before starting HAART, change of antiretroviral therapy due to toxicity, opportunistic infections during HAART, level of CD4 + lymphocytes below 100 cells/ml at start of HAART, adherence and clinical stage were independently associated with virologic failure. In the group of patient with no history of antiretroviral use before starting HAART, age, opportunistic infections during HAART were associated with virologic failure. CONCLUSION This study identified factors associated with virologic failure. Further studies are needed to evaluate whether the use of these factors can help to identify prospectively patients at high risk of failure, and to design interventions aimed to reduce this risk. PMID:23450408

Jorge, Alave R; Jorge, Paz B; Elsa, Gonzalez L; Miguel, Campos S; Rodriguez, Martin; Willig, James; Juan, Echevarría Z

2013-01-01

51

Antiretroviral therapy and the kidney.  

PubMed

Acute kidney injury (AKI) and chronic kidney disease (CKD) are more common in the HIV-infected population than in the general population. AKI is associated with an increased risk of heart failure, cardiovascular disease, end-stage renal disease (ESRD), and mortality. Tenofovir is associated with severe AKI in a small percentage of patients and with subclinical abnormalities in many more. HIV-associated nephropathy is now a relatively rare form of CKD, because of the widespread use of potent antiretroviral therapy. The CKD spectrum in HIV-infected patients has become more frequently characterized by comorbid CKD, with an increased frequency of CKD related to diabetes or hypertension being observed. Kidney transplantation is a therapeutic option for HIV-infected patients with ESRD if their HIV infection is controlled, although rates of acute graft rejection and drug-drug interactions are high. This article summarizes a presentation by Christina M. Wyatt, MD, at the IAS-USA continuing education program held in Washington, DC, in June 2013. PMID:25101531

Wyatt, Christina M

2014-01-01

52

The latest in antiretroviral therapy.  

PubMed

The XVI International AIDS Conference (AIDS 2006), organized by the International AIDS Society (IAS), took place August 12-18 in Toronto, Canada. It was attended by over 26,000 participants from more than 170 countries and featured more than 4,500 abstracts as well as an array of community and cultural activities. The theme of the meeting was "Time to deliver", emphasizing the continued need and urgency in bringing effective HIV prevention and treatment strategies to those living with and affected by HIV/AIDS. The meeting's agenda was broad and included policy and programmatic topics as well as scientific research. This report focuses on reports presented at the conference that directly deal with antiretroviral therapy. This is primarily because of the nature of the venue where it is intended to be published (Drug News & Perspectives) as well as the expertise of the author. It is not a lack of recognition of the other equally important topics and discussions that took place at AIDS 2006. The author is solely responsible for the selection of topics and presentations to be included in this report. PMID:17160151

Temesgen, Zelalem

2006-10-01

53

Anxiety and Depression Symptoms as Risk Factors for Non-adherence to Antiretroviral Therapy in Brazil  

Microsoft Academic Search

Depression and anxiety are common among HIV-infected people and rank among the strongest predictors of non-adherence to antiretroviral\\u000a therapy (ART). This longitudinal study aimed to assess whether symptoms of anxiety and depression are predictors of non-adherence\\u000a among patients initiating ART at two public referral centers (n = 293) in Belo Horizonte, Brazil. Prevalence of severe anxiety and depression symptoms before starting ART

Lorenza Nogueira Campos; Mark Drew Crosland Guimarăes; Robert H. Remien

2010-01-01

54

Decay Kinetics of Human Immunodeficiency Virus-Specific Effector Cytotoxic T Lymphocytes after Combination Antiretroviral Therapy  

Microsoft Academic Search

Little is known of the changes in human immunodeficiency virus type 1 (HIV-1)-specific effector cytotoxic T lymphocytes (CTL) after potent antiretroviral therapy. Using HLA\\/peptide tetrameric complexes, we show that after starting treatment, there are early rapid fluctuations in the HIV-1-specific CTL response which last 1 to 2 weeks. These fluctuations are followed by an exponential decay (median half-life, 45 days)

G. S. OGG; X. JIN; S. BONHOEFFER; P. MOSS; M. A. NOWAK; S. MONARD; J. P. SEGAL; Y. CAO; S. L. ROWLAND-JONES; A. HURLEY; M. MARKOWITZ; D. D. HO; A. J. MCMICHAEL; D. F. NIXON

1999-01-01

55

When to start, what to start and other treatment controversies in pediatric HIV infection.  

PubMed

Over the last decade there have been dramatic changes in the management of pediatric HIV infection. Whilst observational studies and several randomized control trials (RCTs) have addressed some questions about when to start antiretroviral therapy (ART) in children and what antiretrovirals to start, many others remain unanswered. In infants, early initiation of ART greatly reduces mortality and disease progression. Treatment guidelines now recommend ART in all infants younger than 1 or 2 years of age depending on geographical setting. In children >1 year of age, US, European (Paediatric European Network for Treatment of AIDS; PENTA) and WHO guidelines differ and debate is ongoing. Recent data from an RCT in Thailand in children with moderate immune suppression indicate that it is safe to monitor asymptomatic children closely without initiating ART, although earlier treatment was associated with improved growth. Untreated HIV progression in children aged over 5 years is similar to that in adults, and traditionally adult treatment thresholds are applied. Recent adult observational and modeling studies showed a survival advantage and reduction of age-associated complications with early treatment. The current US guidelines have lowered CD4+ cell count thresholds for ART initiation for children aged >5 years to 500?cells/mm3. Co-infections influence the choice of drugs and the timing of starting ART. Drug interactions, overlapping toxicities and adherence problems secondary to increased pill burden are important issues. Rapid changes in the pharmacokinetics of antiretrovirals in the first years of life, limited pharmacokinetic data in children and genetic variation in metabolism of many antiretrovirals make correct dosing difficult. Adherence should always be addressed prior to starting ART or switching regimens. The initial ART regimen depends on previous exposure, including perinatal administration for prevention of mother to child transmission (PMTCT), adherence, co-infections, drug availability and licensing. A European cohort study in infants indicated that treatment with four drugs produced superior virologic suppression and immune recovery. Protease inhibitor (PI)-based ART has the advantage of a high barrier to viral resistance. A recent RCT conducted in several African countries showed PI-based ART to be advantageous in children aged <3 years compared with nevirapine-based ART irrespective of previous nevirapine exposure. Another trial in older children from resource rich settings showed both regimens were equally effective. Treatment interruption remains a controversial issue in children, but one study in Europe demonstrated no short-term detrimental effects. ART in children is a rapidly evolving area with many new antiretrovirals being developed and undergoing trials. The aim of ART has shifted from avoiding mortality and morbidity to achieving a normal life expectancy and quality of life, minimizing toxicities and preventing early cancers and age-related illnesses. PMID:23013459

Turkova, Anna; Webb, Rachel H; Lyall, Hermione

2012-12-01

56

HIV-1 Antiretroviral Drug Therapy Eric J. Arts1  

E-print Network

HIV-1 Antiretroviral Drug Therapy Eric J. Arts1 and Daria J. Hazuda2 1 Ugandan CFAR Laboratories will review the basic principles of antiretroviral drug therapy, the mode of drug action, and the factors leading to treatment failure (i.e., drug resistance). BASIC PRINCIPLES OF ANTIRETROVIRAL THERAPY Before

Levin, Judith G.

57

Antiretroviral use in Ouagadougou, Burkina Faso.  

PubMed

Burkina Faso has the second highest seroprevalence rate for HIV in West Africa, estimated at 6.5% of the population. Although it is one of the poorest countries in the world, antiretrovirals have been used on an extremely limited basis in Burkina Faso since at least the early 1990s. In this article we will review the evolution of antiretroviral availability in this country, describe the mechanisms by which drugs are being accessed, and review our experience with expanding antiretroviral access through drug donations in community-based settings. Finally, we will discuss some of the implications for future attempts to expand access to treatment for people living with HIV in Africa. PMID:14565617

Nguyen, Vinh-Kim; Grennan, Troy; Peschard, Karine; Tan, Darell; Tiendrébéogo, Issoufou

2003-07-01

58

Antiretroviral Drug Resistance and Routine Therapy, Cameroon  

PubMed Central

Among 128 patients routinely receiving highly active antiretroviral therapy in an HIV/AIDS outpatient clinic in Cameroon, 16.4% had drug resistance after a median of 10 months. Of these, 12.5% had resistance to nucleoside reverse transcriptase inhibitors (NRTIs), 10.2% to non-NRTIs, and 2.3% to protease inhibitors. PMID:16707062

Kouanfack, Charles; Vergne, Laurence; Tardy, Michčle; Zekeng, Léopold; Noumsi, Nathalie; Butel, Christelle; Bourgeois, Anke; Mpoudi-Ngolé, Eitel; Koulla-Shiro, Sinata; Peeters, Martine; Delaporte, Eric

2006-01-01

59

The Starting Early Starting Smart Story.  

ERIC Educational Resources Information Center

Starting Early Starting Smart (SESS) is an early childhood public/private initiative designed to identify new, empirical knowledge about the effectiveness of integrating substance abuse prevention, addictions treatment, and mental health services with primary health care and childcare service settings (e.g., Head Start, day care, preschool) to…

Casey Family Programs, Seattle, WA.

60

Bones, Fractures, Antiretroviral Therapy and HIV  

PubMed Central

The course of HIV infection has been dramatically transformed by the success of antiretroviral therapy from a universally fatal infection to a manageable chronic disease. With these advances in HIV disease management, age-related comorbidities, including metabolic bone disease, have become more prominent in the routine care of persons living with HIV infection. Recent data have highlighted the role of HIV, initiation of antiretroviral therapy (ART), and hepatitis C virus (HCV) co-infection in bone mineral density (BMD) loss and fracture incidence. Additionally, the underlying mechanism for the development of metabolic bone disease in the setting of HIV has received considerable attention. This review will highlight recently published and presented data and synthesize the current state of the field. These data highlight the need for proactive prevention for fragility fractures. PMID:24535243

Battalora, Linda A.; Young, Ben; Overton, Edgar T.

2014-01-01

61

The Promise of Antiretrovirals for HIV Prevention  

PubMed Central

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

Flash, Charlene; Krakower, Douglas; Mayer, Kenneth H.

2013-01-01

62

Modeling Antiretroviral Drug Responses for HIV-1 infected Patients Using Differential Equation Models  

PubMed Central

Summary We review mathematical modeling and related statistical issues of HIV dynamics primarily in response to antiretroviral drug therapy in this article. We start from a basic model of virus infection and then review a number of more advanced models with considering, e.g., pharmacokinetic factors, adherence and drug resistance. Specifically, we illustrate how mathematical models can be developed and parameterized to understand effects of long-term treatment and different treatment strategies on disease progression. In addition, we discuss a variety of parameter estimation methods for differential equation models that are applicable to either within- or between-host viral dynamics. PMID:23603208

Xiao, Yanni; Miao, Hongyu; Tang, Sanyi; Wu, Hulin

2014-01-01

63

WHO guidelines for antiretroviral therapy in serodiscordant couples in sub-Saharan Africa: how many fit?  

PubMed

To evaluate the implication of WHO guidelines for serodiscordant couples, we interviewed HIV-infected adults on their partner's serostatus. We found that 12% with more than 500 CD4+ cells/?l should be recommended antiretroviral treatment (ART) because their partner was seronegative; 24% could be recommended not to start ART because their partner was seropositive; and 64% could not be given any recommendation regarding ART early initiation because they had either no stable partnership (30%) or were in a stable partnership with a partner whose status they were not aware of (34%). PMID:24804862

Kouamé, Gérard; Danel, Christine; Moh, Raoul; Badjé, Anani; Jean, Kevin; N'takpe, Jean-Baptiste; Gabillard, Delphine; Le Carrou, Jérome; du Loű, Annabel Desgrées; Deschamps, Nina; Eholie, Serge; Anglaret, Xavier

2014-06-19

64

KNOWLEDGE AQUIRED THROUGH INDEPENDENT RESEARCH Five Classes of Antiretroviral Drugs  

E-print Network

RESEARCH KNOWLEDGE AQUIRED THROUGH INDEPENDENT RESEARCH Five Classes of Antiretroviral Drugs CLASS DISCUSSION Algorithms to simulate the impact of drug combinations in HIV patients SCIENTIFIC Signaling Pathways of the Cell Effects of Antiretroviral Drugs in the Human Body Function of the Human

Auerbach, Scott M.

65

Switching antiretroviral therapy to minimize metabolic complications  

PubMed Central

Advances in HIV therapy have made living with HIV for decades a reality for many patients. However, antiretroviral therapy has been associated with multiple long-term complications, including dyslipidemia, fat redistribution, insulin resistance and increased cardiovascular risk. As newer agents with improved metabolic profiles have become available, there is growing interest in the safety and efficacy of switching ART as a strategy to reduce long-term complications. This article reviews recently published data on switching ART to minimize the contributions of specific agents to these complications. PMID:22171239

Lake, Jordan E; Currier, Judith S

2011-01-01

66

Drug interactions and antiretroviral drug monitoring.  

PubMed

Owing 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 that 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

Foy, Matthew; Sperati, C John; Lucas, Gregory M; Estrella, Michelle M

2014-09-01

67

Factors associated with timely initiation of antiretroviral therapy in two HIV clinics in Lilongwe, Malawi.  

PubMed

The World Health Organization (WHO) estimates that only 30% of eligible, HIV-infected individuals start antiretroviral therapy (ART). This study seeks to explore the geographic and individual factors associated with starting ART on time. This retrospective study includes 15,734 HIV-positive adults initiating ART at two HIV clinics in Lilongwe, Malawi. The outcome was starting ART within two weeks of meeting ART eligibility as defined by the Malawi ART guidelines. Euclidean distance from patient neighbourhood to their clinic was calculated using Google Earth. Logistic regression models assessed factors influencing starting ART on time. Of 15,734 adults initiating ART, 8178 were from Lighthouse (LH) and 7556 were from Martin Preuss Center (MPC). Combined, 68.7% started treatment on time. Patients who were eligible for ART based on a CD4 cell count <250 cells/mm(3) versus WHO stage were less likely to begin ART on time at both LH (odds ratio [OR] 0.16; 95% CI 0.13-0.19) and MPC (OR 0.24; 95% CI 0.21-0.28). Likelihood of starting on time decreased with each kilometer further from clinic location among LH patients (OR 0.97; 95% CI 0.94-0.99); distance was not significant at MPC. In conclusion, predictors differed by clinic. Distance to clinic and type of eligibility for ART significantly influence starting ART on time. PMID:23467293

Johnson, D C; Feldacker, C; Tweya, H; Phiri, S; Hosseinipour, M C

2013-01-01

68

Variable Impact on Mortality of AIDS-Defining Events Diagnosed during Combination Antiretroviral Therapy: Not All AIDS-Defining Conditions Are Created Equal  

PubMed Central

Background The extent to which mortality differs following individual acquired immunodeficiency syndrome (AIDS)–defining events (ADEs) has not been assessed among patients initiating combination antiretroviral therapy. Methods We analyzed data from 31,620 patients with no prior ADEs who started combination antiretroviral therapy. Cox proportional hazards models were used to estimate mortality hazard ratios for each ADE that occurred in >50 patients, after stratification by cohort and adjustment for sex, HIV transmission group, number of anti-retroviral drugs initiated, regimen, age, date of starting combination antiretroviral therapy, and CD4+ cell count and HIV RNA load at initiation of combination antiretroviral therapy. ADEs that occurred in <50 patients were grouped together to form a “rare ADEs” category. Results During a median follow-up period of 43 months (interquartile range, 19–70 months), 2880 ADEs were diagnosed in 2262 patients; 1146 patients died. The most common ADEs were esophageal candidiasis (in 360 patients), Pneumocystis jiroveci pneumonia (320 patients), and Kaposi sarcoma (308 patients). The greatest mortality hazard ratio was associated with non-Hodgkin’s lymphoma (hazard ratio, 17.59; 95% confidence interval, 13.84–22.35) and progressive multifocal leukoencephalopathy (hazard ratio, 10.0; 95% confidence interval, 6.70–14.92). Three groups of ADEs were identified on the basis of the ranked hazard ratios with bootstrapped confidence intervals: severe (non-Hodgkin’s lymphoma and progressive multifocal leukoencephalopathy [hazard ratio, 7.26; 95% confidence interval, 5.55–9.48]), moderate (cryptococcosis, cerebral toxoplasmosis, AIDS dementia complex, disseminated Mycobacterium avium complex, and rare ADEs [hazard ratio, 2.35; 95% confidence interval, 1.76–3.13]), and mild (all other ADEs [hazard ratio, 1.47; 95% confidence interval, 1.08–2.00]). Conclusions In the combination antiretroviral therapy era, mortality rates subsequent to an ADE depend on the specific diagnosis. The proposed classification of ADEs may be useful in clinical end point trials, prognostic studies, and patient management. PMID:19275498

2011-01-01

69

Current Perspectives on HIV-1 Antiretroviral Drug Resistance  

PubMed Central

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

Iyidogan, Pinar; Anderson, Karen S.

2014-01-01

70

Head Start Automation Manual.  

ERIC Educational Resources Information Center

The task for the National Data Management Project is to share technological capabilities with the Head Start Community in order to implement improved services for children and families involved in Head Start. Many Head Start programs have incorporated technology into their programs, including word processing, database management systems,…

Maryland Univ., College Park. Univ. Coll.

71

Head Start Facilities Manual.  

ERIC Educational Resources Information Center

A quality Head Start facility should provide a physical environment responsive both to the needs of the children and families served and to the needs of staff, volunteers, and community agencies that share space with Head Start. This manual is a tool for Head Start grantees and delegate agencies for assessing existing facilities, making…

Research Assessment Management, Inc., Silver Spring, MD.

72

Plasma and Intracellular Antiretroviral Concentrations in HIV-Infected Patients under Short Cycles of Antiretroviral Therapy  

PubMed Central

Study of plasma and intracellular concentrations of atazanavir, lopinavir, nevirapine, and efavirenz was conducted on 48 patients under short cycles of antiretroviral therapy. Intracellular concentrations (IC) were still measurable for all drugs after 85?h or 110?h drug intake despite the absence of drug in plasma for atazanavir and lopinavir. A linear relationship between plasma and intracellular efavirenz was observed. Further studies to fully understand the impact of IC in the intermittent antiviral treatment are required. PMID:25431661

Zehnacker, Laura; Abe, Emuri; Mathez, Dominique; Alvarez, Jean-Claude; Leibowitch, Jacques; Azoulay, Stéphane

2014-01-01

73

HLA-Bw4 homozygosity is associated with an impaired CD4 T cell recovery after initiation of antiretroviral therapy.  

PubMed

We assessed the influence of human leukocyte antigen (HLA) alleles HLA-Bw4 and HLA-Bw6 on CD4 T cell recovery after starting successful combination antiretroviral therapy in 265 individuals. The median gains in the CD4 T cell count after 4 years were 258 cells/microL for HLA-Bw4 homozygotes, 321 cells/microL for HLA-Bw4/Bw6 heterozygotes, and 363 cells/microL for HLA-Bw6 homozygotes (P = .01, compared with HLA-Bw4 homozygotes). HLA-Bw4 homozygosity appears to predict an impaired CD4 T cell recovery after initiation of combination antiretroviral therapy. PMID:18466093

Rauch, Andri; Nolan, David; Furrer, Hansjakob; McKinnon, Elizabeth; John, Mina; Mallal, Simon; Gaudieri, Silvana; Günthard, Huldrych F; Schmid, Patrick; Battegay, Manuel; Hirschel, Bernard; Telenti, Amalio; James, Ian

2008-06-15

74

Antiretroviral Drugs Used in the Treatment of HIV Infection  

MedlinePLUS

... 6 months *manufacturer/sponsor at time of approval Generic drugs used in the Treatment of HIV Infection Approved ... drugs for pediatric treatment of HIV infection Approved generic formulations of antiretroviral drugs used in the treatment of HIV infection Approved ...

75

Approved Antiretroviral Drugs Used for Pediatric Treatment of HIV Infection  

MedlinePLUS

... Drugs Used in the Treatment of HIV Infection Generic Drugs Used in the Treatment of HIV Infection More ... drugs for pediatric treatment of HIV infection Approved generic formulations of antiretroviral drugs used in the treatment of HIV infection Approved ...

76

Microneedle delivery for improved efficacy of antiretroviral and antibiotic drugs  

E-print Network

Two classes of drugs, antiretrovirals and antibiotics, could benefit greatly from delivery through microneedles. Microneedles (MN) offer an increase in efficacy for these drugs by providing delivery to the lymphatic system ...

Stauber, Zachary Jason

2012-01-01

77

Facilitating Compound Progression of Antiretroviral Agents via Modeling and Simulation  

Microsoft Academic Search

Pharmacotherapy in human immunodeficiency virus (HIV)-infected patients and the development of safe and effective antiretroviral\\u000a dosing regimens has been hindered by numerous issues, including the rapid development of viral resistance to drug therapy,\\u000a the narrow therapeutic window of the drug compounds, and lack of fundamental knowledge concerning the sources of variation\\u000a in exposure and response to antiretroviral agents. Sources of

Jeffrey S. Barrett

2007-01-01

78

The Survival Benefits of Antiretroviral Therapy in South Africa  

PubMed Central

Background.?We sought to quantify the survival benefits attributable to antiretroviral therapy (ART) in South Africa since 2004. Methods.?We used the Cost-Effectiveness of Preventing AIDS Complications–International model (CEPAC) to simulate 8 cohorts of human immunodeficiency virus (HIV)–infected patients initiating ART each year during 2004–2011. Model inputs included cohort-specific mean CD4+ T-cell count at ART initiation (112–178 cells/µL), 24-week ART suppressive efficacy (78%), second-line ART availability (2.4% of ART recipients), and cohort-specific 36-month retention rate (55%–71%). CEPAC simulated survival twice for each cohort, once with and once without ART. The sum of the products of per capita survival differences and the total numbers of persons initiating ART for each cohort yielded the total survival benefits. Results.?Lifetime per capita survival benefits ranged from 9.3 to 10.2 life-years across the 8 cohorts. Total estimated population lifetime survival benefit for all persons starting ART during 2004–2011 was 21.7 million life-years, of which 2.8 million life-years (12.7%) had been realized by December 2012. By 2030, benefits reached 17.9 million life-years under current policies, 21.7 million life-years with universal second-line ART, 23.3 million life-years with increased linkage to care of eligible untreated patients, and 28.0 million life-years with both linkage to care and universal second-line ART. Conclusions.?We found dramatic past and potential future survival benefits attributable to ART, justifying international support of ART rollout in South Africa. PMID:24307741

April, Michael D.; Wood, Robin; Berkowitz, Bethany K.; Paltiel, A. David; Anglaret, Xavier; Losina, Elena; Freedberg, Kenneth A.; Walensky, Rochelle P.

2014-01-01

79

Cardiometabolic risk factors among HIV patients on antiretroviral therapy  

PubMed Central

Background HIV and combination antiretroviral therapy (cART) may increase cardiovascular disease (CVD) risk. We assessed the early effects of cART on CVD risk markers in a population with presumed low CVD risk. Methods Adult patients (n=118) in Lusaka, Zambia were recruited at the time of initiation of cART for HIV/AIDS. Cardiometabolic risk factors were measured before and 90?days after starting cART. Participants were grouped according to cART regimens: Zidovudine + Lamivudine + Nevirapine (n=58); Stavudine + Lamivudine + Nevirapine (n=43); and ‘other’ (Zidovudine + Lamivudine + Efavirenz, Stavudine + Lamivudine + Efavirenz, Tenofovir + Emtricitabine + Efavirenz or Tenofovir + Emtricitabine + Nevirapine, n=17). ANOVA was used to test whether changes in cardiometabolic risk markers varied by cART regimen. Results From baseline to 90?days after initiation of cART, the prevalence of low levels of high-density lipoprotein cholesterol (<1.04?mmol/L for men and <1.30?mmol/L for women) significantly decreased (78.8% vs. 34.8%, P<0.001) while elevated total cholesterol (TC ?5.18?mmol/L, 5.1% vs. 11.9%, P=0.03) and the homeostasis model assessment of insulin resistance ?3.0 (1.7% vs. 17.0%, P<0.001) significantly increased. The prevalence of TC:HDL-c ratio ?5.0 significantly decreased (44.9% vs. 6.8%, P<0.001). These changes in cardiometabolic risk markers were independent of the cART regimen. Conclusion Our results suggest that short-term cART is associated with a cardioprotective lipid profile in Zambia and a tendency towards insulin resistance regardless of the cART regimen. PMID:23575345

2013-01-01

80

Smart Start News, 1999.  

ERIC Educational Resources Information Center

Smart Start is a comprehensive public-private initiative to help all North Carolina children enter school healthy and ready to succeed, and provides children from birth to age five access to high-quality and affordable child care, health care, and other critical services. This document comprises the first two issues of "Smart Start News," a…

Harris, Monica, Ed.

1999-01-01

81

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

NASA Astrophysics Data System (ADS)

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.

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

2013-10-01

82

Antiretroviral procurement and supply chain management.  

PubMed

Procurement, the country-level process of ordering antiretrovirals (ARVs), and supply chain management, the mechanism by which they are delivered to health-care facilities, are critical processes required to move ARVs from manufacturers to patients. To provide a glimpse into the ARV procurement and supply chain, the following pages provide an overview of the primary stakeholders, principal operating models, and policies and regulations involved in ARV procurement. Also presented are key challenges that need to be addressed to ensure that the supply chain is not a barrier to the goal of universal coverage. This article will cover the steps necessary to order and distribute ARVs, including different models of delivery, key stakeholders involved, strategic considerations that vary depending on context and policies affecting them. The single drug examples given illustrate the complications inherent in fragmented supply and demand-driven models of procurement and supply chain management, and suggest tools for navigating these hurdles that will ultimately result in more secure and reliable ARV provision. Understanding the dynamics of ARV supply chain is important for the global health community, both to ensure full and efficient treatment of persons living with HIV as well as to inform the supply chain decisions for other public health products. PMID:25310145

Ripin, David J; Jamieson, David; Meyers, Amy; Warty, Umesh; Dain, Mary; Khamsi, Cyril

2014-01-01

83

Starting a Small Business  

NSDL National Science Digital Library

This is the first of several lessons on starting a small business. This class is intended for adults entrepreneurs who may be thinking of starting a business. This lesson gives economic information on small businesses. It also provides information to help the student determine whether they are ready to be a business owner and whether their particular business could succeed. QUESTION: If you were to start a small business or home occupation, what would it be? Create a document giving a brief description of a potential business idea. (You will not be required to share the information with class members.) LESSON: Please read the following articles. 1. Go to the ...

Sonya Duke

2008-10-07

84

Suboptimal CD4 reconstitution despite viral suppression in an urban cohort on Antiretroviral Therapy (ART) in sub-Saharan Africa: Frequency and clinical significance  

Microsoft Academic Search

BACKGROUND: A proportion of individuals who start antiretroviral therapy (ART) fail to achieve adequate CD4 cell reconstitution despite sustained viral suppression. We determined the frequency and clinical significance of suboptimal CD4 reconstitution despite viral suppression (SO-CD4) in an urban HIV research cohort in Kampala, Uganda METHODS: We analyzed data from a prospective research cohort of 559 patients initiating ART between

Damalie Nakanjako; Agnes Kiragga; Fowzia Ibrahim; Barbara Castelnuovo; Moses R Kamya; Philippa J Easterbrook

2008-01-01

85

Start School Later  

NSDL National Science Digital Library

Last month, Pediatrics, the official journal of the American Academy of Pediatrics (AAP), issued a formal policy statement concerning School Start Times for Adolescents (http://pediatrics.aappublications.org/content/early/2014/08/19/peds.2014-1697.abstract?sid=3f739b0e-a552-4a4a-bd0a-907809e20255). In essence, the AAP called for schools to start later, citing sleep deprivation among teenagers as â??an important public health issue.â?ť This site from Start School Later, a group advocating for â??health, safety and equity in education,â?ť provides good, if somewhat one-sided, information on the topic. If youâ??re unfamiliar, start with Research & Info, which provides links to a number of informative sites about adolescent sleep needs and the impact of early school start times. Success Stories takes readers to schools around the country that have experimented with, and benefited from, later start times. If you're inspired, you can also Get Involved. Whatever your position on the issue, this is an informative and interesting site.

86

HIV and Perceptions of Mortality Risk: Learning from the Provision of Antiretroviral Therapy  

E-print Network

provision of antiretroviral therapies (ART), which dramatically slow the progression of the disease, has (CITE). Without receiving antiretroviral therapy (ART), a person who contracts HIV may live for 10HIV and Perceptions of Mortality Risk: Learning from the Provision of Antiretroviral Therapy

Mateo, Jill M.

87

Antiretroviral HIV treatment and care for injecting drug users: an evidence-based overview  

E-print Network

1 COMMENTARY Antiretroviral HIV treatment and care for injecting drug users: an evidence the advent of highly-active antiretroviral treatment (HAART). The overall benefit from antiretroviral HIV treatment has, however, been lesser in HIV-infected IDUs than in other patient groups (e.g. men who have sex

Paris-Sud XI, Université de

88

Quality of sleep: associations with antiretroviral nonadherence.  

PubMed

Poor quality of sleep (QOS) is frequently reported in HIV-positive individuals; however, despite its clinical and public health significance, few studies have examined the correlation between QOS and antiretroviral (ARV) adherence. The objective of this study was to estimate the prevalence of sleep disturbances, determine the characteristics of those with poor QOS, and establish the relationship between QOS and ARV nonadherence among HIV-positive individuals. We conducted a cross-sectional secondary data analysis of 2845 HIV-positive adults taking ARV therapy from the Healthy Living Project baseline cohort. Mean self-reported ARV nonadherence was estimated using a 3-day measure. QOS was assessed using three questions regarding sleep pattern changes, amount of bother from difficulty falling/staying asleep, and amount of bother from vivid dreams. Over 68% of individuals reported sleep pattern changes, 50.3% reported difficulty falling/staying asleep, and 20.5% reported bother from vivid dreams. Depression, suicidal ideation, unemployment, use of illicit substances, history of incarceration, and HIV viral load were all independently associated with poor QOS. Individuals reporting feeling bothered about difficulty falling/staying asleep had a 1.66 higher odds of nonadherence (95% confidence interval [CI]=1.18, 2.33; p=0.004). Those reporting the highest degree of bother from difficulty falling/staying asleep and from vivid dreams had a 1.42 (95% CI=1.13, 1.78; p=0.002) and 1.31 (95% CI=0.98, 1.75; p=0.07) higher odds of nonadherence, respectively. With higher incremental reports of poor QOS there were considerable increases in ARV nonadherence. Recognition and timely treatment of sleep difficulties may result in reduced ARV nonadherence with beneficial clinical and public health implications. PMID:21770763

Saberi, Parya; Neilands, Torsten B; Johnson, Mallory O

2011-09-01

89

In vivo assessment of antiretroviral therapy-associated side effects  

PubMed Central

Antiretroviral therapy has been associated with side effects, either from the drug itself or in conjunction with the effects of human immunodeficiency virus infection. Here, we evaluated the side effects of the protease inhibitor (PI) indinavir in hamsters consuming a normal or high-fat diet. Indinavir treatment increased the hamster death rate and resulted in an increase in triglyceride, cholesterol and glucose serum levels and a reduction in anti-oxLDL auto-antibodies. The treatment led to histopathological alterations of the kidney and the heart. These results suggest that hamsters are an interesting model for the study of the side effects of antiretroviral drugs, such as PIs. PMID:25075786

Ramos-Sanchez, Eduardo Milton; Goto, Hiro; Rivero, Dolores Helena Rodriguez Ferreira; Mauad, Thais; de Souza, Fernando Nogueira; Monteiro, Andrea Moreira; Gidlund, Magnus

2014-01-01

90

In vivo assessment of antiretroviral therapy-associated side effects.  

PubMed

Antiretroviral therapy has been associated with side effects, either from the drug itself or in conjunction with the effects of human immunodeficiency virus infection. Here, we evaluated the side effects of the protease inhibitor (PI) indinavir in hamsters consuming a normal or high-fat diet. Indinavir treatment increased the hamster death rate and resulted in an increase in triglyceride, cholesterol and glucose serum levels and a reduction in anti-oxLDL auto-antibodies. The treatment led to histopathological alterations of the kidney and the heart. These results suggest that hamsters are an interesting model for the study of the side effects of antiretroviral drugs, such as PIs. PMID:25075786

Ramos-Sanchez, Eduardo Milton; Goto, Hiro; Rivero, Dolores Helena Rodriguez Ferreira; Mauad, Thais; de Souza, Fernando Nogueira; Monteiro, Andrea Moreira; Gidlund, Magnus

2014-07-01

91

Ophthalmic manifestations of HIV in the highly active anti-retroviral therapy era.  

PubMed

HIV-related eye disease can be classified as retinal HIV microangiopathy, opportunistic infections, neuro-ophthalmic manifestations and unusual malignancies. There is a 52-100% lifetime accumulative risk of HIV patients developing eye problems. Seventy-seven per cent of patients with ocular manifestations of HIV had CD4 counts < 200 cells/?L. Cytomegalovirus (CMV) is the most prevalent opportunistic infection, however, Africa has a low incidence of this, and more commonly squamous cell carcinoma, compared to the western hemisphere. Due to highly active antiretroviral therapy (HAART), the anti-CMV therapy may be discontinued if the CD4+ T cell count is > 100 cells/?L for a minimum of three months. Despite HAART, patients with a CD4 count < 50 cells/?L have a similar risk of developing CMV retinitis as compared to the pre-HAART era. Opportunistic infections include CMV, herpetic retinopathy (progressive outer retinal necrosis - PORN), less commonly toxoplasmosis, pneumocystis and cryptococcus. Malignancies associated with HIV include Kaposi's sarcoma and conjunctival squamous cell carcinoma. Cranial nerve palsies, optic disc swelling and atrophy are characteristic neuro-ophthalmic features. They usually occur secondary to meningitis/encephalitis (from cryptococcus and tuberculosis). With the advent of HAART, new complications have developed in CMV retinitis: immune recovery uveitis (IRU) and cystoid macula oedema (CMO). Immune recovery uveitis occurs in 71% of patients if HAART is started before the induction of the anti-CMV treatment. However, this is reduced to 31% if HAART is started after the induction treatment. Molluscum contagiosum and Kaposi's sarcoma can spontaneously resolve on HAART. Highly active anti-retroviral therapy has reduced the frequencies of opportunistic infections and improved the remission duration in HIV patients. PMID:24756590

Mowatt, L

2013-01-01

92

The development of antiretroviral therapy and its impact on the HIV-1/AIDS pandemic  

PubMed Central

In the last 25 years, HIV-1, the retrovirus responsible for the Acquired Immunodeficiency Syndrome (AIDS), has gone from being an “inherently untreatable” infectious agent to one eminently susceptible to a range of approved therapies. During a five-year period, starting in the mid-1980s, my group at the National Cancer Institute played a role in the discovery and development of the first generation of antiretroviral agents, starting in 1985 with Retrovir® (zidovudine, AZT) in a collaboration with scientists at the Burroughs-Wellcome Company (now GlaxoSmithKline). We focused on AZT and related congeners in the dideoxynucleoside family of nucleoside reverse transcriptase inhibitors (NRTIs), taking them from the laboratory to the clinic in response to the pandemic of AIDS, then a terrifying and lethal disease. These drugs proved, above all else, that HIV-1 infection is treatable, and such proof provided momentum for new therapies from many sources, directed at a range of viral targets, at a pace that has rarely if ever been matched in modern drug development. Antiretroviral therapy has brought about a substantial decrease in the death rate due to HIV-1 infection, changing it from a rapidly lethal disease into a chronic manageable condition, compatible with very long survival. This has special implications within the classic boundaries of public health around the world, but at the same time in certain regions may also affect a cycle of economic and civil instability in which HIV-1/AIDS is both cause and consequence. Many challenges remain, including 1.) the life-long duration of therapy; 2.) the ultimate role of pre-exposure prophylaxis (PrEP); 3.) the cardiometabolic side effects or other toxicities of long-term therapy; 4.) the emergence of drug-resistance and viral genetic diversity (non-B subtypes); 5.) the specter of new cross-species transmissions from established retroviral reservoirs in apes and Old World monkeys; and 6.) the continued pace of new HIV-1 infections in many parts of the world. All of these factors make refining current therapies and developing new therapeutic paradigms essential priorities, topics covered in articles within this special issue of Antiviral Research. Fortunately, there are exciting new insights into the biology of HIV-1, its interaction with cellular resistance factors, and novel points of attack for future therapies. Moreover, it is a short journey from basic research to public health benefit around the world. The current science will lead to new therapeutic strategies with far-reaching implications in the HIV-1/AIDS pandemic. 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. PMID:20018391

Broder, Samuel

2010-01-01

93

The next generation of the World Health Organization's global antiretroviral guidance.  

PubMed

The 2013 World Health Organization's (WHO) Consolidated guidelines on the use of antiretroviral drugs for treating and preventing HIV infection provide more than 50 new recommendations across the continuum of HIV care, including recommendations on HIV testing, using antiretroviral drugs for prevention, linking individuals to HIV care and treatment services, initiating and maintaining antiretroviral therapy (ART) and monitoring treatment. Guidance is provided across all age groups and populations of adults, pregnant and breastfeeding women, adolescents and key populations. The guidelines are based on a public health approach to expanding the use of ARV drugs for HIV treatment and prevention, with a particular focus on resource-limited settings. The most important new clinical recommendations include: treating adults, adolescents and older children earlier - starting ART in all individuals with a CD4 cell count of 500 cells/mm(3) or less (but giving priority to those with advanced clinical disease or a CD4 cell count less than 350 cells/mm(3)); starting ART at any CD4 cell count in certain populations, including those with active TB (existing recommendation), Hepatitis B infection and severe chronic liver disease, HIV-positive partners in serodiscordant couples (existing recommendation), pregnant and breastfeeding women, and children younger than 5 years of age; a preferred first-line ART regimen of Tenofovir+3TC or FTC+ Efavirenz as a once-daily fixed-dose combination for adults, pregnant women, and children aged 3 years and older; and the use of viral load testing as the preferred approach to monitoring the response to ART and to diagnose treatment failure. Guidance is also provided on enhancing the efficiency and effectiveness of HIV services, including strategies to improve retention in care, and adherence to ART; task-shifting to address human resource gaps; decentralizing delivery of ART to primary health care, and integrating ART services within maternal and child health, TB or drug dependency clinics. There is additional guidance for programme managers on how to plan HIV programmes and use resources most efficiently. PMID:23819908

Hirnschall, Gottfried; Harries, Anthony D; Easterbrook, Philippa J; Doherty, Meg C; Ball, Andrew

2013-01-01

94

French 2013 guidelines for antiretroviral therapy of HIV-1 infection in adults  

PubMed Central

Introduction These guidelines are part of the French Experts’ recommendations for the management of people living with HIV/AIDS, which were made public and submitted to the French health authorities in September 2013. The objective was to provide updated recommendations for antiretroviral treatment (ART) of HIV-positive adults. Guidelines included the following topics: when to start, what to start, specific situations for the choice of the first session of antiretroviral therapy, optimization of antiretroviral therapy after virologic suppression, and management of virologic failure. Methods Ten members of the French HIV 2013 expert group were responsible for guidelines on ART. They systematically reviewed the most recent literature. The chairman of the subgroup was responsible for drafting the guidelines, which were subsequently discussed within, and finalized by the whole expert group to obtain a consensus. Recommendations were graded for strength and level of evidence using predefined criteria. Economic considerations were part of the decision-making process for selecting preferred first-line options. Potential conflicts of interest were actively managed throughout the whole process. Results ART should be initiated in any HIV-positive person, whatever his/her CD4 T-cell count, even when >500/mm3. The level of evidence of the individual benefit of ART in terms of mortality or progression to AIDS increases with decreasing CD4 cell count. Preferred initial regimens include two nucleoside reverse transcriptase inhibitors (tenofovir/emtricitabine or abacavir/lamivudine) plus a non-nucleoside reverse transcriptase inhibitor (efavirenz or rilpivirine), or a ritonavir-boosted protease inhibitor (atazanavir or darunavir). Raltegravir, lopinavir/r, and nevirapine are recommended as alternative third agents, with specific indications and restrictions. Specific situations such as HIV infection in women, primary HIV infection, severe immune suppression with or without identified opportunistic infection, and person who injects drugs are addressed. Options for optimization of ART once virologic suppression is achieved are discussed. Evaluation and management of virologic failure are described, the aim of any intervention in such situation being to reduce plasma viral load to <50 copies/ml. Conclusion These guidelines recommend that any HIV-positive individual should be treated with ART. This recommendation was issued both for the patient’s own sake and for promoting treatment as prevention. PMID:24942364

Hoen, Bruno; Bonnet, Fabrice; Delaugerre, Constance; Delobel, Pierre; Goujard, Cécile; L’Hénaff, Marianne; Persiaux, Renaud; Rey, David; Rouzioux, Christine; Taburet, Anne-Marie; Morlat, Philippe

2014-01-01

95

The next generation of the World Health Organization's global antiretroviral guidance  

PubMed Central

The 2013 World Health Organization’s (WHO) Consolidated guidelines on the use of antiretroviral drugs for treating and preventing HIV infection provide more than 50 new recommendations across the continuum of HIV care, including recommendations on HIV testing, using antiretroviral drugs for prevention, linking individuals to HIV care and treatment services, initiating and maintaining antiretroviral therapy (ART) and monitoring treatment. Guidance is provided across all age groups and populations of adults, pregnant and breastfeeding women, adolescents and key populations. The guidelines are based on a public health approach to expanding the use of ARV drugs for HIV treatment and prevention, with a particular focus on resource-limited settings. The most important new clinical recommendations include: treating adults, adolescents and older children earlier – starting ART in all individuals with a CD4 cell count of 500 cells/mm3 or less (but giving priority to those with advanced clinical disease or a CD4 cell count less than 350 cells/mm3); starting ART at any CD4 cell count in certain populations, including those with active TB (existing recommendation), Hepatitis B infection and severe chronic liver disease, HIV-positive partners in serodiscordant couples (existing recommendation), pregnant and breastfeeding women, and children younger than 5 years of age; a preferred first-line ART regimen of Tenofovir+3TC or FTC+ Efavirenz as a once-daily fixed-dose combination for adults, pregnant women, and children aged 3 years and older; and the use of viral load testing as the preferred approach to monitoring the response to ART and to diagnose treatment failure. Guidance is also provided on enhancing the efficiency and effectiveness of HIV services, including strategies to improve retention in care, and adherence to ART; task-shifting to address human resource gaps; decentralizing delivery of ART to primary health care, and integrating ART services within maternal and child health, TB or drug dependency clinics. There is additional guidance for programme managers on how to plan HIV programmes and use resources most efficiently. PMID:23819908

Hirnschall, Gottfried; Harries, Anthony D; Easterbrook, Philippa J; Doherty, Meg C; Ball, Andrew

2013-01-01

96

Antiretroviral therapy in Zambia: colours, 'spoiling', 'talk' and the meaning of antiretrovirals.  

PubMed

We examine responses to the roll-out of antiretroviral drugs (ARVs) in Zambia in 2004, focusing on material features of the drugs (colour, shape, size, origin), 'spoiling' (concern about toxicity, side effects of the drugs) and rumours ('talk' about the drugs). Data consists of interviews with 10 people living with HIV and 21 healthcare practitioners. We found that the colour symbolism of 'traditional medicine' has some influence on ideas about ARVs, suggesting possible 'meaning responses' that could affect treatment outcomes. Respondents also become concerned when colours, shapes and side effects differ from expectations. 'Talk' about ARVs concerns risks of medication, sustainability of treatment programmes and people's feelings of vulnerability within larger socio-economic contexts in which countries like Zambia are disadvantaged. Understanding the associations that pharmaceuticals evoke can improve treatment programmes by elucidating public and patient concerns and sensitising healthcare professionals to the historical and political circumstances that condition the 'meaning' of ARVs. PMID:18952338

Schumaker, Lynette Louise; Bond, Virginia A

2008-12-01

97

QUICK START Installing Outlook  

E-print Network

to set it up for the first time. First check that Outlook is installed but don't open it yet. From report that your e-mail account is configured. Tick the box to Manually configure server settings to download all of your mail the first time you use it. 1 2 Getting started Check that you are set up

Sussex, University of

98

Starting in School  

ERIC Educational Resources Information Center

Through its signature initiative, Liberal Education and America's Promise (LEAP), the Association of American Colleges and Universities (AAC&U) is promoting a vision for learning that begins in school: Starting in School . . . Rigorous and rich curriculum focused on the essential learning outcomes; comprehensive, individualized, and…

Albertine, Susan

2012-01-01

99

Head Start Blues.  

ERIC Educational Resources Information Center

Noting that many students' experiences with police officers is negative, Heartland Programs Head Start in Salina, Kansas, initiated the Cop Day Program to develop a positive image of law enforcement. Police officer participated in classroom activities at the teachers' discretion once a month. Teachers and administrators noticed improvement in…

Hoffman, Stephen M.

1998-01-01

100

Start a Rock Collection  

NSDL National Science Digital Library

Learners follow a three-step process to start their own rock collection. Learners will collect rocks, record information about each rock on a Rock Chart, observe and sort their rocks, and create a rock display. This activity also includes a book list with resources for rock classification.

2012-06-26

101

Starting an Investment Club  

E-print Network

An investment club is a group of people who learn about investments together and pool their money to purchase stocks or bonds. Learn how to start such a club, how to manage the tax aspects of joint investments, and how to benefit from club...

Johnson, Jason; Thompson, Bill; Polk, Wade

2002-08-12

102

PAINTING CHECKLIST GETTING STARTED  

E-print Network

PAINTING CHECKLIST GETTING STARTED o Choose your colour scheme o Test colours using sample pots o Measure the area to be painted · Choose paint finish, matt, semi-gloss, gloss etc · Type of paint to use, water-based etc · State of repair of current surface · Painting over oil-based/gloss paint or wallpaper

Peters, Richard

103

StartMe  

NSDL National Science Digital Library

The StartMe application gives Internet users the opportunity to create their own personal browser startpage with their favorite bookmarks and RSS feeds. The drag and drop interface is user-friendly, particularly for computer neophytes. Visitors can also incorporate extensions for popular browsers or tweak the appearance of their startpage as they see fit. This version is compatible with all operating systems.

104

Home Start Evaluation Study.  

ERIC Educational Resources Information Center

Case studies of seven Home Start programs are given as the third section of an evaluation study. Communities involved are Huntsville, Alabama; Fairbanks, Alaska; Fort Defiance, Arizona; Dardanelle, Arkansas; Wichita, Kansas; Gloucester, Massachusetts; and Reno, Nevada. Although each study varies in format, each describes in detail the degree and…

High/Scope Educational Research Foundation, Ypsilanti, MI.

