Improved adipose tissue function with initiation of protease inhibitor-only ART.

OBJECTIVES: Use of ART containing HIV PIs has previously been associated with toxicity in subcutaneous adipose tissue (SAT), potentially contributing to the development of lipodystrophy and insulin resistance. However, the effect of PIs on SAT function in ART-naive patients independent of other ART classes is unknown. This study aimed to elucidate the effect of initiating PI-only ART on SAT function in ART-naive subjects. METHODS: In the HIVNAT-019 study, 48 HIV-infected, ART-naive Thai adults commencing PI-only ART comprising lopinavir/ritonavir/saquinavir for 24 weeks underwent assessments of fasting metabolic parameters and body composition. In a molecular substudy, 20 subjects underwent SAT biopsies at weeks 0, 2 and 24 for transcriptional, protein, mitochondrial DNA (mtDNA) and histological analyses. ClinicalTrials.gov registration number: NCT00400738. RESULTS: Over 24 weeks, limb fat increased (+416.4 g, P = 0.023), coinciding with larger adipocytes as indicated by decreased adipocyte density in biopsies (-32.3 cells/mm2, P = 0.047) and increased mRNA expression of adipogenesis regulator PPARG at week 2 (+58.1%, P = 0.003). Increases in mtDNA over 24 weeks (+600 copies/cell, P = 0.041), decreased NRF1 mRNA expression at week 2 (-33.7%, P < 0.001) and increased COX2/COX4 protein ratio at week 24 (+288%, P = 0.038) indicated improved mitochondrial function. Despite decreased AKT2 mRNA at week 2 (-28.6%, P = 0.002) and increased PTPN1 mRNA at week 24 (+50.3%, P = 0.016) suggesting insulin resistance, clinical insulin sensitivity [by homeostasis model assessment (HOMA-IR)] was unchanged. CONCLUSIONS: Initiation of PI-only ART showed little evidence of SAT toxicity, the changes observed being consistent with a return to health rather than contributing to lipodystrophy.

Cardiovascular prevention model from Kenyan slums to migrants in the Netherlands.

Cardiovascular diseases (CVD) are the main cause of morbidity and mortality worldwide. As prevention and treatment of CVD often requires active screening and lifelong follow up it is a challenge for health systems both in high-income and low and middle-income countries to deliver adequate care to those in need, with efficient use of resources.We developed a health service model for primary prevention of CVD suitable for implementation in the Nairobi slums, based on best practices from public health and the private sectors. The model consists of four key intervention elements focusing on increasing awareness, incentives for promoting access to screening and treatment, and improvement of long-term adherence to prescribed medications. More than 5,000 slum dwellers aged ≥35 years and above have been screened in the study resulting in more than 1000 diagnosed with hypertension and referred to the clinic.Some marginalized groups in high-income countries like African migrants in the Netherlands also have low rates of awareness, treatment and control of hypertension as the slum population in Nairobi. The parallel between both groups is that they have a combination of risky lifestyle, are prone to chronic diseases such as hypertension, have limited knowledge about hypertension and its complications, and a tendency to stay away from clinics partly due to cultural beliefs in alternative forms of treatment, and lack of trust in health providers. Based on these similarities it was suggested by several policymakers that the model from Nairobi can be applied to other vulnerable populations such as African migrants in high-income countries. The model can be contextualized to the local situation by adapting the key steps of the model to the local settings.The involvement and support of African communities' infrastructures and health care staff is crucial, and the most important enabler for successful implementation of the model in migrant communities in high-income countries. Once these stakeholders have expressed their interest, the impact of the adapted intervention can be measured through an implementation research approach including collection of costs from health care providers' perspective and health effects in the target population, similar to the study design for Nairobi.

Global response to HIV: treatment as prevention, or treatment for treatment?

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

Treatment as prevention--where next?

Uptake of antiretroviral regimens with associated durable virologic suppression has been shown to reduce the risk of HIV transmission. Expanding antiretroviral therapy (ART) programs at a population level may serve as a vital strategy in the elimination of the AIDS epidemic. The global expansion of ART programs has greatly improved access to life-saving therapies and is likely to achieve the target of 15 million individuals on therapy set by UNAIDS. In addition to the incontrovertible gains in terms of life expectancy, growing evidence demonstrates that durable virologic suppression is associated with significant reductions in HIV transmission amongst heterosexual couples and men who have sex with men. Expansion of successful ART programs, best monitored by a program-level continuum of care cascade to assess progress in diagnosis, retention in care, and virologic suppression, is associated with reductions in HIV incidence at a population level. Expanding and sustaining successful ART delivery at a global level is a key component in a comprehensive approach to combating the HIV epidemic over the next two decades.

Advanced