105

Physician Specialization and Antiretroviral Therapy for HIV  

PubMed Central

BACKGROUND Since the introduction of the first protease inhibitor in January 1996, there has been a dramatic change in the treatment of persons infected with HIV. The changing nature of HIV care has important implications for the types of physicians that can best care for patients with HIV infection. OBJECTIVE To assess the association of specialty training and experience in the care of HIV disease with the adoption and use of highly active antiretroviral (ARV) therapy (HAART). DESIGN Observational cohort study of patients under care for HIV infection and their physicians. PATIENTS AND SETTING This analysis used data collected from a national probability sample of noninstitutionalized persons with HIV infection participating in the HIV Costs and Service Utilization Study and their primary physicians. We analyzed 1,820 patients being cared for by 374 physicians. MEASUREMENTS Rates of HAART use at 12 months and 18 months after the approval of the first protease inhibitor. RESULTS Forty percent of the physicians were formally trained in infectious diseases (ID), 38% were general medicine physicians with self-reported expertise in the care of HIV, and 22% were general medicine physicians without self-reported expertise in the care of HIV. The majority of physicians (69%) reported a current HIV caseload of 50 patients or more. In multivariable models controlling for patient characteristics, there were no differences between generalist experts and ID physicians in rates of HAART use in December 1996. When compared to ID physicians, however, patients being treated by non-expert general medicine physicians were less likely to be on HAART (odds ratio [OR], 0.32; 95% confidence interval [95% CI], 0.17 to 0.61). Patients being treated by low-volume physicians were also much less likely to be on HAART therapy than those treated by high-volume physicians (OR, 0.26; 95% CI, 0.14 to 0.48). These findings were attenuated by June 1997, suggesting that over time, the broader physician community successfully adopted HAART therapy. This finding is consistent with prior research on the diffusion of innovations. CONCLUSIONS Similar proportions of patients treated by expert generalists and ID specialists were on appropriate HAART therapy by December 1996 and July 1997. Patients treated by non-expert generalists, most of whom were the lowest-volume physicians, were much less likely to be on appropriate ARV therapy in the earlier time period. Our findings demonstrate that expert generalists who develop specialized expertise are able to provide care of quality comparable to that of specialists. PMID:12709089

Landon, Bruce E; Wilson, Ira B; Cohn, Susan E; Fichtenbaum, Carl J; Wong, Mitchell D; Wenger, Neil S; Bozzette, Samuel A; Shapiro, Martin F; Cleary, Paul D

2003-01-01

106

The emergence of drug resistant HIV variants and novel anti-retroviral therapy  

PubMed Central

After its identification in 1980s, HIV has infected more than 30 million people worldwide. In the era of highly active anti-retroviral therapy, anti-retroviral drug resistance results from insufficient anti-retroviral pressure, which may lead to treatment failure. Preliminary studies support the idea that anti-retroviral drug resistance has evolved largely as a result of low-adherence of patients to therapy and extensive use of anti-retroviral drugs in the developed world; however, a highly heterogeneous horde of viral quasi-species are currently circulating in developing nations. Thus, the prioritizing of strategies adopted in such two worlds should be quite different considering the varying anti-retroviral drug resistance prevalence. In this article, we explore differences in anti-retroviral drug resistance patterns between developed and developing countries, as they represent two distinct ecological niches of HIV from an evolutionary standpoint. PMID:23835806

Paydary, Koosha; Khaghani, Parisa; Emamzadeh-Fard, Sahra; Alinaghi, Seyed Ahmad Seyed; Baesi, Kazem

2013-01-01

107

Implementation and Effectiveness of Antiretroviral Therapy in Greenland  

PubMed Central

Analyses from the Danish HIV Cohort Study showed that, despite comparable economic means and general education of healthcare personnel, antiretroviral treatment of HIV in Greenland began later and has been implemented at a slower pace with lower therapeutic effectiveness than in Denmark. However, implementation and quality of care improved considerably in recent years. PMID:18258077

Ladefoged, Karin; Obel, Niels

2008-01-01

108

Neurological and psychiatric adverse effects of antiretroviral drugs.  

PubMed

Antiretroviral drugs are associated with a variety of adverse effects on the central and peripheral nervous systems. The frequency and severity of neuropsychiatric adverse events is highly variable, with differences between the antiretroviral classes and amongst the individual drugs in each class. In the developing world, where the nucleoside reverse transcriptase inhibitor (NRTI) stavudine remains a commonly prescribed antiretroviral, peripheral neuropathy is an important complication of treatment. Importantly, this clinical entity is often difficult to distinguish from human immunodeficiency virus (HIV)-induced peripheral neuropathy. Several clinical trials have addressed the efficacy of various agents in the treatment of NRTI-induced neurotoxicity. NRTI-induced neurotoxicity is caused by inhibition of mitochondrial DNA polymerase. This mechanism is also responsible for the mitochondrial myopathy and lactic acidosis that occur with zidovudine. NRTIs, particularly zidovudine and abacavir, may also cause central nervous system (CNS) manifestations, including mania and psychosis. The non-nucleoside reverse transcriptase inhibitor (NNRTI) efavirenz is perhaps the antiretroviral most commonly associated with CNS toxicity, causing insomnia, irritability and vivid dreams. Recent studies have suggested that the risk of developing these adverse effects is increased in patients with various cytochrome P450 2B6 alleles. Protease inhibitors cause perioral paraesthesias and may indirectly increase the relative risk of stroke by promoting atherogenesis. HIV integrase inhibitors, C-C chemokine receptor type 5 (CCR5) inhibitors and fusion inhibitors rarely cause neuropsychiatric manifestations. PMID:24362768

Abers, Michael S; Shandera, Wayne X; Kass, Joseph S

2014-02-01

109

The toxicogenetics of antiretroviral therapy: the evil inside.  

PubMed

The most important factor limiting the success of an antiretroviral therapy regimes is toxicity. Toxicity can depend on a number of factors; some of these are intrinsic to the host and may not only affect the latter's outward appearance, but also determine the intensity these toxic effects may reach. The former is exemplified by idiosyncratic or hypersensitivity reactions, whereas the latter is usually appreciated in metabolic disturbances or fat redistribution syndromes. Some of the determinants of antiretroviral toxicity are genetic in origin and have been the subject of intense study in recent years. Some of these are linked to a single nucleotide polymorphism (SNP), whereas others depend on a complex interaction between multiple genes variations. One of these tests (HLA B*5701) is now being applied in clinical practice and widely used to prevent the risk of hypersensitivity reactions to abacavir. Many other genetic determinants of antiretroviral drug toxicity have been suggested as an explanation for nucleoside analogue toxicity; these include lactic acidosis, peripheral neuropathy and pancreatitis, and have also been suggested as a potential basis for the non-nucleoside toxicity derived from immunogenetic factors involved in nevirapine hypersensitivity to SNPs in efavirenz enzyme metabolism, amongst other things. Metabolic toxicity, mainly due to protease inhibitors (PIs) is far more complex and depends on the interaction of various genes. The same seems to be true for fat redistribution syndromes and atherosclerosis, although a clear picture of the genetic factors operating in these syndromes is yet to emerge. The ultimate goal of pharmacogenetics is to customize antiretroviral therapy by identifying the genes that can maximize efficacy whilst helping avoid known side effects of antiretroviral drugs. PMID:21110805

Gutierrez, Maria del M; Mateo, M G; Vidal, F; Domingo, P

2011-01-01

110

Pharmacokinetic and pharmacodynamic drug interactions between antiretrovirals and oral contraceptives.  

PubMed

More than 50 % of women living with HIV in low- and middle-income countries are of reproductive age, but there are limitations to the administration of oral contraception for HIV-infected women receiving antiretroviral therapy due to drug-drug interactions caused by metabolism via the cytochrome P450 isoenzymes and glucuronidation. However, with the development of newer antiretrovirals that use alternative metabolic pathways, options for contraception in HIV-positive women are increasing. This paper aims to review the literature on the pharmacokinetics and pharmacodynamics of oral hormonal contraceptives when given with antiretroviral agents, including those currently used in developed countries, older ones that might still be used in salvage regimens, or those used in resource-limited settings, as well as newer drugs. Nucleos(t)ide reverse transcriptase inhibitors (NRTIs), the usual backbone to most combined antiretroviral treatments (cARTs) are characterised by a low potential for drug-drug interactions with oral contraceptives. On the other hand non-NRTIs (NNRTIs) and protease inhibitors (PIs) may interact with oral contraceptives. Of the NNRTIs, efavirenz and nevirapine have been demonstrated to cause drug-drug interactions; however, etravirine and rilpivirine appear safe to use without dose adjustment. PIs boosted with ritonavir are not recommended to be used with oral contraceptives, with the exception of boosted atazanavir which should be used with doses of at least 35 µg of estrogen. Maraviroc, an entry inhibitor, is safe for co-administration with oral contraceptives, as are the integrase inhibitors (INIs) raltegravir and dolutegravir. However, the INI elvitegravir, which is given in combination with cobicistat, requires a dose of estrogen of at least 30 µg. Despite the growing evidence in this field, data are still lacking in terms of large cohort studies, randomised trials and correlations to real clinical outcomes, such as pregnancy rates, in women on antiretrovirals and hormonal contraception. PMID:25331712

Tittle, Victoria; Bull, Lauren; Boffito, Marta; Nwokolo, Nneka

2015-01-01

111

Importance of Baseline Prognostic Factors With Increasing Time Since Initiation of Highly Active Antiretroviral Therapy  

PubMed Central

Background The extent to which the prognosis for AIDS and death of patients initiating highly active antiretroviral therapy (HAART) continues to be affected by their characteristics at the time of initiation (baseline) is unclear. Methods We analyzed data on 20,379 treatment-naive HIV-1–infected adults who started HAART in 1 of 12 cohort studies in Europe and North America (61,798 person-years of follow-up, 1844 AIDS events, and 1005 deaths). Results Although baseline CD4 cell count became less prognostic with time, individuals with a baseline CD4 count <25 cells/µL had persistently higher progression rates than individuals with a baseline CD4 count >350 cells/µL (hazard ratio for AIDS = 2.3, 95% confidence interval [CI]: 1.0 to 2.3; mortality hazard ratio = 2.5, 95% CI: 1.2 to 5.5, 4 to 6 years after starting HAART). Rates of AIDS were persistently higher in individuals who had experienced an AIDS event before starting HAART. Individuals with presumed transmission by means of injection drug use experienced substantially higher rates of AIDS and death than other individuals throughout follow-up (AIDS hazard ratio = 1.6, 95% CI: 0.8 to 3.0; mortality hazard ratio = 3.5, 95% CI: 2.2 to 5.5, 4 to 6 years after starting HAART). Conclusions Compared with other patient groups, injection drug users and patients with advanced immunodeficiency at baseline experience substantially increased rates of AIDS and death up to 6 years after starting HAART. PMID:18043315

2012-01-01

112

A Start-up company to start your career  

E-print Network

is not a `for-profit' business · But still must recoup costs · Harvard typically takes ~8% in equity · CompanyA Start-up company to start your career Professional Development Seminar March 6, 2013 #12;What is a start-up company? · Small, just started · Typically 1-5 years old · Often no products, no sales

113

Enhanced antiretroviral therapy in rhesus macaques improves RT-SHIV viral decay kinetics.  

PubMed

Using an established nonhuman primate model, rhesus macaques were infected intravenously with a chimeric simian immunodeficiency virus (SIV) consisting of SIVmac239 with the human immunodeficiency virus type 1 (HIV-1) reverse transcriptase from clone HXBc2 (RT-SHIV). The impacts of two enhanced (four- and five-drug) highly active antiretroviral therapies (HAART) on early viral decay and rebound were determined. The four-drug combination consisted of an integrase inhibitor, L-870-812 (L-812), together with a three-drug regimen comprising emtricitabine [(-)-FTC], tenofovir (TFV), and efavirenz (EFV). The five-drug combination consisted of one analog for each of the four DNA precursors {using TFV, (-)-FTC, (-)-?-D-(2R,4R)-1,3-dioxolane-2,6-diaminopurine (amdoxovir [DAPD]), and zidovudine (AZT)}, together with EFV. A cohort treated with a three-drug combination of (-)-FTC, TFV, and EFV served as treated controls. Daily administration of a three-, four-, or five-drug combination of antiretroviral agents was initiated at week 6 or 8 after inoculation and continued up to week 50, followed by a rebound period. Plasma samples were collected routinely, and drug levels were monitored using liquid chromatography-tandem mass spectrometry (LC-MS-MS). Viral loads were monitored with a standard TaqMan quantitative reverse transcriptase PCR (qRT-PCR) assay. Comprehensive analyses of replication dynamics were performed. RT-SHIV infection in rhesus macaques produced typical viral infection kinetics, with untreated controls establishing persistent viral loads of >10(4) copies of RNA/ml. RT-SHIV loads at the start of treatment (V0) were similar in all treated cohorts (P > 0.5). All antiretroviral drug levels were measureable in plasma. The four-drug and five-drug combination regimens (enhanced HAART) improved suppression of the viral load (within 1 week; P < 0.01) and had overall greater potency (P < 0.02) than the three-drug regimen (HAART). Moreover, rebound viremia occurred rapidly following cessation of any treatment. The enhanced HAART (four- or five-drug combination) showed significant improvement in viral suppression compared to the three-drug combination, but no combination was sufficient to eliminate viral reservoirs. PMID:24777106

North, Thomas W; Villalobos, Andradi; Hurwitz, Selwyn J; Deere, Jesse D; Higgins, Joanne; Chatterjee, Payel; Tao, Sijia; Kauffman, Robert C; Luciw, Paul A; Kohler, James J; Schinazi, Raymond F

2014-07-01

114

Enhanced Antiretroviral Therapy in Rhesus Macaques Improves RT-SHIV Viral Decay Kinetics  

PubMed Central

Using an established nonhuman primate model, rhesus macaques were infected intravenously with a chimeric simian immunodeficiency virus (SIV) consisting of SIVmac239 with the human immunodeficiency virus type 1 (HIV-1) reverse transcriptase from clone HXBc2 (RT-SHIV). The impacts of two enhanced (four- and five-drug) highly active antiretroviral therapies (HAART) on early viral decay and rebound were determined. The four-drug combination consisted of an integrase inhibitor, L-870-812 (L-812), together with a three-drug regimen comprising emtricitabine [(?)-FTC], tenofovir (TFV), and efavirenz (EFV). The five-drug combination consisted of one analog for each of the four DNA precursors {using TFV, (?)-FTC, (?)-?-d-(2R,4R)-1,3-dioxolane-2,6-diaminopurine (amdoxovir [DAPD]), and zidovudine (AZT)}, together with EFV. A cohort treated with a three-drug combination of (?)-FTC, TFV, and EFV served as treated controls. Daily administration of a three-, four-, or five-drug combination of antiretroviral agents was initiated at week 6 or 8 after inoculation and continued up to week 50, followed by a rebound period. Plasma samples were collected routinely, and drug levels were monitored using liquid chromatography-tandem mass spectrometry (LC–MS-MS). Viral loads were monitored with a standard TaqMan quantitative reverse transcriptase PCR (qRT-PCR) assay. Comprehensive analyses of replication dynamics were performed. RT-SHIV infection in rhesus macaques produced typical viral infection kinetics, with untreated controls establishing persistent viral loads of >104 copies of RNA/ml. RT-SHIV loads at the start of treatment (V0) were similar in all treated cohorts (P > 0.5). All antiretroviral drug levels were measureable in plasma. The four-drug and five-drug combination regimens (enhanced HAART) improved suppression of the viral load (within 1 week; P < 0.01) and had overall greater potency (P < 0.02) than the three-drug regimen (HAART). Moreover, rebound viremia occurred rapidly following cessation of any treatment. The enhanced HAART (four- or five-drug combination) showed significant improvement in viral suppression compared to the three-drug combination, but no combination was sufficient to eliminate viral reservoirs. PMID:24777106

North, Thomas W.; Villalobos, Andradi; Hurwitz, Selwyn J.; Deere, Jesse D.; Higgins, Joanne; Chatterjee, Payel; Tao, Sijia; Kauffman, Robert C.; Luciw, Paul A.; Kohler, James J.

2014-01-01

115

Antiretroviral effect of lovastatin on HIV1-infected individuals without highly active antiretroviral therapy (The LIVE study): a phase-II randomized clinical trial  

Microsoft Academic Search

BACKGROUND: Highly active antiretroviral therapy produces a significant decrease in HIV-1 replication and allows an increase in the CD4 T-cell count, leading to a decrease in the incidence of opportunistic infections and mortality. However, the cost, side effects and complexity of antiretroviral regimens have underscored the immediate need for additional therapeutic approaches. Statins exert pleiotropic effects through a variety of

Carlos J Montoya; Fabian Jaimes; Edwin A Higuita; Sandra Convers-Páez; Santiago Estrada; Francisco Gutierrez; Pedro Amariles; Newar Giraldo; Cristina Peńaloza; Maria T Rugeles

2009-01-01

116

Impact of HIV type 1 genetic subtype on the outcome of antiretroviral therapy.  

PubMed

The objective of this study was to investigate the short-term virological outcome of antiretroviral combination therapy (ART) in relation to infection with different HIV-1 genetic subtypes. Antiretroviral drug-naive patients in Sweden were prospectively enrolled and followed for 6 months when starting ART in the period from January 1998 to January 2002. Plasma-HIV-1 RNA levels, CD4 counts, and type of ART regimen were recorded. The HIV-1 subtype was determined by direct sequencing of regions of the env or pol genes. Data from 172 patients who harbored subtypes A, B, C, D, G, and CRF01_AE were analyzed (32 A, 44 B, 34 C, 18 D, 5 G, and 19 CRF01_AE). Of all patients 84% had undetectable plasma HIV-1 RNA levels after 6 months of ART. Patients infected with CRF01_AE more often had undetectable HIV-1 RNA plasma levels than patients infected with subtypes A or D. However, the possibility that this difference is due to ethnicity cannot be ruled out. Of patients of African origin, 77% had undetectable viral load after 6 months of treatment, while the corresponding figures for Caucasians and Asians were 91% and 100%, respectively. Thus, we have found an overall good short-term virological outcome after the initiation of ART in a cohort of ARV-naive patients of diverse ethnic background infected with different HIV-1 genetic subtypes. In univariate analysis ethnicity, but not genetic subtype, correlated with virological response. However, the impact of ethnicity was moderate. Patients of African origin, who had the poorest outcome, showed a 77% virological response rate. PMID:15795528

Atlas, Ann; Granath, Fredrik; Lindström, Anna; Lidman, Knut; Lindbäck, Stefan; Alaeus, Annette

2005-03-01

117

StartUpNation  

NSDL National Science Digital Library

It would seem that more and more people are interested in developing their own business, and a number of websites are dedicated to helping these persons achieve that goal. One valuable website in that realm is StartUpNation. Created by Jeff and Rich Sloan, the site contains a well-designed homepage that includes links to sections dedicated to areas of interest to the prospective entrepreneur, including those that deal with customer service and creating strategic marketing plans. A good place to start is the â??Lean from the Expertsâ?ť area, located on the left-hand side of the homepage. Here, visitors can learn from successful individuals, such as Glenn Coggeshell of Black Dot Coffee. Along the same side, visitors can also read about how to choose a business for themselves and also how to plan to make this business a reality. In keeping with the times, the site also affords users the opportunity to sign up for RSS feeds and the ability to listen (and download) a number of podcasts.

118

Missouri: Early Head Start Initiative  

ERIC Educational Resources Information Center

Missouri's Early Head Start/Child Care Partnership Project expands access to Early Head Start (EHS) services for children birth to age 3 by developing partnerships between federal Head Start, EHS contractors, and child care providers. Head Start and EHS contractors that participate in the initiative provide services through community child care…

Center for Law and Social Policy, Inc. (CLASP), 2012

2012-01-01

119

Minnesota: Early Head Start Initiatiive  

ERIC Educational Resources Information Center

Minnesota provides supplemental state funding to existing federal Head Start and Early Head Start (EHS) grantees to increase their capacity to serve additional infants, toddlers, and pregnant women. The initiative was started in 1997 when the state legislature earmarked $1 million of the general state Head Start supplemental funds for children…

Center for Law and Social Policy, Inc. (CLASP), 2012

2012-01-01

120

Cotrimoxazole prophylaxis and antiretroviral therapy: an observational cohort study in China  

PubMed Central

Abstract Objective To assess if cotrimoxazole prophylaxis administered early during antiretroviral therapy (ART) reduces mortality in Chinese adults who are infected with human immunodeficiency virus (HIV). Methods We did a retrospective observational cohort study using data from the Chinese national free antiretroviral database. Patients older than 14 years who started ART between 1 January 2010 and 31 December 2012 and had baseline CD4+ T-lymphocyte (CD4+ cell) count less than 200 cells/µL were followed until death, loss to follow-up or 31 December 2013. Hazard ratios (HRs) for several variables were calculated using multivariate analyses. Findings The analysis involved 23?816 HIV-infected patients, 2706 of whom died during the follow-up. Mortality in patients who did and did not start cotrimoxazole during the first 6 months of ART was 5.3 and 7.0 per 100 person–years, respectively. Cotrimoxazole was associated with a 37% reduction in mortality (hazard ratio, HR: 0.63; 95% confidence interval, CI: 0.56–0.70). Cotrimoxazole in addition to ART reduced mortality significantly over follow-up lasting 6 months (HR: 0.65; 95% CI: 0.59–0.73), 12 months (HR: 0.58; 95% CI: 0.49–0.70), 18 months (HR: 0.49; 95% CI: 0.38–0.63) and 24 months (HR: 0.66; 95% CI: 0.48–0.90). The mortality reduction was evident in patients with baseline CD4+ cell counts less than 50 cells/µL (HR: 0.60; 95% CI: 0.54–0.67), 50–99 cells/µL (HR: 0.66; 95% CI: 0.56–0.78) and 100–199 cells/µL (HR: 0.78; 95% CI: 0.62–0.98). Conclusion Cotrimoxazole prophylaxis started early during ART reduced mortality and should be offered to HIV-infected patients in low- and middle-income countries.

Cheng, Wei; Wu, Yasong; Wen, Yi; Ma, Ye; Zhao, Decai; Dou, Zhihui; Zhang, Weiwei; Bulterys, Marc

2015-01-01

121

Long-Term Antiretroviral Treatment Initiated at Primary HIV-1 Infection Affects the Size, Composition, and Decay Kinetics of the Reservoir of HIV-1-Infected CD4 T Cells  

PubMed Central

ABSTRACT Initiation of antiretroviral therapy during the earliest stages of HIV-1 infection may limit the seeding of a long-lasting viral reservoir, but long-term effects of early antiretroviral treatment initiation remain unknown. Here, we analyzed immunological and virological characteristics of nine patients who started antiretroviral therapy at primary HIV-1 infection and remained on suppressive treatment for >10 years; patients with similar treatment duration but initiation of suppressive therapy during chronic HIV-1 infection served as controls. We observed that independently of the timing of treatment initiation, HIV-1 DNA in CD4 T cells decayed primarily during the initial 3 to 4 years of treatment. However, in patients who started antiretroviral therapy in early infection, this decay occurred faster and was more pronounced, leading to substantially lower levels of cell-associated HIV-1 DNA after long-term treatment. Despite this smaller size, the viral CD4 T cell reservoir in persons with early treatment initiation consisted more dominantly of the long-lasting central-memory and T memory stem cells. HIV-1-specific T cell responses remained continuously detectable during antiretroviral therapy, independently of the timing of treatment initiation. Together, these data suggest that early HIV-1 treatment initiation, even when continued for >10 years, is unlikely to lead to viral eradication, but the presence of low viral reservoirs and durable HIV-1 T cell responses may make such patients good candidates for future interventional studies aiming at HIV-1 eradication and cure. IMPORTANCE Antiretroviral therapy can effectively suppress HIV-1 replication to undetectable levels; however, HIV-1 can persist despite treatment, and viral replication rapidly rebounds when treatment is discontinued. This is mainly due to the presence of latently infected CD4 T cells, which are not susceptible to antiretroviral drugs. Starting treatment in the earliest stages of HIV-1 infection can limit the number of these latently infected cells, raising the possibility that these viral reservoirs are naturally eliminated if suppressive antiretroviral treatment is continued for extremely long periods of time. Here, we analyzed nine patients who started on antiretroviral therapy within the earliest weeks of the disease and continued treatment for more than 10 years. Our data show that early treatment accelerated the decay of infected CD4 T cells and led to very low residual levels of detectable HIV-1 after long-term therapy, levels that were otherwise detectable in patients who are able to maintain a spontaneous, drug-free control of HIV-1 replication. Thus, long-term antiretroviral treatment started during early infection cannot eliminate HIV-1, but the reduced reservoirs of HIV-1 infected cells in such patients may increase their chances to respond to clinical interventions aiming at inducing a drug-free remission of HIV-1 infection. PMID:24965451

Buzon, Maria J.; Martin-Gayo, Enrique; Pereyra, Florencia; Ouyang, Zhengyu; Sun, Hong; Li, Jonathan Z.; Piovoso, Michael; Shaw, Amy; Dalmau, Judith; Zangger, Nadine; Martinez-Picado, Javier; Zurakowski, Ryan; Yu, Xu G.; Telenti, Amalio; Walker, Bruce D.; Rosenberg, Eric S.

2014-01-01

122

Long-Term CD4+ Cell Count in Response to Combination Antiretroviral Therapy  

PubMed Central

Objective There is a continuous debate on how to adequately evaluate long-term CD4+ cell count in response to combination antiretroviral therapy (ART) among human immunodeficiency virus (HIV)-infected individuals. Our study evaluated the long-term CD4+ cell count response (up to ten years) after initiation of ART and described the differences in the CD4+ cell count response stratified by pretreatment CD4+ cell count, and other socio-demographic, behavioral, and clinical factors. Methods The study population included patients starting ART in the clinical cohorts of Rio de Janeiro, Brazil, and Baltimore, United States. Inverse probability of censoring weighting was used to estimate mean annual CD4+ cell counts while adjusting for choice of initial ART regimen, ART discontinuation and losses-to-follow-up. Results From 1997 to 2011, 3116 individuals started ART; preferred initial regimen was NNRTI-based (63%). The median follow-up time was 5 years, 10% of the individuals had nine or more years of follow-up. Observed CD4+ cell counts increased throughout the ten years of follow-up. Weighted results, in contrast, increased up to year four and plateaued thereafter with 50% of the population reaching CD4+ cell counts of 449/?L or more. Out of all stratification variables considered, only individuals with pre-treatment CD4+ cell counts ?350/?L showed increasing CD4+ cell counts over time with 76% surpassing the CD4+ cell count >500/?L threshold at year ten. Conclusion The present study corroborates the growing body of knowledge advocating early start of ART by showing that only patients who start ART early fully recover to normal CD4+ cell counts. PMID:24695533

Luz, Paula M.; Grinsztejn, Beatriz; Velasque, Luciane; Pacheco, Antonio G.; Veloso, Valdilea G.; Moore, Richard D.; Struchiner, Claudio J.

2014-01-01

123

Growth response to antiretroviral treatment in HIV-infected children: A cohort study from Lilongwe, Malawi  

PubMed Central

Summary Objective Malnutrition is common in HIV-infected children in Africa and an indication for antiretroviral treatment (ART). We examined anthropometric status and response to ART in children treated at a large public-sector clinic in Malawi. Methods All children aged <15 years who started ART between January 2001 and December 2006 were included and followed until March 2008. Weight and height were measured at regular intervals from 1 year before to 2 years after the start of ART. Sex- and age-standardized z-scores were calculated for weight-for-age (WAZ) and height-for-age (HAZ). Predictors of growth were identified in multivariable mixed-effect models. Results A total of 497 children started ART and were followed for 972 person-years. Median age (inter-quartile range; IQR) was 8 years (4 to 11 years). Most children were underweight (52% of children), stunted (69%), in advanced clinical stages (94% in WHO stages 3 or 4) and had severe immunodeficiency (77%). After starting ART median (IQR) WAZ and HAZ increased from ?2.1 (?2.7 to ?1.3) and ?2.6 (?3.6 to ?1.8) to ?1.4 (?2.1 to ?0.8) and ?1.8 (?2.4 to ?1.1) at 24 months, respectively (p<0.001). In multivariable models, baseline WAZ and HAZ scores were the most important determinants of growth trajectories on ART. Conclusions Despite a sustained growth response to ART among children remaining on therapy, normal values were not reached. Interventions leading to earlier HIV diagnosis and initiation of treatment could improve growth response. PMID:20561308

Weigel, Ralf; Phiri, Sam; Chiputula, Fred; Gumulira, Joe; Brinkhof, Martin; Gsponer, Thomas; Tweya, Hannock; Egger, Matthias; Keiser, Olivia

2013-01-01

124

Did Universal Access to ARVT in Mexico Impact Suboptimal Antiretroviral Prescriptions?  

PubMed Central

Background. Universal access to antiretroviral therapy (ARVT) started in Mexico in 2001; no evaluation of the features of ARVT prescriptions over time has been conducted. The aim of the study is to document trends in the quality of ARVT-prescription before and after universal access. Methods. We describe ARVT prescriptions before and after 2001 in three health facilities from the following subsystems: the Mexican Social Security (IMSS), the Ministry of Health (SSA), and National Institutes of Health (INS). Combinations of drugs and reasons for change were classified according to current Mexican guidelines and state-of-the-art therapy. Comparisons were made using ?2 tests. Results. Before 2001, 29% of patients starting ARVT received HAART; after 2001 it increased to 90%. The proportion of adequate prescriptions decreased within the two periods of study in all facilities (P value < 0.01). The INS and SSA were more likely to be prescribed adequately (P value < 0.01) compared to IMSS. The distribution of reasons for change was not significantly different during this time for all facilities (P value > 0.05). Conclusions. Universal ARVT access in Mexico was associated with changes in ARVT-prescription patterns over time. Health providers' performance improved, but not homogeneously. Training of personnel and guidelines updating is essential to improve prescription. PMID:24396592

Caro-Vega, Yanink; Sierra-Madero, Juan; Colchero, M. Arantxa; Crabtree-Ramírez, Brenda; Bautista-Arredondo, Sergio

2013-01-01

125

Antiretroviral treatment French guidelines 2013: economics influencing science.  

PubMed

Guidelines for the preferred choice of initial combination antiretroviral therapy in those living with HIV are provided by several national and international committees. Following the recent presentation of the 2013 French guidelines on antiretroviral therapy, there has been a debate regarding whether and/or how economics should influence guideline decisions and to what extent this should counterbalance valid scientific evidence. We discuss here the reasons for the unique nature of some of the proposals made by the French guidelines panel. Indeed, some recommendations are debatable. In the new French guidelines, economic considerations significantly influence and, in some instances, take precedence over the scientific evidence, leading to guidelines that are significantly different from those of other national and international committees. PMID:24443513

Raffi, F; Reynes, J

2014-05-01

126

Dangerous medicines: Unproven AIDS cures and counterfeit antiretroviral drugs  

PubMed Central

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

Amon, Joseph J

2008-01-01

127

Start Smart: Steps to Starting a Business Workshop Registration The Start Smart workshop will cover  

E-print Network

. ----------------------------------------------------------------------------------------------------------------------------------------------- START SMART REGISTRATION Name Daytime phone Address E-mail address City State Zip Optional: NameStart Smart: Steps to Starting a Business Workshop Registration The Start Smart workshop will cover and mail it with your check* or credit card information to: WSU Tri-Cities Business LINKS 2710 Crimson Way

Collins, Gary S.

128

Pharmacogenetics of adverse effects due to antiretroviral drugs.  

PubMed

The availability of highly active antiretroviral therapy has markedly improved the survival rate and quality of life in patients infected with HIV. At present, however, there is still no cure for HIV and those undergoing treatment have to do so for life. The use of antiretroviral drugs has been associated with several toxicities that limit their success. Some acute and chronic toxicities associated with these drugs include hypersensitivity reactions, neurotoxicity, nephropathy, liver damage, and the appearance of body fat redistribution syndrome and the different metabolic alterations that accompany it. Some of these toxicities are family- or even drug-specific. Since not all patients that take a particular antiretroviral medication develop the adverse effect that has been attributed to that drug, it has therefore been postulated that there must be a genetically conditioned individual predisposition to developing the adverse effect. Pharmacogenetics is the science that studies interindividual variations in the response to and toxicity of pharmaceuticals due to variations in the genetic composition of individuals - in other words, how a person's genetic make-up influences the favorable or adverse effects of a certain treatment. Sufficient advances have been made in this discipline to allow this fertile field of research to move out of the basic science laboratory and into clinical applications. The present article reviews the investigations that have been published regarding the association between genetic determinants of persons infected with HIV and clinical toxicity resulting from different antiretroviral drugs. Special emphasis is devoted to the studies that have resulted in clinical applications such as that of the pre-screening of HLA B*5701 for avoiding abacavir-related hypersensitivity syndrome. PMID:20216907

Vidal, Francesc; Gutiérrez, Félix; Gutiérrez, Mar; Olona, Montserrat; Sánchez, Victoria; Mateo, Gracia; Peraire, Joaquim; Viladés, Consuelo; Veloso, Sergi; López-Dupla, Miguel; Domingo, Pere

2010-01-01

129

Antiretroviral treatment interruptions and risk of non-opportunistic diseases  

Microsoft Academic Search

Structured treatment interruptions have been studied as a strategy to reduce antiretroviral toxicities and expenditures in\\u000a the treatment of HIV-infected individuals. Paradoxically, in addition to the increased incidence of death and opportunistic\\u000a infections, these interruptions in therapy have resulted in the development of a number of non-opportunistic diseases, including\\u000a cardiovascular events, renal insufficiency, hepatic failure, and non-AIDS-defining malignancies. Hypotheses regarding

Kenneth A. Lichtenstein

2009-01-01

130

Antiretroviral treatment strategies in resource-limited settings  

Microsoft Academic Search

To date, a minority of persons living with HIV worldwide has benefited from the advances in HIV therapeutics fueled by the\\u000a scientific community, policy-makers, advocates, and the pharmaceutical industry in the global North. A growing body of evidence\\u000a demonstrates that access to highly active antiretroviral therapy can be successfully scaled-up in less wealthy nations in\\u000a the South. High rates of

Anna K. Person; Habib O. Ramadhani; Nathan M. Thielman

2007-01-01

131

Antiretroviral therapy initiation in an Australian cohort: implications for increased use of antiretroviral therapy.  

PubMed

Human immunodeficiency virus (HIV) management is entering a "universal test and treat" phase, although the benefits from this approach in developed world scenarios are uncertain. We analyzed 79 combination anti-retroviral therapy (cART)-naďve HIV-positive individuals who were intensively prospectively followed from 2004 to 2013. We studied HIV-related illnesses, potential HIV transmissions, impact on sexual behavior, and factors impeding earlier cART initiation. Sixty-eight (86 %) subjects commenced cART at a mean of 6.0 years after diagnosis: 71 % with a CD4 T-cell count <350 cells/?l. A significant minority of subjects (29 %) resisted initiation of cART despite physician recommendation for a mean of 18 months. Only one HIV-related illness occurred in a patient who had not previously recorded a CD4 T-cell count <500 cell/?l, totaling 195 person-years of observation. A 40 % increase in sexually transmitted infections (STIs) occurred after commencing cART. We detected six HIV transmissions in our cohort, all of which were before initiating cART and 5 of them had a prior CD4 T-cell count <500 cells/?l. Illnesses related to cART deferral were rare and most HIV transmissions we detected occurred in people with a prior CD4 T-cell count <500 cells/?l. Our study raises concerns about increasing STI rates after cART initiation. Focusing resources on cART initiation among patients with CD4 T-cell counts <500 cells/?l and enhancing safe sexual practices should remain a priority. PMID:25139203

Stratov, I; Kent, S J

2015-02-01

132

Factors associated with suboptimal adherence to antiretroviral therapy in Asia  

PubMed Central

Introduction Adherence to antiretroviral therapy (ART) plays an important role in treatment outcomes. It is crucial to identify factors influencing adherence in order to optimize treatment responses. The aim of this study was to assess the rates of, and factors associated with, suboptimal adherence (SubAdh) in the first 24 months of ART in an Asian HIV cohort. Methods As part of a prospective resistance monitoring study, the TREAT Asia Studies to Evaluate Resistance Monitoring Study (TASER-M) collected patients’ adherence based on the World Health Organization-validated Adherence Visual Analogue Scale. SubAdh was defined in two ways: (i) <100% and (ii) <95%. Follow-up time started from ART initiation and was censored at 24 months, loss to follow-up, death, treatment switch, or treatment cessation for >14 days. Time was divided into four intervals: 0–6, 6–12, 12–18 and 18–24 months. Factors associated with SubAdh were analysed using generalized estimating equations. Results Out of 1316 patients, 32% ever reported <100% adherence and 17% ever reported <95%. Defining the outcome as SubAdh <100%, the rates of SubAdh for the four time intervals were 26%, 17%, 12% and 10%. Sites with an average of >2 assessments per patient per year had an odds ratio (OR)=0.7 (95% confidence interval (CI) (0.55 to 0.90), p=0.006), compared to sites with ?2 assessments per patient per year. Compared to heterosexual exposure, SubAdh was higher in injecting drug users (IDUs) (OR=1.92, 95% CI (1.23 to 3.00), p=0.004) and lower in homosexual exposure (OR=0.52, 95% CI (0.38 to 0.71), p<0.001). Patients taking a nucleoside transcriptase inhibitor and protease inhibitor (NRTI+PI) combination were less likely to report adherence <100% (OR=0.36, 95% CI (0.20 to 0.67), p=0.001) compared to patients taking an NRTI and non-nucleoside transcriptase inhibitor (NRTI+NNRTI) combination. SubAdh decreased with increasing time on ART (all p<0.001). Similar associations were found with adherence <95% as the outcome. Conclusions We found that SubAdh, defined as either <100% and <95%, was associated with mode of HIV exposure, ART regimen, time on ART and frequency of adherence measurement. The more frequently sites assessed patients, the lower the SubAdh, possibly reflecting site resourcing for patient counselling. Although social desirability bias could not be excluded, a greater emphasis on more frequent adherence counselling immediately following ART initiation and through the first six months may be valuable in promoting treatment and programme retention. PMID:24836775

Jiamsakul, Awachana; Kumarasamy, Nagalingeswaran; Ditangco, Rossana; Li, Patrick CK; Phanuphak, Praphan; Sirisanthana, Thira; Sungkanuparph, Somnuek; Kantipong, Pacharee; Lee, Christopher KC; Mustafa, Mahiran; Merati, Tuti; Kamarulzaman, Adeeba; Singtoroj, Thida; Law, Matthew

2014-01-01

133

Anaemia and zidovudine-containing antiretroviral therapy in paediatric antiretroviral programmes in the IeDEA Paediatric West African Database to evaluate AIDS  

PubMed Central

Introduction There is a risk of anaemia among HIV-infected children on antiretroviral therapy (ART) containing zidovudine (ZDV) recommended in first-line regimens in the WHO guidelines. We estimated the risk of severe anaemia after initiation of a ZDV-containing regimen in HIV-infected children included in the IeDEA West African database. Methods Standardized collection of data from HIV-infected children (positive PCR<18 months or positive serology ?18 months) followed up in HIV programmes was included in the regional IeDEA West Africa collaboration. Ten clinical centres from seven countries contributed (Benin, Burkina Faso, Côte d'Ivoire, Gambia, Ghana, Mali and Senegal) to this collection. Inclusion criteria were age <16 years and starting ART. We explored the data quality of haemoglobin documentation over time and the incidence and predictors of severe anaemia (Hb<7g/dL) per 100 child-years of follow-up over the duration of first-line antiretroviral therapy. Results As of December 2009, among the 2933 children included in the collaboration, 45% were girls, median age was five years; median CD4 cell percentage was 13%; median weight-for-age z-score was ?2.7; and 1772 (60.4%) had a first-line ZDV-containing regimen. At baseline, 70% of the children with a first-line ZDV-containing regimen had a haemoglobin measure available versus 76% in those not on ZDV (p?0.01): the prevalence of severe anaemia was 3.0% (n=38) in the ZDV group versus 10.2% (n=89) in those without (p<0. 01). Over the first-line follow-up, 58.9% of the children had ?1 measure of haemoglobin available in those exposed to ZDV versus 60.4% of those not (p=0.45). Severe anaemia occurred in 92 children with an incidence of 2.47 per 100 child-years of follow-up in those on a ZDV-containing regimen versus 4.25 in those not (p?0.01). Adjusted for age at ART initiation and first-line regimen, a weight-for-age z-score ??3 was a strong predictor associated with a 5.59 times risk of severe anaemia (p<0.01). Conclusions Severe anaemia is frequent at baseline and guides the first-line ART prescription, but its incidence seems rare among children on ART. Severe malnutrition at baseline is a strong predictor for development of severe anaemia, and interventions to address this should form an integral component of clinical care. PMID:24047928

Renner, Lorna A; Dicko, Fatoumata; Kouéta, Fla; Malateste, Karen; Gueye, Ramatoulaye D; Aka, Edmond; Eboua, Tanoh K; Azondékon, Alain; Okomo, Uduok; Touré, Pety; Ekouévi, Didier; Leroy, Valeriane

2013-01-01

134

START Background Report START, September 2013 1 BACKGROUND REPORT  

E-print Network

START Background Report © START, September 2013 1 BACKGROUND REPORT Al-Shabaab Attack on Westgate evening, Sept. 24. Media sources report that Somali militant organization al-Shabaab has claimed deaths as of Sept. 25. START has developed this background report highlighting attacks attributed to al-Shabaab

Hill, Wendell T.

135

From Head Start to Sure Start: Reflections on Policy Transfer  

ERIC Educational Resources Information Center

This article uses the history of debates over the US Head Start programme (1965), Early Head Start (1994) and the UK Sure Start initiative (1998), as a window on to policy transfer. In all the three, the aim was that early intervention could offer a means of boosting children's educational attainment and of countering the wider effects of poverty…

Welshman, John

2010-01-01

136

Wet start for 1982  

NASA Astrophysics Data System (ADS)

The first half of the 1982 water year (October 1, 1981-March 31, 1982) saw streamflow conditions across the country get off to a generally wet start, with almost 90% of the key index gaging stations reporting normal to above normal flows, according to the U.S. Geological Survey, Department of the Interior.USGS hydrologists said that the overall wet water picture was reflected in the nation's Big Five rivers—Mississippi, Missouri, St. Lawrence, Ohio, and Columbia—which averaged above normal for 4 of the first 6 months of the new water year. The water year used by hydrologists runs from October 1 to September 1 of the following calendar year and is designed to roughly follow the growing season and to begin and end during a period of generally low streamflow. Hydrologists use the Big Five, which together drain more than half of the conterminous United States, as a quick check on the status of the nation's water resources. Combined flow of the Big Five averaged 787 billion gallons a day (bgd) during the first half of the 1982 water year, 14% above normal.

137

Maternal or Infant Antiretroviral Drugs to Reduce HIV-1 Transmission  

PubMed Central

Background We evaluated the efficacy of a maternal triple-drug antiretroviral regimen or infant nevirapine prophylaxis for 28 weeks during breast-feeding to reduce postnatal transmission of human immunodeficiency virus type 1 (HIV-1) in Malawi. Methods We randomly assigned 2369 HIV-1–positive, breast-feeding mothers with a CD4+ lymphocyte count of at least 250 cells per cubic millimeter and their infants to receive a maternal antiretroviral regimen, infant nevirapine, or no extended postnatal antiretroviral regimen (control group). All mothers and infants received perinatal prophylaxis with single-dose nevirapine and 1 week of zidovudine plus lamivudine. We used the Kaplan–Meier method to estimate the cumulative risk of HIV-1 transmission or death by 28 weeks among infants who were HIV-1–negative 2 weeks after birth. Rates were compared with the use of the log-rank test. Results Among mother–infant pairs, 5.0% of infants were HIV-1–positive at 2 weeks of life. The estimated risk of HIV-1 transmission between 2 and 28 weeks was higher in the control group (5.7%) than in either the maternal-regimen group (2.9%, P = 0.009) or the infant-regimen group (1.7%, P<0.001). The estimated risk of infant HIV-1 infection or death between 2 and 28 weeks was 7.0% in the control group, 4.1% in the maternal-regimen group (P = 0.02), and 2.6% in the infant-regimen group (P<0.001). The proportion of women with neutropenia was higher among those receiving the antiretroviral regimen (6.2%) than among those in either the nevirapine group (2.6%) or the control group (2.3%). Among infants receiving nevirapine, 1.9% had a hypersensitivity reaction. Conclusions The use of either a maternal antiretroviral regimen or infant nevirapine for 28 weeks was effective in reducing HIV-1 transmission during breast-feeding. (ClinicalTrials.gov number, NCT00164736.) PMID:20554982

Chasela, Charles S.; Hudgens, Michael G.; Jamieson, Denise J.; Kayira, Dumbani; Hosseinipour, Mina C.; Kourtis, Athena P.; Martinson, Francis; Tegha, Gerald; Knight, Rodney J.; Ahmed, Yusuf I.; Kamwendo, Deborah D.; Hoffman, Irving F.; Ellington, Sascha R.; Kacheche, Zebrone; Soko, Alice; Wiener, Jeffrey B.; Fiscus, Susan A.; Kazembe, Peter; Mofolo, Innocent A.; Chigwenembe, Maggie; Sichali, Dorothy S.; van der Horst, Charles M.

2012-01-01

138

Free HIV Antiretroviral Therapy Enhances Adherence among Individuals on Stable Treatment: Implications for Potential Shortfalls in Free Antiretroviral Therapy  

PubMed Central

Objective To estimate the population-level causal effect of source of payment for HIV medication on treatment adherence using Marginal Structural Models. Methods Data were obtained from an observational cohort of 76 HIV-infected individuals with at least 24 weeks of antiretroviral therapy treatment from 2002 to 2007 in Kampala, Uganda. Adherence was the primary outcome and it was measured using the 30-day visual analogue scale. Marginal structural models (MSM) were used to estimate the effect of source of payment for HIV medication on adherence, adjusting for confounding by income, duration on antiretroviral therapy (ART), timing of visit, prior adherence, prior CD4+ T cell count and prior plasma HIV RNA. Traditional association models were also examined and the results compared. Results Free HIV treatment was associated with a 3.8% improvement in adherence in the marginal structural model, while the traditional statistical models showed a 3.1–3.3% improvement in adherence associated with free HIV treatment. Conclusion Removing a financial barrier to treatment with ART by providing free HIV treatment appears to significantly improve adherence to antiretroviral therapy. With sufficient information on confounders, MSMs can be used to make robust inferences about causal effects in epidemiologic research. PMID:24039704

Byakika-Tusiime, Jayne; Polley, Eric C.; Oyugi, Jessica H.; Bangsberg, David R.

2013-01-01

139

When Will I Start Developing?  

MedlinePLUS

... for Kids for Teens Teens Home Body Mind Sexual Health Food & Fitness Diseases & Conditions Infections Q&A School & ... Anger When Will I Start Developing? KidsHealth > Teens > Sexual Health > Your Changing Body > When Will I Start Developing? ...

140

Maryland Early Head Start Initiative  

ERIC Educational Resources Information Center

Since 2000, Maryland has provided state supplemental funds to Head Start and Early Head Start (EHS) programs to improve access. Local EHS programs may use funds, through child care partnerships, to extend the EHS day or year. Maryland's approach to building on EHS includes: (1) Increase the capacity of existing Head Start and EHS programs to…

Center for Law and Social Policy, Inc. (CLASP), 2012

2012-01-01

141

PENTA 2009 guidelines for the use of antiretroviral therapy in paediatric HIV-1 infection.  

PubMed

PENTA Guidelines aim to provide practical recommendations for treating children with HIV infection in Europe. Changes to guidance since 2004 have been informed by new evidence and by expectations of better outcomes following the ongoing success of antiretroviral therapy (ART). Participation in PENTA trials of simplifying treatment is encouraged. The main changes are in the following sections: 'When to start ART': Treatment is recommended for all infants, and at higher CD4 cell counts and percentages in older children, in line with changes to adult guidelines. The number of age bands has been reduced to simplify and harmonize with other paediatric guidelines. Greater emphasis is placed on CD4 cell count in children over 5 years, and guidance is provided where CD4% and CD4 criteria differ. 'What to start with': A three-drug regimen of two nucleoside reverse transcriptase inhibitors (NRTIs) with either a nonnucleoside reverse transcriptase inhibitor (NNRTI) or a boosted protease inhibitor (PI) remains the first choice combination. Lamivudine and abacavir are the NRTI backbone of choice for most children, based on long-term follow-up in the PENTA 5 trial. Stavudine is no longer recommended. Whether to start with an NNRTI or PI remains unclear, but PENPACT 1 trial results in 2009 may help to inform this. All PIs should be ritonavir boosted. Recommendations on use of resistance testing, therapeutic drug monitoring and HLA testing draw from data in adults and from European paediatric cohort studies. Recently updated US and WHO paediatric guidelines provide more detailed review of the evidence base. Differences between guidelines are highlighted and explained. PMID:19878352

Welch, Steve; Sharland, Mike; Lyall, E G Hermione; Tudor-Williams, Gareth; Niehues, Tim; Wintergerst, Uwe; Bunupuradah, Torsak; Hainaut, Marc; Della Negra, Marinella; Pena, Maria José Mellado; Amador, José Tomas Ramos; Gattinara, Guido Castelli; Compagnucci, Alexandra; Faye, Albert; Giaquinto, Carlo; Gibb, Diana M; Gandhi, Kate; Forcat, Silvia; Buckberry, Karen; Harper, Lynda; Königs, Christoph; Patel, Deepak; Bastiaans, Diane

2009-11-01

142

Retention in care under universal Antiretroviral Therapy for HIV Infected Pregnant and Breastfeeding Women (“Option B+”) in Malawi  

PubMed Central

OBJECTIVE To explore the levels and determinants of loss to follow-up (LTF) under universal lifelong antiretroviral therapy (ART) for pregnant and breastfeeding women (“Option B+”) in Malawi. DESIGN, SETTING, and PARTICIPANTS We examined retention in care, beginning at date of ART initiation and up to six months, for women in the Option B+ program. We analysed nation-wide facility-level data on women who started ART at 540 facilities (n=21 939). The study included individual-level data on patients who started ART at 19 large facilities (n=11 534). RESULTS Of the women who started ART under Option B+ (n=21 939), 17% appeared to be LTF six months after start. Most losses occurred in the first 3 months of therapy. Option B+ patients who started therapy during pregnancy were five times more likely than women who started ART in WHO stage 3/4 or with a CD4 cell count ?350 cells/?l, to never return after their initial clinic visit (odds ratio 5.0, 95% CI 4.2-6.1). Option B+ patients who started therapy while breastfeeding were twice as likely to miss their first follow-up visit (odds ratio 2.2, 95% CI 1.8-2.8). LTF was highest in pregnant Option B+ patients who began ART at large clinics on the day they were diagnosed with HIV. LTF varied considerably between facilities, ranging from 0% to 58%. CONCLUSION Decreasing LTF will improve the effectiveness of the Option B+ approach. Tailored interventions, like community- or family-based PMTCT models could improve its effectiveness. PMID:24468999

TWEYA, Hannock; JAHN, Andreas; van OOSTERHOUT, Joep J.; CHIMBWANDIRA, Frank; CHIRWA, Zengani; NG’AMBI, Wingston; BAKALI, Alan; PHIRI, Sam; MYER, Landon; VALERI, Fabio; ZWAHLEN, Marcel; WANDELER, Gilles

2014-01-01

143

Host sequence motifs shared by HIV predict response to antiretroviral therapy  

Microsoft Academic Search

BACKGROUND: The HIV viral genome mutates at a high rate and poses a significant long term health risk even in the presence of combination antiretroviral therapy. Current methods for predicting a patient's response to therapy rely on site-directed mutagenesis experiments and in vitro resistance assays. In this bioinformatics study we treat response to antiretroviral therapy as a two-body problem: response

William Dampier; Perry Evans; Lyle Ungar; Aydin Tozeren

2009-01-01

144

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

Microsoft Academic Search

BACKGROUND: 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

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

2007-01-01

145

Impact of a Rural Village Women (Asha) Intervention on Adherence to Antiretroviral Therapy in Southern India  

PubMed Central

Background Despite the increased prevalence of HIV in the rural female population of India, adherence to antiretroviral therapy continues to be low due to several barriers which discourage rural women. Objectives To assess the effectiveness of an intervention (Asha-Life) delivered by Accredited Social Health Activists to improve antiretroviral therapy adherence of rural women living with AIDS in India compared to that of a usual care group. Method A total of 68 rural women living with AIDS, aged 18–45 years, participated in a prospective, randomized pilot clinical trial and were assessed for several factors affecting adherence, such as sociodemographic characteristics, health history, CD4 cell count, enacted stigma, depressive symptomology, help getting antiretroviral therapy, and perceived therapy benefits. Results Findings at 6 months revealed that, while both groups improved their adherence to antiretroviral therapy, there was greater improvement in the Asha-Life group (p < .001), who reported a greater reduction in barriers to antiretroviral therapy than those in the usual care group. Discussion Antiretroviral therapy adherence showed significant increase in the Asha-Life cohort, in which basic education on HIV/AIDS, counseling on antiretroviral therapy, financial assistance, and better nutrition was provided. The Asha-Life intervention may have great potential in improving antiretroviral therapy adherence and decreasing barriers among rural women living with AIDS in India. PMID:22872107

Nyamathi, Adeline; Hanson, Alecia Y.; Salem, Benissa E.; Sinha, Sanjeev; Ganguly, Kalyan K.; Leake, Barbara; Yadav, Kartik; Marfisee, Mary

2012-01-01

146

Guidelines for the Use of Antiretroviral Agents in HIV-1-Infected Adults and Adolescents  

E-print Network

therapy (ART). This new section provides an overview of costs as they relate to adherence, including important measure of response to ART, and should be monitored during therapy to assure consistent viral and Antiretroviral Therapy · In the past, this guideline has not formally discussed costs related to antiretroviral

Levin, Judith G.

147

AIDS . Author manuscript Long-term immunologic response to antiretroviral therapy in low-income  

E-print Network

in resource-limited settings, where antiretroviral therapy (ART) is being scaled up using a public health to ART among patients remaining on therapy. Public health and programmatic interventions leading to antiretroviral therapy (ART) are important measures of the efficacy of ART in individual patients

Paris-Sud XI, Université de

148

Evolution and recombination of genes encoding HIV-1 drug resistance and tropism during antiretroviral therapy  

E-print Network

therapy (ART) is a high priority to improve understanding of HIV-1 pathogenesis and therapy. To understand antiretroviral therapy (ART) in some infected individuals resulting in the emergence of drug resistance mutations et al., 2008). Combination antiretroviral therapy (cART) has been successful in suppressing HIV-1

Suchard, Marc A.

149

Uncertainty quantification for a model of HIV-1 patient response to antiretroviral therapy interruptions  

E-print Network

with antiretroviral therapy (ART) can have disparate outcomes. A recent study showed that 11 HIV-1 patients maintained that are able to suppress HIV-1 after the termination of long-term ART therapy have low HIV-1 reservoirsUncertainty quantification for a model of HIV-1 patient response to antiretroviral therapy

150

Early anthropometric and immunological success of antiretroviral therapy do not predict virological success in  

E-print Network

therapy (ART) is a critical step. In sub-Saharan Africa, few people have access to plasma viral load (VL of antiretroviral therapy (ART) is to suppress human immunodeficiency virus (HIV) replication. This is consideredPage 1 Early anthropometric and immunological success of antiretroviral therapy do not predict

Paris-Sud XI, Université de

151

Transmission of HIV-1 minority resistant variants and response to first-line antiretroviral therapy  

E-print Network

of drug-resistant HIV-1 can impair the virological response to antiretroviral therapy (ART). Minority drugs (ARV) is one important factor limiting the effect of antiretroviral therapy (ART). In ART therapy O Peuchant 1 , R Thiébaut 2 , S Capdepont 1 , V Lavignolle-Aurillac 2 , D Neau 2,3 , P Morlat 3

Paris-Sud XI, Université de

152

Evolution of Drug-resistant Viral Populations during Interruption of Antiretroviral Therapy  

E-print Network

therapy (ART), some HIV-2 infected patients still fail treatment due to drug resistance, poor adherence1 Evolution of Drug-resistant Viral Populations during Interruption of Antiretroviral Therapy antiretroviral treatment (ART) interruption allows determination of the evolution of3 drug-resistant viruses

Ahlers, Guenter

153

Antiretroviral Treatment and Prevention of Peripartum and Postnatal HIV Transmission in  

E-print Network

the original author and source are credited. Abbreviations: 3TC, lamivudine; ART, antiretroviral therapy; ARV-course antiretroviral (scARV) PMTCT regimens. Methods and Findings The MTCT-Plus Initiative is a multi-country, family-centred HIV care and treatment program for pregnant and postpartum women and their families. Pregnant women

Paris-Sud XI, Université de

154

Prevalence of mutations related to HIV1 antiretroviral resistance in Brazilian patients failing HAART  

Microsoft Academic Search

Background: Current guidelines for antiretroviral (ARV) therapy recommend at least triple-drug combination, the so-called highly active antiretroviral therapy (HAART). Not all patients respond to HAART and the development of drug resistance remains one of the most serious obstacles to sustained suppression of HIV. Objective: In an attempt to correlate the HIV therapeutic failure with reverse transcriptase (RT) and protease resistance

Amilcar Tanuri; Elena Caridea; Maria C. Dantas; Marisa G. Morgado; Daise L. C. Mello; Sandra Borges; Marisa Tavares; Selma B. Ferreira; Guilherme Santoro-Lopes; Claudia R. F. Martins; André L. C. Esteves; Ricardo S. Diaz; Sandra M. S. Andreo; Luiz A. P. Ferreira; Rodrigo Rodrigues; Tania Reuter; Ana M. S. Cavalcanti; Suelene M. de Oliveira; Heraclito B. de Barbosa; Paulo R. Teixeira; Pedro N. Chequer

2002-01-01

155

Approaches to rationing antiretroviral treatment: ethical and equity implications.  

PubMed Central

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

Bennett, Sara; Chanfreau, Catherine

2005-01-01

156

Medication Possession Ratio Predicts Antiretroviral Regimens Persistence in Peru  

PubMed Central

Objectives 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. Design And Methods Retrospective cohort study including ART naďve, 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. Results 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). Conclusions The capture and utilization of program level parameters such as MPR can provide valuable insight into patient-level treatment outcomes. PMID:24098475

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

157

Antiretroviral Adherence During Pregnancy and Postpartum in Latin America  

PubMed Central

Abstract Adherence to antiretrovirals by pregnant women (and postpartum women if breastfeeding) is crucial to effectively decrease maternal viral load and decrease the risk of mother-to-child transmission of HIV. Our objectives were to describe self-reported adherence to antiretrovirals during the antepartum (after 22 weeks of pregnancy) and postpartum periods (6–12 weeks and 6 months), and identify predictors of adherence among HIV-infected women enrolled and followed in a prospective cohort study from June 2008 to June 2010 at multiple sites in Latin America. Adherence was evaluated using the number of missed and expected doses during the 3 days before the study visit. At the pre-delivery visit, 340 of 376 women (90%) reported perfect adherence. This rate significantly decreased by 6–12 weeks (171/214 [80%]) and 6 months postpartum (163/199 [82%], p<0.01). The odds for less than perfect adherence at the pre-delivery visit was significantly higher for pregnant women with current tobacco use (odds ratio [OR]=2.9, 95% confidence interval [CI]: 1.46–6.14; p=0.0029). At 6–12 weeks postpartum, the probability of non-perfect adherence increased by 6% for each 1 year increase in age (OR=1.06, 95% CI: 1.00–1.12, p=0.0497). At 6 months postpartum, the odds of nonperfect adherence was higher for those who were currently using alcohol (OR=3.04, 95% CI: 1.34–6.90; p=0.0079). Although a self-report measure of adherence based on only 3 days may lead to overestimation of actual adherence over time, women with perfect adherence had lower viral loads and higher CD4 counts. Adherence to antiretrovirals decreased significantly postpartum. Interventions should target women at high risk for lower adherence during pregnancy and postpartum, including tobacco and alcohol users. PMID:22663185

Harris, D. Robert; Kakehasi, Fabiana; Haberer, Jessica E.; Cahn, Pedro; Losso, Marcelo; Teles, Elizabete; Pilotto, Jose H.; Hofer, Cristina B.; Read, Jennifer S.

2012-01-01

158

Effect of Pregnancy and the Postpartum Period on Adherence to Antiretroviral Therapy Among HIV-Infected Women Established on Treatment.  

PubMed

: Among women who become pregnant after initiating highly active antiretroviral therapy (HAART), few data describe the effect of pregnancy and postpartum on adherence. We conducted a retrospective clinical cohort study among therapy-naive women (age, 18-45 years) initiating HAART in Johannesburg, South Africa. Among 7510 women in our analysis, 896 experienced a pregnancy after starting HAART. Compared with nonpregnant periods of follow-up, there was an increased risk of nonadherence during the postpartum period (weighted risk ratio: 1.46, 95% confidence interval: 1.17 to 1.82) but not during pregnancy itself (weighted risk ratio: 0.95, 95% confidence interval: 0.78 to 1.17). PMID:25559590

Henegar, Cassidy E; Westreich, Daniel J; Maskew, Mhairi; Miller, William C; Brookhart, M Alan; Van Rie, Annelies

2015-04-01

159

Epidemiology and Management of Antiretroviral-Associated Cardiovascular Disease  

PubMed Central

Risk and manifestations of cardiovascular disease (CVD) in patients infected with human immunodeficiency virus (HIV) will continue to evolve as improved treatments and life expectancy of these patients increases. Although initiation of antiretroviral (ARV) therapy has been shown to reduce this risk, some ARV medications may induce metabolic abnormalities, further compounding the risk of CVD. In this patient population, both pharmacologic and nonpharmacologic strategies should be employed to treat and reduce further risk of CVD. This review summarizes epidemiology data of the risk factors and development of CVD in HIV and provides recommendations to manage CVD in HIV-infected patients. PMID:25866592

Chastain, Daniel B; Henderson, Harold; Stover, Kayla R

2015-01-01

160

Health literacy, antiretroviral adherence, and HIV-RNA suppression  

Microsoft Academic Search

BACKGROUND: Low health literacy has been associated with worse adherence to antiretroviral therapy (ART) and higher HIV-RNA levels, but\\u000a these relationships have not been evaluated in longitudinal analyses.\\u000a \\u000a \\u000a METHODS: We evaluated literacy using the Rapid Estimate of Adult Literacy in Medicine (REALM) (?6th grade, 7th to 8th grade, ?9th\\u000a grade) in the HIV-Alcohol Longitudinal Cohort study of HIV-infected persons with

Michael K. Paasche-Orlow; Debbie M. Cheng; Anita Palepu; Seville Meli; Vincent Faber; Jeffrey H. Samet

2006-01-01

161

Closing the Gap Antiretroviral Therapy for the Developing World  

NSDL National Science Digital Library

In this problem-based learning/role playing case, students apply their knowledge of the biology of HIV/AIDS and antiretroviral therapy to developing foreign aid policy for the HIV/AIDS crisis in sub-Saharan Africa. The case was created for a non-majors course in human biology taken mostly by juniors or seniors. It has also been used in a microbiology course for pre-nursing students and in an upper-level microbiology course for biology majors.

Robin Pals-Rylaarsdam

2003-01-01

162

Training needs assessment for clinicians at antiretroviral therapy clinics: evidence from a national survey in Uganda  

PubMed Central

Background To increase access to antiretroviral therapy in resource-limited settings, several experts recommend "task shifting" from doctors to clinical officers, nurses and midwives. This study sought to identify task shifting that has already occurred and assess the antiretroviral therapy training needs among clinicians to whom tasks have shifted. Methods The Infectious Diseases Institute, in collaboration with the Ugandan Ministry of Health, surveyed health professionals and heads of antiretroviral therapy clinics at a stratified random sample of 44 health facilities accredited to provide this therapy. A sample of 265 doctors, clinical officers, nurses and midwives reported on tasks they performed, previous human immunodeficiency virus training, and self-assessment of knowledge of human immunodeficiency virus and antiretroviral therapy. Heads of the antiretroviral therapy clinics reported on clinic characteristics. Results Thirty of 33 doctors (91%), 24 of 40 clinical officers (60%), 16 of 114 nurses (14%) and 13 of 54 midwives (24%) who worked in accredited antiretroviral therapy clinics reported that they prescribed this therapy (p < 0.001). Sixty-four percent of the people who prescribed antiretroviral therapy were not doctors. Among professionals who prescribed it, 76% of doctors, 62% of clinical officers, 62% of nurses and 51% of midwives were trained in initiating patients on antiretroviral therapy (p = 0.457); 73%, 46%, 50% and 23%, respectively, were trained in monitoring patients on the therapy (p = 0.017). Seven percent of doctors, 42% of clinical officers, 35% of nurses and 77% of midwives assessed that their overall knowledge of antiretroviral therapy was lower than good (p = 0.001). Conclusion Training initiatives should be an integral part of the support for task shifting and ensure that antiretroviral therapy is used correctly and that toxicity or drug resistance do not reverse accomplishments to date. PMID:19698146

Lutalo, Ibrahim M; Schneider, Gisela; Weaver, Marcia R; Oyugi, Jessica H; Sebuyira, Lydia Mpanga; Kaye, Richard; Lule, Frank; Namagala, Elizabeth; Scheld, W Michael; McAdam, Keith PWJ; Sande, Merle A

2009-01-01

163

Comparing adherence to two different HIV antiretroviral regimens: an instrumental variable analysis.  

PubMed

The objective of this observational cohort study was to compare adherence to protease inhibitor (PI)-based regimens or non-nucleoside reverse transcriptase inhibitor (NNRTI)-based regimens. HIV-seropositive, antiretroviral-naďve patients initiating therapy between 1998 and 2006 were identified using Veterans Health Administration databases. First-year adherence ratios were calculated as proportion of days covered (PDC). Multivariable regressions were run with an indicator for PDC >95, 90, 85, and 80 % as the dependent variable and an indicator for a PI-based regimen as the key independent variable. We controlled for residual unmeasured confounding by indication using an instrumental variable technique, using the physician's prescribing preference as the instrument. Out of 929 veterans on PI-based and 747 on NNRTI-based regimens, only 19.7 % of PI patients had PDC >80 %, compared to 35.1 % of NNRTI patients. In multivariable analysis, starting a PI regimen was significantly associated with poor adherence for all 4 adherence thresholds using conventional regressions and instrumental variable methods. PMID:22869102

Nelson, Richard E; Nebeker, Jonathan R; Hayden, Candace; Reimer, Larry; Kone, Karen; LaFleur, Joanne

2013-01-01

164

Four years of experience with antiretroviral therapy in adult patients in Karachi, Sindh, Pakistan.  

PubMed

The Sindh AIDS Control Program (SACP) in Pakistan began dispensing combination antiretroviral therapy (ART) in May 2006 in Karachi. This study aimed to assess the management and outcomes of ART-treated patients. Data were extracted from medical records of adult patients registered with the SACP who received ART between May 2006 and May 2010. In total, 300 patients received ART, of whom 77.7% were men. The median CD4 cell count at the time of joining the SACP was 130 cells/mm(3). ART was nevirapine-based in 69.1% of cases and was correctly prescribed in 97.3%. Of 257 patients who received ?1 month of ART, >90% were regular with their medications and appointments. Of the 300 patients, 70 (23.3%) had HIV-related deaths and 4 (1.3%) had non-HIV-related deaths, whereas 32 (10.7%) transferred out and 16 (5.3%) stopped attending the clinic and could not be traced. Estimated survival in the first 6 months stratified by initial CD4 lymphocyte count ?50 cells/mm(3) and <50 cells/mm(3) was 85.8% (95% CI 80.8-90.0%) and 52.2% (95% CI 40.9-63.1%), respectively. Viral suppression was achieved in 95.4% of those who survived beyond 3 months of starting ART. ART can be managed adequately with excellent patient adherence and satisfactory clinical outcomes in a resource-limited setting. PMID:24029671

Baqi, Shehla; Abro, Azra G; Salahuddin, Naseem; Ashraf Memon, M; Qamar Abbas, S; Baig-Ansari, Naila

2012-12-01

165

Postexposure Prophylactic Effect of Hepatitis B Virus (HBV)-Active Antiretroviral Therapy against HBV Infection  

PubMed Central

Retrospective study indicates that hepatitis B virus (HBV)-active nucleoside (nucleotide) analogues (NAs) used for antiretroviral therapy reduce the incidence of acute HBV infections in human immunodeficiency virus (HIV)-infected patients. Learning from HIV postexposure prophylaxis (PEP), we explored the possibility of using NAs in PEP following HBV exposure, if preexposure prophylaxis is feasible clinically. Using freshly isolated primary human hepatocytes cultured in vitro, we analyzed the effect of HBV-active tenofovir and lamivudine in primary HBV infection and also the effect of treatment with these NAs after HBV infection. HBV-active NAs applied from 24 h before inoculation could not prevent the secretion of hepatitis B surface antigen into the culture medium, and cessation of the NAs after inoculation allowed the cells to establish an apparent HBV infection. In contrast, hepatitis B immune globulin was able to prevent HBV infection completely. NA treatment before infection, however, can control the spread of HBV infection, as detected by immunohistochemistry. Practically, starting NA treatment within 2 days of primary HBV infection inhibited viral spread effectively, as well as preexposure treatment. We demonstrated that preexposure NA treatment was not able to prevent the acquisition of HBV infection but prevented viral spread by suppressing the production of mature progeny HBV virions. The effect of postexposure treatment within 2 days was similar to the effect of preexposure treatment, suggesting the possibility of HBV PEP using HBV-active NAs in HIV- and HBV-susceptible high-risk groups. PMID:25512419

Watanabe, Tsunamasa; Hamada-Tsutsumi, Susumu; Yokomaku, Yoshiyuki; Imamura, Junji; Sugiura, Wataru

2014-01-01

166

START Background Report START, May 2014 1 BACKGROUND REPORT  

E-print Network

START Background Report © START, May 2014 1 BACKGROUND REPORT Boko Haram Recent Attacks On Tuesday, April 15, 2014, the terrorist organization Boko Haram attacked a girls' school in Chibok, Borno state, in northern Nigeria, abducting between 250-300 young school girls. Boko Haram's leader, Abubakar Shekau

Hill, Wendell T.

167

START Background Report START, August 2013 1 BACKGROUND REPORT  

E-print Network

(AQAP), using data from START's Global Terrorism Database (GTD). ATTACKS ON U.S. TARGETS ABROAD Between Terrorist Attacks against U.S. Targets Abroad, 1970-2012 Source: Global Terrorism Database #12;START building housing French paratroopers. These attacks were claimed by Islamic Jihad, a name used by Hezbollah

Hill, Wendell T.

168

Antiretroviral therapy: effects on orofacial health and health care.  

PubMed

This study summarizes the adverse effects of antiretroviral therapy (ART) agents against HIV on orofacial health and health care. Current antiretroviral agents fall mainly into three major classes: nucleoside reverse-transcriptase inhibitors (NRTIs), non-nucleoside reverse-transcriptase inhibitors (NNRTIs) and protease inhibitors (PIs) - now with the new classes of fusion inhibitors, entry inhibitors--CCR5 co-receptor antagonists and HIV integrase strand transfer inhibitors. Many of the ART agents can have adverse orofacial effects, or can give rise to allergies or drug interactions--the optimum anti-HIV drug has yet to be found. There are few orofacial adverse effects that characterize a particular ART class, but erythema multiforme (EM), ulcers and xerostomia may be associated with reverse-transcriptase inhibitors (RTI); parotid lipomatosis, taste disturbance, xerostomia and perioral paraesthesia mainly related to PIs. Facial lipoatrophy is a common adverse effect of NRTIs; EM is more frequently associated with NNRTIs. Thus, although most of the more recent ART drugs and combinations of them show improved safety profiles, some may give rise to orofacial adverse effects, and may affect oral health care. PMID:23530806

Diz Dios, P; Scully, C

2014-03-01

169

A Systematic Review Comparing Antiretroviral Adherence Descriptive and Intervention Studies  

PubMed Central

We examined the extent to which studies aimed at testing interventions to improve antiretroviral adherence have targeted the facilitators of and barriers known to affect adherence. Of the 88 reports reviewed, 41 were reports of descriptive studies conducted with U.S. HIV-positive women and 47 were reports of intervention studies conducted with U.S. HIV-positive persons. We extracted from the descriptive studies all findings addressing any factor linked to antiretroviral adherence and from the intervention studies, information on the nature of the intervention, the adherence problem targeted, the persons targeted for the intervention, and the intervention outcomes desired. We discerned congruence between the prominence of substance abuse as a factor identified in the descriptive studies as a barrier to adherence and its prominence as the problem most addressed in those reports of intervention studies that specified the problems targeted for intervention. We also discerned congruence between the prominence of family and provider support as factors identified in the descriptive studies as facilitators of adherence and the presence of social support as an intervention component and outcome variable. Less discernible in the reports of intervention studies was specific attention to other factors prominent in the descriptive studies, which may be due to the complex nature of the problem, individualistic and rationalist slant of interventions, or simply the ways interventions were presented. Our review raises issues about niche standardization and intervention tailoring, targeting, and fidelity. PMID:20024751

Sandelowski, Margarete; Voils, Corrine I.; Chang, Yunkyung; Lee, Eun-Jeong

2009-01-01

170

Drug-Drug Interactions: Antiretroviral Drugs and Recreational Drugs.  

PubMed

With the advances in antiretroviral (ARV) therapy, patients with Human Immunodeficiency Virus (HIV) infection are living longer, however, some patients encounter co- morbidities which sometimes require treatment. Therefore, during the treatment with ARV drugs these patients could take people take several recreational drugs (e.g. amphetamines, hallucinogenes, opiates, or alcohol) with a possible development of drug-drug interactions (DDIs). In particular, Nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs/NtRTIs) are mainly excreted through the kidney and are not substrate of the cytochrome P450 or P-glycoprotein, therefore the DDIs during this treatment are minimal. In contrast, the other ARV drugs (i.e. non-nucleoside reverse-transcriptase inhibitors, Protease inhibitors, Integrase inhibitors, chemokine receptor 5 antagonists and HIV-fusion inhibitors) are an important class of antiretroviral medications that are frequent components of HAART regimens but shown several DDIs related to interaction with the cytochrome P450 or P-glycoprotein. In this paper we will review data concerning the possibility of DDI in HIV patients treated with ARV and taking recreational drugs. PMID:25429704

Staltari, Orietta; Leporini, Christian; Caroleo, Benedetto; Russo, Emilio; Siniscalchi, Antonio; De Sarro, Giovambattista; Gallelli, Luca

2014-11-26

171

Caregiver psychosocial characteristics and children's adherence to antiretroviral therapy.  

PubMed

Although parents and caregivers may have primary responsibility for their children's medication- taking, surprisingly few studies have examined caregiver psychosocial correlates of children's adherence to antiretroviral therapy (ART). This cross-sectional, descriptive study examined the relationship between caregiver psychosocial characteristics and medication adherence among children with HIV. Fifty-four caregivers of children with HIV completed a demographic questionnaire, the Parenting Stress Index, the Brief Symptom Inventory, the Family Support Scale, and the Support Functions Scale. Adherence to ART was measured with children's 6-month pharmacy refill histories. Children and caregivers were primarily African American, urban, and poor (63% reported <$15,000 annual household income). Univariate analyses showed that an adherent classification (>/= 80% refill rate) was associated with shorter duration of highly active antiretroviral therapy (HAART) treatment, nondisclosure of the HIV diagnosis to the child, lower caregiver income level, having a nonbiologically related caregiver, and less caregiver psychiatric distress. In a multivariate logistic regression, duration of child's HAART treatment, child HIV disclosure status, caregiver income, and caregiver psychiatric distress accounted for 63% of the variance in adherence. Findings highlight the complexity of children's adherence to ART and the need for multicenter studies with greater sample sizes to explore in more detail the effects of caregiver psychological distress and child HIV disclosure status on adherence as well as the ways in which regimen fatigue and adherence fluctuate over time. PMID:16789856

Marhefka, Stephanie L; Tepper, Vicki J; Brown, Jennifer L; Farley, John J

2006-06-01

172

HIV-associated lipodystrophy: impact of antiretroviral therapy.  

PubMed

In the late 1990s, reports of unusual changes in body fat distribution named 'lipodystrophy' (LD) began to appear in HIV patients mitigating the enormous enthusiasm about improvement of survival and quality of life provided by the combinations of antiretroviral (ARV) drug classes, the so-called highly active antiretroviral therapy (HAART), which had just become available at that time. The objective of this paper is to critically review the literature on LD and to discuss the impact of newer ARV agents, namely atazanavir, darunavir and raltegravir, as well as strategies of the late HAART era, including single-tablet regimens and nucleoside-sparing regimens. Studies in which LD was measured by dual-energy x-ray absorptiometry or by abdominal computed tomography or magnetic resonance imaging scan only, were included. We were unable to identify studies depicting a negative impact of drugs or ARV regimens on limb fat loss. On the contrary, a few studies identified a negative impact of atazanavir/ritonavir or darunavir/ritonavir on trunk fat increase. It should be noted that this anthropometric measure is a poor instrument since it cannot distinguish between subcutaneous and visceral fat. We conclude that presumably the body fat changes currently observed in HIV-infected patients is the net result of competing phenomena: on one side the natural history of lipohypertrophy as a result of HIV and HAART impact, and on the other side the physiological body fat changes observed in the aging population. PMID:24002702

Guaraldi, Giovanni; Stentarelli, Chiara; Zona, Stefano; Santoro, Antonella

2013-09-01

173

[Positioning of lopinavir/ritonavir in antiretroviral treatment schemes].  

PubMed

Lopinavir/ritonavir (LPV/r) was approved for use in the treatment of human immunodeficiency virus (HIV) infection in 2001 and is the protease inhibitor that has been most widely studied in clinical trials. Despite the time interval since its approval, all the evidence accumulated in the last 14 years indicates that LPV/r continues to occupy an important position among antiretroviral drugs. Firstly, LPV/r plus 2 nucleoside/nucleotide analogs is still considered a good option for initial antiretroviral therapy (ART). Secondly, numerous studies have evaluated the efficacy and safety of new initial ART strategies based on LPV/r in dual therapy. The results obtained suggest that LPV/r plus lamivudine (3TC) or raltegravir can be as effective in initial ART as standard triple therapy and justify their consideration as alternative regimens in this scenario. Thirdly, LPV/r is a pioneer drug, as well as being the agent with the largest amount of evidence from clinical trials on simplification to monotherapy (LPV/r) or dual therapy (LPV/r + 3TC). Lastly, LPV/r is highly useful is special situations. It has a low risk of liver toxicity in patients with chronic liver disease, its use is preferred in the treatment of patients with HIV-2, and it is safe and effective in preventing vertical HIV transmission. PMID:25542874

Camacho, Ángela; Rivero, Antonio

2014-11-01

174

A three-tier framework for monitoring antiretroviral therapy in high HIV burden settings  

PubMed Central

The provision of antiretroviral therapy (ART) in low and middle-income countries is a chronic disease intervention of unprecedented magnitude and is the dominant health systems challenge for high-burden countries, many of which rank among the poorest in the world. Substantial external investment, together with the requirement for service evolution to adapt to changing needs, including the constant shift to earlier ART initiation, makes outcome monitoring and reporting particularly important. However, there is growing concern at the inability of many high-burden countries to report on the outcomes of patients who have been in care for various durations, or even the number of patients in care at a particular point in time. In many instances, countries can only report on the number of patients ever started on ART. Despite paper register systems coming under increasing strain, the evolution from paper directly to complex electronic medical record solutions is not viable in many contexts. Implementing a bridging solution, such as a simple offline electronic version of the paper register, can be a pragmatic alternative. This paper describes and recommends a three-tiered monitoring approach in low- and middle-income countries based on the experience implementing such a system in the Western Cape province of South Africa. A three-tier approach allows Ministries of Health to strategically implement one of the tiers in each facility offering ART services. Each tier produces the same nationally required monthly enrolment and quarterly cohort reports so that outputs from the three tiers can be aggregated into a single database at any level of the health system. The choice of tier is based on context and resources at the time of implementation. As resources and infrastructure improve, more facilities will transition to the next highest and more technologically sophisticated tier. Implementing a three-tier monitoring system at country level for pre-antiretroviral wellness, ART, tuberculosis and mother and child health services can be an efficient approach to ensuring system-wide harmonization and accurate monitoring of services, including long term retention in care, during the scale-up of electronic monitoring solutions. PMID:24780511

Osler, Meg; Hilderbrand, Katherine; Hennessey, Claudine; Arendse, Juanita; Goemaere, Eric; Ford, Nathan; Boulle, Andrew

2014-01-01

175

A three-tier framework for monitoring antiretroviral therapy in high HIV burden settings.  

PubMed

The provision of antiretroviral therapy (ART) in low and middle-income countries is a chronic disease intervention of unprecedented magnitude and is the dominant health systems challenge for high-burden countries, many of which rank among the poorest in the world. Substantial external investment, together with the requirement for service evolution to adapt to changing needs, including the constant shift to earlier ART initiation, makes outcome monitoring and reporting particularly important. However, there is growing concern at the inability of many high-burden countries to report on the outcomes of patients who have been in care for various durations, or even the number of patients in care at a particular point in time. In many instances, countries can only report on the number of patients ever started on ART. Despite paper register systems coming under increasing strain, the evolution from paper directly to complex electronic medical record solutions is not viable in many contexts. Implementing a bridging solution, such as a simple offline electronic version of the paper register, can be a pragmatic alternative. This paper describes and recommends a three-tiered monitoring approach in low- and middle-income countries based on the experience implementing such a system in the Western Cape province of South Africa. A three-tier approach allows Ministries of Health to strategically implement one of the tiers in each facility offering ART services. Each tier produces the same nationally required monthly enrolment and quarterly cohort reports so that outputs from the three tiers can be aggregated into a single database at any level of the health system. The choice of tier is based on context and resources at the time of implementation. As resources and infrastructure improve, more facilities will transition to the next highest and more technologically sophisticated tier. Implementing a three-tier monitoring system at country level for pre-antiretroviral wellness, ART, tuberculosis and mother and child health services can be an efficient approach to ensuring system-wide harmonization and accurate monitoring of services, including long term retention in care, during the scale-up of electronic monitoring solutions. PMID:24780511

Osler, Meg; Hilderbrand, Katherine; Hennessey, Claudine; Arendse, Juanita; Goemaere, Eric; Ford, Nathan; Boulle, Andrew

2014-01-01

176

Transmitted drug resistance to rilpivirine among antiretroviral-naďve patients living with HIV from northern Poland  

PubMed Central

Introduction Rilpivirine (RPV) is a second-generation non-nucleoside reverse transcriptase inhibitor (NNRTI) that was recently approved for the treatment of antiretroviral-naďve individuals with HIV-1 viral load of <100,000 copies/ml. As transmission of the drug resistance mutations to this NNRTI may affect treatment outcomes, the frequency of primary, RPV-associated drug resistance mutations was assessed in this study. Methods For the study, 244 viral genome sequences from antiretroviral-naďve individuals were obtained by bulk sequencing. RPV-associated mutations were divided into RPV resistance mutations (K101E/P, E138A/G/K/Q/R, V179L, Y181C/I/V, Y188L, H221Y, F227C and M230I/L) according to the International AIDS Society-USA (IAS-USA) mutation list and variants potentially affecting RPV susceptibility (L100I, K101H/T, E138S, V179F/D/G/T, G190A/E/S, F227L and M230V) based on the in vitro and in vivo data. Results IAS-USA RPV drug resistance mutations were found in 5.3% sequences, with E138A and E138G being the most common (3.7 and 0.8%, respectively), followed by K101E (0.4%) and Y181C (0.4%), with no significant differences in the frequency between subtype B and non-B clades. Mutations potentially reducing RPV susceptibility were found in 2.5% of sequences, and they included V179D (1.6%) and G190A (0.8%), with equal distribution among non-B (n=2, 2.5%) and subtype B (n=4, 2.5%) clades. Clustering of RPV mutations was infrequent. Conclusions Prevalence of RPV-associated drug resistance mutations was low in the analysed sample and did not vary across the subtypes. The frequency of variants with potential influence on RPV susceptibility was similar among non-B variants if compared to B clades. Transmitted drug resistance to RPV is uncommon, which makes this a good option for the treatment of ARV-naďve patients; however, genotype resistance testing should remain compulsory before starting an RPV-based regimen. PMID:24746180

Parczewski, Mi?osz; Urba?ska, Anna; Maciejewska, Katarzyna; Witak-J?dra, Magdalena; Leszczyszyn-Pynka, Magdalena

2014-01-01

177

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

PubMed Central

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 instructions about regimens; and regimens tailored to individual patients’ lifestyles. Healthcare workers should address some of the practical and cultural issues around ART medicine whilst policy-makers should develop appropriate social policy to promote adherence among ART-prescribed patients. PMID:22563464

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

2012-01-01

178

Maine: Early Head Start Initiatives  

ERIC Educational Resources Information Center

Maine has two initiatives that build on Early Head Start (EHS). The first initiative, Fund for a Healthy Maine, has since 2001 provided tobacco settlement money to existing Head Start and EHS programs to expand the number of children who receive full-day, full-year services. Local programs have the option of using these funds for EHS, depending on…

Center for Law and Social Policy, Inc. (CLASP), 2012

2012-01-01

179

Research Services START UP FUNDS  

E-print Network

/compliance/chreb/ Conjoint Faculties Research Ethics Board New website: www.ucalgary.ca/research/ethics/cfreb Animal Care-up spending (prior to any recruitment of research participants or the acquisition of animals) and timeResearch Services START UP FUNDS www.ucalgary.ca/research START UP FUNDS From time to time some

de Leon, Alex R.

180

COMPONENT User's Guide Getting started  

E-print Network

the files it will create a Program Manager group called COMPONENT. This group will display icons on the COMPONENT icon with the mouse. When COMPONENT starts your screen should look like this: Log window (a child the program starts a single child window titled Log is open on the desktop. This window is used by COMPONENT

Page, Roderic

181

Nebraska: Early Head Start Initiative  

ERIC Educational Resources Information Center

Since 1999, Nebraska's Early Head Start Infant/Toddler Quality Initiative has supported Early Head Start (EHS) and community child care partnerships to improve the quality and professionalism of infant and toddler care. EHS programs apply to receive funding to establish partnerships with center-based or home-based child care.The initiative has…

Center for Law and Social Policy, Inc. (CLASP), 2012

2012-01-01

182

The journey to antiretroviral therapy in Karnataka, India: who was lost on the road?  

PubMed Central

Introduction One important operational challenge facing antiretroviral treatment (ART) programmes in low- and middle-income countries is the loss to follow-up between diagnosis of human immunodeficiency virus (HIV) and initiation of ART. This is a major obstacle to achieving universal access to ART. This study from Karnataka, India, tried to measure such losses by determining the number of HIV-positive individuals diagnosed, the number of them reaching ART centres, the number initiated on ART and the reasons for non-initiation of ART. Methods A review of records routinely maintained under the National AIDS Control Programme (NACP) was carried out in six districts of Karnataka. HIV-positive persons diagnosed during the months from January to June 2011 in 233 public HIV-testing sites were followed up until December 2011 based on the pre-ART registers. A chi-square test was used to assess statistical significance. Results Of 2291 HIV-positive persons diagnosed (52% male; mean age of 35 years), 1829 (80%) reached ART centres. Of the latter, 1166 (64%) were eligible for ART, and 959 (82%) were initiated on treatment. Overall losses (attrition) on the road between HIV diagnosis and ART initiation were 669 (29%). Deaths, migration and not willing to go to the ART centres were cited as the main known reasons for not reaching ART centres. For ART-eligible individuals who did not initiate ART, the most common known reasons for non-initiation included dying before initiation of ART and not being willing to start ART. Conclusions In a large state of India, eight in ten HIV-positive persons reached ART centres, and of those found ART eligible, 82% start treatment. Although this is an encouraging achievement, the programme needs to take further steps to improve the current performance by further reducing pre-ART attrition. We recommend online registering of diagnosed HIV-positive patients to track the patients more efficiently. PMID:23985346

Shastri, Suresh; Sathyanarayna, Srinath; Nagaraja, Sharath Burugina; Kumar, Ajay MV; Rewari, Bharat; Harries, Anthony D; Zachariah, Rony

2013-01-01

183

Effectiveness of first-line antiretroviral therapy in the IPEC cohort, Rio de Janeiro, Brazil  

PubMed Central

Background While Brazil has had a long-standing policy of free access to antiretroviral therapy (ART) for all in need, the epidemiological impact of ART on human immunodeficiency virus (HIV) RNA suppression in this middle-income country has not been well evaluated. We estimate first-line ART effectiveness in a large Brazilian cohort and examine the socio-demographic, behavioral, clinical and structural factors associated with virologic suppression. Methods Virologic suppression on first-line ART at 6, 12, and 24 months from start of ART was defined as having a viral load measurement ?400 copies/mL without drug class modification and/or discontinuation. Drug class modification and/or discontinuation were defined based on the class of a particular drug. Quasi-Poisson regression was used to quantify the association of factors with virologic suppression. Results From January 2000 through June 2010, 1311 patients started first-line ART; 987 (75%) patients used NNRTI-based regimens. Virologic suppression was achieved by 77%, 76% and 68% of patients at 6, 12 and 24 months, respectively. Factors associated with virologic suppression at 12 months were: >8 years of formal education (compared to <4 years, risk ratio (RR) 1.13, 95% confidence interval (95% CI) 1.03-1.24), starting ART in 2005-2010 (compared to 2000-2004, RR 1.25 95% CI 1.15-1.35), and clinical trial participation (compared to no participation, RR 1.08 95% CI 1.01-1.16). Also at 12 months, women showed less virologic suppression compared to heterosexual men (RR 0.90 95% CI 0.82-0.99). For the 24-month endpoint, in addition to higher education, starting ART in the later period, and clinical trial participation, older age and an NNRTI-based regimen were also independently associated with virologic suppression. Conclusions Our results show that in Brazil, a middle-income country with free access to treatment, over three-quarters of patients receiving routine care reached virologic suppression on first-line ART by the end of the first year. Higher education, more recent ART initiation and clinical trial participation were associated with improved outcomes both for the 12-month and the 24-month endpoints, suggesting that further studies are needed to understand what aspects relating to these factors lead to higher virologic suppression. PMID:25206924

2014-01-01

184

The START III bargaining space  

SciTech Connect

The declining state of the Russian military and precarious Russian economic condition will give the US considerable advantages at the START III bargaining table. Taking the US-RF asymmetries into account, this paper discusses a menu of START III measures the US could ask for, and measures it could offer in return, in attempting to negotiate an equitable treaty. Measures the US might seek in a START III treaty include: further reductions in deployed strategic nuclear warheads, irreversibility of reductions through warhead dismantlement; beginning to bring theater nuclear weapons under mutual control, and increased transparency into the Russian nuclear weapons complex. The US may, however, wish to apply its bargaining advantages to attempting to achieve the first steps toward two long-range goals that would enhance US security: bringing theater nuclear weapons into the US-RF arms control arena, and increasing transparency into the Russian nuclear weapons complex. In exchange for measures relating to these objectives, the US might consider offering to Russia: Further strategic weapons reductions approaching levels at which the Russians believe they could maintain a degree of parity with the US; Measures to decrease the large disparities in potential deliver-system uploading capabilities that appear likely under current START II/START III scenarios; and Financial assistance in achieving START II/START III reductions as rapidly as is technically possible.

Karas, T.H.

1998-08-01

185

78 FR 2038 - Notice of Availability of Proposed New Starts and Small Starts Policy Guidance  

Federal Register 2010, 2011, 2012, 2013, 2014

...guidance to sponsors of New Starts and Small Starts projects, and inviting comment...apply in evaluating projects seeking New Starts and Small Starts funding...criteria required for New Starts and Small Starts projects. DATES: Comments...

2013-01-09

186

Cutaneous Adverse Reactions to Highly Antiretroviral Therapy in HIV-Positive Patients  

PubMed Central

Adverse drug reactions to highly antiretroviral therapy (HAART) are major obstacles in its success. Although overall mortality from HIV has dramatically declined owing to HAART, these antiretroviral regimens have been associated with a wide spectrum of severe cutaneous reactions. The severity of cutaneous adverse reactions varies greatly, and some may be difficult to manage. To optimize adherence and efficacy of antiretroviral treatment, clinicians must focus on preventing adverse effects whenever possible, and distinguish those that are self-limited from those that are potentially serious. This paper presents the case of a serious cutaneous adverse reaction to Atripla in a HIV-positive 50-year-old Caucasian woman. PMID:24932169

Pistone, G.; Pistone, A.; Sorbello, D.; Viviano, E.; Bongiorno, M.R.

2014-01-01

187

Could antiretroviral neurotoxicity play a role in the pathogenesis of cognitive impairment in treated HIV disease?  

PubMed

Whilst effective antiretroviral therapy is protective against the more severe forms of HIV-associated brain disease, there remains a large burden of clinically symptomatic cognitive impairment in the modern era. Although several potential pathogenic mechanisms have been proposed, the underlying pathology remains elusive. In this review, we summarize the evidence describing neuronal toxicity of antiretroviral agents themselves in both preclinical and clinical situations, as well as the potential pathological mechanisms underlying this toxicity. We also consider the implications for future practice and clinical research in which case determining optimal antiretroviral combinations that effectively suppress HIV replication whilst minimizing neurotoxic effects on the central nervous system may become paramount. PMID:25426811

Underwood, Jonathan; Robertson, Kevin R; Winston, Alan

2014-11-25

188

Insurability of HIV-positive people treated with antiretroviral therapy in Europe: collaborative analysis of HIV cohort studies  

PubMed Central

Objective: To increase equitable access to life insurance for HIV-positive individuals by identifying subgroups with lower relative mortality. Design: Collaborative analysis of cohort studies. Methods: We estimated relative mortality from 6 months after starting antiretroviral therapy (ART), compared with the insured population in each country, among adult patients from European cohorts participating in the ART Cohort Collaboration (ART-CC) who were not infected via injection drug use, had not tested positive for hepatitis C, and started triple ART between 1996–2008. We used Poisson models for mortality, with the expected number of deaths according to age, sex and country specified as offset. Results: There were 1236 deaths recorded among 34?680 patients followed for 174?906 person-years. Relative mortality was lower in patients with higher CD4 cell count and lower HIV-1 RNA 6 months after starting ART, without prior AIDS, who were older, and who started ART after 2000. Compared with insured HIV-negative lives, estimated relative mortality of patients aged 20–39 from France, Italy, United Kingdom, Spain and Switzerland, who started ART after 2000 had 6-month CD4 cell count at least 350?cells/?l and HIV-1 RNA less than104?copies/ml and without prior AIDS was 459%. The proportion of exposure time with relative mortality below 300, 400, 500 and 600% was 28, 43, 61 and 64%, respectively, suggesting that more than 50% of patients (those with lower relative mortality) could be insurable. Conclusion: The continuing long-term effectiveness of ART implies that life insurance with sufficiently long duration to cover a mortgage is feasible for many HIV-positive people successfully treated with ART for more than 6 months. PMID:23449349

Kaulich-Bartz, Josee; Dam, Wayne; May, Margaret T.; Lederberger, Bruno; Widmer, Urs; Phillips, Andrew N.; Grabar, Sophie; Mocroft, Amanda; Vilaro, Josep; van Sighem, Ard; Moreno, Santiago; Dabis, François; Monforte, Antonella D’Arminio; Teira, Ramon; Ingle, Suzanne M.; Sterne, Jonathan A.C.

2013-01-01

189

Trainee: _________________________________ PI: _________________________________ Employee Start Date: ______________________  

E-print Network

Trainee: _________________________________ PI: _________________________________ Employee Start Date: ______________________ SCIPP Laboratory-Specific Safety Training Checklist Prior to beginning&S Laboratory Safety Training 2. Read and understand the contents of the UCSC Lab Safety Manual (http

California at Santa Cruz, University of

190

Quantum Espresso Quick Start Introduction  

E-print Network

Quantum Espresso Quick Start Introduction Quantum Espresso (http://www.quantum properties eg., phonon dispersion, NMR shifts and band structure to name a few. Quantum Espresso is available. Matter 21, 395502 (2009). Online Guide for QE : http://www.quantum

Bjørnstad, Ottar Nordal

191

Psychiatric Advance Directives: Getting Started  

MedlinePLUS

... Getting Started State by State Info FAQs Educational Webcasts Links Current Research In the News Legal Issues ... How to write a Psychiatric Advance Directive?" View webcast (15:04) What are Psychiatric Advance Directives? View ...

192

Viral tropism and antiretroviral drug resistance in HIV-1 subtype C-infected patients failing highly active antiretroviral therapy in Johannesburg, South Africa.  

PubMed

Reports show that up to 30% of antiretroviral drug-naive patients in Johannesburg have CXCR4-utilizing HIV-1 subtype C. We assessed whether HIV-1 subtype C-infected individuals failing highly active antiretroviral therapy (HAART) have a higher proportion of CXCR4-utilizing viruses compared to antiretroviral drug-naive patients. The V3 loop was sequenced from plasma from 100 randomly selected HAART-failing patients, and tropism was established using predictive algorithms. All patients harbored HIV-1 subtype C with at least one antiretroviral drug resistance mutation. Viral tropism prediction in individuals failing HAART revealed similar proportions (29%) of X4-utilizing viruses compared to antiretroviral drug-naive patients (30%). Findings are in contrast to reports from Durban in which 60% of HAART-failing subjects harbored X4/dual/mixed-tropic viruses. Despite differences in proportions of X4-tropism within South Africa, the high proportion of thymidine analogue mutations (TAMs) and CXCR4-utilizing HIV-1 highlights the need for intensified monitoring of HAART patients and the predicament of diminishing drug options, including CCR5 antagonists, for patients failing therapy. PMID:24224886

Ketseoglou, Irene; Lukhwareni, Azwidowi; Steegen, Kim; Carmona, Sergio; Stevens, Wendy S; Papathanasopoulos, Maria A

2014-03-01

193

Viral Tropism and Antiretroviral Drug Resistance in HIV-1 Subtype C-Infected Patients Failing Highly Active Antiretroviral Therapy in Johannesburg, South Africa  

PubMed Central

Abstract Reports show that up to 30% of antiretroviral drug-naive patients in Johannesburg have CXCR4-utilizing HIV-1 subtype C. We assessed whether HIV-1 subtype C-infected individuals failing highly active antiretroviral therapy (HAART) have a higher proportion of CXCR4-utilizing viruses compared to antiretroviral drug-naive patients. The V3 loop was sequenced from plasma from 100 randomly selected HAART-failing patients, and tropism was established using predictive algorithms. All patients harbored HIV-1 subtype C with at least one antiretroviral drug resistance mutation. Viral tropism prediction in individuals failing HAART revealed similar proportions (29%) of X4-utilizing viruses compared to antiretroviral drug-naive patients (30%). Findings are in contrast to reports from Durban in which 60% of HAART-failing subjects harbored X4/dual/mixed-tropic viruses. Despite differences in proportions of X4-tropism within South Africa, the high proportion of thymidine analogue mutations (TAMs) and CXCR4-utilizing HIV-1 highlights the need for intensified monitoring of HAART patients and the predicament of diminishing drug options, including CCR5 antagonists, for patients failing therapy. PMID:24224886

Ketseoglou, Irene; Lukhwareni, Azwidowi; Steegen, Kim; Carmona, Sergio; Stevens, Wendy S.

2014-01-01

194

Metabolic complications of antiretroviral therapy in HIV-infected children.  

PubMed

The purpose of this review is to describe the metabolic complications associated with antiretroviral therapy in HIV-infected children. As a result of extensive research over the last 10 years, there is a greater awareness and understanding of these conditions. However, in resource-limited settings, where the majority of HIV-infected children live, the prevalence and risk factors of metabolic complications are largely unknown. Limited diagnostic resources contribute to this impediment. Therapies for these conditions are still under investigation, including prevention and optimal treatment of reduced bone mineral density, osteopaenia and osteoporosis. Future research goals should be directed towards closing the diagnostic and treatment gaps between rich and poor settings. PMID:18370857

Eley, Brian

2008-01-01

195

Antiretroviral Therapy in Resource-Poor Countries: Illusions and Realities  

PubMed Central

The prospects for antiretroviral therapy in resource-poor settings have changed recently and considerably with the availability of generic drugs, the drastic price reduction of brand-name drugs, and the simplification of treatment. However, such cost reductions, although allowing the implementation of large-scale donor programs, have yet to render treatment accessible and possible in the general population. Successfully providing HIV treatment in high-prevalence/high-caseload countries may require that we redefine the problem as a public health mass therapy program rather than a multiplication of clinical situations. The public health goal cannot simply be the reduction of morbidity and mortality for those treated but must be the reduction in morbidity and mortality for the many, that is, at a population level. PMID:15933242

Desvarieux, Moďse; Landman, Roland; Liautaud, Bernard; Girard, Pierre-Marie

2005-01-01

196

[Policy dilemmas in providing antiretroviral treatment in Brazil].  

PubMed

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. PMID:21120341

do Lago, Regina Ferro; Costa, Nilson do Rosário

2010-11-01

197

Antiretroviral-based HIV prevention strategies for women  

PubMed Central

Almost three decades have elapsed since researchers identified HIV as the cause of AIDS, with current estimates from UNAIDS that 33.4 million adults were living with HIV/AIDS in 2008. Two-thirds of this burden of disease is in Sub-Saharan Africa, and 60% of those infected are women. The disease still remains incurable and current prevention strategies including abstinence, male/female condom use and male circumcision are only partially effective. New strategies to curb the epidemic are urgently needed. Scientists are diligently exploring HIV prevention methods that are safe, effective and affordable. These new biological interventions include oral pre- exposure prophylaxis using oral antiretroviral (ARV) drugs, ARV treatment in HIV-infected persons to reduce transmission and topical ARV-based microbicide formulations. PMID:20954882

Chirenje, Z Mike; Marrazzo, Jeanne; Parikh, Urvi M.

2015-01-01

198

African Mitochondrial DNA Subhaplogroups and Peripheral Neuropathy during Antiretroviral Therapy  

PubMed Central

Susceptibility to peripheral neuropathy during antiretroviral therapy with nucleoside reverse transcriptase inhibitors (NRTIs) was previously associated with a European mitochondrial DNA (mtDNA) haplogroup among non-Hispanic white persons. To determine if NRTI-associated peripheral neuropathy was related to mtDNA variation in non-Hispanic black persons, we sequenced mtDNA of participants from AIDS Clinical Trials Group study 384. Of 156 non-Hispanic blacks with genomic data, 51 (33%) developed peripheral neuropathy. In a multivariate model, African mtDNA subhaplogroup L1c was an independent predictor of peripheral neuropathy (OR=3.7, 95% CI 1.1-12.0). An African mtDNA subhaplogroup is for the first time implicated in susceptibility to NRTI-associated toxicity. PMID:20402593

Canter, Jeffrey A.; Robbins, Gregory K.; Selph, Doug; Clifford, David B.; Kallianpur, Asha R.; Shafer, Robert; Levy, Shawn; Murdock, Deborah G.; Ritchie, Marylyn D.; Haas, David W.; Hulgan, Todd

2010-01-01

199

Antiretroviral bioanalysis methods of tissues and body biofluids  

PubMed Central

Research in the many areas of HIV treatment, eradication and prevention has necessitated measurement of antiretroviral (ARV) concentrations in nontraditional specimen types. To determine the knowledgebase of critical details for accurate bioanalysis, a review of the literature was performed and summarized. Bioanalytical assays for 31 ARVs, including metabolites, were identified in 205 publications measuring various tissues and biofluids. 18 and 30% of tissue or biofluid methods, respectively, analyzed more than one specimen type; 35–37% of the tissue or biofluid methods quantitated more than one ARV. 20 and 76% of tissue or biofluid methods, respectively, were used for the analysis of human specimens. HPLC methods with UV detection predominated, but chronologically MS detection began to surpass. 40% of the assays provided complete intra- and inter-assay validation data, but only 9% of publications provided any stability data with even less for the prevalent ARV in treatments. PMID:23394701

DiFrancesco, Robin; Maduke, Getrude; Patel, Rutva; Taylor, Charlene R; Morse, Gene D

2013-01-01

200

Fibrinolytic changes in pregnant women on highly active antiretroviral therapy  

PubMed Central

Objectives: To report on the changes in fibrinolytic activity in human immunodeficiency virus (HIV) infected pregnant women who are undergoing highly active antiretroviral therapy (HAART). Methods: Blood was collected from 50 HIV positive women on HAART (test subjects), and 50 HIV positive women not on HAART (controls). These women were attending the prevention of mother to child clinic (PMTCT) of the University of Benin Teaching Hospital, Benin City, Nigeria from January to June 2014. Standard manual techniques were used to estimate plasma fibrinogen concentration (PFC), euglobulin lysis time (ELT), packed cell volume (PCV), and plasma viscosity (PV). Results: The mean ± standard error of mean (SEM) of PFC was 4.02±0.13g/l and ELT from the test subjects was 378±15 mins was significantly higher (p<0.05) compared with the control subjects (PFC 3.46±0.12g/l and ELT 267±9.0mins). The PCV or hematocrit values in the test subject was 29.1±0.38%, which was significantly lower (p<0.05) compared with the control subject (31.3±0.43%). The PV in the test subject was 1.76±0.02 mPa/s, while the control subjects was higher (1.73±0.02 mPa/s). This increase was not statistically significant (p>0.05). There were differences in the various parameters investigated when the various trimesters were compared. These differences did not, however, follow a particular pattern. Conclusion: Highly active antiretroviral therapy can cause changes in fibrinolytic activity that may predispose pregnant women to hyperfibrinogenemia and anemia. PMID:25719585

Osime, Odaburhine E.; Ese-Onakewhor, Joseph U.; Kolade, Samson O.

2015-01-01

201

Methamphetamine use and neuropsychiatric factors are associated with antiretroviral nonadherence  

PubMed Central

The present study assesses the impact of methamphetamine (METH) on antiretroviral (ART) adherence among HIV+ persons, as well as examines the contribution of neurocognitive impairment and other neuropsychiatric factors (i.e., major depressive disorder (MDD), Antisocial Personality Disorder (ASPD), and Attention Deficit Disorder (ADHD)) for ART nonadherence. We examined HIV+ persons with DSM-IV-diagnosed lifetime history of METH abuse/dependence (HIV+/METH+; n = 67) as compared to HIV+ participants with no history of METH abuse/dependence (HIV+/METH?; n = 50). Ancillary analyses compared these groups with a small group of HIV+/METH+ persons with current METH abuse/dependence (HIV+/CU METH+; n = 8). Nonadherence was defined as self-report of any skipped ART dose in the last four days. Neurocognitive functioning was assessed with a comprehensive battery, covering seven neuropsychological domains. Lifetime METH diagnosis was associated with higher rates of detectable levels of plasma and CSF HIV RNA. When combing groups (i.e., METH+ and METH? participants), univariate analyses indicated co-occurring ADHD, ASPD, and MDD predicted ART nonadherence (p’s<0.10; not lifetime METH status or neurocognitive impairment). A significant multivariable model including these variables indicated that only MDD uniquely predicted ART nonadherence after controlling for the other variables (p<0.05). Ancillary analyses indicated that current METH users (use within 30 days) were significantly less adherent (50% prevalence of nonadherence) than lifetime METH+ users and HIV+/METH-participants, and that neurocognitive impairment was associated with nonadherence (p’s<0.05). METH use disorders are associated with worse HIV disease outcomes and ART medication nonadherence. Interventions often target substance use behaviors alone to enhance antiretroviral treatment outcomes; however, in addition to targeting substance use behaviors, interventions to improve ART adherence may also need to address coexisting neuropsychiatric factors and cognitive impairment to improve ART medication taking. PMID:22530794

Moore, David J.; Blackstone, Kaitlin; Woods, Steven Paul; Ellis, Ronald J.; Atkinson, J. Hampton; Heaton, Robert K.; Grant, Igor

2012-01-01

202

Fanconi Syndrome and Antiretrovirals: It Is Never Too Late.  

PubMed

Antiretroviral medications such as tenofovir have been associated with Fanconi syndrome (FS) usually identified within the first 1-29 months after exposure to the medication. We present a case of life-threatening FS which developed in a 37-year-old woman with HIV after 8 years of asymptomatic tenofovir use. The patient was diagnosed with HIV in 1996 at 20 years of age, hepatitis C 10 years later, and Staphylococcus aureus sepsis with secondary osteomyelitis of the spine 3 years before admission for FS. She developed nausea, vomiting, diarrhea, and generalized weakness over a 2-week time period and presented to the hospital. In the emergency department, her serum potassium was 1.5 mEq/L, bicarbonate was 12 mEq/L, chloride was 111 mEq/L, phosphorus was 1.8 mg/dL, and creatinine was 1.95 mg/dL (baseline, 1.4). Arterial blood gas revealed a non-anion gap (hyperchloremic) metabolic acidosis. Type 2 renal tubular acidosis induced by antiretroviral therapy (ART) was suspected and the ART was discontinued with resolution of the renal abnormalities within 7 days. A non-tenofovir-containing ART regimen consisting of lamivudine/abacavir and efavirenz was begun, and over the next 8 months, the patient was without recurrence of the FS. This case report demonstrates the acute development of FS after prolonged exposure to tenofovir without exposure to additional nephrotoxins such as nonsteroidal medications or aminoglycosides. Tenofovir can cause FS at any time and should be considered in any patient presenting with renal tubular acidosis type 2 while on tenofovir regardless of the duration of drug exposure. PMID:24914503

Luni, Faraz Khan; Khan, Abdur Rahman; Prashar, Rohini; Vetteth, Sandeep; Duggan, Joan M

2014-06-01

203

Novel antiretroviral drugs and renal function monitoring of HIV patients.  

PubMed

Chronic kidney disease is a major comorbidity in patients affected by HIV infection. In addition, the introduction of new antiretroviral agents that interact with creatinine transporters is raising some concerns. In this review we analyze the currently available data about three new antiretroviral drugs and one new pharmacokinetic enhancer. Three of them (rilpivirine, cobicistat, dolutegravir) have shown some interactions with renal function, while tenofovir alafenamide fumarate reduces the plasmatic concentration of the parent drug. The future use of tenofovir alafenamide seems to be encouraging in order to reduce the renal interaction of tenofovir. Rilpivirine, cobicistat, and dolutegravir reduce the tubular secretion of creatinine, inducing a decrease of estimated glomerular filtration rate according to creatinine. Rilpivirine and dolutegravir block the uptake of creatinine from the blood, inhibiting organic cation transporter 2, and cobicistat interacts with the efflux inhibiting multidrug and toxin extrusion protein 1. This effect can then be considered a "reset" of the estimated glomerular filtration rate according to creatinine. However, clinicians should carefully monitor renal function in order to identify possible alterations suggestive of a true renal functional impairment. Owing to the interference of these drugs with creatinine secretion, an alternative way of estimation of glomerular filtration rate would be desirable. However, at the moment, other methods of direct glomerular filtration rate measurement have a high impact on the patient, are not readily available, or are not reliable in HIV patients. Consequently, use of classic formulas to estimate glomerular filtration rate is still recommended. Also, tubular function needs to be carefully monitored with simple tests such as proteinuria, phosphatemia, urinary excretion of phosphate, normoglycemic glycosuria, and excretion of uric acid. PMID:25102336

Maggi, Paolo; Montinaro, Vincenzo; Mussini, Cristina; Di Biagio, Antonio; Bellagamba, Rita; Bonfanti, Paolo; Calza, Leonardo; Cherubini, Chiara; Corsi, Paola; Gargiulo, Miriam; Montella, Francesco; Rusconi, Stefano

2014-01-01

204

Alcohol consumption enhances antiretroviral painful peripheral neuropathy by mitochondrial mechanisms.  

PubMed

A major dose-limiting side effect of human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) chemotherapies, such as the nucleoside reverse transcriptase inhibitors (NRTIs), is a small-fiber painful peripheral neuropathy, mediated by its mitochondrial toxicity. Co-morbid conditions may also contribute to this dose-limiting effect of HIV/AIDS treatment. Alcohol abuse, which alone also produces painful neuropathy, is one of the most important co-morbid risk factors for peripheral neuropathy in patients with HIV/AIDS. Despite the prevalence of this problem and its serious impact on the quality of life and continued therapy in HIV/AIDS patients, the mechanisms by which alcohol abuse exacerbates highly active antiretroviral therapy (HAART)-induced neuropathic pain has not been demonstrated. In this study, performed in rats, we investigated the cellular mechanism by which consumed alcohol impacts antiretroviral-induced neuropathic pain. NRTI 2',3'-dideoxycytidine (ddC; 50 mg/kg) neuropathy was mitochondrial-dependent and PKC?-independent, and alcohol-induced painful neuropathy was PKC?-dependent and mitochondrial-independent. At low doses, ddC (5 mg/kg) and alcohol (6.5% ethanol diet for 1 week), which alone do not affect nociception, together produce profound mechanical hyperalgesia. This hyperalgesia is mitochondrial-dependent but PKC?-independent. These experiments, which provide the first model for studying the impact of co-morbidity in painful neuropathy, support the clinical impression that alcohol consumption enhances HIV/AIDS therapy neuropathy, and provide evidence for a role of mitochondrial mechanisms underlying this interaction. PMID:20726883

Ferrari, Luiz F; Levine, Jon D

2010-09-01

205

Highly active antiretroviral therapy: Does it Sound toxic?  

PubMed Central

Objective The main objective of the current study is to monitor the auditory status in a group of adults with AIDS, receiving Highly Active Antiretroviral Therapy (HAART) (3TC -lamivudine, D4T – stavudine, and efavirenz) in a hospital outpatient clinic in Gauteng. A total sample of 54 adults (between the ages of 18 and 50 years) in the experimental group and 16 in the control group were assessed prospectively following a repeated measures design. All participants were assessed at baseline at three months, and at six months into the treatment. Materials and Methods The participants underwent case history interviews and medical record reviews, otoscopy, and tympanometry, as well as conventional pure tone audiometry and distortion product otoacoustic emission testing. Both descriptive and inferential statistics were used to analyze the data. Results On audiological monitoring, statistically significant changes (P<0.05) were established, only in the experimental group, for pure tone audiometry — with clinically significant changes found at high frequencies. Statistically significant changes with clinically significant changes were obtained for distortion product otoacoustic emissions (DPOAEs) in the experimental group, particularly at high frequencies — implying subclinical hearing function changes; while lack of statistically significant changes with no clinically significant changes were found in the control group. The subclinical hearing changes in the experimental group were also evident in the findings of the subclinical hearing loss group, who, although they had normal pure tone function after six months of follow up, presented with clinical changes on DPOAEs at 6 and 8 kHz. Conclusions Findings highlight the need for closer monitoring of the effects of antiretroviral drugs (ARVs) on hearing, through the use of more sensitive tools of assessment when conducting drug trials. PMID:21430965

Khoza-Shangase, Katijah

2011-01-01

206

Risk factors of chronic hepatitis in antiretroviral-treated HIV infection, without hepatitis B or C viral infection  

PubMed Central

Background Increasing rates of non-AIDS defining illnesses, and in particular liver diseases, have been found after the initiation of highly active antiretroviral therapy. However, there is little evidence concerning the risk factors for and clinical characteristics of liver disease in antiretroviral (ARV)-treated HIV infection, in the absence of hepatitis B or C viral co-infection. Methods A nested case–control study of HIV infected volunteers, matched by starting date of anti-retroviral treatment, was conducted in a Thai cohort studied from Nov 2002 - July 2012. Cases were defined as those subjects with an elevated alanine aminotransferase (ALT???40 IU/L) at two consecutive visits six months apart, while controls were defined as individuals who never demonstrated two consecutive elevated ALT results and had a normal ALT result (< 40 IU/L) at their last visit. Both groups had normal ALT levels prior to ARV initiation. Clinical demographics and risk factors for chronic hepatitis including HIV-related illness, ARV treatment and metabolic diseases were collected and analyzed. Conditional logistic regression was used to determine risk factors for chronic hepatitis in HIV infection. Results A total of 124 matched pairs with HIV infection were followed over 3,195 person-years. The mean age (±SD) was 33.0?±?7.3 years, with 41.1% of subjects being male. The incidence of chronic hepatitis was 5.4 per 100 person-years. The median time from initiation of ARV to chronic hepatitis was 1.3 years (IQR, 0.5-3.5). From univariate analysis; male sex, plasma HIV-1 RNA level?>?5 log 10 copies/ml, metabolic syndrome at baseline visit, high BMI?>?23 kg/m2, abnormal HDL cholesterol at time of ALT elevation and treatment experience with NNRTI plus boosted PI were selected (p value?

2013-01-01

207

HBV influence on Response to Antiretroviral Therapy in Horizontally HIV-HBV Coinfected Patient during Early Childhood  

PubMed Central

Background: There are few studies on pediatric HIV-HBV coinfection, so evidences about relationships between the two viruses are scarce. Objectives: influence of HBV infection on virological and immunological response to antiretroviral therapy (ART) in antiretroviral-naďve horizontally HIV-HBV coinfected subjects during early childhood. Material and methods: observational study on 826 HIV+ subjects in evidence of Craiova Regional Centre (CRC); we analyzed the immunological and virological response at 6-12 months after starting first antiretroviral regimens compared in 2 groups: horizontally HIV-HBV coinfected subjects during early childhood (CoS) versus horizontally HIV infected subjects during early childhood without HBV infection (non-CoS). Results: Number of subjects: CoS-66 subjects, non-CoS-132 subjects. Demographic data: CoS-gender ratio F:M=0.886, the majority lived in rural area (57.58%), mean age on diagnosis-9.288±4.607 years, non-CoS-gender ratio F:M=0.859, the majority lived in urban area (53.79%), mean age on diagnosis-10.742±5.107 years. At baseline, HIV category was: CoS-A-1.52%, B-80.30%, C-18.18%, non-CoS-A-2.27%, B-70.45%, C-27.27% (p Chi2=0.332), the mean CD4+ cell count was: CoS-148.33±148.10 cells/ml, non-CoS-163.17±155.39 cells/ml (p Student=0.521) and the mean HIV viral load (HIV VL) was: CoS-5.06±0.80 lgcopies/ml (for 29 subjects), non-CoS-5.04±0.84 lgcopies/ml (for 61 subjects) (p Student=0.978). At the end of the studied period, the mean increase in CD4+ cell count was: CoS-177.068±141.676 cells/ml, non-CoS-176.015±191.751 cells/ml (p Student=0.969) and the mean decrease in HIV VL was: CoS-5.04±0.79 lgcopies/ml, non-COS-4.69±2.04 lgcopies/ml (p Student=0.911). Conclusions: The presence of HBV coinfection does not influence immunological or virological response to ART. PMID:24778861

Niculescu, Irina; Cup?a, A.M.; Stoian, Andreea Cristina; Dumitrescu, FLorentina; Giubelan, L.I.; Alexandru, D.O.

2013-01-01

208

Incidence and predictors of regimen-modification from first-line antiretroviral therapy in Thailand: a cohort study.  

PubMed

BackgroundAntiretroviral therapy markedly reduced mortality in HIV-infected individuals. However, in the previous studies, up to 50% of patients are compelled to modify their regimen in middle and low-income countries where salvage drug is still limited. This cohort study aimed to investigate the incidence and predictors of regimen modification from the first-line antiretroviral regimen in northern Thailand.MethodsAll HIV-infected patients starting antiretroviral therapy (ART) with generic drug (GPOvir®; stavudine, lamivudine and nevirapine) at a governmental hospital in northern Thailand from 2002 to 2007 were recruited. Baseline characteristics and detailed information of regimen modification until the end of 2010 were ascertained from cohort database and medical charts. As a potential genetic predictor of regimen modification, HLA B allele was determined by bead-based array hybridization (WAKFlow® HLA typing kit). We investigated predictors of the regimen modification using Coxżs proportional hazard models.ResultsOf 979 patients, 914 were eligible for the analysis. The observed events of regimen modification was 377, corresponding to an incidence 13.8/100 person-year-observation (95%CI:12.5-15.3) over 2,728 person years (PY) follow up. The main reasons for regimen modification were adverse effects (73.5%), especially lipodystrophy (63.2%) followed by rash (17.7%). Sixty three patients (17.1%) changed the regimen due to treatment failure. 2% and 19% of patients had HLA-B*35:05 and B*4001, respectively. HLA-B*35:05 was independently associated with rash-related regimen modification (aHR 7.73, 95%CI:3.16-18.9) while female gender was associated with lipodystrophy (aHR 2.11, 95%CI:1.51-2.95). Female gender (aHR 0.54, 95%CI: 0.30-0.96), elder age (aHR 0.56, 95%CI: 0.32-0.99) and having HLA-B*40:01 (aHR 0.29, 95%CI: 0.10-0.82) were protective for treatment failure related modification.ConclusionHLA-B*35:05 and female gender were strong predictors of regimen modification due to rash and lipodystrophy, respectively. Female gender, elder age, and having HLA-B*40:01 had protective effects on treatment failure-related regimen modification. This study provides further information of regimen modification for future tailored ART in Asia. PMID:25361850

Tsuchiya, Naho; Pathipvanich, Panita; Wichukchinda, Nuanjun; Rojanawiwat, Archawin; Auwanit, Wattana; Ariyoshi, Koya; Sawanpanyalert, Pathom

2014-10-30

209

Adherence to standards of quality HIV/AIDS care and antiretroviral therapy in the West Nile Region of Uganda.  

PubMed

BackgroundOver one million people in Uganda are estimated to be infected with HIV and about 20% of these were already accessing antiretroviral therapy (ART), by 2010. There is a dearth of data on adherence to antiretroviral therapy and yet high client load on a weak and resource constrained health system impacts on provision of quality HIV/AIDS care. We assessed adherence to standards of HIV care among health workers in the West Nile Region of Uganda.MethodsWe conducted a cross sectional study in nine health facilities. Records of a cohort of 270 HIV clients that enrolled on ART 12 months prior were assessed. The performance of each health facility on the different indicators of standards of HIV/AIDS care was determined and compared with the recommended national guidelines.ResultsWe found that 94% of HIV clients at all the facilities were assessed for ART eligibility using WHO clinical staging while only two thirds (64.8%) were assessed using CD4. Only 42% and 37% of HIV clients at district hospitals and health centers respectively, received basic laboratory work up prior to ART initiation and about a half (46.7%) of HIV clients at these facilities received the alternative standard 1st line antiretroviral (ARV) regimen. Standards of ART adherence and tuberculosis assessment declined from over 70% to less than 50% and from over 90% to less than 70% respectively, during follow up visits with performance being poorer at the higher level regional referral facility compared to the lower level facilities.ConclusionsAdherence to standards of HIV/AIDS care at facilities was inadequate. Performance was better at the start of ART but declined during the follow up period. Higher level facilities were more likely to adhere to standards like CD4 monitoring and maintaining HIV clients on standard ARV regimen. Efforts geared towards strengthening the health system, including support supervision and provision of care guidelines and job aides are needed, especially for lower level facilities. PMID:25399661

Burua, Aldomoro; Nuwaha, Fred; Waiswa, Peter

2014-11-18

210

The complexities of antiretroviral drug-drug interactions: role of ABC and SLC transporters.  

PubMed

Treatment of human immunodeficiency virus (HIV) infection involves a combination of several antiviral agents belonging to different pharmacological classes. This combination is referred to as highly active antiretroviral therapy (HAART). This treatment has proved to be very effective in suppressing HIV replication, but antiretroviral drugs have complex pharmacokinetic properties involving extensive drug metabolism and transport by membrane-associated drug carriers. Combination drug therapy often introduces complex drug-drug interactions that can result in toxic or sub-therapeutic drug concentrations, compromising treatment. This review focuses on the role of ATP-binding cassette (ABC) membrane-associated efflux transporters and solute carrier (SLC) uptake transporters in antiretroviral drug disposition, and identifies clinically important antiretroviral drug-drug interactions associated with changes in drug transport. PMID:20004485

Kis, Olena; Robillard, Kevin; Chan, Gary N Y; Bendayan, Reina

2010-01-01

211

Ocular Syphilis in HIV-Positive Patients Receiving Highly Active Antiretroviral Therapy  

Microsoft Academic Search

BackgroundFrom October 2001 to October 2002, we have observed a surprisingly high incidence of ocular syphilis in human immunodeficiency virus-positive (HIV+) patients receiving highly active antiretroviral therapy at our clinic.

Gayle P. Balba; Princy N. Kumar; Andrea N. James; Anurag Malani; Allan G. Palestine; James N. Welch; Joseph G. Timpone

2006-01-01

212

A Mathematical Model of Antiretroviral Therapy Evaluation for HIV Type 1  

NASA Astrophysics Data System (ADS)

Treating HIV-infected patients with a combination of several antiretroviral drugs can lead to emergence of the drug-resistant strain. This work proposes a mathematical model to evaluate the emergence of HIV-1 drug resistant during antiretroviral therapy. The model assumes that all susceptible individuals who can be infected by the wildtype strain (sensible to the treatment) or by drug-resistant virus receive antiretroviral therapy. Patients on treatment regimen can evolve to a state of success or failure and for the individuals in therapeutic fail the therapeutic schema is changed. The analysis of system is performed. The existence and stability of the steady states are considered. We address an analytical expression for the reproductive number in a community where antiretroviral therapy are widely used to treat HIV and where both drug sensitive and drug resistant strains are co-circulating.

Raimundo, Silvia Martorano; Venturino, Ezio; Mo Yang, Hyun

2009-09-01

213

AIDS. Author manuscript Early antiretroviral therapy of HIV-infected infants in resource-limited  

E-print Network

be adressed to: Renaud Becquet MESH Keywords Anti-HIV Agents Countries ; Drug Administration Schedule ; HIV Infections ; drug therapy ; transmission ; virology ; HIV-1 pediatric antiretroviral drug formulations, lack of personnel with health care expertise in treatment

Boyer, Edmond

214

Racial Differences in Response to Antiretroviral Therapy for HIV Infection: An AIDS Clinical Trials Group (ACTG) Study Analysis  

PubMed Central

Background.?In the United States, black individuals infected with human immunodeficiency virus (HIV) have higher rates of virologic failure on antiretroviral therapy (ART) and of death compared to white individuals. The cause for these disparities is uncertain. We sought to examine differences in virologic outcomes among antiretroviral-naive clinical trial participants starting randomized ART and to investigate factors to explain the differences. Methods.?Individual-level data from participants initiating ART in 5 AIDS Clinical Trials Group studies were analyzed. Included studies were those conducted during 1998–2006 with a primary outcome of virologic failure. The primary outcome measure was time to virologic failure, regardless of ART changes. Results.?A total of 2495 individuals (1151 black; 1344 white) were included with a median follow-up of 129 weeks. Compared to whites, blacks had an increased hazard of virologic failure (hazard ratio [HR]; 1.7; 95% confidence interval [CI], 1.4–1.9; P < .001), with no evidence of heterogeneity across regimens (P = .97); the association remained after adjustment for measured confounders (HR, 1.4; 95% CI, 1.2–1.6; P < .001). Increased hazard of virologic failure was associated with younger age, higher pretreatment HIV type 1 RNA level, lower pretreatment CD4 cell count, hepatitis C antibody, less education, and recent nonadherence to treatment. Sensitivity analyses with different endpoint definitions demonstrated similar results. Conclusions.?In this analysis, blacks had a 40% higher virologic failure risk than whites that was not explained by measured confounders. The observation was consistent over a range of regimens, suggesting that the difference may be driven by social factors; however, biological factors cannot be ruled out. Further research should identify the sources of racial disparities and develop strategies to reduce them. PMID:24046302

Ribaudo, Heather J.; Smith, Kimberly Y.; Robbins, Gregory K.; Flexner, Charles; Haubrich, Richard; Chen, Yun; Fischl, Margaret A.; Schackman, Bruce R.; Riddler, Sharon A.; Gulick, Roy M.

2013-01-01

215

Determinants of survival in adult HIV patients on antiretroviral therapy in Eastern Uttar Pradesh: A prospective study  

PubMed Central

Background & objectives: The National AIDS Control Organization (NACO) of India has been providing free ARV (antiretroviral) drugs since 2004. By 2012, 486,173 patients had received treatment through the antiretroviral therapy (ART) centres. The objective of this observational study was to assess the factors determining survival of patients on ART under routine programme conditions in an ART centre in north India five years after its inception. Methods: Treatment naive HIV positive patients who were enrolled in the ART centre between May 2009 and May 2010 and started on ART as per the Revised NACO guidelines 2009, were included in the study and outcome was assessed after two years of follow up. Results: A total of 1689 patients were included in the analysis, of whom 272 (16.10%) expired, 205 (12.13%) were lost to follow up (LFU), 526 (31.14%) were transferred out to other facilities and 686 (40.63%) were alive at the end of two years. Majority (92%) of the deaths occurred in the first six months of therapy. Age >30 yr, male gender, poor functional status, haemoglobin level <11 g/dl, body weight <45 kg and CD4 count <100/?l at baseline had significantly higher relative hazard of death. Most LFU also occurred in the first six months and these patients had significantly low CD4 count, weight, haemoglobin level and higher number of patients in Stages III and IV as compared to those who survived. Interpretation & conclusions: The study findings revealed poor survival in the first six months of therapy especially in those with severe immunosuppression. This emphasizes the need for early enrolment into the programme. The high LFU occurring early after initiation of therapy suggests the urgent need to build an efficient patient retrieval system in the programme. PMID:25488442

Chakravarty, Jaya; Tiwary, Narendra K.; Prasad, Shashi Ranjan; Shukla, Saurabh; Tiwari, Anurag; Mishra, Rabindra Nath; Sundar, Shyam

2014-01-01

216

Evaluation of a 6Year Highly Active Antiretroviral Therapy in Chinese HIV1Infected Patients  

Microsoft Academic Search

Objective: To evaluate the long-term efficacy and tolerability of nevirapine (NVP)-based regimens in the treatment of human immunodeficiency virus (HIV)-infected Chinese patients in routine clinical practice. Methods: From October 2002 to May 2004, 57 HIV-1-infected patients commenced antiretroviral therapy (ART), and were followed up to December 2008. These antiretroviral-naďve patients, who originally received two nucleoside reverse transcriptase inhibitors and NVP,

Hua-ying Zhou; Yu-huang Zheng; Yan He; Zi Chen; Meng Liu; Wei Yin; Chun Liu

2010-01-01

217

Epidemiologic studies of adverse effects of anti-retroviral drugs: how well is statistical power reported  

Microsoft Academic Search

SUMMARY Purpose To determine whether there is a difference in average statistical power between pharmacoepidemiologic studies of anti-retroviral adverse drug effects (ADEs) sponsored by for-profit versus non-profit organizations. Methods We studied all published pharmacoepidemiologic studies of ADEs associated with the 15 anti-retroviral drugs approved through the end of 1999. A priori, the primary outcome was the power of each study

Scott D. Halpern; Todd D. Barton; Robert Gross; Sean Hennessy; Jesse A. Berlin; Brian L. Strom

2005-01-01

218

Technology-Based Self-Care Methods of Improving Antiretroviral Adherence: A Systematic Review  

Microsoft Academic Search

BackgroundAs HIV infection has shifted to a chronic condition, self-care practices have emerged as an important topic for HIV-positive individuals in maintaining an optimal level of health. Self-care refers to activities that patients undertake to maintain and improve health, such as strategies to achieve and maintain high levels of antiretroviral adherence.Methodology\\/Principal FindingsTechnology-based methods are increasingly used to enhance antiretroviral adherence;

Parya Saberi; Mallory O. Johnson

2011-01-01

219

Correlates of antiretroviral and antidepressant adherence among depressed HIV-infected patients.  

PubMed

Although crucial for efficacy of pharmacotherapy, adherence to prescribed medication regimens for both antiretrovirals and antidepressants is often suboptimal. As many depressed HIV-infected individuals are prescribed both antiretrovirals and antidepressants, it is important to know whether correlates of nonadherence are similar or different across type of regimen. The HIV Translating Initiatives for Depression into Effective Solutions (HI-TIDES) study was a single-blinded, longitudinal, randomized controlled effectiveness trial comparing collaborative care to usual depression care at three Veterans Affairs HIV clinics. The current investigation utilized self-report baseline interview and chart-abstracted data. Participants were 225 depressed HIV-infected patients who were prescribed an antidepressant (n=146), an antiretroviral (n=192), or both (n=113). Treatment adherence over the last 4 days was dichotomized as "less than 90% adherence" or "90% or greater adherence." After identifying potential correlates of nonadherence, we used a seemingly unrelated regression (SUR) bivariate probit model, in which the probability of adherence to HIV medications and the probability of adherence to antidepressant medications are modeled jointly. Results indicated that 75.5% (n=146) of those prescribed antiretrovirals reported 90%-plus adherence to their antiretroviral prescription and 76.7% (n=112) of those prescribed antidepressants reported 90%-plus adherence to their antidepressant prescription, while 67% of those prescribed both (n=113) reported more than 90% adherence to both regimens. SUR results indicated that education, age, and HIV symptom severity were significant correlates of antiretroviral medication adherence while gender and generalized anxiety disorder diagnosis were significant correlates of adherence to antidepressant medications. In addition, antiretroviral adherence did not predict antidepressant adherence (?=1.62, p=0.17), however, antidepressant adherence did predict antiretroviral adherence (?=2.30, p<0.05). PMID:22536930

Bottonari, Kathryn A; Tripathi, Shanti P; Fortney, John C; Curran, Geoff; Rimland, David; Rodriguez-Barradas, Maria; Gifford, Allen L; Pyne, Jeffrey M

2012-05-01

220

The clinical characteristics and antiretroviral dosing patterns of HIV-infected patients receiving dialysis  

Microsoft Academic Search

The clinical characteristics and antiretroviral dosing patterns of HIV-infected patients receiving dialysis.BackgroundHuman immunodeficiency virus (HIV)-related renal disease is the third leading cause of end-stage renal disease (ESRD) among African Americans aged 24 to 60 years. This study describes the clinical characteristics and antiretroviral dosing patterns of HIV-infected patients receiving dialysis to define the clinical needs of this growing population.MethodsDemographic and

Lynda Anne Szczech; Robert Kalayjian; Rudolph Rodriguez; Samir Gupta; Joseph Coladonato; Jonathan Winston

2003-01-01

221

Early mortality among adults accessing antiretroviral treatment programmes in sub-Saharan Africa  

Microsoft Academic Search

Two-thirds of the world's HIV-infected people live in sub-Saharan Africa, and more than 1.5 million of them die annually. As access to antiretroviral treatment has expanded within the region; early pessimism concerning the delivery of antiretroviral treatment using a large-scale public health approach has, at least in the short term, proved to be broadly unfounded. Immunological and virological responses to

Stephen D. Lawn; Anthony D. Harries; Xavier Anglaret; Landon Myer; Robin Wood

2008-01-01

222

Therapeutic immunization with an inactivated HIV-1 Immunogen plus antiretrovirals versus antiretroviral therapy alone in asymptomatic HIV-infected subjects.  

PubMed

To determine whether the addition of an inactivated-gp120-depleted HIV-1 Immunogen to antiretrovirals (ARTs) conferred a beneficial effect on delaying time to virologic failure relative to that obtained by ARTs alone, a phase II clinical trial was performed in 243 asymptomatic, ART naďve, HIV-1 seropositive adults. The Cox model showed that HIV-1 Immunogen treatment was associated with a 34% decrease in the risk of virologic failure (P = 0.056). When the analysis incorporated baseline HIV-RNA stratification the risk of virologic failure in the HIV-1 Immunogen Arm was significantly reduced a 37% compared to the IFA placebo Arm (P = 0.034). The data suggest that therapeutic immunization plus ARTs could influence virologic control. PMID:15297045

Fernandez-Cruz, E; Moreno, S; Navarro, J; Clotet, B; Bouza, E; Carbone, J; Peńa, J M; Pérez Molina, J; Podzamczer, D; Rubio, R; Ocańa, I; Pulido, F; Viciana, P; Maradona, J A; Blazquez, R; Barros, C; Quereda, C; Rodriguez-Sainz, C; Gil, J; Abad, M L; Díaz, L; Cantó, C; Muńoz, M A; Ferrer, E; Jou, A; Sirera, G; Díaz, M; Lopez, F; Gatell, J M; Gonzalez-Lahoz, J

2004-08-13

223

Long-term virological outcome in children on antiretroviral therapy in the UK and Ireland  

PubMed Central

Objective: To assess factors at the start of antiretroviral therapy (ART) associated with long-term virological response in children. Design: Multicentre national cohort. Methods: Factors associated with viral load below 400?copies/ml by 12 months and virologic failure among children starting 3/4-drug ART in the UK/Irish Collaborative HIV Paediatric Study were assessed using Poisson models. Results: Nine hundred and ninety-seven children started ART at a median age of 7.7 years (inter-quartile range 2.9–11.7), 251 (25%) below 3 years: 411 (41%) with efavirenz and two nucleoside reverse transcriptase inhibitors (EFV?+?2NRTIs), 264 (26%) with nevirapine and two NRTIs (NVP?+?2NRTIs), 119 (12%; 106 NVP, 13 EFV) with non-nucleoside reverse transcriptase inhibitor and three NRTIs (NNRTI?+?3NRTIs), and 203 (20%) with boosted protease inhibitor-based regimens. Median follow-up after ART initiation was 5.7 (3.0–8.8) years. Viral load was less than 400?copies/ml by 12 months in 92% [95% confidence interval (CI) 91–94%] of the children. Time to suppression was similar across regimens (P?=?0.10), but faster over calendar time, with older age and lower baseline viral load. Three hundred and thirty-nine (34%) children experienced virological failure. Although progression to failure varied by regimen (P?

Duong, Trinh; Judd, Ali; Collins, Intira Jeannie; Doerholt, Katja; Lyall, Hermione; Foster, Caroline; Butler, Karina; Tookey, Pat; Shingadia, Delane; Menson, Esse; Dunn, David T.; Gibb, Di M.

2014-01-01

224

Predictors of suboptimal CD4 response among women achieving virologic suppression in a randomized antiretroviral treatment trial, Africa  

PubMed Central

Background A subset of HIV-1 infected patients starting highly active antiretroviral treatment (HAART) experience suboptimal CD4 response (SCR) despite virologic suppression. We studied the rate of and risk factors for SCR among women starting HAART in the ACTG A5208 study conducted in 7 African countries. 741 HAART-naive women with screening CD4 count <200 cells/?L were randomized to start HAART with Tenofovir/Emtricitabine plus either Nevirapine or Lopinavir/Ritonavir. Methods This analysis includes the 625 women who remained on-study through 48 weeks without experiencing protocol-defined virologic failure. We defined SCR as?starting HAART, 11% of women with virologic suppression through 48 weeks experienced SCR. These patients were also less likely to achieve CD4???350 cells/?L by 96 weeks. The underlying causes and long term clinical implications of SCR deserve further investigation. Trial registration Clinicaltrials.gov Identifier: NCT00089505 PMID:24938526

2014-01-01

225

78 FR 49372 - Notice of Availability of New Starts and Small Starts Policy Guidance  

Federal Register 2010, 2011, 2012, 2013, 2014

...commitment criteria for New Starts and Small Starts projects. The final...organizations, a private business, and an interested citizen...2013. Sponsors of New Starts and Small Starts projects...procedural changes made to the steps in the New Starts...

2013-08-14

226

76 FR 37174 - Capital Investment Program-New Starts and Small Starts Program Funds  

Federal Register 2010, 2011, 2012, 2013, 2014

...information on the New Starts, contact Eric Hu...gov mailto:, for project specific issues...Starts and Small Starts programs. After...amount allocated for New Starts and Small Starts...Agreement (FFGA) projects, four pending...

2011-06-24

227

HLA B?5701 status, disease progression, and response to antiretroviral therapy  

PubMed Central

Objective: In addition to hypersensitivity reactions to abacavir, HLA B?5701 has been associated with slow or nonprogression of HIV infection. We explored the effect of HLA B?5701 on CD4+ cell count and viral load in untreated patients and on responses to nonabacavir-containing combination antiretroviral therapy (cART) in a large UK-based cohort. Design: Analysis of a cohort of HIV-infected adults. Methods: In untreated patients, CD4+ cell count and viral load at study entry were compared in HLAB?5701-positive and HLAB?5701-negative individuals and linear regression tested for an interaction effect of viral load and HLA B?5701 on CD4+ cell count. In patients starting a nonabacavir cART regimen, Cox proportional hazards models compared virological responses to cART among HLA B?5701-negative, HLA B?5701-positive, and those not tested. Six-month and 12-month changes in CD4+ cell count were used as outcomes in linear regression to compare immunological response to cART in these groups. Results: ART-naive HLA B?5701-positive individuals had higher CD4+ cell count (P?<0.0001) and lower viral load (P?<0.0001) at study entry than negatives; however, HLA B?5701 status was not found to effect the association between viral load and CD4+ cell count (interaction P value?=?0.09). HLA B?5701-positive patients were more likely to achieve viral suppression than negative patients on a nonabacavir regimen [hazard ratio?=?1.29, 95% confidence interval, CI (1.15–1.54)] and less likely to experience viral rebound [hazard ratio?=?0.61, 95% CI (0.37–0.99)]. Conclusion: Better virological but not immunological responses to cART were seen in HLA B?5701-positive patients on nonabacavir regimens. This study provides further evidence of the potentially beneficial effect of HLA B?5701 on HIV progression. PMID:23921616

2013-01-01

228

Getting Started: Study Abroad 101  

E-print Network

Getting Started: Study Abroad 101 Education Abroad Virginia Tech 526 Prices Fork Rd., Room 131 www more aid to study abroad! · NOTE: FA works differently for non-VT and VT Direct programs: aid released graduation · 50% felt the overseas experience helped them get their first jobs · 84% felt that studying

Buehrer, R. Michael

229

Head Start Center Design Guide.  

ERIC Educational Resources Information Center

This guide contains suggested criteria for planning, designing, and renovating Head Start centers so that they are safe, child-oriented, developmentally appropriate, beautiful, environmentally sensitive, and functional. The content is based on the U.S. General Services Administration's Child Care Center Design Guide, PBS-P140, which was intended…

Administration for Children, Youth, and Families (DHHS), Washington, DC. Head Start Bureau.

230

Rigor Made Easy: Getting Started  

ERIC Educational Resources Information Center

Bestselling author and noted rigor expert Barbara Blackburn shares the secrets to getting started, maintaining momentum, and reaching your goals. Learn what rigor looks like in the classroom, understand what it means for your students, and get the keys to successful implementation. Learn how to use rigor to raise expectations, provide appropriate…

Blackburn, Barbara R.

2012-01-01

231

Start Where Your Students Are  

ERIC Educational Resources Information Center

Starting where your students are means understanding how currencies are negotiated and traded in the classroom. Any behavior that students use to acquire the knowledge and skills needed in the classroom functions as currency. Teachers communicate the kinds of currencies they accept in their classrooms, such as getting good grades; students do…

Jackson, Robyn R.

2010-01-01

232

Math Club Starting in Kindergarten  

ERIC Educational Resources Information Center

Starting a math club as early as kindergarten and having a range of grade levels in attendance can be successful. With the help of the older students, the varied age groups are entertained and excited about attending math club. The purpose of the club is to enrich the classroom mathematics curriculum with hands-on activities and to have members…

Perry, Ann M.

2011-01-01

233

Where innovation starts Dies Natalis  

E-print Network

#12;Wim Schaefer Professor TU/e Architecture, Building and Planning department Sustainable urban: sustainable urban regions. This challenge to the cooperation of scientists, technical designers, industryWhere innovation starts Dies Natalis Sustainability 27 April 2012 Program for the Academic Ceremony

Franssen, Michael

234

Whitepaper: Starting a New Program  

NSDL National Science Digital Library

This is a white paper on starting a geospatial educational program. The paper covers the growth of geospatial technology and introduces a model for creating a program in the field. Useful logic model templates are included to help educators going through the process. This paper would be a useful resource for educators and administrators creating a program from scratch at their institution.

Johnson, Ann B.

235

Off to a Good Start.  

ERIC Educational Resources Information Center

Caring Start is a mobile-clinic program that provides prenatal care, well-baby clinics, childhood immunizations, counseling services, and contraceptives to rural poor families in northwest Pennsylvania. Before the mobile clinic, many rural women (mostly teenagers) went without prenatal health care due to lack of transportation. (LP)

Hoffman, Carl

1994-01-01

236

Starting apparatus for internal combustion engines  

DOEpatents

This report is a patent description for a system to start an internal combustion engine. Remote starting and starting by hearing impaired persons are addressed. The system monitors the amount of current being drawn by the starter motor to determine when the engine is started. When the engine is started the system automatically deactivates the starter motor. Five figures are included.

Dyches, G.M.; Dudar, A.M.

1995-01-01

237

Head Start Impact Study: First Year Findings  

ERIC Educational Resources Information Center

The Congressionally-mandated Head Start Impact Study is being conducted across 84 nationally representative grantee/delegate agencies. Approximately 5,000 newly entering 3- and 4-year-old children applying for Head Start were randomly assigned to either a Head Start group that had access to Head Start program services or to a non-Head Start group…

Puma, Michael; Bell, Stephen; Cook, Ronna; Heid, Camilla; Lopez, Michael

2005-01-01

238

Effects of Highly Active Antiretroviral Therapy Duration and Regimen on Risk for Mother-to-Child Transmission of HIV in Johannesburg, South Africa  

PubMed Central

Background Limited information exists about effects of different highly active antiretroviral therapy (HAART) regimens and duration of regimens on mother-to-child transmission (MTCT) of HIV among women in Africa who start treatment for advanced immunosuppression. Methods Between January 2004 to August 2008, 1,142 women were followed at antenatal antiretroviral clinics in Johannesburg. Predictors of MTCT (positive infant HIV DNA PCR at 4-6 weeks) were assessed with multivariate logistic regression. Results Mean age was 30.2 years (SD=5.0) and median baseline CD4 count was 161 cells/mm3 (SD=84.3). HAART duration at time of delivery was a mean 10.7 weeks (SD=7.4) for the 85% of women who initiated treatment during pregnancy and 93.4 weeks (SD=37.7) for those who became pregnant on HAART. Overall MTCT rate was 4.9% (43/874), with no differences detected between HAART regimens. MTCT rates were lower in women who became pregnant on HAART than those initiating HAART during pregnancy (0.7% versus 5.7%; p=0.01). In the latter group, each additional week of treatment reduced odds of transmission by 8% (95% CI: 0.87-0.99, p=0.02). Conclusion Late initiation of HAART is associated with increased risk of MTCT. Strategies are needed to facilitate earlier identification of HIV-infected women. PMID:20216425

Hoffman, Risa; Black, Vivian; Technau, Karl; Joan van der Merwe, Karin; Currier, Judith; Coovadia, Ashraf; Chersich, Matthew

2010-01-01

239

Persistence of genotypic resistance to nelfinavir among women exposed to prophylactic antiretroviral therapy during pregnancy.  

PubMed

We assessed the development of drug resistance in women exposed to antiretroviral therapy (ART) for prevention of mother-to-child transmission (PMTCT) after 24 weeks postpartum in a prospective cohort of HIV-1-infected women. HIV-1-infected women, who received prophylactic ART during pregnancy, had genotypic resistance testing performed at the start (T1) of and 24 weeks after ART interruption (T2). The women had CD4 counts >250 cells/ml and no AIDS defining conditions. Of the 30 eligible women, the median age was 27 years [25-75% interquartile range (IQR): 21-32] and the median gestational age of ART initiation was 22 weeks (IQR: 19-27): 19 (63.3%) received zidovudine (ZDV) plus lamivudine (3TC) plus nelfinavir (NFV). At entry, most women (96.7%) were asymptomatic (CDC93 A1/A2), with a median CD4 count of 446 (IQR: 353-686) and median viral load (VL) of 8560 copies/ml (IQR: 3,252-19,515). No HIV-1 vertical transmission was observed. HIV subtype B was the most prevalent (70%). The development of new mutations associated with ART resistance was analyzed at T2. NFV resistance was observed in 4 out of 17 (23.5%) patients exposed to this drug: two major mutations D30N (1/17) and L90M (1/17) and minor mutations (N88S, 2/17). Mutations on positions 44, 69, and 118 (1/28) were present on reverse transcriptase (RT) analysis. No new nonnucleoside reverse transcriptase inhibitor (NNRTI)-associated mutation was observed. In this cohort, ART regimens were very efficient at blocking HIV vertical transmission. However, the high rate of NFV-resistant mutations observed in the postpartum period indicates the need for discussion of ART choices during pregnancy and the potential impact on future therapeutic options for these women. Women previously exposed to ART for PMTCT who will start HIV treatment should have genotypic resistance testing performed. PMID:18160009

Kakehasi, Fabiana M; Tupinambás, Unaí; Cleto, Silvia; Aleixo, Agdemir; Lin, Elisa; Melo, Victor H; Aguiar, Regina A L P; Pinto, Jorge A

2007-12-01

240

Development of HIV Reservoir Targeted Long Acting Nanoformulated Antiretroviral Therapies  

PubMed Central

Human immunodeficiency virus (HIV) infection commonly results in a myriad of comorbid conditions secondary to immune deficiency. Infection also affects broad organ system function. Although current antiretroviral therapy (ART) reduces disease morbidity and mortality through effective control of peripheral viral load, restricted infection in HIV reservoirs including gut, lymphoid and central nervous system tissues, is not eliminated. What underlies these events is, in part, poor ART penetrance into each organ across tissue barriers, viral mutation and the longevity of infected cells. We posit that one means to improve these disease outcomes is through nanotechnology. To this end, this review discusses a broad range of cutting-edge nanomedicines and nanomedicine platforms that are or can be used to improve ART delivery. Discussion points include how polymer-drug conjugates, dendrimers, micelles, liposomes, solid lipid nanoparticles and polymeric nanoparticles can be harnessed to best yield cell-based delivery systems. When completely developed, such nanomedicine platforms have the potential to clear reservoirs of viral infection. PMID:25174930

Edagwa, Benson J; Zhou, Tian; McMillan, JoEllyn M; Liu, Xin-Ming; Gendelman, Howard E

2014-01-01

241

Namibian prisoners describe barriers to HIV antiretroviral therapy adherence.  

PubMed

Little is available in scholarly literature about how HIV-positive prisoners, especially in low-income countries, access antiretroviral therapy (ART) medication. We interviewed 18 prisoners at a large prison in Namibia to identify barriers to medication adherence. The lead nurse researcher was a long-standing clinic employee at the prison, which afforded her access to the population. We identified six significant barriers to adherence, including (1) the desire for privacy and anonymity in a setting where HIV is strongly stigmatized; (2) the lack of simple supports for adherence, such as availability of clocks; (3) insufficient access to food to support the toll on the body of ingesting taxing ART medications; (4) commodification of ART medication; (5) the brutality and despair in the prison setting, generally leading to discouragement and a lack of motivation to strive for optimum health; and (6) the lack of understanding about HIV, how it is transmitted, and how it is best managed. Because most prisoners eventually transition back to communitysettings when their sentences are served, investments in prison health represent important investments in public health. PMID:24499371

Shalihu, Nauyele; Pretorius, Louise; van Dyk, Agnes; Vander Stoep, Ann; Hagopian, Amy

2014-01-01

242

Antiretroviral treatment induced catatonia in 16-year-old boy.  

PubMed

We present a 16-year-old boy, who had presented to us with catatonic features of mutism, withdrawal, passive negativism, grimacing, gesturing, echopraxia, and excitement of 5 days duration while taking antiretroviral therapy (ART) for a period of 2 years. He had history of birth asphyxia and acquired HIV infection from his father when the same syringe and needle was used on both of them in a medical setting where the father and son had consulted for treatment of pyrexia of unknown origin. He was the eldest of a three children family in which the biologic father had acquired HIV through extramarital sexual contact with HIV-infected sex workers but was unaware of his HIV positive status till our patient, the 16-year-old was admitted and treated for pulmonary tuberculosis at 14 years of age. The boy's mother had only acquired HIV after having three children with the HIV-positive husband, thus leaving the other two children HIV negative. The catatonia completely resolved within 2 days after the ART was withheld, and risperidone 1 mg twice a day was prescribed. This case highlights the risks of ART and breach of universal precautions. PMID:25624940

Lingeswaran, Anand

2014-01-01

243

In Vitro Assessment of Antiretroviral Drugs Demonstrates Potential for Ototoxicity  

PubMed Central

Several studies have reported an increased incidence of auditory dysfunction among HIV/AIDS patients. We used auditory HEI-OC1 cells in cell viability, flow cytometry and caspases 3/7-activation studies to investigate the potential ototoxicity of fourteen HIV antiretroviral agents: Abacavir, AZT, Delavirdine, Didenosine, Efavirenz, Emtricitabine, Indinavir, Lamivudine, Nefinavir, Nevirapine, Tenofovir, Ritonavir, Stavudine and Zalcitabine, as well as combinations of these agents as used in the common anti-HIV cocktails Atripla™, Combivir™, Epzicom™, Trizivir™, and Truvada™. Our results suggested that most of the single assayed anti-HIV drugs are toxic for HEI-OC1 auditory cells. The cocktails, on the other hand, decreased auditory cells’ viability with high significance, with the following severity gradient: Epzicom ~ Trizivir ? Atripla ~ Combivir > Truvada. Interestingly, our results suggest that Trizivir- and Epzicom-induced cell death would be mediated by a caspase-independent mechanism. L-Carnitine, a natural micronutrient known to protect HEI-OC1 cells against some ototoxic drugs as well as to decrease neuropathies associated with anti-HIV treatments, increased viability of cells treated with Lamivudine and Tenofovir as well as with the cocktail Atripla, but had only minor effects on cells treated with other drugs and drug combinations. Altogether, these results suggest that some frequently used anti-HIV agents could have deleterious effects on patients hearing, and provide arguments in favor of additional studies aimed at elucidating the potential ototoxicity of current as well as future anti-HIV drugs. PMID:24487230

Thein, Pru; Kalinec, Gilda M.; Park, Channy; Kalinec, Federico

2014-01-01

244

Hospitalization risk following initiation of highly active antiretroviral therapy  

PubMed Central

Objectives While highly active antiretroviral therapy (HAART) decreases long-term morbidity and mortality, its short-term effect on hospitalization rates is unknown. The primary objective of this study was to determine hospitalization rates over time in the year after HAART initiation for virological responders and nonresponders. Methods Hospitalizations among 1327 HAART-naďve subjects in an urban HIV clinic in 1997–2007 were examined before and after HAART initiation. Hospitalization rates were stratified by virological responders (? 1 log10 decrease in HIV-1 RNA within 6 months after HAART initiation) and nonresponders. Causes were determined through International Classification of Diseases, 9th Revision (ICD-9) codes and chart review. Multivariate negative binomial regression was used to assess factors associated with hospitalization. Results During the first 45 days after HAART initiation, the hospitalization rate of responders was similar to their pre-HAART baseline rate [75.1 vs. 78.8/100 person-years (PY)] and to the hospitalization rate of nonresponders during the first 45 days (79.4/100 PY). The hospitalization rate of responders fell significantly between 45 and 90 days after HAART initiation and reached a plateau at approximately 45/100 PY from 91 to 365 days after HAART initiation. Significant decreases were seen in hospitalizations for opportunistic and nonopportunistic infections. Conclusions The first substantial clinical benefit from HAART may be realized by 90 days after HAART initiation; providers should keep close vigilance at least until this time. PMID:20002778

Berry, SA; Manabe, YC; Moore, RD; Gebo, KA

2011-01-01

245

Experiences of participating in an antiretroviral treatment adherence club.  

PubMed

In an effort to streamline the management of large numbers of patients receiving antiretroviral therapy (ART) in South Africa, adherence clubs were introduced in some districts in the Western Cape since 2008. Adherence clubs are group clinic visits of approximately 30 ART users who receive group adherence counselling and obtain a supply of medication. We sought to document the experiences of patients attending adherence clubs and health care workers (HCW's) at clinics where clubs were operating. Participants were six ART adherence club members and seven HCW's, which included HIV nurses, medical doctors, pharmacists and counsellors. Data in the form of one-on-one interviews were collected at the Infectious Diseases Clinic of a large district hospital in a peri-urban area in the Western Cape region of South Africa. The interviews covered ART users' experiences of the clubs, advantages and challenges that arose in the context of the club-based method of providing treatment, and the concerns faced by ART users and HCW's with regard to the clubs. The data were analysed using thematic analysis. There were clear benefits to the introduction of adherence clubs, most importantly the reduced amount of time ART users needed to spend at the clinic. Yet, various problems also emerged, the most important one being the logistical problems associated with the timely and correct delivery of drugs. These benefits and disadvantages are discussed in the context of providing ART services to large numbers of patients in post-apartheid South Africa. PMID:25168720

Dudhia, Raashika; Kagee, Ashraf

2015-06-01

246

Mobile clinics for antiretroviral therapy in rural Mozambique  

PubMed Central

Abstract Problem Despite seven years of investment from the President's Emergency Plan For AIDS Relief (PEPFAR), the expansion of human immunodeficiency virus (HIV)-related services continues to challenge Mozambique’s health-care infrastructure, especially in the country’s rural regions. Approach In 2012, as part of a national acceleration plan for HIV care and treatment, Namacurra district employed a mobile clinic strategy to provide temporary manpower and physical space to expand services at four rural peripheral clinics. This paper describes the strategy deployed, the uptake of services and the key lessons learnt in the first 18 months of implementation. Local setting In 2012, Namacurra´s adult population was estimated to be 125?425, and of those 15?803 were estimated to be HIV infected. Although there is consistent government support of antiretroviral therapy (ART) programmes, national coverage remains low, with less than 15% of those eligible having received ART by December 2012. Relevant changes Between April 2012 and September 2013, Namacurra district enrolled 4832 new patients into HIV care and treatment. By using the mobile clinic strategy for ART expansion, the district was able to expand provision of ART from two to six (of a desired seven) clinics by September 2013. Lessons learnt Mobile clinic strategies could rapidly expand HIV care and treatment in under-funded settings in ways that both build local capacity and are sustainable for local health systems. The clinics best serve as a transition to improved capacity at fixed-site services. PMID:25378759

Jequicene, Tito; Blevins, Meridith; José, Eurico; Lankford, Julie R; Wester, C William; Fuchs, Martina C; Vermund, Sten H

2014-01-01

247

Novel drug delivery approaches on antiviral and antiretroviral agents  

PubMed Central

Viruses have the property to replicate very fast in host cell. It can attack any part of host cell. Therefore, the clinical efficacy of antiviral drugs and its bioavailability is more important concern taken into account to treat viral infections. The oral and parenteral routes of drug administration have several shortcomings, however, which could lead to the search for formulating better delivery systems. Now, a day's novel drug delivery systems (NDDS) proved to be a better approach to enhance the effectiveness of the antivirals and improve the patient compliance and decrease the adverse effect. The NDDS have reduced the dosing frequency and shorten the duration of treatment, thus, which could lead the treatment more cost-effective. The development of NDDS for antiviral and antiretroviral therapy aims to deliver the drug devoid of toxicity, with high compatibility and biodegradability, targeting the drug to specific sites for viral infection and in some instances it also avoid the first pass metabolism effect. This article aims to discuss the usefulness of novel delivery approaches of antiviral agents such as niosomes, microspheres, microemulsions, nanoparticles that are used in the treatment of various Herpes viruses and in human immunodeficiency virus (HIV) infections. PMID:23057001

Sharma, Pooja; Chawla, Anuj; Arora, Sandeep; Pawar, Pravin

2012-01-01

248

Lamivudine-PEGylated chitosan: a novel effective nanosized antiretroviral agent.  

PubMed

Due to the fact that a definite treatment for AIDS disease has not been discovered so far, antiretroviral drugs are relatively significant in controlling the disease. In this study, Lamivudine- which is an old and effective anti-AIDS drug- was connected to PEGylated chitosan nanoparticle in order to produce a new and greater version of Lamivudine. First, physicochemical studies such as HNMR, FTIR spectroscopy and CHN analysis were performed to ensure the proper synthesis. Following that, Lamivudine-PEGylated Chitosan (LPC) drug was evaluated in terms of its inhibitory capability in producing HIV virions and its cytotoxicity in different doses. HIV virions were created by transfection of psPAX2, PmzNL4-3 and pMD2.G plasmids into HEK293T cell line. Also, assessment of the P24 amounts of cell supernatant was performed using ELISA method. Among the different doses of LPC drug (0.1, 1, 10 and 100?M), it was found that 0.1?M was the most effective and least toxic dose compared to Lamivudine in the same dose. Results of this study indicate that LPC drug has the ability to inhibit HIV virus replication in a more significant way in comparison to the old drug. Besides, the drug has a low cytotoxicity and is effective with a lower dose. PMID:23808639

Aghasadeghi, Mohammad R; Heidari, Hossein; Sadat, Seyed M; Irani, Shiva; Amini, Safieh; Siadat, Seyed D; Fazlhashemy, Mohammad E; Zabihollahi, Rezvan; Atyabi, Seyed M; Momen, Seyed B; Khosraavy, Mohammad S; Davari, Mehdi; Darvish Mohammadi, Tahmineh; Doroudian, Mohammad; Ardestani, Mehdi S

2013-06-01

249

30 CFR 75.1913 - Starting aids.  

Code of Federal Regulations, 2013 CFR

...2013-07-01 2013-07-01 false Starting aids. 75.1913 Section 75.1913 Mineral Resources...Diesel-Powered Equipment § 75.1913 Starting aids. (a) Volatile fuel starting aids shall be used in accordance with...

2013-07-01

250

30 CFR 75.1913 - Starting aids.  

Code of Federal Regulations, 2014 CFR

...2014-07-01 2014-07-01 false Starting aids. 75.1913 Section 75.1913 Mineral Resources...Diesel-Powered Equipment § 75.1913 Starting aids. (a) Volatile fuel starting aids shall be used in accordance with...

2014-07-01

251

30 CFR 75.1913 - Starting aids.  

Code of Federal Regulations, 2011 CFR

...2011-07-01 2011-07-01 false Starting aids. 75.1913 Section 75.1913 Mineral Resources...Diesel-Powered Equipment § 75.1913 Starting aids. (a) Volatile fuel starting aids shall be used in accordance with...

2011-07-01

252

30 CFR 75.1913 - Starting aids.  

Code of Federal Regulations, 2010 CFR

...2010-07-01 2010-07-01 false Starting aids. 75.1913 Section 75.1913 Mineral Resources...Diesel-Powered Equipment § 75.1913 Starting aids. (a) Volatile fuel starting aids shall be used in accordance with...

2010-07-01

253

30 CFR 75.1913 - Starting aids.  

Code of Federal Regulations, 2012 CFR

...2012-07-01 2012-07-01 false Starting aids. 75.1913 Section 75.1913 Mineral Resources...Diesel-Powered Equipment § 75.1913 Starting aids. (a) Volatile fuel starting aids shall be used in accordance with...

2012-07-01

254

Drug Abuse Prevention Starts with Parents  

MedlinePLUS

... Abuse Prevention Starts with Parents Ages & Stages Listen Drug Abuse Prevention Starts with Parents Article Body Drugs, including ... for a time when drugs may be offered. Drug abuse prevention starts with parents learning how to talk ...

255

School start times for adolescents.  

PubMed

The American Academy of Pediatrics recognizes insufficient sleep in adolescents as an important public health issue that significantly affects the health and safety, as well as the academic success, of our nation's middle and high school students. Although a number of factors, including biological changes in sleep associated with puberty, lifestyle choices, and academic demands, negatively affect middle and high school students' ability to obtain sufficient sleep, the evidence strongly implicates earlier school start times (ie, before 8:30 am) as a key modifiable contributor to insufficient sleep, as well as circadian rhythm disruption, in this population. Furthermore, a substantial body of research has now demonstrated that delaying school start times is an effective countermeasure to chronic sleep loss and has a wide range of potential benefits to students with regard to physical and mental health, safety, and academic achievement. The American Academy of Pediatrics strongly supports the efforts of school districts to optimize sleep in students and urges high schools and middle schools to aim for start times that allow students the opportunity to achieve optimal levels of sleep (8.5-9.5 hours) and to improve physical (eg, reduced obesity risk) and mental (eg, lower rates of depression) health, safety (eg, drowsy driving crashes), academic performance, and quality of life. PMID:25156998

2014-09-01

256

Implementing HIV-1 Genotypic Resistance Testing in Antiretroviral Therapy Programs in Africa: Needs, Opportunities, and Challenges  

PubMed Central

Tremendous progress has been made with the scale-up of antiretroviral therapy in Africa, with an estimated seven million people now receiving antiretroviral therapy in the region. The long-term success of antiretroviral therapy programs depends on appropriate strategies to deal with potential threats, one of which is the emergence and spread of antiretroviral drug resistance. Whilst public health surveillance forms the mainstay of the World Health Organization approach to antiretroviral drug resistance, there is likely to be increasing demand for access to drug resistance testing as programs mature and as HIV clinical management becomes more complex. African-owned research initiatives have helped to develop affordable resistance testing appropriate for use in the region, and have developed delivery models for resistance testing at different levels of the public health system. Some upper-middle-income countries such as Botswana and South Africa have introduced drug resistance testing for selected patient groups to guide clinical management. The scale-up of resistance testing will require substantial expansion of clinical and laboratory capacity in the region, but the expertise and resources exist in Africa to support this. The long-term population health impact and cost-effectiveness of resistance testing in the region will also require further investigation. PMID:24322382

Lessells, Richard J.; Avalos, Ava; de Oliveira, Tulio

2014-01-01

257

HIV and the heart: the impact of antiretroviral therapy: a global perspective.  

PubMed

From a global perspective, cardiovascular disease (CVD) in human immunodeficiency virus (HIV) may result from cardiac involvement upon presentation of opportunistic infections in the presence of advanced immunosuppression, be a consequence of HIV-induced immune activation or derive from antiretroviral therapy-associated dyslipidaemia and insulin resistance. Indeed, in developed countries with unlimited access to antiretroviral therapy CVD has become one of the major causes of death in HIV. Therefore, cardiovascular risk reduction and lifestyle modifications are essential and careful selection of the antiretroviral drugs according to underlying cardiovascular risk factors of great importance. In developing countries with delayed roll-out of antiretroviral therapy pericardial disease (often related to TB), HIV-associated cardiomyopathy, and HIV-associated pulmonary hypertension are the most common cardiac manifestations in HIV. In Africa, the epicentre of the HIV epidemic, dynamic socio-economic and lifestyle factors characteristic of epidemiological transition appear to have positioned the urban African community at the cross-roads between historically prevalent and 'new' forms of CVD, such as coronary artery disease. In this context, cardiovascular risk assessment of HIV-infected patients will become a critical element of care in developing countries similar to the developed world, and access to antiretroviral therapy with little or no impact on lipid and glucose metabolism of importance to reduce CVD in HIV. PMID:24126882

Thienemann, Friedrich; Sliwa, Karen; Rockstroh, Jürgen Kurt

2013-12-01

258

Synergistic effect resulting from combinations of a bifunctional HIV-1 antagonist with antiretroviral drugs.  

PubMed

Development of new anti-HIV therapeutics remains necessary for patients with HIV/AIDS who fail to respond to the current antiretroviral drugs. In this study, we investigated the potential cooperative effects of 2DLT, a bifunctional HIV-1 antagonist with viral inactivation and fusion inhibition activities, combined with different antiretroviral drugs, including HIV entry inhibitors, nucleoside and nonnucleoside reverse-transcriptase inhibitors (NRTIs and NNRTIs), and protease inhibitors. We found that combining 2DLT with these antiretroviral drugs resulted in synergism or strong synergism against infection by both X4 and R5 HIV-1 strains. Although 2DLT alone is highly effective against both NRTI- and NNRTI-resistant HIV-1 strains, combining 2DLT with zidovudine, stavudine, or nevirapine resulted in synergistic or strong synergistic antiviral effect against single or multiple RTI-resistant HIV-1 strains, suggesting that 2DLT can be further developed as a novel anti-HIV-1 drug for addition to the highly active antiretroviral therapy regimen for salvage therapy of patients with HIV/AIDS who are refractory to current antiretroviral drugs. PMID:24977378

Xu, Wei; Wang, Qian; Yu, Fei; Lu, Lu; Jiang, Shibo

2014-09-01

259

Temporal Trends in the Characteristics of Children at Antiretroviral Therapy Initiation in Southern Africa: The IeDEA-SA Collaboration  

PubMed Central

Background Since 2005, increasing numbers of children have started antiretroviral therapy (ART) in sub-Saharan Africa and, in recent years, WHO and country treatment guidelines have recommended ART initiation for all infants and very young children, and at higher CD4 thresholds for older children. We examined temporal changes in patient and regimen characteristics at ART start using data from 12 cohorts in 4 countries participating in the IeDEA-SA collaboration. Methodology/Principal Findings Data from 30,300 ART-naďve children aged <16 years at ART initiation who started therapy between 2005 and 2010 were analysed. We examined changes in median values for continuous variables using the Cuzick's test for trend over time. We also examined changes in the proportions of patients with particular disease severity characteristics (expressed as a binary variable e.g. WHO Stage III/IV vs I/II) using logistic regression. Between 2005 and 2010 the number of children starting ART each year increased and median age declined from 63 months (2006) to 56 months (2010). Both the proportion of children <1 year and ?10 years of age increased from 12 to 19% and 18 to 22% respectively. Children had less severe disease at ART initiation in later years with significant declines in the percentage with severe immunosuppression (81 to 63%), WHO Stage III/IV disease (75 to 62%), severe anemia (12 to 7%) and weight-for-age z-scorestart of therapy. However, even in 2010, a substantial number of infants and children started ART with advanced disease. These results highlight the importance of efforts to improve access to HIV diagnostic testing and ART in children. PMID:24363808

Davies, Mary-Ann; Phiri, Sam; Wood, Robin; Wellington, Maureen; Cox, Vivian; Bolton-Moore, Carolyn; Timmerman, Venessa; Moultrie, Harry; Ndirangu, James; Rabie, Helena; Technau, Karl; Giddy, Janet; Maxwell, Nicola; Boulle, Andrew; Keiser, Olivia; Egger, Matthias; Eley, Brian

2013-01-01

260

The Financial Burden of Morbidity in HIV-Infected Adults on Antiretroviral Therapy in Co^te d'Ivoire  

E-print Network

antiretroviral therapy (ART) in Co^te d'Ivoire. Methodology/Principal Findings: We conducted a crossThe Financial Burden of Morbidity in HIV-Infected Adults on Antiretroviral Therapy in Co^te d-sectional survey. After obtaining informed consent, we interviewed HIV-infected adults taking ART who had

Paris-Sud XI, Université de

261

Cellular HIV-1 DNA load predicts HIV-RNA rebound and the outcome of highly active antiretroviral therapy  

E-print Network

Cellular HIV-1 DNA load predicts HIV-RNA rebound and the outcome of highly active antiretroviral HIV-1 DNA prior to highly active antiretroviral therapy (HAART) initiation predicts its outcome initiation were available. Cellular HIV-1 DNA quantification was performed by a molecular beacon-based real

262

Practical ethics. A fresh start?  

PubMed

You are a newly hired CEO and need to hire a chief operating officer. You really wanted to hire a previous employee, Joe, a COO whose abilities put him ahead of the competition. He was a star performer who has a gift for working with physicians--something that needs special attention at your hospital. Now you've learned he's had several public scenes while drinking in restaurants. He's told you those were isolated incidents, due to personal problems that are over. He'd like to move and make a fresh start. What do you do? PMID:17703546

Palmer, Isaac; Neufelder, Daniel

2007-06-01

263

Contagiousness under antiretroviral therapy and stigmatization toward people with HIV.  

PubMed

Perceived contagiousness is a major dimension underlying HIV-related stigmatization. Antiretroviral therapy (ART) can diminish contagiousness by reducing viral load levels in HIV-infected individuals. To test the assumption that reductions in contagiousness can lead to a decrease in stigmatizing reactions, we conducted an experimental online study. A sample of 752 participants (50.9% female) read a short vignette depicting an HIV-positive individual with either a high or a low viral load and were either given or not given information about the association between viral load and contagiousness. Subsequently, participants were asked to rate their willingness to stigmatize this individual by responding to two measures of social and physical distance. Differences between the low and the high viral load information groups and the combined no-information groups (forming a quasi-control group) were analyzed using analysis of covariance (ANCOVA), controlling for gender and baseline perceptions of contagiousness. The covariates, perceived contagiousness at baseline and gender, were associated with social and physical distancing, but the viral load/information factor was only significant in physical distancing. Planned contrast analyses confirmed that physical distancing in the informed group was lower in the low viral load condition compared to the high viral load condition and to the control group. We thus found evidence for the significant role of perceived contagiousness in the HIV-related stigma and were able to experimentally demonstrate the potential of ART to reduce HIV-related stigmatization by lowering viral load and contagiousness, when these changes are accompanied by a decreased perception of contagiousness. PMID:24779483

Drewes, Jochen; Kleiber, Dieter

2014-01-01

264

The HIV antiretroviral drug efavirenz has LSD-like properties.  

PubMed

Anecdotal reports have surfaced concerning misuse of the HIV antiretroviral medication efavirenz ((4S)-6-chloro-4-(2-cyclopropylethynyl)-4-(trifluoromethyl)-2,4-dihydro-1H-3,1-benzoxazin-2-one) by HIV patients and non-infected teens who crush the pills and smoke the powder for its psychoactive effects. Molecular profiling of the receptor pharmacology of efavirenz pinpointed interactions with multiple established sites of action for other known drugs of abuse including catecholamine and indolamine transporters, and GABAA and 5-HT(2A) receptors. In rodents, interaction with the 5-HT(2A) receptor, a primary site of action of lysergic acid diethylamine (LSD), appears to dominate efavirenz's behavioral profile. Both LSD and efavirenz reduce ambulation in a novel open-field environment. Efavirenz occasions drug-lever responding in rats discriminating LSD from saline, and this effect is abolished by selective blockade of the 5-HT(2A) receptor. Similar to LSD, efavirenz induces head-twitch responses in wild-type, but not in 5-HT(2A)-knockout, mice. Despite having GABAA-potentiating effects (like benzodiazepines and barbiturates), and interactions with dopamine transporter, serotonin transporter, and vesicular monoamine transporter 2 (like cocaine and methamphetamine), efavirenz fails to maintain responding in rats that self-administer cocaine, and it fails to produce a conditioned place preference. Although its molecular pharmacology is multifarious, efavirenz's prevailing behavioral effect in rodents is consistent with LSD-like activity mediated via the 5-HT(2A) receptor. This finding correlates, in part, with the subjective experiences in humans who abuse efavirenz and with specific dose-dependent adverse neuropsychiatric events, such as hallucinations and night terrors, reported by HIV patients taking it as a medication. PMID:23702798

Gatch, Michael B; Kozlenkov, Alexey; Huang, Ren-Qi; Yang, Wenjuan; Nguyen, Jacques D; González-Maeso, Javier; Rice, Kenner C; France, Charles P; Dillon, Glenn H; Forster, Michael J; Schetz, John A

2013-11-01

265

The HIV Antiretroviral Drug Efavirenz has LSD-Like Properties  

PubMed Central

Anecdotal reports have surfaced concerning misuse of the HIV antiretroviral medication efavirenz ((4S)-6-chloro-4-(2-cyclopropylethynyl)-4-(trifluoromethyl)-2,4-dihydro-1H-3,1-benzoxazin-2-one) by HIV patients and non-infected teens who crush the pills and smoke the powder for its psychoactive effects. Molecular profiling of the receptor pharmacology of efavirenz pinpointed interactions with multiple established sites of action for other known drugs of abuse including catecholamine and indolamine transporters, and GABAA and 5-HT2A receptors. In rodents, interaction with the 5-HT2A receptor, a primary site of action of lysergic acid diethylamine (LSD), appears to dominate efavirenz's behavioral profile. Both LSD and efavirenz reduce ambulation in a novel open-field environment. Efavirenz occasions drug-lever responding in rats discriminating LSD from saline, and this effect is abolished by selective blockade of the 5-HT2A receptor. Similar to LSD, efavirenz induces head-twitch responses in wild-type, but not in 5-HT2A-knockout, mice. Despite having GABAA-potentiating effects (like benzodiazepines and barbiturates), and interactions with dopamine transporter, serotonin transporter, and vesicular monoamine transporter 2 (like cocaine and methamphetamine), efavirenz fails to maintain responding in rats that self-administer cocaine, and it fails to produce a conditioned place preference. Although its molecular pharmacology is multifarious, efavirenz's prevailing behavioral effect in rodents is consistent with LSD-like activity mediated via the 5-HT2A receptor. This finding correlates, in part, with the subjective experiences in humans who abuse efavirenz and with specific dose-dependent adverse neuropsychiatric events, such as hallucinations and night terrors, reported by HIV patients taking it as a medication. PMID:23702798

Gatch, Michael B; Kozlenkov, Alexey; Huang, Ren-Qi; Yang, Wenjuan; Nguyen, Jacques D; González-Maeso, Javier; Rice, Kenner C; France, Charles P; Dillon, Glenn H; Forster, Michael J; Schetz, John A

2013-01-01

266

Rapid starting methanol reactor system  

DOEpatents

The invention relates to a methanol-to-hydrogen cracking reactor for use with a fuel cell vehicular power plant. The system is particularly designed for rapid start-up of the catalytic methanol cracking reactor after an extended shut-down period, i.e., after the vehicular fuel cell power plant has been inoperative overnight. Rapid system start-up is accomplished by a combination of direct and indirect heating of the cracking catalyst. Initially, liquid methanol is burned with a stoichiometric or slightly lean air mixture in the combustion chamber of the reactor assembly. The hot combustion gas travels down a flue gas chamber in heat exchange relationship with the catalytic cracking chamber transferring heat across the catalyst chamber wall to heat the catalyst indirectly. The combustion gas is then diverted back through the catalyst bed to heat the catalyst pellets directly. When the cracking reactor temperature reaches operating temperature, methanol combustion is stopped and a hot gas valve is switched to route the flue gas overboard, with methanol being fed directly to the catalytic cracking reactor. Thereafter, the burner operates on excess hydrogen from the fuel cells.

Chludzinski, Paul J. (38 Berkshire St., Swampscott, MA 01907); Dantowitz, Philip (39 Nancy Ave., Peabody, MA 01960); McElroy, James F. (12 Old Cart Rd., Hamilton, MA 01936)

1984-01-01

267

Induction of P-Glycoprotein by Antiretroviral Drugs in Human Brain Microvessel Endothelial Cells  

PubMed Central

The membrane-associated drug transporter P-glycoprotein (P-gp) plays an essential role in drug efflux from the brain. Induction of this protein at the blood-brain barrier (BBB) could further affect the ability of a drug to enter the brain. At present, P-gp induction mediated by antiretroviral drugs at the BBB has not been fully investigated. Since P-gp expression is regulated by ligand-activated nuclear receptors, i.e., human pregnane X receptor (hPXR) and human constitutive androstane receptor (hCAR), these receptors could represent potential pathways involved in P-gp induction by antiretroviral drugs. The aims of this study were (i) to determine whether antiretroviral drugs currently used in HIV pharmacotherapy are ligands for hPXR or hCAR and (ii) to examine P-gp function and expression in human brain microvessel endothelial cells treated with antiretroviral drugs identified as ligands of hPXR and/or hCAR. Luciferase reporter gene assays were performed to examine the activation of hPXR and hCAR by antiretroviral drugs. The hCMEC/D3 cell line, which is known to display several morphological and biochemical properties of the BBB in humans, was used to examine P-gp induction following 72 h of exposure to these agents. Amprenavir, atazanavir, darunavir, efavirenz, ritonavir, and lopinavir were found to activate hPXR, whereas abacavir, efavirenz, and nevirapine were found to activate hCAR. P-gp expression and function were significantly induced in hCMEC/D3 cells treated with these drugs at clinical concentrations in plasma. Together, our data suggest that P-gp induction could occur at the BBB during chronic treatment with antiretroviral drugs identified as ligands of hPXR and/or hCAR. PMID:23836171

Chan, Gary N. Y.; Patel, Rucha; Cummins, Carolyn L.

2013-01-01

268

Induction of P-glycoprotein by antiretroviral drugs in human brain microvessel endothelial cells.  

PubMed

The membrane-associated drug transporter P-glycoprotein (P-gp) plays an essential role in drug efflux from the brain. Induction of this protein at the blood-brain barrier (BBB) could further affect the ability of a drug to enter the brain. At present, P-gp induction mediated by antiretroviral drugs at the BBB has not been fully investigated. Since P-gp expression is regulated by ligand-activated nuclear receptors, i.e., human pregnane X receptor (hPXR) and human constitutive androstane receptor (hCAR), these receptors could represent potential pathways involved in P-gp induction by antiretroviral drugs. The aims of this study were (i) to determine whether antiretroviral drugs currently used in HIV pharmacotherapy are ligands for hPXR or hCAR and (ii) to examine P-gp function and expression in human brain microvessel endothelial cells treated with antiretroviral drugs identified as ligands of hPXR and/or hCAR. Luciferase reporter gene assays were performed to examine the activation of hPXR and hCAR by antiretroviral drugs. The hCMEC/D3 cell line, which is known to display several morphological and biochemical properties of the BBB in humans, was used to examine P-gp induction following 72 h of exposure to these agents. Amprenavir, atazanavir, darunavir, efavirenz, ritonavir, and lopinavir were found to activate hPXR, whereas abacavir, efavirenz, and nevirapine were found to activate hCAR. P-gp expression and function were significantly induced in hCMEC/D3 cells treated with these drugs at clinical concentrations in plasma. Together, our data suggest that P-gp induction could occur at the BBB during chronic treatment with antiretroviral drugs identified as ligands of hPXR and/or hCAR. PMID:23836171

Chan, Gary N Y; Patel, Rucha; Cummins, Carolyn L; Bendayan, Reina

2013-09-01

269

Perception of Antiretroviral Generic Medicines: One-Day Survey of HIV-Infected Patients and Their Physicians in France  

PubMed Central

Background In the interest of cost effectiveness, switching antiretroviral brand name medications to generics is recommended in France since 2013. The study objective was to evaluate the perception of generics per se and antiretroviral generics in HIV-infected patients and their hospital physicians Methods and Findings 556 out of 703 (79%) adult HIV+ outpatients and 116 physicians in 33 clinics were included in a multicentric cross-sectional survey performed in September 2013. Patients completed a self-questionnaire on their perception and acceptability of generics. Physicians completed a questionnaire on their acceptability of switching antiretroviral to generic. Socio-demographic data, medical history and HIV history were collected. Among the 556 patients with a median HIV duration of 13 years, 77% were France native, 59% in active employment, 100% covered by social insurance, 95% on antiretroviral therapy. Seventy-six percent of the patients accepted generics and 55% trusted them overall. Antiretroviral generics were accepted by 44% of them but only by 17% if the pill burden was going to increase. The factor significantly associated with acceptability of antiretroviral generics was acceptance of generics per se (p<0.001). Among the 116 physicians following a median of 100 HIV-patients/year, 75% would prescribe generics, dropping to 26% if the combo had to be broken. Factors significantly associated with willingness to prescribe antiretroviral generics were the absence of concern regarding the chemical entity (OR = 0.33), being aware that the patient would accept generics for other pathologies (OR = 2.04) and would accept antiretroviral generics (OR = 1.94). No factor related to sociodemographic conditions, HIV status or comorbidities was associated with the acceptability of antiretroviral generics. Conclusions Acceptability of antiretroviral generics in this French population was mostly dictated by the patient’s and physician’s knowledge and use of generics overall. It should be improved with an efficient information of both patients and physicians. PMID:25658627

Jacomet, Christine; Allavena, Clotilde; Peyrol, Fleur; Pereira, Bruno; Joubert, Laurence Morand; Bagheri, Haleh; Cotte, Laurent; Garaffo, Rodolphe; Gerbaud, Laurent; Dellamonica, Pierre

2015-01-01

270

Implementing antiretroviral therapy programs in resource-constrained settings: lessons from Monze, Zambia.  

PubMed

We describe the impact of an antiretroviral therapy program on human resource utilization and service delivery in a rural hospital in Monze, Zambia, using qualitative data. We assess project impact on staff capacity utilization, service delivery, and community perception of care. Increased workload resulted in fatigue, low staff morale, and exacerbated critical manpower shortages, but also an increase in users of antiretroviral therapy, improvement in hospital infrastructure and funding, and an overall community satisfaction with service delivery. Integrating HAART programs within existing hospital units and services may be a good alternative to increase overall efficiency. PMID:21368850

Adedimeji, Adebola; Malokota, Oliver; Manafa, Ogenna

2011-05-01

271

Antiretroviral Adherence and the Nature of HIV-Associated Verbal Memory Impairment  

PubMed Central

The authors investigated the relationship between antiretroviral adherence and HIV-associated verbal memory impairment. HIV-positive participants demonstrated poorer verbal memory than HIV-negative participants. Both good (?90%) and poor (<90%) adherers displayed encoding deficits as compared with controls, but only poor adherers exhibited retrieval deficits. Encoding deficits primarily accounted for reduced delayed recall in good adherers, but both encoding and retrieval deficits accounted for reduced delayed recall in poor adherers. The retrieval difference between the adherence groups might be explained by a neuroprotective effect of good antiretroviral adherence or preexisting HIV-related retrieval deficits that result in poorer adherence. PMID:21948894

Wright, Matthew J.; Woo, Ellen; Foley, Jessica; Ettenhofer, Mark L.; Cottingham, Maria E.; Gooding, Amanda L.; Jang, Jiah; Kim, Michelle S.; Castellon, Steve A.; Miller, Eric N.; Hinkin, Charles H.

2013-01-01

272

Hospitalized HIV-infected patients in the era of highly active antiretroviral therapy.  

PubMed

We interviewed 1038 HIV-positive inpatients in public hospitals in Miami, Florida, and Atlanta, Georgia, to examine patient factors associated with use of HIV care, use of antiretroviral therapy, and unprotected sexual intercourse. Multivariate analyses and multiple logistic regression models showed that use of crack cocaine and heavy drinking were associated with never having had an HIV-care provider, high-risk sexual behavior, and not receiving antiretroviral therapy. Inpatient interventions that link and retain HIV-positive persons in primary care services could prevent HIV transmission and unnecessary hospitalizations. PMID:19372520

Metsch, Lisa R; Bell, Christine; Pereyra, Margaret; Cardenas, Gabriel; Sullivan, Tanisha; Rodriguez, Allan; Gooden, Lauren; Khoury, Nayla; Kuper, Tamy; Brewer, Toye; del Rio, Carlos

2009-06-01

273

Slow human immunodeficiency virus type 1 evolution in viral reservoirs in infants treated with effective antiretroviral therapy.  

PubMed

A longitudinal study of viral reservoirs in children initiating highly active antiretroviral therapy (HAART) in early infancy was undertaken to test the hypothesis that early effective treatment affects the persistence of replication-competent viral latency and the evolution of HIV-1 in resting CD4(+) T cells. An end point dilution culture assay was used to measure the frequencies of latently-infected resting CD4(+) T cells harboring replication-competent virus in early and late treated children. Gag, pol, and env also were sequenced and compared to pretreatment sequences. HIV-1-specific humoral and cellular immune responses were also assessed. Blood samples were obtained from 12 HIV-1-infected children who started HAART at a median of 1.9 months of age and who maintained suppression of HIV-1 replication for up to 5.5 years. Replication-competent HIV-1 was recovered from 10/12 (84%) subjects. Evolution in gag, pol, and env was restricted for years in early-treated children. HAART initiated from early infancy does not prevent the establishment of a reservoir of latent provirus, but does significantly limit the evolution of HIV-1 in viral reservoirs. The effect of early therapy on HIV-1 evolution may have implications for long-term pharmacologic control of HIV-1. PMID:17411371

Persaud, Deborah; Ray, Stuart C; Kajdas, Joleen; Ahonkhai, Aima; Siberry, George K; Ferguson, Kimberly; Ziemniak, Carrie; Quinn, Thomas C; Casazza, Joseph P; Zeichner, Steven; Gange, Stephen J; Watson, Douglas C

2007-03-01

274

Prospective Predictors of Unprotected Anal Intercourse among HIV-Seropositive Men Who Have Sex with Men Initiating Antiretroviral Therapy  

PubMed Central

Contemporary HIV prevention efforts are increasingly focused on those already living with HIV/AIDS (i.e., “prevention with positives”). Key to these initiatives is research identifying the most risky behavioral targets. Using a longitudinal design, we examined socio-demographic and psychosocial factors that prospectively predicted unprotected anal intercourse (UAI) in a sample of 134 HIV-seropositive men who have sex with men (MSM) initiating, changing, or re-starting an antiretroviral therapy (ARV) regimen as part of a behavioral intervention study. Computer-based questionnaires were given at baseline and 6 months. In a sequential logistic regression, baseline measures of UAI (Step 1), socio-demographic factors such as Latino ethnicity (Step 2), and psychosocial factors such as crystal methamphetamine use, greater life stress, and lower trait anxiety (Step 3) were predictors of UAI at 6 months. Problem drinking was not a significant predictor. Prevention efforts among MSM living with HIV/AIDS might focus on multiple psychosocial targets, like decreasing their crystal methamphetamine use and teaching coping skills to deal with life stress. PMID:23640652

Pantalone, David W.; Huh, David; Nelson, Kimberly M.; Pearson, Cynthia R.; Simoni, Jane M.

2013-01-01

275

D-dimer and CRP levels are elevated prior to antiretroviral treatment in patients who develop IRIS  

PubMed Central

Biomarkers could be useful in evaluating immune reconstitution inflammatory syndrome (IRIS). A cohort of 45 HIV-1-infected, antiretroviral treatment (ART)-naďve patients with baseline CD4 T cell counts ?100 cells/?L who were started on ART, suppressed HIV-RNA to <50 copies/mL, and seen every 1-3 months for 1 year were retrospectively evaluated for suspected or confirmed IRIS. D-dimer, C-reactive protein (CRP), and selected autoantibodies were analyzed at baseline, 1 and 3 months post-ART in cryopreserved plasma. Median differences between cases and controls were compared with Mann-Whitney and Fischer's exact tests. Sixteen patients (35.6%) developed IRIS (median of 35 days post-ART initiation): unmasking=8, paradoxical=7, autoimmune=1. Pre-ART D-dimer and CRP were higher in IRIS cases versus controls (D-dimer: 0.89mg/L versus 0.66mg/L, p=0.037; CRP: 0.74mg/L versus 0.39mg/L, p=0.022), while D-dimer was higher in unmasking cases at IRIS onset (2.04mg/L versus 0.36mg/L, p=0.05). These biomarkers may be useful in identifying patients at risk for IRIS. PMID:20227921

Porter, Brian O.; Ouedraogo, G. Laissa; Hodge, Jessica; Smith, Margo; Pau, Alice; Roby, Gregg; Kwan, Richard; Bishop, Rachel; Rehm, Catherine; Mican, JoAnn; Sereti, Irini

2010-01-01

276

Reconstitution of immune responses to Pneumocystis carinii pneumonia in patients with HIV infection who receive highly active antiretroviral therapy.  

PubMed

We describe a reconstitution syndrome of immune responses to Pneumocystis carinii pneumonia (PCP) in 2 HIV-infected individuals who received highly active antiretroviral therapy (HAART). Patient 1, who had been successfully treated for PCP 3 years before the initiation of HAART, developed cough and pulmonary shadows 6 weeks after the start of HAART. Patient 2 was introduced HAART immediately after completing the responsive treatment of PCP, and then showed dyspnea and diffuse pulmonary infiltrates 7 months later. Histologic findings of lung-tissue samples showed granulomatous tissue (patient 1) and organizing pneumonia with thickening of alveolar septa (patient 2), and immunohistochemical findings revealed both CD4 and CD8 cell subsets represented in the lesions. The tissue and bronchoalveolar lavage (BAL) specimens showed no organisms, but PCR methods with the BAL samples were positive for P. carinii DNA. It is hypothesized that these second respiratory episodes may have arisen as immune reconstitution syndrome in response to residual P. carinii antigen in the lung. PMID:15080497

Takahashi, Takashi; Nakamura, Tetsuya; Iwamoto, Aikichi

2002-01-01

277

Characterization of peripheral and mucosal immune responses in rhesus macaques on long-term tenofovir and emtricitabine combination antiretroviral therapy  

PubMed Central

Background The goal of antiretroviral therapy (ART) is to suppress virus replication to limit immune system damage. Some have proposed combining ART with immune therapies to boost antiviral immunity. For this to be successful, ART must not impair physiological immune function. Methods We studied the impact of ART (tenofovir and emtricitabine) on systemic and mucosal immunity in uninfected and SIV-infected Chinese rhesus macaques. Subcutaneous ART was initiated 2 weeks after tonsillar inoculation with SIVmac239. Results There was no evidence of immune dysregulation as a result of ART in either infected or uninfected animals. Early virus-induced alterations in circulating immune cell populations (decreased central memory T cells and myeloid dendritic cells) were detected, but normalized shortly after ART initiation. ART-treated animals showed marginal SIV-specific T cell responses during treatment, which increased after ART discontinuation. Elevated expression of CXCL10 in oral, rectal and blood samples and APOBEC3G mRNA in oral and rectal tissues was observed during acute infection and was down-regulated after starting ART. ART did not impact the ability of the animals to respond to tonsillar application of polyICLC with increased CXCL10 expression in oral fluids and CD80 expression on blood myeloid dendritic cells. Conclusion Early initiation of ART prevented virus induced damage and did not impede mucosal or systemic immune functions. PMID:22820802

Jasny, E.; Geer, S.; Frank, I.; Vagenas, P.; Aravantinou, M.; Salazar, A.M.; Lifson, J.D.; Piatak, M; Gettie, A.; Blanchard, J.; Robbiani, M.

2012-01-01

278

How to Start Interventional Radiology  

PubMed Central

Interventional techniques aim to find safer and better ways to treat vascular diseases even in many instances, the interventional radiology solutions has been considered the only treatment option for the patients. Interventional radiologists are specialists who perform minimally invasive procedures instead of surgery or other treatments. These procedures apply various imaging and catheterization procedures in order to diagnose and treat diseases. In each country, interventional radiology practice establishment of varies according to local factors, but following a standard strategy seems better to set up this facility. According to above mentioned points, we decided to establish this specialty in our hospital since 2001 as the pioneer center in Iran. In this presentation we will discuss about our experience for start interventional radiology. PMID:24693402

Ghanaati, Hossein; Firouznia, Kavous; Jalali, Amir Hossein; Shakiba, Madjid

2013-01-01

279

Prevalence of transmitted HIV-1 antiretroviral resistance among patients initiating antiretroviral therapy in Brazil: a surveillance study using dried blood spots  

PubMed Central

Introduction In Brazil, the use of antiretrovirals is widespread: more than 260,000 individuals are currently undergoing treatment. We conducted a survey targeting antiretroviral-naďve individuals who were initiating antiretroviral therapy (ART) according to local guidelines. This survey covered five Brazilian regions. Methods The HIV Threshold Survey methodology (HIV-THS) of the World Health Organization was utilized, and subjects were selected from seven highly populated cities representative of all Brazilian macro-regions. Dried blood spots (DBS) were collected on SS903 collection cards and were transported by regular mail at room temperature to a single central laboratory for genotyping. Results We analysed samples from 329 individuals initiating highly active antiretroviral therapy (HAART), 39 (11.8%) of whom were harbouring transmitted drug resistance (TDR). The mean CD4+ T cell count was 253 cells/µL, and the mean viral load was 142,044 copies/mL. The regional prevalence of resistance was 17.0% in the Northeast, 12.8% in the Southeast, 10.6% in the Central region, 8.5% in the North and 8.5% in the South. The inhibitor-specific TDR prevalence was 6.9% for nucleoside reverse transcriptase inhibitors, 4.9% for non-nucleoside reverse transcriptase inhibitors and 3.9% for protease inhibitors; 3.6% of individuals presented resistance to more than one class of inhibitors. Overall, there were trends towards higher prevalences of subtype C towards the South and subtype F towards the North. Of the DBS samples collected, 9.3% failed to provide reliable results. Discussion We identified variable TDR prevalence, ranging from intermediate to high levels, among individuals in whom HIV disease progressed, thus implying that resistance testing before initiating ART could be effective in Brazil. Our results also indicate that the use of DBS might be especially valuable for providing access to testing in resource-limited and remote settings. PMID:25249214

de Moraes Soares, Celina M P; Vergara, Tania R C; Brites, Carlos; Brito, Jose D U; Grinberg, Gorki; Caseiro, Marcos M; Correa, Carlos; Suffert, Theodoro A; Pereira, Flavio R; Camargo, Michelle; Janini, Luiz M; Komninakis, Shirley; Sucupira, Maria C A; Diaz, Ricardo S

2014-01-01

280

Uptake of WHO Recommendations for First-Line Antiretroviral Therapy in Kenya, Uganda, and Zambia  

PubMed Central

Introduction Antiretroviral therapy (ART) guidelines were significantly changed by the World Health Organization in 2010. It is largely unknown to what extent these guidelines were adopted into clinical practice. Methods This was a retrospective observational analysis of first-line ART regimens in a sample of health facilities providing ART in Kenya, Uganda, and Zambia between 2007-2008 and 2011-2012. Data were analyzed for changes in regimen over time and assessed for key patient- and facility-level determinants of tenofovir (TDF) utilization in Kenya and Uganda using a mixed effects model. Results Data were obtained from 29,507 patients from 146 facilities. The overall percentage of patients initiated on TDF-based therapy increased between 2007-2008 and 2011-2012 from 3% to 37% in Kenya, 2% to 34% in Uganda, and 64% to 87% in Zambia. A simultaneous decrease in stavudine (d4T) utilization was also noted, but its use was not eliminated, and there remained significant variation in facility prescribing patterns. For patients initiating ART in 2011-2012, we found increased odds of TDF use with more advanced disease at initiation in both Kenya (odds ratio [OR]: 2.78; 95% confidence interval [CI]: 1.73-4.48) and Uganda (OR: 2.15; 95% CI: 1.46-3.17). Having a CD4 test performed at initiation was also a significant predictor in Uganda (OR: 1.43; 95% CI: 1.16-1.76). No facility-level determinants of TDF utilization were seen in Kenya, but private facilities (OR: 2.86; 95% CI: 1.45-5.66) and those employing a doctor (OR: 2.86; 95% CI: 1.48-5.51) were more likely to initiate patients on TDF in Uganda. Discussion d4T-based ART has largely been phased out over the study period. However, significant in-country and cross-country variation exists. Among the most recently initiated patients, those with more advanced disease at initiation were most likely to start TDF-based treatment. No facility-level determinants were consistent across countries to explain the observed facility-level variation. PMID:25807553

Duber, Herbert C.; Dansereau, Emily; Masters, Samuel H.; Achan, Jane; Burstein, Roy; DeCenso, Brendan; Gasasira, Anne; Ikilezi, Gloria; Kisia, Caroline; Masiye, Felix; Njuguna, Pamela; Odeny, Thomas; Okiro, Emelda; Roberts, D. Allen; Gakidou, Emmanuela

2015-01-01

281

Clinical Mentorship of Nurse Initiated Antiretroviral Therapy in Khayelitsha, South Africa: A Quality of Care Assessment  

PubMed Central

Introduction To combat the AIDS epidemic and increase HIV treatment access, the South African government implemented a nurse-based, doctor-supported model of care that decentralizes administration of antiretroviral treatment (ART) for HIV positive patients through nurse initiated and managed ART. Médecins Sans Frontičres (MSF) implemented a mentorship programme to ensure successful task-shifting, subsequently assessing the quality of clinical care provided by nurses. Methods A before-after cross-sectional study was conducted on nurses completing the mentorship programme in Khayelitsha, South Africa, from February 2011-September 2012. Routine clinical data from 229 patient folders and 21 self-assessment questionnaires was collected to determine the number of patients initiated on ART by nurses; quality of ART management before-after mentorship; patient characteristics for doctor and nurse ART initiations; and nurse self-assessments after mentorship. Results Twenty one nurses were authorized by one nurse mentor with one part-time medical officer's support, resulting in nurses initiating 77% of ART eligible patients. Improvements in ART management were found for drawing required bloods (91% vs 99%, p?=?0.03), assessing adherence (50% vs 78%, p<0.001) and WHO staging (63% vs 91%, p<0.001). Nurse ART initiation indicators were successfully completed at 95–100% for 11 of 16 indicators: clinical presentation; patient weight; baseline blood work (CD4, creatinine, haemoglobin); STI screening; WHO stage, correlating medical history; medications prescribed appropriately; ART start date; and documented return date. Doctors initiated more patients with TB/HIV co-infection and WHO Stage 3 and 4 disease than nurses. Nurse confidence improved for managing HIV-infected children and pregnant women, blood result interpretation and long-term side effects. Conclusions Implementation of a clinical mentorship programme in Khayelitsha led to nurse initiation of a majority of eligible patients, enabling medical officers to manage complex cases. As mentorship can increase clinical confidence and enhance professional development, it should be considered essential for universal ART access in resource limited settings. PMID:24887260

Green, Ann; de Azevedo, Virginia; Patten, Gabriela; Davies, Mary-Ann; Ibeto, Mary; Cox, Vivian

2014-01-01

282

Heterosexual HIV-1 infectiousness and antiretroviral use: Systematic review of prospective studies of discordant couples  

PubMed Central

Background Recent studies have estimated the reduction in HIV-1 infectiousness with antiretroviral therapy (ART), but high-quality studies such as randomized control trials, accompanied by rigorous adherence counselling, are likely to overestimate the effectiveness of treatment-as-prevention in real-life settings. Methods We attempted to summarize the effect of ART on HIV transmission by undertaking a systematic review and meta-analysis of HIV-1 infectiousness per heterosexual partnership (incidence rate and cumulative incidence over study follow-up) estimated from prospective studies of discordant couples. We used random-effects Poisson regression models to obtain summary estimates. When possible, the analyses were further stratified by direction of transmission (man-to-woman or woman-to-man) and economic setting (high- or low-income countries). Potential causes of heterogeneity of estimates were explored through subgroup analyses. Results Fifty publications were included. Nine allowed comparison between ART and non-ART users within studies (ART-stratified studies), where summary incidence rates were 3.6/100 person-years (95% confidence interval= 2.0-6.5) and 0.2/100 person-years (0.07-0.7) for non-ART- and ART-using couples, respectively (p<0.001), constituting a 91% (79%-96%) reduction in per-partner HIV-1 incidence rate with ART use. The 41 studies that did not stratify by ART use provided estimates with high levels of heterogeneity (I2 statistic) and few reported levels of ART use, making interpretation difficult. Nevertheless, estimates tended to be lower with than without ART use. Infectiousness tended to be higher for low-income than high-income settings, but there was no clear pattern by direction of transmission (man-to-woman and woman-to-man). Conclusions ART substantially reduces HIV-1 infectiousness within discordant couples, based on observational studies, and could play a major part in HIV-1 prevention efforts. However the non-zero risk from partners receiving ART demonstrates that appropriate counselling and other risk reduction strategies for discordant couples are still required. Additional estimates of ART effectiveness by adherence level from real-life settings will be important, especially for persons starting treatment early without symptoms. PMID:23222513

Baggaley, Rebecca F; White, Richard G; Hollingsworth, T Déirdre; Boily, Marie-Claude

2015-01-01

283

Transmitted antiretroviral drug resistance in treatment naďve HIV-infected persons in London in 2011 to 2013  

PubMed Central

Introduction Previously published UK data on HIV transmitted drug resistance (TDR) shows that it ranges between 3 and 9.4% [1,2]. However, there are no recent data from populations where HIV transmission rates are increasing. The aim of this study was to assess the prevalence of TDR in untreated HIV-infected individuals attending three HIV specialist clinics under the HIV Directorate, Chelsea and Westminster Hospital and based throughout London – the Kobler Clinic, 56 Dean Street and West London Centre for Sexual Health. Methods We included all patients with a HIV diagnosis, no history of antiretroviral therapy (ART) intake, attending one of the three clinics (Kobler (K), 56 Dean Street (DS) and West London (WL)), between 2011 and 2013 who started antiretrovirals. Reverse transcriptase (RT) and protease region sequencing was performed using Vircotype virtual phenotype resistance analysis. Drug resistance mutations were identified according to Stanford University HIV Drug Resistance Database (http://hivdb.stanford.edu/). Results Among 1705 HIV-1-infected patients enrolled in the study, 1252 were males (919 were MSM), 107 were females and 346 had no gender recorded. Ethnicity was 51.1% white British/Irish/other, 6.1% African, 2.1% Caribbean, 2.8% Asian, 1.3% Indian/Pakistani/Bangladeshi, 4.2%, other, 3.2% not stated, and 29.2% unknown. 547 were from K (84.3% males, 48.3% MSM), 826 were from DS (84.3% males, 71.9% MSM), and 109 from WL (87.2% males, 56.0% MSM), 223 from other sites not specified. 77.5% (1321 of 1705) of patients had baseline viral resistance testing performed. Prevalence of primary resistance in those with a baseline viral resistance test was 13.5% overall: 19.3% in K, 14.9% in DS, and 14.7% in WL. The most common mutations detected were: NRTI: 184V, 215F, 41L; NNRTI 103N, 179D, 90I; PI 90M, 46I, and 82A. Among patients who tested with TDR, 79.1% had one single mutation, 18.7% and 2.2% exhibited dual or triple class-resistant viruses, respectively. Conclusions This study across a large HIV Medicine Directorate reported an overall TDR prevalence which is higher than that previously published and with significant rates of NNRTI resistance at baseline. PMID:25397492

McFaul, Katie; Lim, Charlotte; Jones, Rachael; Asboe, David; Pozniak, Anton; Sonecha, Sonali; Boffito, Marta; Nwokolo, Nneka

2014-01-01

284

Host and Viral Determinants of Mx2 Antiretroviral Activity  

PubMed Central

ABSTRACT Myxovirus resistance 2 (Mx2/MxB) has recently been uncovered as an effector of the anti-HIV-1 activity of type I interferons (IFNs) that inhibits HIV-1 at an early stage postinfection, after reverse transcription but prior to proviral integration into host DNA. The mechanistic details of Mx2 antiviral activity are not yet understood, but a few substitutions in the HIV-1 capsid have been shown to confer resistance to Mx2. Through a combination of in vitro evolution and unbiased mutagenesis, we further map the determinants of sensitivity to Mx2 and reveal that multiple capsid (CA) surfaces define sensitivity to Mx2. Intriguingly, we reveal an unanticipated sensitivity determinant within the C-terminal domain of capsid. We also report that Mx2s derived from multiple primate species share the capacity to potently inhibit HIV-1, whereas selected nonprimate orthologs have no such activity. Like TRIM5?, another CA targeting antiretroviral protein, primate Mx2s exhibit species-dependent variation in antiviral specificity against at least one extant virus and multiple HIV-1 capsid mutants. Using a combination of chimeric Mx2 proteins and evolution-guided approaches, we reveal that a single residue close to the N terminus that has evolved under positive selection can determine antiviral specificity. Thus, the variable N-terminal region can define the spectrum of viruses inhibited by Mx2. IMPORTANCE Type I interferons (IFNs) inhibit the replication of most mammalian viruses. IFN stimulation upregulates hundreds of different IFN-stimulated genes (ISGs), but it is often unclear which ISGs are responsible for inhibition of a given virus. Recently, Mx2 was identified as an ISG that contributes to the inhibition of HIV-1 replication by type I IFN. Thus, Mx2 might inhibit HIV-1 replication in patients, and this inhibitory action might have therapeutic potential. The mechanistic details of how Mx2 inhibits HIV-1 are currently unclear, but the HIV-1 capsid protein is the likely viral target. Here, we determine the regions of capsid that specify sensitivity to Mx2. We demonstrate that Mx2 from multiple primates can inhibit HIV-1, whereas Mx2 from other mammals (dogs and sheep) cannot. We also show that primate variants of Mx2 differ in the spectrum of lentiviruses they inhibit and that a single residue in Mx2 can determine this antiviral specificity. PMID:24760893

Busnadiego, Idoia; Kane, Melissa; Rihn, Suzannah J.; Preugschas, Hannah F.; Hughes, Joseph; Blanco-Melo, Daniel; Strouvelle, Victoria P.; Zang, Trinity M.; Willett, Brian J.; Boutell, Chris

2014-01-01

285

Timing of Antiretroviral Therapy after Diagnosis of Cryptococcal Meningitis  

PubMed Central

Background Cryptococcal meningitis accounts for 20 to 25% of acquired immunodeficiency syndrome–related deaths in Africa. Antiretroviral therapy (ART) is essential for survival; however, the question of when ART should be initiated after diagnosis of cryptococcal meningitis remains unanswered. Methods We assessed survival at 26 weeks among 177 human immunodeficiency virus–infected adults in Uganda and South Africa who had cryptococcal meningitis and had not previously received ART. We randomly assigned study participants to undergo either earlier ART initiation (1 to 2 weeks after diagnosis) or deferred ART initiation (5 weeks after diagnosis). Participants received amphotericin B (0.7 to 1.0 mg per kilogram of body weight per day) and fluconazole (800 mg per day) for 14 days, followed by consolidation therapy with fluconazole. Results The 26-week mortality with earlier ART initiation was significantly higher than with deferred ART initiation (45% [40 of 88 patients] vs. 30% [27 of 89 patients]; hazard ratio for death, 1.73; 95% confidence interval [CI], 1.06 to 2.82; P = 0.03). The excess deaths associated with earlier ART initiation occurred 2 to 5 weeks after diagnosis (P = 0.007 for the comparison between groups); mortality was similar in the two groups thereafter. Among patients with few white cells in their cerebrospinal fluid (<5 per cubic millimeter) at randomization, mortality was particularly elevated with earlier ART as compared with deferred ART (hazard ratio, 3.87; 95% CI, 1.41 to 10.58; P = 0.008). The incidence of recognized cryptococcal immune reconstitution inflammatory syndrome did not differ significantly between the earlier-ART group and the deferred-ART group (20% and 13%, respectively; P = 0.32). All other clinical, immunologic, virologic, and microbiologic outcomes, as well as adverse events, were similar between the groups. Conclusions Deferring ART for 5 weeks after the diagnosis of cryptococcal meningitis was associated with significantly improved survival, as compared with initiating ART at 1 to 2 weeks, especially among patients with a paucity of white cells in cerebrospinal fluid. (Funded by the National Institute of Allergy and Infectious Diseases and others; COAT ClinicalTrials.gov number, NCT01075152.) PMID:24963568

Boulware, David R.; Meya, David B.; Muzoora, Conrad; Rolfes, Melissa A.; Huppler Hullsiek, Katherine; Musubire, Abdu; Taseera, Kabanda; Nabeta, Henry W.; Schutz, Charlotte; Williams, Darlisha A.; Rajasingham, Radha; Rhein, Joshua; Thienemann, Friedrich; Lo, Melanie W.; Nielsen, Kirsten; Bergemann, Tracy L.; Kambugu, Andrew; Manabe, Yukari C.; Janoff, Edward N.; Bohjanen, Paul R.; Meintjes, Graeme

2014-01-01

286

Financing equitable access to antiretroviral treatment in South Africa  

PubMed Central

Background While South Africa spends approximately 7.4% of GDP on healthcare, only 43% of these funds are spent in the public system, which is tasked with the provision of care to the majority of the population including a large proportion of those in need of antiretroviral treatment (ART). South Africa is currently debating the introduction of a National Health Insurance (NHI) system. Because such a universal health system could mean increased public healthcare funding and improved access to human resources, it could improve the sustainability of ART provision. This paper considers the minimum resources that would be required to achieve the proposed universal health system and contrasts these with the costs of scaled up access to ART between 2010 and 2020. Methods The costs of ART and universal coverage (UC) are assessed through multiplying unit costs, utilization and estimates of the population in need during each year of the planning cycle. Costs are from the provider’s perspective reflected in real 2007 prices. Results The annual costs of providing ART increase from US$1 billion in 2010 to US$3.6 billion in 2020. If increases in funding to public healthcare only keep pace with projected real GDP growth, then close to 30% of these resources would be required for ART by 2020. However, an increase in the public healthcare resource envelope from 3.2% to 5%-6% of GDP would be sufficient to finance both ART and other services under a universal system (if based on a largely public sector model) and the annual costs of ART would not exceed 15% of the universal health system budget. Conclusions Responding to the HIV-epidemic is one of the many challenges currently facing South Africa. Whether this response becomes a “resource for democracy” or whether it undermines social cohesiveness within poor communities and between rich and poor communities will be partially determined by the steps that are taken during the next ten years. While the introduction of a universal system will be complex, it could generate a health system responsive to the needs of all South Africans. PMID:20594368

2010-01-01

287

Effects on Anthropometry and Appetite of Vitamins and Minerals Given in Lipid Nutritional Supplements for Malnourished HIV-Infected Adults Referred for Antiretroviral Therapy: Results From the NUSTART Randomized Controlled Trial  

PubMed Central

Background: The evidence base for effects of nutritional interventions for malnourished HIV-infected patients starting antiretroviral therapy (ART) is limited and inconclusive. Objective: We hypothesized that both vitamin and mineral deficiencies and poor appetite limit weight gain in malnourished patients starting ART and that vitamin and mineral supplementation would improve appetite and permit nutritional recovery. Design: The randomized controlled Nutritional Support for Africans Starting Antiretroviral Therapy trial was conducted in Mwanza, Tanzania, and Lusaka, Zambia. ART-naive adults referred for ART and with body mass index <18.5 kg/m2 received lipid-based nutritional supplements either without (LNS) or with added vitamins and minerals (LNS-VM), beginning before ART initiation. Participants were given 30 g/d LNS from recruitment until 2 weeks after starting ART and 250 g/d from weeks 2 to 6 of ART. Results: Of 1815 patients recruited, 365 (20%) died during the study and 813 (45%) provided data at 12 weeks. Controlling for baseline values, anthropometric measures were consistently higher at 12-week ART in the LNS-VM than in the LNS group but statistically significant only for calf and mid-upper arm circumferences and triceps skinfold. Appetite did not differ between groups. Using piecewise mixed-effects quadratic models including all patients and time points, the main effects of LNS-VM were seen after starting ART and were significant for weight, body mass index, and mid-upper arm circumference. Conclusions: Provision of high levels of vitamins and minerals to patients referred for ART, delivered with substantial macronutrients, increased nutritional recovery but did not seem to act through treatment group differences in appetite. PMID:25501607

Rehman, Andrea M.; Woodd, Susannah; PrayGod, George; Chisenga, Molly; Siame, Joshua; Koethe, John R.; Heimburger, Douglas C.; Kelly, Paul; Friis, Henrik

2015-01-01

288

The Roles of HIV-1 Proteins and Antiretroviral Drug Therapy in HIV-1-Associated Endothelial Dysfunction  

PubMed Central

Since the emergence of highly active antiretroviral therapy (HAART), human immunodeficiency virus-1 (HIV-1)-infected patients have demonstrated dramatic decreases in viral burden and opportunistic infections, and an overall increase in life expectancy. Despite these positive HAART-associated outcomes, it has become increasingly clear that HIV-1 patients have an enhanced risk of developing cardiovascular disease over time. Clinical studies are instrumental in our understanding of vascular dysfunction in the context of HIV-1 infection. However, most clinical studies often do not distinguish whether HIV-1 proteins, HAART, or a combination of these 2 factors cause cardiovascular complications. This review seeks to address the roles of both HIV-1 proteins and antiretroviral drugs in the development of endothelial dysfunction because endothelial dysfunction is the hallmark initial step of many cardiovascular diseases. We analyze recent in vitro and in vivo studies examining endothelial toxicity in response to HIV-1 proteins or in response to the various classes of antiretroviral drugs. Furthermore, we discuss the multiple mechanisms by which HIV-1 proteins and HAART injure the vascular endothelium in HIV-1 patients. By understanding the molecular mechanisms of HIV-1 protein- and antiretroviral-induced cardiovascular disease, we may ultimately improve the quality of life of HIV-1 patients through better drug design and the discovery of new pharmacological targets. PMID:18525451

Kline, Erik R.; Sutliff, Roy L.

2008-01-01

289

Antiretroviral therapy (ART) adherence and correlates to nonadherence among people on ART in Estonia  

Microsoft Academic Search

There are little data on antiretroviral therapy (ART) adherence among patients in Eastern Europe, despite the high incidence of HIV infection and the growing number of HIV-infected individuals who are being prescribed ART. The aim of this study was to measure rates of adherence to ART and factors associated with nonadherence among patients receiving care at an outpatient HIV clinic

Anneli Uusküla; Kaja-Triin Laisaar; Mait Raag; Jelena Šmidt; Svetlana Semjonova; Juta Kogan; K. Rivet Amico; Anjali Sharma; Jack Dehovitz

2012-01-01

290

Recombination favors the evolution of drug resistance in HIV-1 during antiretroviral therapy  

E-print Network

Recombination favors the evolution of drug resistance in HIV-1 during antiretroviral therapy the relationship between recombination and the fixation time of multiple drug resistance mutations after HIV-1 drug et al. [Bretscher, Althaus, Muller, Bonhoeffer, 2004. Recombination in HIV and the evolution of drug

Posada, David

291

Supporting patient adherence to antiretrovirals using mobile phone reminders: Patient responses from South India  

Microsoft Academic Search

There has been exponential growth in the use of mobile phones in India over the last few years, and their potential benefits as a healthcare tool has raised tremendous interest. We used mobile phone reminders to help support adherence to antiretroviral therapy (ART) among HIV patients at an infectious disease clinic in a tertiary hospital in Bangalore. Between March and

Kristi Sidney; Jimmy Antony; Rashmi Rodrigues; Karthika Arumugam; Shubha Krishnamurthy; George Dsouza; Ayesha De Costa; Anita Shet

2012-01-01

292

Barriers to Antiretroviral Medication Adherence in Young HIV-Infected Children  

ERIC Educational Resources Information Center

The purpose of this exploratory study was to examine, from the perspectives of both HIV-infected children and such children's primary guardians, the barriers children face in adhering to combination antiretroviral therapies. Nine HIV-infected young children and 14 guardians of HIV-positive children were interviewed about what the children's lives…

Roberts, Kathleen Johnston

2005-01-01

293

Supporting patient adherence to antiretrovirals using mobile phone reminders: patient responses from South India  

Microsoft Academic Search

There has been exponential growth in the use of mobile phones in India over the last few years, and their potential benefits as a healthcare tool has raised tremendous interest. We used mobile phone reminders to help support adherence to antiretroviral therapy (ART) among HIV patients at an infectious disease clinic in a tertiary hospital in Bangalore. Between March and

Kristi Sidney; Jimmy Antony; Rashmi Rodrigues; Karthika Arumugam; Shubha Krishnamurthy; George Dsouza; Ayesha De Costa; Anita Shet

2011-01-01

294

on TB therapy, which they usually need more urgently, and then give them antiretroviral  

E-print Network

on TB therapy, which they usually need more urgently, and then give them antiretroviral drugs when you talk to academic researchers whose job it is to go and look for problems," says Paul Nunn For more than a decade, the World Health Organization (WHO) has relied on Direct Observed Therapy Short

Cai, Long

295

ASPD Blunts the Effects of HIV and Antiretroviral Treatment on Event-Related Brain Potentials  

Microsoft Academic Search

Several studies have demonstrated that antiretroviral therapy diminishes the adverse effects of HIV\\/AIDS on brain function. Yet, few studies have examined the role of comorbid psychiatric disorders in limiting the magnitude of recovery. The present study examined the effects of the presence versus absence of one such disorder – antisocial personality disorder (ASPD) – on brain function in an HIV-1

Lance O. Bauer; John D. Shanley

2006-01-01

296

Osmotic pump tablets for delivery of antiretrovirals to the vaginal mucosa  

PubMed Central

Vaginal pre-exposure prophylaxis has focused heavily on gel formulations. Low adherence linked with frequent dosing and short therapeutic duration has emerged as the major reason for inconsistent efficacy outcomes with gels in clinical trials. Osmotic pumps can achieve versatile drug release profiles however, have not been explored for vaginal delivery. In this report, we describe an osmotic pump tablet (OPT) that can deliver antiretrovirals for several days. We also describe configuring the OPT for pH sensitive delivery where the drug delivery system consistently delivers a antiretroviral at vaginal pH and then gives a burst release triggered by a coitally associated pH increase. We have investigated the vaginal OPT for multiple day delivery of a potent antiretroviral, IQP-0528 in a sheep model. To effectively register spatial drug distribution we also engineered a tool to precisely collect multiple vaginal fluid samples. In a 10-day duration post single application, high micromolar mucosal levels were obtained with peak concentration more than 6 logs higher than IQP-0528 EC50. Overall, our results show successful implementation of the osmotic pump technology for vaginal antiretroviral delivery. PMID:23973812

Rastogi, Rachna; Teller, Ryan S.; Mesquita, Pedro M. M.; Herold, Betsy C.; Kiser, Patrick F.

2013-01-01

297

Adherence to Antiretroviral Therapy for Pediatric HIV Infection: Review of the Literature and Recommendations for Research  

Microsoft Academic Search

This review described and compared empirical investigations of adherence to pediatric antiretroviral therapy (ART) and predictors\\/correlates of adherence with regard to methodology and outcome. Thirteen empirical studies of children's adherence to ART, conducted between the years 1981 and 2002 were identified. Investigations varied by age of participant, drug therapy regimen, method of adherence assessment, and by the reporting of predictors\\/correlates

Ric G. Steele; Dennis Grauer

2003-01-01

298

Presence of an Inducible HIV1 Latent Reservoir during Highly Active Antiretroviral Therapy  

Microsoft Academic Search

Although highly active antiretroviral therapy (HAART) in the form of triple combinations of drugs including protease inhibitors can reduce the plasma viral load of some HIV-1-infected individuals to undetectable levels, it is unclear what the effects of these regimens are on latently infected CD4+ T cells and what role these cells play in the persistence of HIV-1 infection in individuals

Tae-Wook Chun; Lieven Stuyver; Stephanie B. Mizell; Linda A. Ehler; Jo Ann M. Mican; Michael Baseler; Alun L. Lloyd; Martin A. Nowak; Anthony S. Fauci

1997-01-01

299

Contrasting predictors of poor antiretroviral therapy outcomes in two South African HIV programmes: a cohort study  

Microsoft Academic Search

BACKGROUND: Many national antiretroviral therapy (ART) programmes encourage providers to identify and address baseline factors associated with poor treatment outcomes, including modifiable adherence-related behaviours, before initiating ART. However, evidence on such predictors is scarce, and providers judgement may often be inaccurate. To help address this evidence gap, this observational cohort study examined baseline factors potentially predictive of poor treatment outcomes

Mison Dahab; Salome Charalambous; Alan S Karstaedt; Katherine L Fielding; Robin Hamilton; Lettie La Grange; Gavin J Churchyard; Alison D Grant

2010-01-01

300

Osmotic pump tablets for delivery of antiretrovirals to the vaginal mucosa.  

PubMed

Vaginal pre-exposure prophylaxis has focused heavily on gel formulations. Low adherence linked with frequent dosing and short therapeutic duration has emerged as the major reason for inconsistent efficacy outcomes with gels in clinical trials. Osmotic pumps can achieve versatile drug release profiles however, have not been explored for vaginal delivery. In this report, we describe an osmotic pump tablet (OPT) that can deliver antiretrovirals for several days. We also describe configuring the OPT for pH sensitive delivery where the drug delivery system consistently delivers an antiretroviral at vaginal pH and then gives a burst release triggered by a coitally associated pH increase. We have investigated the vaginal OPT for multiple day delivery of a potent antiretroviral, IQP-0528 in a sheep model. To effectively register spatial drug distribution we also engineered a tool to precisely collect multiple vaginal fluid samples. In a 10-day duration post single application, high micromolar mucosal levels were obtained with peak concentration more than 6 logs higher than the EC50 of IQP-0528. Overall, our results show successful implementation of the osmotic pump technology for vaginal antiretroviral delivery. PMID:23973812

Rastogi, Rachna; Teller, Ryan S; Mesquita, Pedro M M; Herold, Betsy C; Kiser, Patrick F

2013-10-01

301

Prioritising prevention strategies for patients in antiretroviral treatment programmes in resource-limited settings  

Microsoft Academic Search

Expanded access to antiretroviral therapy (ART) offers opportunities to strengthen HIV prevention in resource-limited settings. We invited 27 ART programmes from urban settings in Africa, Asia and South America to participate in a survey, with the aim to examine what preventive services had been integrated in ART programmes. Twenty-two programmes participated; eight (36%) from South Africa, two from Brazil, two

A. Spaar; C. Graber; F. Dabis; A. Coutsoudis; L. Bachmann; J. McIntyre; M. Schechter; H. W. Prozesky; S. Tuboi; D. Dickinson; N. Kumarasamy; M. Pujdades-Rodriquez; E. Sprinz; H. J. Schilthuis; P. Cahn; N. Low; M. Egger

2010-01-01

302

Association of antiretroviral resistance genotypes with response to therapy comparison of three  

E-print Network

Review Association of antiretroviral resistance genotypes with response to therapy ­ comparison , and AJ Leigh Brown1 * 1Centre for HIV Research, Institute of Cell, Animal and Population Biology-MAIL} Antiviral Therapy 7:1­9 ©2002 International Medical Press 1359-6535/02/$17.00 1 Genotype-based resistance

Brown, Andrew Leigh

303

HIV and antiretroviral therapy in the brain: neuronal injury and repair  

Microsoft Academic Search

Approximately 40 million people worldwide are infected with human immunodeficiency virus (HIV). Despite HIV's known propensity to infect the CNS and cause neurological disease, HIV neurocognitive disorders remain under-recognized. Although combination antiretroviral therapy has improved the health of millions of those living with HIV, the penetration into the CNS of many such therapies is limited, and patients' quality of life

Dianne Langford; Eliezer Masliah; Ronald Ellis

2007-01-01

304

Modelling HIV epidemics in the antiretroviral era: the UNAIDS Estimation and Projection package 2009  

E-print Network

Modelling HIV epidemics in the antiretroviral era: the UNAIDS Estimation and Projection package for country-level estimation and short-term projection of HIV/AIDS epidemics based on fitting observed HIV of ART on incidence and the resulting increases in HIV prevalence in populations with high ART coverage

Raftery, Adrian

305

Future HIV Therapy Priority paper evaluation Antiretroviral therapy among HIV-infected breastfeeding mothers  

E-print Network

Future HIV Therapy Priority paper evaluation 1/10 Antiretroviral therapy among HIV-infected breastfeeding mothers: a promising strategy to prevent HIV transmission through breastmilk in Africa Renaud-00177039,version1-10Nov2009 Author manuscript, published in "Future HIV Therapy 2007;1(1):17-21" DOI : 10

Paris-Sud XI, Université de

306

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

ERIC Educational Resources Information Center

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 Uruguay,…

Delbene, Roxana

2012-01-01

307

Peyronie's disease in men with HIV responding to highly active antiretroviral therapy.  

PubMed

The pathogenesis of Peyronie's disease (induratio penis plastica) is unclear, but immune phenomena appear likely to be involved. Two cases are presented where the condition developed in temporal association with a virological response to highly active antiretroviral therapy (HAART) in men with HIV infection. It is suggested that this may represent another manifestation of immune restoration disease. PMID:15139986

Rogers, G D; French, M A

2004-05-01

308

Antiretroviral effect of lovastatin on HIV-1-infected individuals without highly active antiretroviral therapy (The LIVE study): a phase-II randomized clinical trial  

PubMed Central

Background Highly active antiretroviral therapy produces a significant decrease in HIV-1 replication and allows an increase in the CD4 T-cell count, leading to a decrease in the incidence of opportunistic infections and mortality. However, the cost, side effects and complexity of antiretroviral regimens have underscored the immediate need for additional therapeutic approaches. Statins exert pleiotropic effects through a variety of mechanisms, among which there are several immunoregulatory effects, related and unrelated to their cholesterol-lowering activity that can be useful to control HIV-1 infection. Methods/design Randomized, double-blinded, placebo controlled, single-center, phase-II clinical trial. One hundred and ten chronically HIV-1-infected patients, older than 18 years and naďve for antirretroviral therapy (i.e., without prior or current management with antiretroviral drugs) will be enrolled at the outpatient services from the most important centres for health insurance care in Medellin-Colombia. The interventions will be lovastatin (40 mg/day, orally, for 12 months; 55 patients) or placebo (55 patients). Our primary aim will be to determine the effect of lovastatin on viral replication. The secondary aim will be to determine the effect of lovastatin on CD4+ T-cell count in peripheral blood. As tertiary aims we will explore differences in CD8+ T-cell count, expression of activation markers (CD38 and HLA-DR) on CD4 and CD8 T cells, cholesterol metabolism, LFA-1/ICAM-1 function, Rho GTPases function and clinical evolution between treated and not treated HIV-1-infected individuals. Discussion Preliminary descriptive studies have suggested that statins (lovastatin) may have anti HIV-1 activity and that their administration is safe, with the potential effect of controlling HIV-1 replication in chronically infected individuals who had not received antiretroviral medications. Considering that there is limited clinical data available on this topic, all these findings warrant further evaluation to determine if long-term administration of statins may benefit the virological and immunological evolution in HIV-1-infected individuals before the use of antiretroviral therapy is required. Trial registration Registration number NCT00721305. PMID:19538732

Montoya, Carlos J; Jaimes, Fabian; Higuita, Edwin A; Convers-Páez, Sandra; Estrada, Santiago; Gutierrez, Francisco; Amariles, Pedro; Giraldo, Newar; Peńaloza, Cristina; Rugeles, Maria T

2009-01-01

309

Influence of HIV antiretrovirals on methadone N-demethylation and transport.  

PubMed

Drug interactions involving methadone and/or HIV antiretrovirals can be problematic. Mechanisms whereby antiretrovirals induce clinical methadone clearance are poorly understood. Methadone is N-demethylated to 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine (EDDP) by CYP2B6 and CYP3A4 in vitro, but by CYP2B6 in vivo. This investigation evaluated human hepatocytes as a model for methadone induction, and tested the hypothesis that methadone and EDDP are substrates for human drug transporters. Human hepatocyte induction by several antiretrovirals of methadone N-demethylation, and CYP2B6 and CYP3A4 transcription, protein expression and catalytic activity, and pregnane X receptor (PXR) activation were evaluated. Methadone and EDDP uptake and efflux by overexpressed transporters were also determined. Methadone N-demethylation was generally not significantly increased by the antiretrovirals. CYP2B6 mRNA and activity (bupropion N-demethylation) were induced by several antiretrovirals, as were CYP3A4 mRNA and protein expression, but only indinavir increased CYP3A activity (alfentanil dealkylation). CYP upregulation appeared related to PXR activation. Methadone was not a substrate for uptake (OCT1, OCT2, OCT3, OATP1A2, OATP1B1, OATP1B3, OATP2B1) or efflux (P-gp, BCRP) transporters. EDDP was a good substrate for P-gp, BCRP, OCT1, OCT3, OATP1A2, and OATP1B1. OATP1A2- and OCT3-mediated EDDP uptake, and BCRP-mediated EDDP efflux transport, was inhibited by several antiretrovirals. Results show that hepatocyte methadone N-demethylation resembles expressed and liver microsomal metabolism more than clinical metabolism. Compared with clinical studies, hepatocytes underreport induction of methadone metabolism by HIV drugs. Hepatocytes are not a good predictive model for clinical antiretroviral induction of methadone metabolism and not a substitute for clinical studies. EDDP is a transporter substrate, and is susceptible to transporter-mediated interactions. PMID:25801005

Campbell, Scott D; Gadel, Sarah; Friedel, Christina; Crafford, Amanda; Regina, Karen J; Kharasch, Evan D

2015-05-15

310

Predicted savings to the UK National Health Service from switching to generic antiretrovirals, 2014–2018  

PubMed Central

Introduction In other disease areas, generic drugs are normally used after patent expiry. Patents on zidovudine, lamivudine, nevirapine and efavirenz have already expired. Patents will expire for abacavir in late 2014, lopinavir/r in 2016, and tenofovir, darunavir and atazanavir in 2017. However, patents on single-tablet regimens do not expire until after 2026. Methods The number of people taking each antiretroviral in the UK was estimated from 23,655 individuals in the UK CHIC cohort (2012 database). Costs of patented drugs were taken from the British National Formulary database, assuming a 30% discount. Costs of generic antiretrovirals were estimated using an 80% discount from patented prices, or actual costs where available. Two options were analysed: 1 – all patients use single-tablet regimens and patented versions of drugs; prices remain stable over time; 2 – all people switch from patented to generic drugs when available, after patent expiry (dates shown above). Results There were an estimated 67,000 people taking antiretrovirals in the UK in 2014, estimated to rise by 8% per year until 2018 (in line with previous rises). The most widely used antiretrovirals in the CHIC cohort were tenofovir (TDF) (75%), emtricitabine (FTC) (69%), efavirenz (EFV) (39%), lamivudine (3TC) (23%), abacavir (ABC) (18%), darunavir (DRV) (21%) and atazanavir (ATV) (16%). The predicted annual UK cost of generic ABC/3TC/EFV (three generic tablets once daily) was Ł1018 per person-year. Costs of patented single-tablet regimens ranged from Ł5000 to Ł7500 per person-year. Assuming continued use of patented antiretrovirals in the UK, the predicted total national costs of antiretroviral treatment were predicted to rise from Ł425 million in 2014 to Ł459 m in 2015, Ł495 m in 2016, Ł536 m in 2017 and Ł578 m in 2018. With a 100% switch to generics, total predicted costs were Ł337 m in 2014, Ł364 m in 2015, Ł382 m in 2016, Ł144 m in 2017 and Ł169 m in 2018. The total predicted saving over five years from a switch to generics was Ł1.1 billion. Conclusions Systematic switching from patented to generic antiretrovirals could potentially save approximately Ł1.1 billion in the UK over the next five years, compared with continued use of patented versions: this money could be spent on urgently needed HIV prevention programmes. Similar savings are feasible for other European countries, given parallel patent expiry dates. More detailed economic evaluation is required to show when patented single-tablet regimens provide value for money, compared to bioequivalent generic versions of 3–4 pills once daily. PMID:25394006

Hill, Andrew; Hill, Teresa; Jose, Sophie; Pozniak, Anton

2014-01-01

311

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

PubMed Central

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 Victoria; however, the sample size was very small. Conclusions For the most part, patterns of ART use were similar across NSW, Victoria and Queensland using a range of available data from cohort studies, community surveys and national prescription databases in Australia. However, there may be a lower proportion of individuals living with HIV on ART in NSW compared to the other states, and there is some indication of a more aggressive treatment approach with PHI patients in NSW compared to Victoria. PMID:18588779

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

312

[Management of antiretroviral treatment in HIV-infected patients exhibiting virologic failure].  

PubMed

THE BASES OF THERAPEUTIC FAILURE: In view of its varying clinical, immunological and virological components, therapeutic failure during HIV infection is debatable. It relies on monitoring the patient during treatment, taking into account prior therapy and the initial level of CD4 and HIV viral charge, and their evolution. Immuno-virological failure can be defined as a detectable viral charge and CD4 lymphocytes lesser than 200 elements/mm3. Therapeutic failure can be related to various factors: poor compliance to treatment, insufficient dosing, poor absorption or drug interactions reducing its efficacy and HIV resistance to antiretrovirals. THE MANAGEMENT OF PATIENTS EXHIBITING CONFIRMED THERAPEUTIC FAILURE: Requires assessment of patient's compliance and the search for drug or nutritional interactions. Pharmacological doses of antiretrovirals are useful in explaining the onset of failure or in adapting the dose. A genotype resistance test will orient the choice of new molecules in patients with reduced therapeutic options. THE CHOICE OF A NEW COMBINATION: Relies on knowledge of prior treatments and the reasons for their withdrawal (failure or intolerance) and the profile of in vitro cross-resistance to antiretrovirals. The optimal prescription combines at least two new molecules and/or a new class of antiretrovirals to which the patient has not yet been exposed. IN PATIENTS IN WHOM THERE IS NO THERAPEUTIC RESOURCES: An association of three classes of antiretrovirals with a total of 5 to 8 molecules are proposed in high-dose therapies. The use of suspension of therapy, to permit re-sensitivity, is presently being studied. THE OBJECTIVE OF TREATMENT: In non-responding patients, it is essential to retain an number of CD4 protectors depending on the clinical progression of the disease, while awaiting new therapeutic options, contrary to first or second line treatment, the priority aim of which remains reaching a undetectable viral charge. PMID:12148259

Pinganaud, C; Goujard, C

2002-06-22

313

Healthy Start Program Participation: The Consumers' Perspective  

Microsoft Academic Search

In 1991, the federal Maternal and Child Health Bureau developed the Healthy Start Initiative as a comprehensive community-based program to eliminate the high rates of poor pregnancy outcomes among women of color. To date, few studies of the programmatic outcomes of this Initiative have examined the views of Healthy Start consumers. To understand the benefits of Healthy Start from their

Christine E. Ley; Valire Carr Copeland; Cheryl Squire Flint

2010-01-01

314

JumpStart III Final Report.  

ERIC Educational Resources Information Center

This final report for the JumpStart III program presents a summary of the entrepreneurship training programs developed by each of the four JumpStart III partners selected in March 1997. Grants for the colleges totaled $354,546 over 2 years. The Jumpstart funding has been only a starting point for these and the other 12 Jumpstart partners in…

Cohen, Arthur M.; Brawer, Florence B.; Kozeracki, Carol A.

315

76 FR 70009 - Head Start Program  

Federal Register 2010, 2011, 2012, 2013, 2014

...anticipate that Head Start agencies will be gathering new information to accomplish...sought to implement the new and expanded requirements of the Head Start Act in a manner that...competition to select a new Head Start or Early Head...

2011-11-09

316

Timing of Antiretroviral Therapy Initiation after a First AIDS-Defining Event: Temporal Changes in Clinical Attitudes in the ICONA Cohort  

PubMed Central

Background Time of starting antiretroviral therapy (ART) after diagnosis of specific AIDS-defining event (ADE) is a crucial aspect. Objectives of this study were to evaluate if in patients diagnosed with ADE the time to ART initiation may vary according to year of diagnosis and type of ADE. Methods All HIV+ persons diagnosed with an ADE over the 6 months prior to or after enrolment in the Icona Foundation study cohort and while ART-naive were grouped according to type of diagnosis: Those with ADE requiring medications interacting with ART [group A], those with ADE treatable only with ART [B] and other ADE [C]. Survival analysis by Kaplan-Meier was used to estimate the percentage of people starting ART, overall and after stratification for calendar period and ADE group. Multivariable Cox regression model was used to investigate association between calendar year of specific ADE and time to ART initiation. Results 720 persons with first ADE were observed over 1996–2013 (group A, n?=?171; B, n?=?115; C, n?=?434). By 30 days from diagnosis, 27% (95% CI: 22–32) of those diagnosed in 1996–2000 had started ART vs. 32% (95% CI: 24–40) in 2001–2008 and 43% (95% CI: 33–47) after 2008 (log-rank p?=?0.001). The proportion of patients starting ART by 30 days was 13% (95% CI 7–19), 40% (95% CI: 30–50) and 38% (95% CI 33–43) in ADE groups A, B and C (log-rank p?=?0.0001). After adjustment for potential confounders, people diagnosed after 2008 remained at increased probability of starting ART more promptly than those diagnosed in 1996–1999 (AHR 1.72 (95% CI 1.16–2.56). Conclusions In our “real-life” setting, the time from ADE to ART initiation was significantly shorter in people diagnosed in more recent years, although perhaps less prompt than expected. PMID:24587081

Cingolani, Antonella; Cozzi-Lepri, Alessandro; Ammassari, Adriana; Mussini, Cristina; Ursitti, Maria Alessandra; Caramello, Pietro; Angarano, Gioacchino; Bonfanti, Paolo; De Luca, Andrea; Mura, Maria Stella; Girardi, Enrico; Antinori, Andrea; Monforte, Antonela D'Arminio

2014-01-01

317

Enhanced normalisation of CD4/CD8 ratio with early antiretroviral therapy in primary HIV infection  

PubMed Central

Introduction Despite normalization of total CD4 counts, ongoing immune dysfunction is noted amongst those on antiretroviral therapy (ART). Low CD4/CD8 ratio is associated with a high risk of AIDS and non-AIDS events and may act as a marker of immune senescence [1]. This ratio is improved by ART although normalization is uncommon (~7%) [2]. The probability of normalization of CD4 count is improved with immediate ART initiation in primary HIV infection (PHI) [3]. We examined whether CD4/CD8 ratio similarly normalized in immediate vs. deferred ART at PHI. Material and Methods Using data from the SPARTAC trial and the UK Register of HIV Seroconverters, we examined the effect of ART with time (continuous) from HIV seroconversion (SC) on CD4/CD8 ratio (?1) adjusted for sex, risk group, ethnicity, enrolment from an African site and both CD4 count and age at ART initiation. We also examined that effect by dichotomizing HIV duration at ART initiation (ART started within six months of SC: early ART; ART initiated>six months after SC: deferred). We also considered time to CD4 count normalization (?900 cells/mm3). Results In total, 353 initiated ART with median (IQR) 97.9 (60.5, 384.5) days from estimated seroconversion; 253/353 early ART, 100 deferred ART. At one year after starting ART, 114/253 (45%) early ART had normalized CD4/8 ratio, compared with 11/99 (11%) in the deferred group, whilst 83/253 (33%) of early ART had normalized CD4 counts, compared with 3/99 (3%) in the deferred group. Individuals initiating within six months of PHI were significantly more likely to reach normal ratio than those initiating later (HR, 95% CI 2.96, 1.75 – 5.01, p<0.001). The longer after SC ART was initiated, the reduced likelihood of achieving normalization of CD4/CD8 ratio (HR 0.98, 95% CI 0.96 – 0.99 for each 30-day increase). CD4 count at ART initiation was also associated with normalization, as expected (HR 1.002, 95% CI 1.001 – 1.002, p<0.001). There was an association between normal CD4/CD8 ratio and being virally suppressed (<400 copies HIV RNA/ml) p<0.001. CD4 count normalization was also significantly more likely for those initiating early (HR 5.00, 95% CI 1.52 – 16.41, p=0.008). Conclusions The likelihood of achieving normalization of CD4/CD8 ratios was increased if ART was initiated within six months of PHI. Higher CD4/CD8 ratio may reflect a more “normal” immune phenotype conferring enhanced prognosis and predict post-treatment control. PMID:25393989

Thornhill, John; Inshaw, Jamie; Oomeer, Soonita; Kaleebu, Pontiano; Cooper, David; Ramjee, Gita; Schechter, Mauro; Tambussi, Giuseppe; Fox, Julie; Maria Miro, Jose; Weber, Jonathan; Babiker, Abdel; Porter, Kholoud; Fidler, Sarah

2014-01-01

318

S. Blower, et al.: Forecasting the Future of HIV Epidemics: the Impact of Antiretroviral Therapies & Imperfect Vaccines AIDSREVIEWS  

E-print Network

Therapies & Imperfect Vaccines S. Blower1*, E.J. Schwartz1 and J. Mills2 1 AIDS Institute & Department of combination antiretroviral ther- apies (ART) and imperfect vaccines on HIV epi- demics. Modeling combination

Blower, Sally

319

The impact of herbal remedies on adverse effects and quality of life in HIV-infected individuals on antiretroviral therapy  

PubMed Central

Introduction Use of herbal remedies among HIV-infected individuals in Africa increased in the past decade, mainly due to traditional beliefs and at times inconsistent access to antiretroviral drugs. In Zimbabwe, accessibility and availability of antiretroviral drugs has increased in recent years; however, the use of herbal remedies remains high. This study was conducted to determine the impact of concomitant use of herbal remedies with antiretroviral drugs on adverse events and on quality of life. Methodology A convenient sample of HIV positive patients at Parirenyatwa group of hospitals' Family Care Clinic (Harare, Zimbabwe) was enrolled. A questionnaire was used to collect data on the adverse event experiences of the patients using herbal remedies for their HIV, as well as the types of herbal remedy used. Quality of life index was measured using an HIV/AIDS targeted quality of life (HAT-QOL) tool developed by the World Health Organization. Results Abdominal pain (odds ratio = 2.7, p-value = 0.01) and rash (odds ratio = 2.5, p-value = 0.02) had significant associations with using herbal remedies during antiretroviral therapy. Improved quality of life index was not significantly associated with herbal remedy use during antiretroviral therapy. Conclusions There is evidence to suggest that some traditional herbal remedies used in Zimbabwe may increase incidence of certain types of adverse events when used in combination with antiretroviral drugs. Use of herbal drugs in combination with antiretroviral therapy does not significantly improve quality of life index in comparison to antiretroviral drug use only. PMID:21330740

Bepe, Nyasha; Madanhi, Nathan; Mudzviti, Tinashe; Gavi, Samuel; Maponga, Charles Chiedza; Morse, Gene D

2012-01-01

320

Durability of first antiretroviral treatment in HIV chronically infected patients: why change and what are the outcomes?  

PubMed Central

Introduction First antiretroviral therapy (ART) is often switched to simpler, more potent or better tolerated regimens [1, 2]. Although discontinuation rates are frequently studied, the durability of regimens is rarely approached. Materials and Methods Retrospective study with the following objectives: analyze first ART schemes and their durability in naive patients with chronic HIV-1 and 2 infections, evaluate factors influencing ART change, second-line ART and consequent virologic and immunologic responses. Patients had follow-ups in a Central University Hospital, started ART between January 2007 and December 2012 and changed first regimens. Clinical data was obtained from medical records and analyzed using the Statistical Package for the Social Sciences (version 20). Results Of the 652 naive patients who started ART, 164 changed regimens. The majority had HIV-1 infection (n=158). The mean age was 43.9 years (standard deviation±14.3), with a male predominance of 57.9%. Regimens with efavirenz were the most common amongst HIV-1 patients (50%) followed by lopinavir/r (22%). In HIV-2 patients, lopinavir/r (n=3) regimens were most prevalent. First ART regimens had a mean duration of 12.1 months. There was no difference between NNRTI (59.8%) and protease inhibitor (40.2%) schemes regarding durability. Adverse reactions were the major cause of ART switching (55.5%) followed by therapy resistance (12.1%). Age was inversely related to durability (p=0.007 Mann-Whitney, Phi coefficient ?0.161) and associated with the appearance of adverse reactions (p=0.04, Chi-square). Younger patients had a reduced risk of adverse reactions by 27%. Adverse reactions increased the risk of inferior durability by 40%. Psychiatric symptoms (28.4%) were the most prevalent, all attributed to efavirenz. The year of ART initiation was associated with different durability rates (p=0.005, Mann-Whitney). Patients started on ART before the year 2010 reduced the probability of inferior ART duration by 25.8%. After second-line ART regimens, TCD4+ counts>500 cell/µL were increased by 38% and favourable virologic outcome achieved in 84%. Conclusions Adverse reactions were the main cause for ART switching, supporting a cautious approach when initiating regimens, particularly in older patients. All ART naive patients who changed initial therapy had favourable immunological and virologic responses. PMID:25397541

Moniz, Patricia; Alçada, Filipa; Peres, Susana; Borges, Fernando; Baptista, Teresa; Claudia Miranda, Ana; Antunes, Isabel; Aldir, Isabel; Ventura, Fernando; Nina, Jaime; Mansinho, Kamal

2014-01-01

321

Special Analysis of Tribal Even Start Projects Data. Even Start Information System.  

ERIC Educational Resources Information Center

This report presents results of special analyses of data on seven of the nine Even Start programs administered by tribes or tribal organizations in 1994-95. The tribal Even Start program is a set-aside component of the U.S. Department of Education's Even Start Family Literacy Program. Even Start combines adult literacy, early childhood education,…

Tao, Fumiyo; Arriola, Christine

322

Family Connections: Helping Early Head Start/Head Start Staff and Parents Address Mental Health Challenges  

ERIC Educational Resources Information Center

Early Head Start/Head Start teachers and staff encounter parents who have wrestled with depression and other adversities every day. This article describes an innovative program of trainings for and consultation to Early Head Start/Head Start staff to help them effectively deal with mental heath challenges faced by parents and children. The program…

Beardslee, William R.; Avery, Mary Watson; Ayoub, Catherine; Watts, Caroline L.

2009-01-01

323

Severe recurrent rhabdomyolysis-induced acute kidney injury in a HIV-infected patient on antiretroviral therapy.  

PubMed

Antiretroviral medications, specifically tenofovir, have been linked to acute tubular necrosis in humans with a suggested mechanism of direct tubular injury. Rhabdomyolysis has rarely been described in patients on highly active antiretroviral therapy (HAART). To the best of our knowledge, severe recurrent rhabdomyolysis-induced acute kidney injury (AKI) in a HIV-infected patient on two different triple antiretroviral regimens has not been reported. We present a HIV-positive patient who first developed heme pigment-induced oliguric AKI due to non-traumatic rhabdomyolysis, 5 days after initiation of triple antiretroviral therapy. Renal function normalized 2 months after discontinuation of antiretroviral therapy. Two weeks after reinitiating a different HAART regimen, our patient developed a recurrent episode of severe rhabdomyolysis-induced AKI. Both rhabdomyolysis and AKI resolved after discontinuation of the second antiretroviral regimen. First tenofovir and subsequently abacavir seem to be the likely culprits in our case. We also briefly discuss tenofovir nephrotoxicity followed by a literature review on rhabdomyolysis in HIV-infected patients. PMID:23883141

Spiegel, Louis R; Schrier, Peter B; Shah, Hitesh H

2013-09-01

324

Microcomputer controlled soft start of motor  

NASA Astrophysics Data System (ADS)

Improving the starting characteristics of a motor is an important part of the motor control. An intelligent soft starting technique was adopted in the starter and used in the present study because of its many advantages compared with conventional starting processes. The core of the soft starter was a single chip (Atmel 8098), its soul was the software and its control object was a Silicon Controlled Rectifier (SCR). The starter achieved not only current-limit starting, but also closed-loop control with a stator current detection circuit. In conclusion, as a result of digital control, starting characteristic can be conveniently chosen according to the load. In addition the starter is of small size, and starting is smooth and reliable due to current feedback.

Gao, Miao; Wang, Yanpeng; Li, Shian

2005-12-01

325

TRIP START TIME DISTRIBUTION Metro 1996  

E-print Network

APPENDIX B TRIP START TIME DISTRIBUTION #12;Metro 1996 0% 2% 4% 6% 8% 10% 12% 14% 430 530 630 730 Start Time - Midpoint of 1 hour Window NHB HBO HBS HBW B.1 #12;Durham 1996 0% 2% 4% 6% 8% 10% 12% 14 2530 2630 2730 Start Time - Midpoint of 1 hour Window NHB HBO HBS HBW B.2 #12;York 1996 0% 2% 4% 6% 8

Toronto, University of

326

START ships lipids across interorganelle space.  

PubMed

The family of StAR related lipid transfer proteins (START) is so-named based on the distinctive capacity for these proteins to transport lipids between membranes. The START domain is a module of about 210 residues, which binds lipids such as glycerolipids, sphingolipids and sterols. This domain has a deep lipid-binding pocket - which shields the hydrophic ligand from the external aqueous environment - covered by a lid. Based on their homology, the fifteen START proteins in mammals have been allocated to six distinct subfamilies, each subfamily being more specialized in the transport and/or sensing of a lipid ligand species. However within the same subgroup, their expression profile and their subcellular localization distinguish them and are critical for their different biological functions. Indeed, START proteins act in a variety of distinct physiological processes, such as lipid transfer between intracellular compartments, lipid metabolism and modulation of signaling events. Mutation or deregulated expression of START proteins is linked to pathological processes, including genetic disorders, autoimmune diseases and cancers. Besides the common single START domain, which is always located at the carboxy-terminal end in mammals, most START proteins harbor additional domains predicted to be critical in favoring lipid exchange. Evidence from well characterized START proteins indicates that these additional domains might be tethering machineries able to bring distinct organelles together and create membrane contact sites prone to lipid exchange via the START domain. PMID:24076129

Alpy, Fabien; Tomasetto, Catherine

2014-01-01

327

CD4 trajectory adjusting for dropout among HIV-positive patients receiving combination antiretroviral therapy in an East African HIV care centre  

PubMed Central

Objective Estimates of CD4 response to antiretroviral therapy (ART) obtained by averaging data from patients in care, overestimate population CD4 response and treatment program effectiveness because they do not consider data from patients who are deceased or not in care. We use mathematical methods to assess and adjust for this bias based on patient characteristics. Design We examined data from 25,261 HIV-positive patients from the East Africa IeDEA Consortium. Methods We used inverse probability of censoring weighting (IPCW) to represent patients not in care by patients in care with similar characteristics. We address two questions: What would the median CD4 be “had everyone starting ART remained on observation?” and “were everyone starting ART maintained on treatment?” Results Routine CD4 count estimates were higher than adjusted estimates even under the best-case scenario of maintaining all patients on treatment. Two years after starting ART, differences between estimates diverged from 30 cells/µL, assuming similar mortality and treatment access among dropouts as patients in care, to over 100 cells/µL assuming 20% lower survival and 50% lower treatment access among dropouts. When considering only patients in care, the proportion of patients with CD4 above 350 cells/µL was 50% adjusted to below 30% when accounting for patients not in care. One-year mortality diverged 6–14% from the naďve estimates depending on assumptions about access to care among lost patients. Conclusions Ignoring mortality and loss to care results in over-estimation of ART response for patients starting treatment and exaggerates the efficacy of treatment programs administering it. PMID:25131801

Kiragga, Agnes N; Lok, Judith J; Musick, Beverly S; Bosch, Ronald J; Mwangi, Ann; Wools-Kaloustian, Kara K; Yiannoutsos, Constantin T

2014-01-01

328

Persistent HIV-1 replication is associated with lower antiretroviral drug concentrations in lymphatic tissues  

PubMed Central

Antiretroviral therapy can reduce HIV-1 to undetectable levels in peripheral blood, but the effectiveness of treatment in suppressing replication in lymphoid tissue reservoirs has not been determined. Here we show in lymph node samples obtained before and during 6 mo of treatment that the tissue concentrations of five of the most frequently used antiretroviral drugs are much lower than in peripheral blood. These lower concentrations correlated with continued virus replication measured by the slower decay or increases in the follicular dendritic cell network pool of virions and with detection of viral RNA in productively infected cells. The evidence of persistent replication associated with apparently suboptimal drug concentrations argues for development and evaluation of novel therapeutic strategies that will fully suppress viral replication in lymphatic tissues. These strategies could avert the long-term clinical consequences of chronic immune activation driven directly or indirectly by low-level viral replication to thereby improve immune reconstitution. PMID:24469825

Fletcher, Courtney V.; Staskus, Kathryn; Wietgrefe, Stephen W.; Rothenberger, Meghan; Reilly, Cavan; Chipman, Jeffrey G.; Beilman, Greg J.; Khoruts, Alexander; Thorkelson, Ann; Schmidt, Thomas E.; Anderson, Jodi; Perkey, Katherine; Stevenson, Mario; Perelson, Alan S.; Douek, Daniel C.; Haase, Ashley T.; Schacker, Timothy W.

2014-01-01

329

Anti-retroviral therapy-induced status epilepticus in "pseudo-HIV serodeconversion".  

PubMed

Diligence in the interpretation of results is essential as information gained from the psychiatric patient's history might often be restricted. Nonobservance of established guidelines may lead to a wrong diagnosis, induce a false therapy and result in life-threatening situations. Communication errors between hospitals and doctors and uncritical acceptance of prior diagnoses add substantially to this problem. We present a patient with alcohol-related dementia who received anti-retroviral therapy that promoted a non-convulsive status epilepticus. HIV serodeconversion was considered after our laboratory result yielded a HIV-negative status. Critical review of previous diagnostic investigations revealed several errors in the diagnosis of HIV infection leading to a "pseudo-serodeconversion." Finally, anti-retroviral therapy could be discontinued. PMID:20851280

Etgen, Thorleif; Eberl, Bernhard; Freudenberger, Thomas

2010-01-01

330

The occurrence of anti-retroviral compounds used for HIV treatment in South African surface water.  

PubMed

The study and quantification of personal care products, such as pharmaceuticals, in surface water has become popular in recent years; yet very little description of these compounds' presence in South African surface water exists in the literature. Antiretrovirals (ARVs), used to treat human immunodeficiency virus (HIV) are rarely considered within this field. A new method for the simultaneous quantification of 12 antiretroviral compounds in surface water using the standard addition method is described. Water samples were concentrated by a generic automated solid phase extraction method and analysed by ultra-high pressure liquid chromatography tandem mass spectrometry (UHPLC-MS/MS). Substantial matrix effect was encountered in the samples with an average method detection limit of 90.4 ng/L. This is the first reported countrywide survey of South African surface water for the quantification of these compounds with average concentrations ranging between 26.5 and 430 ng/L. PMID:25681819

Wood, Timothy Paul; Duvenage, Cornelia S J; Rohwer, Egmont

2015-04-01

331

Unplanned antiretroviral treatment interruptions in southern Africa: how should we be managing these?  

PubMed

Adherence to antiretroviral therapy is essential for maximising individual treatment outcomes and preventing the development of drug resistance. It is, however, frequently compromised due to predictable, but adverse, scenarios in the countries most severely affected by HIV/AIDS. This paper looks at lessons from three specific crises in southern Africa: the 2008 floods in Mozambique, the ongoing political and economic crisis in Zimbabwe, and the 2007 public sector strike in South Africa. It considers how these crises impacted on the delivery of antiretroviral therapy and looks at some of the strategies employed to mitigate any adverse effects. Based on this it makes recommendations for keeping patients on treatment and limiting the development of drug resistance where treatment interruptions are inevitable. PMID:20356383

Veenstra, Nina; Whiteside, Alan; Lalloo, David; Gibbs, Andrew

2010-01-01

332

Antiretroviral concentrations in small hair samples as a feasible marker of adherence in rural Kenya.  

PubMed

Antiretroviral hair levels objectively quantify drug exposure over time and predict virologic responses. We assessed the acceptability and feasibility of collecting small hair samples in a rural Kenyan cohort. Ninety-five percentage of participants (354/373) donated hair. Although median self-reported adherence was 100% (interquartile range, 96%-100%), a wide range of hair concentrations likely indicates overestimation of self-reported adherence and the advantages of a pharmacologic adherence measure. Higher nevirapine hair concentrations observed in women and older adults require further study to unravel behavioral versus pharmacokinetic contributors. In resource-limited settings, hair antiretroviral levels may serve as a low-cost quantitative biomarker of adherence. PMID:24694932

Hickey, Matthew D; Salmen, Charles R; Tessler, Robert A; Omollo, Dan; Bacchetti, Peter; Magerenge, Richard; Mattah, Brian; Salmen, Marcus R; Zoughbie, Daniel; Fiorella, Kathryn J; Geng, Elvin; Njoroge, Betty; Jin, Chengshi; Huang, Yong; Bukusi, Elizabeth A; Cohen, Craig R; Gandhi, Monica

2014-07-01

333

Recent trends in the spectrum of opportunistic infections in human immunodeficiency virus infected individuals on antiretroviral therapy in South India  

PubMed Central

Background: Opportunistic infections (OI) are the major cause of morbidity and mortality among human immunodeficiency virus (HIV) infected individuals. The pattern of OIs differs widely, hence it is necessary to correlate spectrum of OIs and CD4 counts among HIV infected individuals in specific localities. Materials and Methods: The present study describes the clinical and laboratory profiles of different OIs among 55 HIV seropositive patients. CD4 count was estimated and antiretroviral therapy (ART) was started in 27 patients as per National Acquired Immunodeficiency Syndrome Control Organization guidelines. These 27 patients were classified into stage 1, stage 2 and stage 3 based on CD4 counts of >500 cells/?l, 200-499 cells/?l and <200 cells/?l respectively. The OIs presented by respective groups were documented. Results: Pulmonary tuberculosis was found to be the most common OI constituting 43.6% of all cases followed by candidiasis (30.9%), cryptosporidial diarrhea (21.8%), herpes zoster (16.3%), cryptococcal meningitis (3.63%), Pneumocystis jirovecii pneumonia (1.81%), and other miscellaneous infections (23.6%). Only 1 patient was found in stage I while 13 patients each were grouped in stage II or stage III. The mean CD4 count in our study population who were on ART was 230 ± 150 cells/µl. Conclusion: The pattern of OIs among our study group did not differ significantly from patients not receiving ART. The effect of ART on CD4 count differs from patient to patient based on the degree of depletion of CD4 count before the initiation of ART, drug adherence, concomitant OIs and their treatment. PMID:25097422

Shahapur, Praveen R.; Bidri, Rajendra C.

2014-01-01

334

Impact of antiretroviral therapy on quality of life in HIV-infected Southeast Asian children in the PREDICT study.  

PubMed

Quality of life (QOL) is an important antiretroviral treatment (ART) outcome. We compared QOL among 299 Thai and Cambodian children ages 1-12 years-old, CD4 15-24% randomized to early (ART at week 0, N=149) versus deferred groups (ART when at CD4 <15%, N=150) and also compared with QOL data from age-matched healthy controls (N=275). Primary caregivers completed PACTG QOL questionnaires at week 0 and every 24 weeks until 144 weeks. Children were enrolled during March 2006 to September 2008. Mean (SD) age of children was 6.3 (2.8) years, 58% were female, 60% were Thai, %CDC N:A:B:C was 2:62:36:0%. During 144 weeks, all children in the early-group and 69 (46%) of deferred-group children started ART. There was no significant difference of QOL scores between treatment groups at baseline (all p>0.05) and at week 144 (all p>0.05). By multivariate analysis, the early-group had higher QOL score changes in five domains, including health perception (p=0.04), physical resilience (p=0.02), psychosocial well-being (p=0.04), social and role functioning (p<0.01), and symptoms (p=0.01) compared to the deferred group. QOL of HIV-infected children in both groups were lower than healthy control in all 7 domains at baseline (all p<0.05) and 5 of 7 domains at weeks 144 (p<0.01). In conclusion, no significant difference of QOL scores between treatment groups. Early ART commencement associated with greater increase of QOL scores over 144 weeks. QOL scores in HIV-infected children were lower than healthy controls. PMID:24191673

Bunupuradah, Torsak; Kosalaraksa, Pope; Vibol, Ung; Hansudewechakul, Rawiwan; Sophonphan, Jiratchaya; Kanjanavanit, Suparat; Ngampiyaskul, Chaiwat; Wongsawat, Jurai; Luesomboon, Wicharn; Vonthanak, Saphonn; Ananworanich, Jintanat; Ruxrungtham, Kiat; Puthanakit, Thanyawee

2013-11-01

335

Impact of Antiretroviral Therapy on Quality of Life in HIV-Infected Southeast Asian Children in the PREDICT Study  

PubMed Central

Abstract Quality of life (QOL) is an important antiretroviral treatment (ART) outcome. We compared QOL among 299 Thai and Cambodian children ages 1–12 years-old, CD4 15–24% randomized to early (ART at week 0, N=149) versus deferred groups (ART when at CD4 <15%, N=150) and also compared with QOL data from age-matched healthy controls (N=275). Primary caregivers completed PACTG QOL questionnaires at week 0 and every 24 weeks until 144 weeks. Children were enrolled during March 2006 to September 2008. Mean (SD) age of children was 6.3 (2.8) years, 58% were female, 60% were Thai, %CDC N:A:B:C was 2:62:36:0%. During 144 weeks, all children in the early-group and 69 (46%) of deferred-group children started ART. There was no significant difference of QOL scores between treatment groups at baseline (all p>0.05) and at week 144 (all p>0.05). By multivariate analysis, the early-group had higher QOL score changes in five domains, including health perception (p=0.04), physical resilience (p=0.02), psychosocial well-being (p=0.04), social and role functioning (p<0.01), and symptoms (p=0.01) compared to the deferred group. QOL of HIV-infected children in both groups were lower than healthy control in all 7 domains at baseline (all p<0.05) and 5 of 7 domains at weeks 144 (p<0.01). In conclusion, no significant difference of QOL scores between treatment groups. Early ART commencement associated with greater increase of QOL scores over 144 weeks. QOL scores in HIV-infected children were lower than healthy controls. PMID:24191673

Bunupuradah, Torsak; Kosalaraksa, Pope; Vibol, Ung; Hansudewechakul, Rawiwan; Sophonphan, Jiratchaya; Kanjanavanit, Suparat; Ngampiyaskul, Chaiwat; Wongsawat, Jurai; Luesomboon, Wicharn; Vonthanak, Saphonn; Ananworanich, Jintanat; Ruxrungtham, Kiat

2013-01-01

336

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

PubMed Central

Objectives 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. Methods A stochastic mathematical model of disease progression, diagnosis, clinical monitoring and survival in HIV infected individuals. Findings 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. Conclusions 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. PMID:21636615

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

2011-01-01

337

Impact of tuberculosis on mortality among HIV-infected patients receiving antiretroviral therapy in Uganda: a prospective cohort analysis  

PubMed Central

Background Tuberculosis (TB) disease affects survival among HIV co-infected patients on antiretroviral therapy (ART). Yet, the magnitude of TB disease on mortality is poorly understood. Methods Using a prospective cohort of 22,477 adult patients who initiated ART between August 2000 and June 2009 in Uganda, we assessed the effect of active pulmonary TB disease at the initiation of ART on all-cause mortality using a Cox proportional hazards model. Propensity score (PS) matching was used to control for potential confounding. Stratification and covariate adjustment for PS and not PS-based multivariable Cox models were also performed. Results A total of 1,609 (7.52%) patients had active pulmonary TB at the start of ART. TB patients had higher proportions of being male, suffering from AIDS-defining illnesses, having World Health Organization (WHO) disease stage III or IV, and having lower CD4 cell counts at baseline (p?

2013-01-01

338

Incomplete Reconstitution of T Cell Subsets on Combination Antiretroviral Therapy in the AIDS Clinical Trials Group Protocol 384  

PubMed Central

Background Initiation of combination antiretroviral therapy (ART) results in higher total CD4 cell counts, a surrogate for immune reconstitution. Whether the baseline CD4 cell count affects reconstitution of immune cell subsets has not been well characterized. Methods Using data from 978 patients (621 with comprehensive immunological assessments) from the AIDS [Acquired Immunodeficiency Syndrome] Clinical Trials Group protocol 384, a randomized trial of initial ART, we compared reconstitution of CD4+, CD4+ naive and memory, CD4+ activation, CD8+, CD8+ activation, B, and natural killer cells among patients in different baseline CD4+ strata. Reference ranges for T cell populations in control patients negative for human immunodeficiency virus (HIV) infection were calculated using data from AIDS Clinical Trials Group protocol A5113. Results Patients in the lower baseline CD4+ strata did not achieve total CD4+ cell counts similar to those of patients in the higher strata during 144 weeks of ART, although CD4+ cell count increases were similar. Ratios of CD4+ naive-memory cell counts and CD4+:CD8+ cell counts remained significantly reduced in patients with lower baseline CD4+ cell counts (?350 cells/mm3). These immune imbalances were most notable for those initiating ART with a baseline CD4+ cell count ?200 cells/mm3, even after adjustment for baseline plasma HIV RNA levels. Conclusions After nearly 3 years of ART, T cell subsets in patients with baseline CD4+ cell counts >350 cells/mm3 achieved or approached the reference range those of control individuals without HIV infection. In contrast, patients who began ART with ?350 CD4+ cells/mm3 generally did not regain normal CD4+ naive-memory cell ratios. These results support current guidelines to start ART at a threshold of 350 cells/mm3 and suggest that there may be immunological benefits associated with initiating therapy at even higher CD4+ cell counts. PMID:19123865

Robbins, Gregory K.; Spritzler, John G.; Chan, Ellen S.; Asmuth, David M.; Gandhi, Rajesh T.; Rodriguez, Benigno A.; Skowron, Gail; Skolnik, Paul R.; Shafer, Robert W.; Pollard, Richard B.

2009-01-01

339

Methamphetamine use and neuropsychiatric factors are associated with antiretroviral non-adherence  

Microsoft Academic Search

The present study assesses the impact of methamphetamine (METH) on antiretroviral therapy (ART) adherence among HIV+ persons, as well as examines the contribution of neurocognitive impairment and other neuropsychiatric factors [i.e., major depressive disorder (MDD), antisocial personality disorder (ASPD), and attention deficit disorder (ADHD)] for ART non-adherence. We examined HIV+ persons with DSM-IV-diagnosed lifetime history of METH abuse\\/dependence (HIV+ \\/METH+

David J. Moore; Kaitlin Blackstone; Steven Paul Woods; Ronald J. Ellis; J. Hampton Atkinson; Robert K. Heaton; Igor Grant

2012-01-01

340

Antidepressant Treatment and Adherence to Antiretroviral Medications Among Privately Insured Persons with HIV\\/AIDS  

Microsoft Academic Search

In order to examine relationships between depression treatments (antidepressant and\\/or psychotherapy utilization) and adherence\\u000a to antiretroviral therapy (ART), we conducted a retrospective analysis of medical and pharmacy insurance claims for privately\\u000a insured persons living with HIV\\/AIDS (PLWHA) diagnosed with depression (n = 1,150). Participants were enrolled in 80 insurance plans from all 50 states. Adherence was suboptimal. Depression treatment\\u000a initiators were significantly

Ayse AkincigilIra; Ira B. Wilson; James T. Walkup; Michele J. Siegel; Cecilia Huang; Stephen Crystal

341

Pubertal Onset in HIV-infected Children in the Era of Combination Antiretroviral Treatment  

PubMed Central

Objective To evaluate associations of perinatal HIV infection (PHIV), HIV disease severity, and combination antiretroviral treatment with age at pubertal onset. Design Analysis of data from two U.S. longitudinal cohort studies [IMPAACT 219C and PHACS AMP], conducted 2000–2012, including PHIV and HIV-exposed uninfected (HEU) youth. Tanner stage assessments of pubertal status (breast and pubic hair in girls; genitalia and pubic hair in boys) were conducted annually. Methods We compared the timing of pubertal onset (Tanner stage ?2) between PHIV and HEU youth using interval-censored models. For PHIV youth, we evaluated associations of HIV disease severity and combination antiretroviral treatment with age at pubertal onset, adjusting for race/ethnicity and birth cohort. Results The mean age at pubertal onset was significantly later for the 2086 PHIV youth compared to 453 HEU children (10.3 vs 9.6, 10.5 vs 10.0, 11.3 vs 10.4, and 11.5 vs 10.7 years according to female breast, female pubic hair, male genitalia, and male pubic hair staging, respectively, all p<0.001). PHIV youth with HIV-1 RNA viral load >10,000 copies/mL (vs ?10,000 copies/mL) or CD4% <15% (vs ?15%) had significantly later pubertal onset (by 4–13 months). Each additional year of combination antiretroviral treatment was associated with a 0.6- to1.2-month earlier mean age at pubertal onset, but this trend did not persist after adjustment for birth cohort. Conclusions Pubertal onset occurs significantly later in PHIV than in HEU youth, especially among those with more severe HIV disease. However, in the current era, combination antiretroviral treatment may result in more normal timing of pubertal onset. PMID:24145244

WILLIAMS, Paige L.; ABZUG, Mark J.; JACOBSON, Denise L.; WANG, Jiajia; VAN DYKE, Russell B.; HAZRA, Rohan; PATEL, Kunjal; DIMEGLIO, Linda A.; MCFARLAND, Elizabeth J.; SILIO, Margarita; BORKOWSKY, William; SEAGE, George R.; OLESKE, James M.; GEFFNER, Mitchell E.

2014-01-01

342

Relevance of experimental models for investigation of genotoxicity induced by antiretroviral therapy during human pregnancy.  

PubMed

The current incidence of human immunodeficiency virus (HIV-1)/AIDS affects around 7000 pregnant women in the United States. When given during pregnancy, the nucleoside analog 3'-azido-3'-deoxythymidine (AZT) significantly reduces maternal-fetal transmission. It has been previously shown that AZT is incorporated into DNA, where it causes mutations in the HPRT and TK genes. It also changes cell cycle gene expression, and induces S-phase arrest, micronuclei, chromosomal aberrations, sister chromatid exchanges, telomeric attrition, and other genotoxic effects in cultured cells. A predicted consequence of these events is genomic instability that together, with clastogenicity may contribute to the carcinogenic potency of AZT. Various aspects of genotoxicity are explored in this contribution seeking to understand the multiple effects of this antiretroviral agent in animal models and humans. This mini-review describes some of the experimental models used to elucidate the genotoxicity induced by antiretroviral therapy during human pregnancy. The use of diverse methods to detect biomarkers of exposure, such as an AZT-specific radioimmunoassay, micronuclei bearing intact chromosomes, and telomeric DNA attrition highlight the role of in vitro models to elucidate exposure and risk. The relevance of the in vitro models is followed by the introduction of the role of the nucleoside analogs in transplacental carcinogenesis along with the description of a transplacental perfusion model and a transplacental carcinogenesis rodent model. In a more direct clinical application the use of AZT-DNA incorporation as a biomarker of exposure, in experiments conducted in vivo in Erythrocebus patas monkeys and in humans, addresses the possibility of elucidation of potential cancer risk in those infants exposed in utero. Two relevant aspects of this contribution are the potential application of some of the models described in this mini-review, as diagnostic tools in antiretroviral-exposed populations, and the use of these models to understand the nature of the genotoxicities and minimize the undesirable side effects of the antiretroviral therapy. PMID:18295533

Olivero, Ofelia A

2008-01-01

343

Discontinuing anticytomegalovirus therapy in patients with immune reconstitution after combination antiretroviral therapy  

Microsoft Academic Search

PURPOSE: To describe our experience with discontinuation of anticytomegalovirus maintenance therapy in patients who have had immune reconstitution after initiation of highly active antiretroviral therapy.METHODS: Fifteen patients with treated cytomegalovirus retinitis, who had immune reconstitution after initiation of highly active retroviral therapy, had anticytomegalovirus maintenance therapy discontinued. Patients were followed closely for relapse of retinitis.RESULTS: Median nadir CD4+ T-cell count,

Douglas A. Jabs; Stephen G. Bolton; J. P. Dunn; Alan G. Palestine

1998-01-01

344

Estimating health workforce needs for antiretroviral therapy in resource-limited settings  

Microsoft Academic Search

BACKGROUND: Efforts to increase access to life-saving treatment, including antiretroviral therapy (ART), for people living with HIV\\/AIDS in resource-limited settings has been the growing focus of international efforts. One of the greatest challenges to scaling up will be the limited supply of adequately trained human resources for health, including doctors, nurses, pharmacists and other skilled providers. As national treatment programmes

Lisa R Hirschhorn; Lulu Oguda; Andrew Fullem; Norbert Dreesch; Paul Wilson

2006-01-01

345

Social Factors Related to Antiretroviral Therapy Use in Injection Drug Users  

Microsoft Academic Search

This study applied a behavioral model of health services use that included health-related attitudes and indicators of social contact and support to use of antiretroviral therapy (ART) in a cross-sectional survey of 241 disadvantaged, inner-city injection drug users (IDUs). Only 44% of this sample reported taking ART despite relatively high levels of health care utilization; ART nonuse was associated with

Jennifer R. Schroeder; Carl A. Latkin; Donald R. Hoover; Amy R. Knowlton; Jonathan Zenilman; Steffanie Strathdee; David D. Celentano

2001-01-01

346

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

Microsoft Academic Search

Directly administered antiretroviral therapy (DAART) can improve health outcomes among HIV-infected drug users. An understanding\\u000a of the utilization of DAART—initiation, adherence, and retention—is critical to successful program design. Here, we use the\\u000a Behavioral Model to assess the enabling, predisposing, and need factors impacting adherence in our randomized, controlled\\u000a trial of DAART versus self-administered therapy (SAT) among 141 HIV-infected drug users.

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

2008-01-01

347

In utero exposure to antiretroviral therapy: feasibility of long-term follow-up  

Microsoft Academic Search

Most uninfected children born to diagnosed HIV-infected women in the United Kingdom (UK) are exposed to antiretroviral therapy (ART) in utero and neonatally, and concerns exist about potential adverse effects of such exposure. We explored the feasibility of using national clinic-based follow-up to investigate the association between ART exposure and adverse health events occurring after the neonatal period. Active surveillance

Claire Hankin; Hermione Lyall; Barbara Willey; Catherine Peckham; Janet Masters; Pat Tookey

2009-01-01

348

Comprehensive In Vitro Analysis of Simian Retrovirus Type 4 Susceptibility to Antiretroviral Agents  

PubMed Central

Simian retrovirus type 4 (SRV-4), a simian type D retrovirus, naturally infects cynomolgus monkeys, usually without apparent symptoms. However, some infected monkeys presented with an immunosuppressive syndrome resembling that induced by simian immunodeficiency virus infection. Antiretrovirals with inhibitory activity against SRV-4 are considered to be promising agents to combat SRV-4 infection. However, although some antiretrovirals have been reported to have inhibitory activity against SRV-1 and SRV-2, inhibitors with anti-SRV-4 activity have not yet been studied. In this study, we identified antiretroviral agents with anti-SRV-4 activity from a panel of anti-human immunodeficiency virus (HIV) drugs using a robust in vitro luciferase reporter assay. Among these, two HIV reverse transcriptase inhibitors, zidovudine (AZT) and tenofovir disoproxil fumarate (TDF), potently inhibited SRV-4 infection within a submicromolar to nanomolar range, which was similar to or higher than the activities against HIV-1, Moloney murine leukemia virus, and feline immunodeficiency virus. In contrast, nonnucleoside reverse transcriptase inhibitors and protease inhibitors did not exhibit any activities against SRV-4. Although both AZT and TDF effectively inhibited cell-free SRV-4 transmission, they exhibited only partial inhibitory activities against cell-to-cell transmission. Importantly, one HIV integrase strand transfer inhibitor, raltegravir (RAL), potently inhibited single-round infection as well as cell-free and cell-to-cell SRV-4 transmission. These findings indicate that viral expansion routes impact the inhibitory activity of antiretrovirals against SRV-4, while only RAL is effective in suppressing both the initial SRV-4 infection and subsequent SRV-4 replication. PMID:23365453

Togami, Hiroaki; Okamoto, Munehiro; Yoshikawa, Rokusuke; Miyazawa, Takayuki; Matsuoka, Masao

2013-01-01

349

Cellular immune responses to HCV core increase and HCV RNA levels decrease during successful antiretroviral therapy  

Microsoft Academic Search

BackgroundHepatitis C virus (HCV) infection is a major cause of morbidity in HIV infected individuals. Coinfection with HIV is associated with diminished HCV-specific immune responses and higher HCV RNA levels.AimsTo investigate whether long-term combination antiretroviral therapy (cART) restores HCV-specific T cell responses and improves the control of HCV replication.MethodsT cell responses were evaluated longitudinally in 80 HIV\\/HCV coinfected individuals by

Janine Rohrbach; Nicola Robinson; Gillian Harcourt; Emma Hammond; Silvana Gaudieri; Meri Gorgievski; Amalio Telenti; Olivia Keiser; Huldrych F Günthard; Bernhard Hirschel; Matthias Hoffmann; Enos Bernasconi; Manuel Battegay; Hansjakob Furrer; Paul Klenerman; Andri Rauch

2010-01-01

350

Quality of Life Outcomes of Antiretroviral Treatment for HIV\\/AIDS Patients in Vietnam  

Microsoft Academic Search

ObjectiveThis study assessed health-related quality of life (HRQOL) and its related factors in HIV\\/AIDS patients taking antiretroviral treatment (ART) in Vietnam.MethodsA cross-sectional study was conducted with 1016 patients (36.2% women, mean age = 35.4) in three epicenters of Vietnam, including Hanoi, Hai Phong, and Ho Chi Minh City. HRQOL was assessed using the Vietnamese version of the WHOQOL-HIV BREF. Factor

Bach Xuan Tran

2012-01-01

351

Quality of Life for Children and Adolescents: Impact of HIV Infection and Antiretroviral Treatment  

Microsoft Academic Search

BACKGROUND.HIV\\/AIDS mortality rates in the United States are declining; pediatric HIV has become a chronic disease, with quality of life (QoL) outcomes assuming greater importance. OBJECTIVES.To compare QoL among HIV-infected and uninfected children and to assess the impact of different antiretroviral regimens on QoL among HIV-infected children. METHODS.Perinatally exposed, HIV-infected (N 1847) and uninfected (N 712) children and adolescents were

Grace M. Lee; Steven L. Gortmaker; Kenneth McIntosh; Michael D. Hughes; James M. Oleske

2010-01-01

352

Variations of CYP3A activity induced by antiretroviral treatment in HIV1 infected patients  

Microsoft Academic Search

Objective To measure the in vivo variations of CYP3A activity induced by anti-HIV drugs in human immunodeficiency virus (HIV)1-positive patients. Methods A low oral dose of midazolam (MID) (0.075 mg) was given to the patients and the 30-min total 1-OH midazolam (1-OHMID)\\/MID ratio was determined. Patients were phenotyped either before the introduction of antiretroviral treatments (control group, 90 patients) or after

Jacques Fellay; Catia Marzolini; Laurent Decosterd; Kerry Powell Golay; Pierre Baumann; Thierry Buclin; Amalio Telenti; Chin B. Eap

2005-01-01

353

[Prevalence of metabolic complications after 10 years of antiretroviral treatment in Senegal].  

PubMed

Among the patients of the cohort still followed after a median of 9 years of antiretroviral treatment (ART), 37% had lipodystrophy, 28% had hypertension and 14% presented with diabetes. This study confirms the association between stavudine and lipodystrophy particulary lipoatrophy and shows that a longer duration of ART was associated with the presence of diabetes. These results highlight the need to implement programs for prevention of cardiovascular risk factors in HIV patients from resource-constrained settings. PMID:24683016

Diouf, A; Cournil, A

2014-10-01

354

Food Insecurity as a Barrier to Sustained Antiretroviral Therapy Adherence in Uganda  

Microsoft Academic Search

BackgroundFood insecurity is emerging as an important barrier to antiretroviral (ARV) adherence in sub-Saharan Africa and elsewhere, but little is known about the mechanisms through which food insecurity leads to ARV non-adherence and treatment interruptions.MethodologyWe conducted in-depth, open-ended interviews with 47 individuals (30 women, 17 men) living with HIV\\/AIDS recruited from AIDS treatment programs in Mbarara and Kampala, Uganda to

Sheri D. Weiser; David M. Tuller; Edward A. Frongillo; Jude Senkungu; Nozmu Mukiibi; David R. Bangsberg

2010-01-01

355

The distribution of viral blips observed in HIV1 infected patients treated with combination antiretroviral therapy  

Microsoft Academic Search

Human immunodeficiency virus type 1 (HIV-1) infected patients treated with combination antiretroviral therapy frequently have\\u000a the level of HIV-1 RNA detectable in plasma driven below the lower limit of detection of current assays, 50 copies ml?1. Patients may continue to exhibit viral loads (VLs) below the assay limit for years, yet on some occasions the VL may be\\u000a above the

Jerome K. Percus; Ora E. Percus; Martin Markowitz; David D. Ho; Michele Di Mascio; Alan S. Perelson

2003-01-01

356

Adherence to antiretroviral therapy among a conflict-affected population in Northeastern Uganda: a qualitative study.  

PubMed

We aimed to determine patient and health worker concerns regarding antiretroviral adherence in a conflict-affected population using focus groups (n = 40) and semi-structured interviews (n = 11). Patient concerns include security attending clinics, food security, distance to health centers and access to health providers. During periods of famine and flooding, the lack of food security and only single daily meals makes taking multiple doses impossible. Possible facilitating strategies included mobile teams, increased security and regularity of drug stocks. PMID:18753867

Olupot-Olupot, Peter; Katawera, Andrew; Cooper, Curtis; Small, Will; Anema, Aranka; Mills, Edward

2008-09-12

357

Interruption of antiretroviral therapy is associated with increased plasma cystatin C  

PubMed Central

Background Cystatin C has been proposed as an alternative marker of renal function. We sought to determine if participants randomized to episodic use of antiretroviral therapy guided by CD4+ count (drug conservation; DC) had altered cystatin C levels compared to those randomised to continuous antiretroviral therapy (viral suppression; VS) in the Strategies for Management of Antiretroviral Therapy Trial, and to identify factors associated with increased cystatin C. Methods 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 DC and VS groups respectively. Logistic regression was used to model the odds of ? 0.15 mg/dl increase in cystatin C (1 standard deviation [SD]) in the first month after randomisation, adjusting for demographic and clinical characteristics. Results At randomisation, mean (SD) cystatin C level was 0.99 (0.26 mg/dl) and 1.01 (0.28 mg/dl) in the DC and VS arms respectively (p=0.29). In the first month after randomisation, 21.8% and 10.6% had ?0.15 mg/dl increase in cystatin C in the DC and VS arm respectively (p=0.0008). The difference in cystatin C between the treatment arms was maintained through 1 year after randomisation. After adjustment, participants in the VS arm had significantly reduced odds of ?0.15 mg/dl increase in cystatin C in the first month (OR 0.42; 95% CI 0.23–0.74, p=0.0023). Conclusions These results demonstrate that interruption of antiretroviral therapy is associated with an increase in cystatin C, which may reflect worsened renal function. PMID:19050388

Mocroft, A; Wyatt, C; Szczech, L; Neuhaus, J; El-Sadr, W; Tracy, R; Kuller, L; Shlipak, M; Angus, B; Klinker, H; Ross, M

2009-01-01

358

Systemic and topical drugs for the prevention of HIV infection: antiretroviral pre-exposure prophylaxis  

PubMed Central

Pre-exposure prophylaxis (PrEP), in which HIV uninfected persons use oral or topical antiretroviral medications to protect against HIV acquisition, is a promising new HIV prevention strategy. The biologic rationale for evaluation of PrEP for sexual HIV prevention included non-human primate models and antiretroviral prophylaxis for HIV-exposed infants. Proof-of-concept that PrEP protects against sexual HIV acquisition has been demonstrated in four clinical trials, which used the antiretroviral medication tenofovir, either as a vaginal gel or as daily oral tenofovir disoproxil fumarate, alone or co-formulated with emtricitabine. Importantly, however, two trials failed to demonstrate HIV protection with PrEP, with low adherence to daily use of PrEP the leading hypothesis for lack of efficacy. Next steps in the field include rigorous evaluation of uptake and adherence to PrEP in implementation settings and research into ‘next-generation’ PrEP agents with longer half-life and less user-dependence. PMID:23020883

Baeten, Jared; Celum, Connie

2013-01-01

359

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

PubMed Central

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

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

2009-01-01

360

HIV-1 Subtype C Reverse Transcriptase and Protease Genotypes in Zimbabwean Patients Failing Antiretroviral Therapy  

PubMed Central

HIV-1 drug resistance mutations have been identified and characterized mostly in subtype B HIV-1 infection. The extent to which antiretroviral drugs select for drug resistance mutations in non-subtype B HIV-1 is not known. We obtained HIV-1 reverse transcriptase (RT) and protease sequences from 21 Zimbabwean patients failing antiretroviral drug therapy. We compared these sequences with 56 published RT and protease subtype C sequences from untreated patients, 990 RT and 1140 protease subtype B sequences from treated patients, and 340 RT and 907 protease subtype B sequences from untreated patients and identified four mutation categories of subtype C HIV-1. Seventeen of the 21 patients (81%) had known drug resistance mutations. Mutations at 15 RT and 11 protease positions were more common in subtype C isolates than in subtype B isolates. HIV-1 subtype C-infected individuals receiving antiretroviral therapy develop many of the known subtype B drug resistance mutations. Comparison of subtype C RT and protease sequences with a large database of subtype B sequences identified subtype C-specific polymorphisms and candidate drug resistance mutations. PMID:12512512

KANTOR, RAMI; ZIJENAH, LYNN S.; SHAFER, ROBERT W.; MUTETWA, SOLOMON; JOHNSTON, ELIZABETH; LLOYD, ROBERT; VON LIEVEN, ANDREA; ISRAELSKI, DENNIS; KATZENSTEIN, DAVID A.

2008-01-01

361

The Impact of Universal Access to Antiretroviral Therapy on HIV Stigma in Botswana  

PubMed Central

Objectives. We sought to examine the impact of treatment access on HIV stigma in Botswana 3 years after the introduction of a national program of universal access to antiretroviral therapy. Methods. We studied the prevalence and correlates of HIV stigma in a population-based study of 1268 adults in Botswana in 2004. We used multivariate logistic regression to assess correlates of stigmatizing attitudes and a new measure, anticipated HIV stigma. Results. Overall, 38% of participants had at least 1 stigmatizing attitude: 23% would not buy food from a shopkeeper with HIV; 5% would not care for a relative with HIV. Seventy percent reported at least 1 measure of anticipated stigma: 54% anticipated ostracism after testing positive for HIV, and 31% anticipated mistreatment at work. Perceived access to antiretroviral therapy was strongly and independently associated with decreased odds of holding stigmatizing attitudes (adjusted odds ratio [AOR] = 0.42; 95% confidence interval [CI] = 0.24, 0.74) and of anticipated stigma (AOR = 0.09; 95% CI = 0.03, 0.30). Conclusions. Our findings suggest that antiretroviral therapy access may be a factor in reducing HIV stigma. Nevertheless, the persistence of stigmatizing attitudes and significant anticipated stigma suggest that HIV stigma must be a target for ongoing intervention. PMID:18703447

Weiser, Sheri D.; Leiter, Karen; Steward, Wayne T.; Percy-de Korte, Fiona; Phaladze, Nthabiseng; Iacopino, Vincent; Heisler, Michele

2008-01-01

362

Methods Development for Blood Borne Macrophage Carriage of Nanoformulated Antiretroviral Drugs  

PubMed Central

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

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

2010-01-01

363

76 FR 50813 - Major Capital Investment Projects; Guidance on News Starts/Small Starts Policies and Procedures  

Federal Register 2010, 2011, 2012, 2013, 2014

...publish policy guidance on the New and Small Starts capital project review and evaluation process...sought public comment on the New Starts and Small Starts project justification criteria...regulations that govern the New Starts and Small Starts...

2011-08-16

364

New Start Program: Third-Year Report.  

ERIC Educational Resources Information Center

Kingsborough Community College's (KCC) New Start Program is designed to assist students facing dismissal at four-year institutions. After referral by the senior college, students who choose to enroll in New Start are admitted to KCC in good academic standing, are permitted to apply up to 30 previously earned credits toward an associate degree, and…

Winchell, Anne

365

Delivering Sure Start in Rural Communities  

ERIC Educational Resources Information Center

This paper explores and questions some of the evidence used to support early childhood interventions in the UK, and reports on discussions with three rural Mini Sure Start project leaders in Devon. Sure Start funding in the UK has been repeatedly increased to provide more centres for 0-3-year-olds and their parents. It is increasingly linked to…

Willan, Jenny

2007-01-01

366

Start up Italy: il talento delle idee  

E-print Network

Start up Italy: il talento delle idee Le start up come opportunità per i giovani di dare spazio persona fisica > Essere residente in Italia Contributo da parte di Bain & Company Italy: > Bain offrirà Istituzioni Finanziarie Giuria: > La giuria è composta da Partner e Manager di Bain & Company Italy Il

Robbiano, Lorenzo

367

Application of SMES Unit in Black Start  

NASA Astrophysics Data System (ADS)

Blackout of large area is a serious threat to modern power system, so power system restoration which is called Black Start is a critical task for reducing economic losses and social unrest caused by blackout. Traditiona black start sometimes may suffer from inflexible black start units and overvoltage and serious oscillation. As a power storage unit, SMES has the ability of fast exchanging active and reactive power with power grid in all four quadrants, so it is proposed as a new solution to improve the black start process in this paper. Comparing to traditional black start, some unique advantages of SMES for black start are presented. Also SMES model and related control strategy are introduced in detail. A simulation model is established based on PSCAD/EMTDC to investigate the validity and flexibility of SMES in black start. Simulation results show that SMES unit can bring thermal generators online, and it has better performance on overvoltage restraint and amping oscillation than traditional black start. Also, the performance of nonlinear PID-controlled SMES is better than that of PID-controlled SMES.

Yang, Jun; Liu, Wenqing; Liu, Pei

368

Administration for Children and Families: Head Start  

ERIC Educational Resources Information Center

This paper presents an overview of the Head Start program. Under the American Recovery and Reinvestment Act (Recovery Act), $1 billion will be provided to the Office of Head Start to promote the school readiness of low-income children, including children on federally-recognized reservations and children of migratory farm workers, by enhancing…

US Department of Health and Human Services, 2010

2010-01-01

369

Assisted Workouts: Starting My Own Workout Program  

ERIC Educational Resources Information Center

As an undergraduate student with cerebral palsy, I found it difficult to achieve my goal of starting a regular exercise program at my school, the University of Central Florida. However, when I started a program called Assisted Workouts in spring 2003. the struggle proved to be well worth it. The program is not only beneficial to me, but it has…

Cousminer, Douglas

2003-01-01

370

Head Start Impact Study. Final Report  

ERIC Educational Resources Information Center

This report addresses the following four questions by reporting on the impacts of Head Start on children and families during the children's preschool, kindergarten, and 1st grade years: (1) What difference does Head Start make to key outcomes of development and learning (and in particular, the multiple domains of school readiness) for low-income…

Puma, Michael; Bell, Stephen; Cook, Ronna; Heid, Camilla; Shapiro, Gary; Broene, Pam; Jenkins, Frank; Fletcher, Philip; Quinn, Liz; Friedman, Janet; Ciarico, Janet; Rohacek, Monica; Adams, Gina; Spier, Elizabeth

2010-01-01

371

Design improvements in air turbine start systems  

Microsoft Academic Search

The main engine air turbine start system, which typically consists of an air turbine staxter and starter control valve, is a key contributor to aircraft dispatch reliability. Evolving aircraft propulsion systems have resulted in more aggressive operational environments, thus providing the impetus to improve the design of the start systems to enhance their durability and aid in improving both dispatch

G. A. Farnsworth; C. W. Plevich; K. Durnal

1992-01-01

372

The Phenomenon of Business Start-Ups.  

ERIC Educational Resources Information Center

A study of four European countries (France, United Kingdom, Italy, and Spain) was conducted to gather data on the business start-up process and its impact on the generation of jobs, small business start-up support programs, training and counseling programs, and characteristics of successful business starters. (The original aim of the study was to…

Melis, Africa

1990-01-01

373

Head Start Impact Study. Technical Report  

ERIC Educational Resources Information Center

This Technical Report is designed to provide technical detail to support the analysis and findings presented in the "Head Start Impact Study Final Report" (U.S. Department of Health and Human Services, January 2010). Chapter 1 provides an overview of the Head Start Impact Study and its findings. Chapter 2 provides technical information on the…

Puma, Michael; Bell, Stephen; Cook, Ronna; Heid, Camilla; Shapiro, Gary; Broene, Pam; Jenkins, Frank; Fletcher, Philip; Quinn, Liz; Friedman, Janet; Ciarico, Janet; Rohacek, Monica; Adams, Gina; Spier, Elizabeth

2010-01-01

374

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

PubMed Central

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

2014-01-01

375

77 FR 3838 - Notice of Availability of Proposed New Starts/Small Starts Policy Guidance  

Federal Register 2010, 2011, 2012, 2013, 2014

...for Major Capital Investment Projects by describing the detailed measures proposed for evaluation of projects seeking New Starts and Small Starts funding and...these measures would be used in project ratings if adopted. The...

2012-01-25

376

Start 2: Thinking one move ahead  

SciTech Connect

At their summit meeting in the spring of 1990, Presidents Bush and Gorbachev issued a joint statement expressing their intentions to continue the process of strategic arms control beyond the Strategic Arms Reduction Treaty (START), which was eventually signed in July 1991, toward agreement on further reductions. They set general goals for negotiation of a follow-on treaty to START, which has been called START II. President Bush`s historic speech on September 27, 1991, reinforced those goals and specified several actions the US would take. It is the purpose of this report to examine possible provisions of START II and the implications of those provisions for achievement of the goals set at the 1990 summit, for verifiability, and for US force planning. This look ahead will contribute to advance planning of appropriate negotiating positions, verification research and development (R&D), and force modernization and restructuring. This report describes the goals for a START II treaty and possible means for achieving them. It postulates one set of provisions for such a treaty, while it examines force structures for the US that could result from adoption of a treaty with these provisions. The adequacy of methods for verifying START II are examined and the implications of a START II treaty are postulated.

Gaines, L.L.

1991-11-01

377

Start 2: Thinking one move ahead  

SciTech Connect

At their summit meeting in the spring of 1990, Presidents Bush and Gorbachev issued a joint statement expressing their intentions to continue the process of strategic arms control beyond the Strategic Arms Reduction Treaty (START), which was eventually signed in July 1991, toward agreement on further reductions. They set general goals for negotiation of a follow-on treaty to START, which has been called START II. President Bush's historic speech on September 27, 1991, reinforced those goals and specified several actions the US would take. It is the purpose of this report to examine possible provisions of START II and the implications of those provisions for achievement of the goals set at the 1990 summit, for verifiability, and for US force planning. This look ahead will contribute to advance planning of appropriate negotiating positions, verification research and development (R D), and force modernization and restructuring. This report describes the goals for a START II treaty and possible means for achieving them. It postulates one set of provisions for such a treaty, while it examines force structures for the US that could result from adoption of a treaty with these provisions. The adequacy of methods for verifying START II are examined and the implications of a START II treaty are postulated.

Gaines, L.L.

1991-11-01

378

Starting Circuit For Erasable Programmable Logic Device  

NASA Technical Reports Server (NTRS)

Voltage regulator bypassed to supply starting current. Starting or "pullup" circuit supplies large inrush of current required by erasable programmable logic device (EPLD) while being turned on. Operates only during such intervals of high demand for current and has little effect any other time. Performs needed bypass, acting as current-dependent shunt connecting battery or other source of power more nearly directly to EPLD. Input capacitor of regulator removed when starting circuit installed, reducing probability of damage to transistor in event of short circuit in or across load.

Cole, Steven W.

1990-01-01

379

Mid South Middle Start: Studies of Three Middle Start Schools in the Mid South Delta  

ERIC Educational Resources Information Center

These three case studies highlight the implementation and impact of Mid South Middle Start by: (1) contributing toward an in-depth understanding of what it means to be a school implementing Middle Start; (2) describing a holistic portrait of the schools' participation in Mid South Middle Start; and (3) assisting the Academy for Educational…

Rose, Lea Williams; Cheney, Nancy

2005-01-01

380

Head Start 2010: Fulfilling the Promise. Report of the Head Start 2010 National Advisory Panel.  

ERIC Educational Resources Information Center

In anticipation of the 35th anniversary of Project Head Start, the National Head Start Association (NHSA) launched a national initiative to discover how Head Start can best serve children and families in the new millennium. A series of hearings and open forums were conducted throughout the country in 1999, along with a special session featuring…

National Head Start Association, Alexandria, VA.

381

Training Head Start Coordinators for Workplace Preparedness. NCCU Head Start Monograph, October 1995.  

ERIC Educational Resources Information Center

This monograph summarizes results from academic capstone activities of graduate students and faculty advisors regarding issues consistent with Head Start national priorities and practice needs. The following theses are summarized: (1) "Multicultural Education in Head Start Programs in North Carolina" (S.K. Gant); (2) "The Impact of Head Start on…

North Carolina Central Univ., Durham.

382

Factors associated with high rates of antiretroviral medication adherence among youth living with perinatal HIV in Thailand.  

PubMed

Antiretroviral medication adherence behaviour among Thai youth with perinatal HIV in Thailand has received growing attention. However, few studies have examined individual predictors of antiretroviral adherence using multiple self-reports. A convenience sample of 89 Thai youth (interquartile range 14-16 years) with perinatal HIV at three paediatric programmes in Chiang Mai completed a structured questionnaire and reported their antiretroviral adherence in the past one, seven and 30 days using count-based recall and a visual analog scale. Mean self-reported adherence rates ranged from 83.5% (past 30 days) to 99.8% (yesterday) of the time. One-inflated beta regression models were used to examine the associations between antiretroviral adherence outcomes, treatment self-efficacy, depression, anxiety, social support and beliefs/attitudes about medications. Higher percentage of medications taken in the past 30 days was independently associated with higher treatment self-efficacy and fewer symptoms of depression. Adherence monitoring would benefit from focal assessment of youth depression and perceived capacity to follow their antiretroviral regimen. PMID:25080289

Kang, Ezer; Delzell, Darcie Ap; Chhabra, Manik; Oberdorfer, Peninnah

2014-07-30

383

Comparisons of anemia, thrombocytopenia, and neutropenia at initiation of HIV antiretroviral therapy in Africa, Asia, and the Americas  

PubMed Central

Summary Background Hematological abnormalities are common manifestations of advanced HIV-1 infection that could affect the outcomes of highly-active antiretroviral therapy (HAART). Although most HIV-1-infected individuals live in resource-constrained countries, there is little information about the frequency of hematological abnormalities such as anemia, neutropenia, and thrombocytopenia among individuals with advanced HIV-1 disease. Methods This study compared the prevalence of pre-antiretroviral therapy hematological abnormalities among 1571 participants in a randomized trial of antiretroviral efficacy in Africa, Asia, South America, the Caribbean, and the USA. Potential covariates for anemia, neutropenia, and thrombocytopenia were identified in univariate analyses and evaluated in separate multivariable models for each hematological condition. Results The frequencies of neutropenia (absolute neutrophil count ? 1.3 × 109/l), anemia (hemoglobin ? 10 g/dl), and thrombocytopenia (platelets ? 125 × 109/l) at initiation of antiretroviral therapy were 14%, 12%, and 7%, respectively, and varied by country (p < 0.0001 for each). In multivariable models, anemia was associated with gender, platelet count, and country; neutropenia was associated with CD4+ lymphocyte and platelet counts; and thrombocytopenia was associated with country, gender, and chronic hepatitis B infection. Conclusions Differences in the frequency of pretreatment hematological abnormalities could have important implications for the choice of antiretroviral regimen in resource-constrained settings. PMID:20961784

Firnhaber, Cynthia; Smeaton, Laura; Saukila, Nasinuku; Flanigan, Timothy; Gangakhedkar, Raman; Kumwenda, Johnstone; La Rosa, Alberto; Kumarasamy, Nagalingeswaran; De Gruttola, Victor; Hakim, James Gita; Campbell, Thomas B.

2010-01-01

384

Evolution of Antiretroviral Drug Costs in Brazil in the Context of Free and Universal Access to AIDS Treatment  

PubMed Central

Background 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. Methods and Findings 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/r, efavirenz, tenofovir, atazanavir, enfuvirtide, and a locally produced generic, fixed-dose combination of zidovudine and lamivudine (AZT/3TC). Because prices declined for many of the patented drugs that constitute the largest share of drug costs, nearly the entire increase in overall drug expenditures between 2001 and 2005 is attributable to increases in drug quantities. Had all drug quantities been held constant from 2001 until 2005 (or for those drugs entering treatment guidelines after 2001, held constant between the year of introduction and 2005), total costs would have increased by only an estimated US$7 million. We estimate that in the absence of price declines for patented drugs, Brazil would have spent a cumulative total of US$2 billion on drugs for HAART between 2001 and 2005, implying a savings of US$1.2 billion from price declines. Finally, in comparing Brazilian prices for locally produced generic ARVs to the lowest international prices meeting global pharmaceutical quality standards, we find that current prices for Brazil's locally produced generics are generally much higher than corresponding global prices, and note that these prices have risen in Brazil while declining globally. We estimate the excess costs of Brazil's locally produced generics totaled US$110 million from 2001 to 2005. Conclusions Despite Brazil's more costly generic ARVs, the net result of ARV price changes has been a cost savings of approximately US$1 billion since 2001. HAART costs have nevertheless risen steeply as Brazil has scaled up treatment. These trends may foreshadow future AIDS treatment cost trends in other developing countries as more people start treatment, AIDS patients live longer and move from first-line to second and third-line treatment, AIDS treatment becomes more complex, generic competition emerges, and newer patented drugs become available. The specific application of the Brazilian model to other countries will depend, however, on the strength of their health systems, intellectual property regulations, epidemiologic

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

2007-01-01

385

The physics of tokamak start-up  

SciTech Connect

Tokamak start-up on present-day devices usually relies on inductively induced voltage from a central solenoid. In some cases, inductive startup is assisted with auxiliary power from electron cyclotron radio frequency heating. International Thermonuclear Experimental Reactor, the National Spherical Torus Experiment Upgrade and JT60, now under construction, will make use of the understanding gained from present-day devices to ensure successful start-up. Design of a spherical tokamak (ST) with DT capability for nuclear component testing would require an alternative to a central solenoid because the small central column in an ST has insufficient space to provide shielding for the insulators in the solenoid. Alternative start-up techniques such as induction using outer poloidal field coils, electron Bernstein wave start-up, coaxial helicity injection, and point source helicity injection have been used with success, but require demonstration of scaling to higher plasma current.

Mueller, D. [Princeton Plasma Physics Laboratory, P.O. Box 451 Princeton, New Jersey 08543 (United States)] [Princeton Plasma Physics Laboratory, P.O. Box 451 Princeton, New Jersey 08543 (United States)

2013-05-15

386

The Physics of Tokamak Start-up  

SciTech Connect

Tokamak start-up on present-day devices usually relies on inductively induced voltage from a central solenoid. In some cases inductive startup is assisted with auxiliary power from electron cyclotron radio frequency heating. ITER, the National Spherical Torus eXperiment Upgrade and JT60, now under construction, will make use of the understanding gained from present-day devices to ensure successful start-up. Design of a spherical tokamak (ST) with DT capability for nuclear component testing would require an alternative to a central solenoid because the small central column in an ST has insufficient space to provide shielding for the insulators in the solenoid. Alternative start-up techniques such as induction using outer poloidal field coils, electron Bernstein wave start-up, coaxial helicity injection and point source helicity injection have been used with success, but require demonstration of scaling to higher plasma current.

D. Mueller

2012-11-13

387

The physics of tokamak start-upa)  

NASA Astrophysics Data System (ADS)

Tokamak start-up on present-day devices usually relies on inductively induced voltage from a central solenoid. In some cases, inductive startup is assisted with auxiliary power from electron cyclotron radio frequency heating. International Thermonuclear Experimental Reactor, the National Spherical Torus Experiment Upgrade and JT60, now under construction, will make use of the understanding gained from present-day devices to ensure successful start-up. Design of a spherical tokamak (ST) with DT capability for nuclear component testing would require an alternative to a central solenoid because the small central column in an ST has insufficient space to provide shielding for the insulators in the solenoid. Alternative start-up techniques such as induction using outer poloidal field coils, electron Bernstein wave start-up, coaxial helicity injection, and point source helicity injection have been used with success, but require demonstration of scaling to higher plasma current.

Mueller, D.

2013-05-01

388

34 CFR 200.16 - Starting points.  

Code of Federal Regulations, 2014 CFR

...Using data from the 2001-2002 school year, each State must establish starting points in reading/language arts and in mathematics for measuring the percentage of students meeting or exceeding the State's proficient level of academic...

2014-07-01

389

34 CFR 200.16 - Starting points.  

Code of Federal Regulations, 2012 CFR

...Using data from the 2001-2002 school year, each State must establish starting points in reading/language arts and in mathematics for measuring the percentage of students meeting or exceeding the State's proficient level of academic...

2012-07-01

390

34 CFR 200.16 - Starting points.  

Code of Federal Regulations, 2013 CFR

...Using data from the 2001-2002 school year, each State must establish starting points in reading/language arts and in mathematics for measuring the percentage of students meeting or exceeding the State's proficient level of academic...

2013-07-01

391

Modeling Start Curves of Bainite Formation  

NASA Astrophysics Data System (ADS)

It is demonstrated that calculations with a physically based model give an accurate description of the start curve of bainite formation in a wide range of steels. The temperature dependence of the overall kinetics, which determines the characteristic C shape of the start curve, is controlled by both the undercooling below the start temperature ( T h - T) and an effective activation energy Q b . A systematic analysis of the model parameters extracted from the best fits of published time-temperature-transformation (TTT) data reveals a material-independent relationship, which means that the activation energy is in accordance with known details of the dislocation-based nucleation model of bainite. It is shown that the C shape of the start curve can be determined for a given alloying content using an empirical relationship derived for Q b and, in combination with the material-independent relationship, the kinetics of bainite can be predicted at all temperature levels.

van Bohemen, S. M. C.

2010-02-01

392

START USING THE NEW ONLINE METER  

E-print Network

START USING THE NEW ONLINE METER REQUEST FORM TOOL CAS login Logging in with your Princeton Net and convenient way for departments to send outgoing metered mail with Mail Services! The new Online Meter Request

Singh, Jaswinder Pal

393

75 FR 57704 - Head Start Program  

Federal Register 2010, 2011, 2012, 2013, 2014

...proposes seven conditions in three critical areas of Head Start program administration...impact of this new system and the critical need to ensure high-quality...Support domain develop children's critical thinking skills, provide ongoing...

2010-09-22

394

34 CFR 200.16 - Starting points.  

Code of Federal Regulations, 2010 CFR

...Using data from the 2001-2002 school year, each State must establish starting points in reading/language arts and in mathematics for measuring the percentage of students meeting or exceeding the State's proficient level of academic...

2010-07-01

395

Root Canal Treatment from Start to Finish  

MedlinePLUS

Illustrations: Root Canal Treatment From Start to Finish 1. A Deep Infection Root canal treatment is needed when an injury or ... the canals and remove debris. 4. Filling the Canals The canals are filled with a permanent material. ...

396

Getting Started Computing at the AI Lab  

E-print Network

This document describes the computing facilities at M.I.T. Artificial Intelligence Laboratory, and explains how to get started using them. It is intended as an orientation document for newcomers to the lab, and will be ...

Stacy, Christopher C.

1982-09-07

397

GETTING STARTED IN MATH AND THE SCIENCES  

E-print Network

GETTING STARTED IN MATH AND THE SCIENCES Some beginning advice.... #12 in math, sciences, etc.,) and your strengths · Not the same as high school (in or Science · Concern about Math/Science preparation · Less than 700 on the SATI

Myers, Lawrence C.

398

Quick Start FV1000CONFOCAL LASER SCANNING  

E-print Network

Quick Start FLUOVIEW FV1000CONFOCAL LASER SCANNING BIOLOGICAL MICROSCOPE FV10-ASWVer1.4 Petition···············································································40 3.10 3D Display laser system correctly, read instruction manuals that come with each laser equipment and light power

Meagher, Mary

399

Timing of antiretroviral therapy and regimen for HIV-infected patients with tuberculosis: the effect of revised HIV guidelines in Malawi  

PubMed Central

Background In July 2011, the Malawi national HIV program implemented the integrated antiretroviral therapy (ART) and prevention of mother-to-child transmission (PMTCT) guidelines. Among the principle goals of the guidelines were increasing ART uptake among TB/HIV co-infected patients and treating TB/HIV patients with a different drug regimen. We, therefore, assessed the effects of the new guidelines on ART uptake, the factors associated with ART uptake and the frequency of ARV-related adverse events in TB/HIV co-infected patients. Methods This was an observational cohort study using routine program data. All ART-naďve adult TB/HIV co-infected patients starting TB treatment over the six months preceding and following implementation of 2011 integrated ART/PMTCT guidelines were included. Results A total of 685 adult TB/HIV co-infected patients were registered in the study; 377 (55%) before and 308 (45%) after the implementation of the new guidelines. ART uptake increased from 70% (240/308) before implementation of the new guidelines to 78% (262/377) after the inception of the new guidelines (P=0.013). The proportion of TB patients initiating ART within two weeks of starting TB treatment increased from 30% before implementation of the new guidelines to 46% after implementation of the new guidelines (p <0.001). The median time from the start of TB treatment to ART initiation dropped from 16 days (IQR 14-31) before the new guidelines to 14 days (IQR 9-20; p?=?0.004) after implementing the new guidelines. Factors associated with ART uptake were enrolment in HIV care before starting TB treatment and being a retreatment TB patient. The overall frequency of ARV-related adverse events was higher in patients on d4T/3TC/NVP (35%) than those on TDF/3TC/EFV (25%) but not significantly different (P=0.052). Conclusion Implementation of the 2011 Malawi Integrated ART/PMTCT guidelines was associated with an overall increase in ART uptake among TB/HIV patients and with an increase in the number of patients initiating ART within two weeks of starting their TB treatment. However, the reduction in time between initiating TB treatment and starting ART was small suggesting that further measures must be implemented to facilitate ART uptake. Early enrolment in HIV care provides opportunities for timely ART initiation among TB patients. PMID:24555530

2014-01-01

400

New "starting points" for resources by subject.  

PubMed

The objective of the Starting Points Web page series at The University of Texas Health Science Center at San Antonio (UT HSC) Libraries is to provide specialized information resources in an organized online format. Highlighted resources include databases, journals, UT HSC campus information, funding sources, PubMed RSS article feeds, and information about professional associations. This paper discusses the development process, planning, challenges, and outcomes of the Starting Points series. PMID:19197747

Prentice, Katherine A; Gaines, Julie K; Levy, Linda S

2009-01-01

401

A New Start from Ground Zero?  

NASA Astrophysics Data System (ADS)

It is pointed out that one of the main reasons of lack of real conceptual progress in the field may lie in the fact that questions concerning the biogenesis of macromolecules have never been asked or addressed in a proper way. We should start again research on the origin of life starting from "ground zero" and focusing on the prebiotic synthesis of ordered sequences of proteins and nucleic acids.

Luisi, Pier Luigi

2015-01-01

402

Pre-antiretroviral therapy serum selenium concentrations predict WHO stages 3, 4 or death but not virologic failure post-antiretroviral therapy.  

PubMed

A case-cohort study, within a multi-country trial of antiretroviral therapy (ART) efficacy (Prospective Evaluation of Antiretrovirals in Resource Limited Settings (PEARLS)), was conducted to determine if pre-ART serum selenium deficiency is independently associated with human immunodeficiency virus (HIV) disease progression after ART initiation. Cases were HIV-1 infected adults with either clinical failure (incident World Health Organization (WHO) stage 3, 4 or death by 96 weeks) or virologic failure by 24 months. Risk factors for serum selenium deficiency (<85 ?g/L) pre-ART and its association with outcomes were examined. Median serum selenium concentration was 82.04 ?g/L (Interquartile range (IQR): 57.28-99.89) and serum selenium deficiency was 53%, varying widely by country from 0% to 100%. In multivariable models, risk factors for serum selenium deficiency were country, previous tuberculosis, anemia, and elevated C-reactive protein. Serum selenium deficiency was not associated with either clinical failure or virologic failure in multivariable models. However, relative to people in the third quartile (74.86-95.10 ?g/L) of serum selenium, we observed increased hazards (adjusted hazards ratio (HR): 3.50; 95% confidence intervals (CI): 1.30-9.42) of clinical failure but not virologic failure for people in the highest quartile. If future studies confirm this relationship of high serum selenium with increased clinical failure, a cautious approach to selenium supplementation might be needed, especially in HIV-infected populations with sufficient or unknown levels of selenium. PMID:25401501

Shivakoti, Rupak; Gupte, Nikhil; Yang, Wei-Teng; Mwelase, Noluthando; Kanyama, Cecilia; Tang, Alice M; Pillay, Sandy; Samaneka, Wadzanai; Riviere, Cynthia; Berendes, Sima; Lama, Javier R; Cardoso, Sandra W; Sugandhavesa, Patcharaphan; Semba, Richard D; Christian, Parul; Campbell, Thomas B; Gupta, Amita

2014-11-01

403

Pre-Antiretroviral Therapy Serum Selenium Concentrations Predict WHO Stages 3, 4 or Death but not Virologic Failure Post-Antiretroviral Therapy  

PubMed Central

A case-cohort study, within a multi-country trial of antiretroviral therapy (ART) efficacy (Prospective Evaluation of Antiretrovirals in Resource Limited Settings (PEARLS)), was conducted to determine if pre-ART serum selenium deficiency is independently associated with human immunodeficiency virus (HIV) disease progression after ART initiation. Cases were HIV-1 infected adults with either clinical failure (incident World Health Organization (WHO) stage 3, 4 or death by 96 weeks) or virologic failure by 24 months. Risk factors for serum selenium deficiency (<85 ?g/L) pre-ART and its association with outcomes were examined. Median serum selenium concentration was 82.04 ?g/L (Interquartile range (IQR): 57.28–99.89) and serum selenium deficiency was 53%, varying widely by country from 0% to 100%. In multivariable models, risk factors for serum selenium deficiency were country, previous tuberculosis, anemia, and elevated C-reactive protein. Serum selenium deficiency was not associated with either clinical failure or virologic failure in multivariable models. However, relative to people in the third quartile (74.86–95.10 ?g/L) of serum selenium, we observed increased hazards (adjusted hazards ratio (HR): 3.50; 95% confidence intervals (CI): 1.30–9.42) of clinical failure but not virologic failure for people in the highest quartile. If future studies confirm this relationship of high serum selenium with increased clinical failure, a cautious approach to selenium supplementation might be needed, especially in HIV-infected populations with sufficient or unknown levels of selenium. PMID:25401501

Shivakoti, Rupak; Gupte, Nikhil; Yang, Wei-Teng; Mwelase, Noluthando; Kanyama, Cecilia; Tang, Alice M.; Pillay, Sandy; Samaneka, Wadzanai; Riviere, Cynthia; Berendes, Sima; Lama, Javier R.; Cardoso, Sandra W.; Sugandhavesa, Patcharaphan; Semba, Richard D.; Christian, Parul; Campbell, Thomas B.; Gupta, Amita

2014-01-01

404

Adherence to antiretroviral therapy among HIV-infected children attending a donor-funded clinic at a tertiary hospital in Nigeria  

Microsoft Academic Search

The success of antiretroviral therapy (ART) depends on a high level of adherence to a life-long regimen of antiretroviral drugs (ARVs). Since the scale-up of access to ARVs in Nigeria, few studies have determined the level of adherence of ART among children. This study was undertaken to determine the level of ART adherence among paediatric patients at an outpatient clinic,

Edna Iroha; Christopher Imokhuede Esezobor; Chinyere Ezeaka; Edamisan Olusoji Temiye; Adebola Akinsulie

2010-01-01

405

Intervening in global markets to improve access to HIV\\/AIDS treatment: an analysis of international policies and the dynamics of global antiretroviral medicines markets  

Microsoft Academic Search

BACKGROUND: Universal access to antiretroviral therapy (ART) in low- and middle-income countries faces numerous challenges: increasing numbers of people needing ART, new guidelines recommending more expensive antiretroviral (ARV) medicines, limited financing, and few fixed-dose combination (FDC) products. Global initiatives aim to promote efficient global ARV markets, yet little is known about market dynamics and the impact of global policy interventions.

Brenda Waning; Margaret Kyle; Ellen Diedrichsen; Lyne Soucy; Jenny Hochstadt; Till Bärnighausen; Suerie Moon

2010-01-01

406

Should patents for antiretrovirals be waived in the developing world? Annual varsity medical debate - London, 21 January 2011  

PubMed Central

The 2011 Varsity Medical Debate, between Oxford and Cambridge Universities, brought students and faculty together to discuss the waiving of patents for antiretroviral therapies in the developing world. With an estimated 29.5 million infected by Human Immunodeficiency Virus (HIV) in low- and middle-income countries and only 5.3 million of those being treated, the effective and equitable distribution of anti-retroviral therapy (ART) is an issue of great importance. The debate centred around three areas of contention. Firstly, there was disagreement about whether patents were the real barrier to the access of anti-retroviral therapy in the developing world. Secondly, there were differing views on the effectiveness of a patent pool. Thirdly, concerns were raised over the impact of waiving patents on research to produce new and better anti retro-viral drugs. PMID:21740573

2011-01-01

407

Implementing a pharmacovigilance program to evaluate cutaneous adverse drug reactions in an antiretroviral access program  

PubMed Central

Background Cutaneous adverse drug reactions (cADRs) can cause significant morbidity and distress in patients especially in the HIV infected population on antiretroviral therapy. Adverse Drug Reaction monitoring and ascertaining causality in resource limited settings still remains a challenge. This study was carried out to evaluate causality and measure incidence of cADRs in HIV infected patients on highly active antiretroviral therapy. The study was also designed to test a 3-step approach in the monitoring and evaluation of ADRs in resource limited settings. Methodology A retrospective patient medical records review was carried out at the Parirenyatwa Family Care Centre, (Harare, Zimbabwe). Cases of cADRs were reported to the Medicines Control Authority of Zimbabwe (Drug regulating body in Zimbabwe) for assessment and causality classification. Results Two hundred and twenty-one patient records were randomly selected and reviewed to determine if any diagnosis of cADRs was made by clinicians. Causality assessment revealed 13.1% of cADRs which were due to an offending agent in the antiretroviral therapy against an initial incidence of 17.6% which had been determined by the physicians. Conclusions cADRs had an incidence of 13.1% within the population under study due to non nucleoside reverse transcriptase inhibitors (NNRTIs). Most reactions were due to the NNRTIs which contributed 72.4 % of all cADRs. A panel of experts from the drug regulatory authority can be used as an implementation based mechanism in ascertaining causality objectively in settings where resources are constrained. PMID:23277506

Mudzviti, Tinashe; Sibanda, Marvelous; Gavi, Samuel; Maponga, Charles Chiedza; Morse, Gene D.

2012-01-01

408

Chest Computed Tomography Findings in HIV-Infected Individuals in the Era of Antiretroviral Therapy  

PubMed Central

Background Chest radiographic abnormalities were common in HIV-infected individuals in the pre-combination antiretroviral therapy era, but findings may differ now due to a changing spectrum of pulmonary complications. Methods Cross-sectional study of radiographic abnormalities in an HIV-infected outpatient population during the antiretroviral therapy era. Demographics, chest computed tomography, and pulmonary function tests were obtained in HIV-infected volunteers without acute respiratory illness from the University of Pittsburgh HIV/AIDS clinic. Overall prevalence of radiographic abnormalities and potential risk factors for having any abnormality, nodules, or emphysema were evaluated using univariate and multivariable analyses. Results A majority of the 121 participants (55.4%) had a radiographic abnormality with the most common being emphysema (26.4%), nodules (17.4%), and bronchiectasis (10.7%). In multivariate models, age (odds ratio [OR] per year ?=?1.07, 95% confidence interval [CI] 1.04–1.14, p<0.001), pneumonia history (OR ?=?3.60, 95% CI ?=?1.27–10.20, p?=?0.016), and having ever smoked (OR ?=?3.66, p?=?0.013, 95% CI ?=?1.31–10.12) were significant predictors of having any radiographic abnormality. Use of antiretroviral therapy, CD4 cell count, and HIV viral load were not associated with presence of abnormalities. Individuals with radiographic emphysema were more likely to have airway obstruction on pulmonary function tests. Only 85.8% participants with nodules had follow-up imaging resulting in 52.4% having stable nodules, 23.8% resolution of their nodules, 4.8% development of a new nodule, and 4.8% primary lung cancer. Conclusions Radiographic abnormalities remain common in HIV-infected individuals with emphysema, nodules, and bronchiectasis being the most common. Age, smoking, and pneumonia were associated with radiographic abnormalities, but HIV-associated factors did not seem to predict risk. PMID:25409510

Clausen, Emily; Wittman, Catherine; Gingo, Matthew; Fernainy, Khaled; Fuhrman, Carl; Kessinger, Cathy; Weinman, Renee; McMahon, Deborah; Leader, Joseph; Morris, Alison

2014-01-01

409

[Cryptococcal neuromeningitidis in HIV-infected patients in Bangui, in the era of antiretroviral treatment].  

PubMed

The cryptococcal neuromeningitis is the most common fungal meningitis infections in the course of HIV/AIDS. This is the number two of opportunist infection of the central nervous system. The authors post the outcomes of a retrospective study conducted related to 122 cases of cryptococcal neuromeningitis observed over for four years ago, in Bangui in the Central African Republic, this at time when antiretroviral treatment has been avaible, corresponding to a prevalence of 6.5%. These infections very aften occur more in female folk, and to patients whose average age is 35 years old, ranging from 18 to 69 years old. The clinical symptoms often found had been headache (98,3.%), fever (95.0%), the impairing of the overall condition of the patient (86.7%) and neck stiffness (85.9%). It makes sense to notice that comorbidity case alowgwith tuberculosis, intestinal candidiasis, bacterial pneumonia and Kaposi's diseases were found out. The screening of the cerebrospinal fluid showed a sound cell count and even low count in 12.2% of cases. Direct examination of cerebrospinal fluid with India ink helps in diagnosis of 97.5% of cases, and the culture carried out from 74 patients was in any case positive. This culture allowed the diagnosis of three patients whose examination along side with India ink has been negative. The CD4 cell count was less than 100/mm(3) in 97.7% of cases. The rate of the fatality cases has been 66.4%, it has been badly impacted by a CD4 count <50/mm(3) and the lack of antiretroviral therapy. Despite the establishment of a national antiretroviral treatment program to do influence the frequency of opportunistic infections whose cryptococcal neuromeningitis, this condition is still present although it is declining. The clinical variability of this disease requires early diagnosis to avoid delayed treatment corollary of a very high mortality as we have observed. PMID:24570116

Gbangba-Ngai, E; Fikouma, V; Mossoro-Kpinde, C D; Tekpa, G; Ouavene, J O; Yangba Mongba, D S A; Mbelesso, P

2014-05-01

410

Emtricitabine: a new nucleoside analogue for once-daily antiretroviral therapy.  

PubMed

Highly active antiretroviral therapy has resulted in a dramatic decline in morbidity and mortality among patients infected with HIV. Nevertheless, this success has to be considered in the context of the current challenges and needs in this field. Adherence, toxicity, potency and resistance are still matters of intense research, which need to improve in order to overcome the current limitations of available drugs. Regarding needs, the improvement of convenience, tolerability and pharmacokinetics run in parallel with toxicity reduction, improvement of activity (both for wild-type and resistant virus), penetration into viral reservoirs and exploitation of new targets. The Food and Drug Administration approved emtricitabine in July 2003 for use in combination with other antiretroviral agents in adults with HIV-1 infection. Approval was based on the results of two Phase III clinical trials. The first was a double-blind study comparing the safety and efficacy of emtricitabine + didanosine + efavirenz to stavudine + didanosine + efavirenz as initial treatment in individuals who had not previously received antiretroviral therapy. At 24 and 48 weeks, patients receiving emtricitabine had significantly higher rates of virological suppression and greater increases in CD4+ counts than stavudine recipients. The second study was an open-label trial in treatment-experienced patients with HIV RNA < 400 copies/ml on a lamivudine-containing regimen in combination with either stavudine or zidovudine and either a protease inhibitor or a non-nucleoside reverse transcriptase inhibitor for at least 12 weeks. Patients were randomised either to continue lamivudine (150 mg b.i.d.) or to switch to emtricitabine 200 mg o.d. while maintaining the same background medications. In this study, the proportion of patients whose viral loads remained suppressed at the < 400 and < 50 copies/ml levels were similar in the two treatment groups. Potency, tolerability, convenient dosing and a low rate of side effects are some of the main characteristics of this new drug. PMID:14680453

Cahn, Pedro

2004-01-01

411

Patient satisfaction with task shifting of antiretroviral services in Ethiopia: implications for universal health coverage.  

PubMed

Formalized task shifting structures have been used to rapidly scale up antiretroviral service delivery to underserved populations in several countries, and may be a promising mechanism for accomplishing universal health coverage. However, studies evaluating the quality of service delivery through task shifting have largely ignored the patient perspective, focusing on health outcomes and acceptability to health care providers and regulatory bodies, despite studies worldwide that have shown the significance of patient satisfaction as an indicator of quality. This study aimed to measure patient satisfaction with task shifting of antiretroviral services in hospitals and health centres in four regions of Ethiopia. This cross-sectional study used data collected from a time-motion study of patient services paired with 665 patient exit interviews in a stratified random sample of antiretroviral therapy clinics in 21 hospitals and 40 health centres in 2012. Data were analyzed using f-tests across provider types, and multivariate logistic regression to identify determinants of patient satisfaction. Most (528 of 665) patients were satisfied or somewhat satisfied with the services received, but patients who received services from nurses and health officers were significantly more likely to report satisfaction than those who received services from doctors [odds ratio (OR) 0.26, P < 0.01]. Investments in the health facility were associated with higher satisfaction (OR 1.07, P < 0.01), while costs to patients of over 120 birr were associated with lower satisfaction (OR 0.14, P < 0.05). This study showed high levels of patient satisfaction with task shifting in Ethiopia. The evidence generated by this study complements previous biomedical and health care provider/regulatory acceptability studies to support the inclusion of task shifting as a mechanism for scaling-up health services to achieve universal health coverage, particularly for underserved areas facing severe health worker shortages. PMID:25274640

Asfaw, Elias; Dominis, Sarah; Palen, John G H; Wong, Wendy; Bekele, Abebe; Kebede, Amha; Johns, Benjamin

2014-09-01

412

Pregnancy Outcome in HIV-1-infected Women Receiving Combination Antiretroviral Therapy Prior versus After Conception  

PubMed Central

Objective Results regarding potential adverse effects of antiretroviral drugs during pregnancy are discrepant and few studies, most from Europe, have provided information about pregnancy outcomes of those already on treatment at conception. The aim of this study was to investigate the impact of antiretrovirals on pregnancy outcome according to the timing of treatment initiation in relation to pregnancy in a cohort of Brazilian HIV infected pregnant women. Methods A prospective cohort of 696 pregnancies followed-up in one single center between 1996 and 2006 was studied. Patients in receipt of antiretrovirals before pregnancy were compared with those treated after the first trimester. The outcomes evaluated were preterm delivery (PTD): < 37 weeks; severe PTD (< 34 weeks); low birth weight (LBW): < 2500 g; very LBW: < 1500 g. Results Patients on pre-conception use of ARV had higher rates of LBW (33.3% vs. 16.5%; p = 0.0002), and a similar trend for PTD (26.3% % vs. 17.7%; p = 0.09). Stratification by type of therapy (dual vs. HAART) according to timing of initiation of ARV showed that patients in use of pre-conception HAART have a higher rate of PTD (20.2% vs. 10.2%, p = 0.03) and LBW (24.2% vs. 10.2%, p = 0.002). After adjusting for several factors, pre-conception HAART was associated with an increased risk for PTD (AOR: 5.0; 95% CI: 1.5 – 17.0, p = 0.009) and LBW (OR: 3.6; 95% CI: 1.7 – 7.7, p = 0.001). Conclusions We identified an increased risk for LBW and PTD in patients in receipt of HAART prior to pregnancy. PMID:18987014

Machado, Elizabeth S.; Hofer, Cristina B.; Costa, Tomaz T.; Nogueira, Susie A.; Oliveira, Ricardo H.; Abreu, Thalita F.; Evangelista, Lucia A.; Farias, Iraína FA; Mercadante, Regina TC; Garcia, Maria de Fátima L; Neves, Renata C; Costa, Veronica M; Lambert, John S.

2010-01-01

413

HIV genomic mutations causing resistance to antiretroviral drugs in seropositive Sicilians.  

PubMed

Through the use of highly active antiretroviral therapy a significant reduction occurred in mortality and morbidity caused by Human Immunodeficiency Virus. The use of antiretroviral drugs resulted in the emergence of resistant viral strains due to mutations that cause a selective advantage to the virus. The aim of our study is to monitor the HIV-1 infection in Sicilians patients evaluating the presence of mutations that make the virus resistant to the therapy. The QIAGEN QIAamp Viral RNA Mini Kit was used to extract HIV-1 viral RNA from 300 patients while the TRUGENE HIV-1 Genotyping Kit and the OpenGene DNA Sequencing System determined viral mutations in the RNA samples. The analysis showed that from 300 subjects, 116 developed Antiretroviral Drug Resistance. The percentage of patients with resistance to nucleoside reverse transcriptase inhibitor (NRTI), non nucleoside reverse transcriptase inhibitor (NNRTI) and protease inhibitor was 26%, 23% and 20%, respectively. Comparison between drug resistances and mutations showed that 134 individuals had mutations in genes codifying for reverse transcriptase but a little more than 50% were associated with resistance to reverse transcriptase inhibitors, in particular 78 and 68 subjects developed drug resistances to NRTI and NNRTI classes respectively. Subjects that showed mutations in genes codifying for protease were 216 but only 59 of these were associated with resistance to protease inhibitors. Our findings emphasize the importance of continued resistance surveillance. Monitoring of transmitted resistance continues to be needed among treatment-exposed patients because of the benefit it provides for the development of drugs effective against the most frequently found drug-resistant viruses. PMID:24813637

Bertuccio, Maria Paola; Picerno, Isa; Celesia, Benedetto Maurizio; Galvagna, Salvatore; Sturniolo, Giuseppe; Spataro, Pasquale; Visalli, Giuseppa

2014-01-01

414

Patient satisfaction with task shifting of antiretroviral services in Ethiopia: implications for universal health coverage  

PubMed Central

Formalized task shifting structures have been used to rapidly scale up antiretroviral service delivery to underserved populations in several countries, and may be a promising mechanism for accomplishing universal health coverage. However, studies evaluating the quality of service delivery through task shifting have largely ignored the patient perspective, focusing on health outcomes and acceptability to health care providers and regulatory bodies, despite studies worldwide that have shown the significance of patient satisfaction as an indicator of quality. This study aimed to measure patient satisfaction with task shifting of antiretroviral services in hospitals and health centres in four regions of Ethiopia. This cross-sectional study used data collected from a time–motion study of patient services paired with 665 patient exit interviews in a stratified random sample of antiretroviral therapy clinics in 21 hospitals and 40 health centres in 2012. Data were analyzed using f-tests across provider types, and multivariate logistic regression to identify determinants of patient satisfaction. Most (528 of 665) patients were satisfied or somewhat satisfied with the services received, but patients who received services from nurses and health officers were significantly more likely to report satisfaction than those who received services from doctors [odds ratio (OR) 0.26, P < 0.01]. Investments in the health facility were associated with higher satisfaction (OR 1.07, P < 0.01), while costs to patients of over 120 birr were associated with lower satisfaction (OR 0.14, P < 0.05). This study showed high levels of patient satisfaction with task shifting in Ethiopia. The evidence generated by this study complements previous biomedical and health care provider/regulatory acceptability studies to support the inclusion of task shifting as a mechanism for scaling-up health services to achieve universal health coverage, particularly for underserved areas facing severe health worker shortages. PMID:25274640

Asfaw, Elias; Palen, John G H; Wong, Wendy; Bekele, Abebe; Kebede, Amha; Johns, Benjamin

2014-01-01

415

Maternal Antiretroviral Use during Pregnancy and Infant Congenital Anomalies: The NISDI Perinatal Study  

PubMed Central

Background We evaluated the association between maternal antiretrovirals (ARVs) during pregnancy and infant congenital anomalies (CAs), utilizing data from the NISDI Perinatal Study. Methods The study population consisted of first singleton pregnancies on study, ? 20 weeks gestation, among women enrolled in NISDI from Argentina and Brazil who delivered between September 2002 and October 2007. CAs were defined as any major structural or chromosomal abnormality, or a cluster of two or more minor abnormalities, according to the conventions of the Antiretroviral Pregnancy Registry. CAs were identified from fetal ultrasound, study visit, and death reports. The conventions of the Antiretroviral Pregnancy Registry were used. Prevalence rates [number of CAs per 100 live births (LBs)] were calculated for specific ARVs, classes of ARVs, and overall exposure to ARVs. Results Of 1229 women enrolled, 995 pregnancy outcomes (974 LBs) met the inclusion criteria. Of these, 60 infants (59 LBs and 1 stillbirth) had at least one CA. The overall prevalence of CAs (per 100 LBs) was 6.2 (95%CI = 4.6, 7.7). The prevalence of CAs after first trimester ARVs (6.2; 95%CI = 3.1, 9.3) was similar to that after second (6.8; 95%CI = 4.5, 9.0) or third trimester (4.3; 95%CI = 1.5, 7.2) exposure. The rate of CAs identified within seven days of delivery was 2.36 (95%CI: 1.4–3.3). Conclusions The prevalence of CAs following first trimester exposure to ARVs was similar to that following second or third trimester exposure. Continued surveillance for CAs among children exposed to ARVs during gestation is needed. PMID:20104119

Joao, Esau C.; Calvet, Guilherme A.; Krauss, Margot R.; Hance, Laura Freimanis; Ortiz, Javier; Ivalo, Silvina A.; Pierre, Russell; Reyes, Mary; Watts, D. Heather; Read, Jennifer S.

2009-01-01

416

Autonomous Regulation and Locus of Control as Predictors of Antiretroviral Medication Adherence  

PubMed Central

The purpose of the current study was to examine the interrelationships between Autonomous Regulation (AR) and locus of control (LOC) and their prediction of Antiretroviral Therapy (ART) adherence among 189 HIV+ patients. Path analyses revealed that neither AR nor LOC directly predicted adherence although AR was indirectly related when mediated by self-efficacy. AR was positively related to internal and doctors LOC, but not related to chance or others LOC. Overall, results support Self Determination Theory’s conceptualization of AR and indicate that AR may be a more robust predictor of medication adherence than LOC variables. PMID:19383658

Lynam, Ian; Catley, Delwyn; Goggin, Kathy; Rabinowitz, Joshua L.; Gerkovich, Mary M.; Williams, Karen; Wright, Julie

2009-01-01

417

Adherence to combination antiretroviral therapies in HIV patients of low health literacy  

Microsoft Academic Search

OBJECTIVE: To test the significance of health literacy relative to other predictors of adherence to treatment for HIV and AIDS.\\u000a \\u000a \\u000a PARTICIPANTS: Community sample of HIV-seropositive men (n=138) and women (n=44) currently taking a triple-drug combination of antiretroviral therapies for HIV infection; 60% were ethnic minorities,\\u000a and 73% had been diagnosed with AIDS.\\u000a \\u000a \\u000a \\u000a \\u000a MEASUREMENTS: An adapted form of the Test of

Seth C. Kalichman; Bineetha Ramachandran; Sheryl Catz

1999-01-01

418

Adherence to highly active antiretroviral therapy and its correlates among HIV infected pediatric patients in Ethiopia  

PubMed Central

Background The introduction of combination antiretroviral therapy (ART) has resulted in striking reductions in HIV-related mortality. Despite increased availability of ART, children remain a neglected population. This may be due to concerns that failure to adhere appears to be related to continued viral replication, treatment failure and the emergence of drug-resistant strains of HIV. This study determines the rates and factors associated with adherence to Antiretroviral (ARV) Drug therapy in HIV-infected children who were receiving Highly Active Antiretroviral Therapy (HAART) in Addis Ababa, Ethiopia in 2008. Methods A cross-sectional study was conducted in five hospitals in Addis Ababa from February 18 – April 28, 2008. The study population entailed parents/caretaker and index children who were following ART in the health facilities. A structured questionnaire was used for data collection. Results A total of 390 children respondents were included in the study with a response rate of 91%. The majority, equaling 205 (52.6%) of the children, were greater than 9 years of age. Fifty five percent of the children were girls. A total of 339 children (86.9%) as reported by caregivers were adherent to antiretroviral drugs for the past 7 days before the interview. Numerous variables were found to be significantly associated with adherence: children whose parents did not pay a fee for treatment [OR = 0.39 (95%CI: 0.16, 0.92)], children who had ever received any nutritional support from the clinic [OR = 0.34 (95%CI: 0.14, 0.79)] were less likely to adhere. Whereas children who took co-trimoxazole medication/syrup besides ARVs [OR = 3.65 (95%CI: 1.24, 10.74)], children who did not know their sero-status [OR = 2.53 (95%CI: 1.24, 5.19)] and children who were not aware of their caregiver's health problem [OR = 2.45 (95%CI: 1.25, 4.81)] were more likely to adhere than their counterparts. Conclusion Adherence to HAART in children in Addis Ababa was higher than other similar setups. However, there are still significant numbers of children who are non-adherent to HAART. PMID:19061515

Biadgilign, Sibhatu; Deribew, Amare; Amberbir, Alemayehu; Deribe, Kebede

2008-01-01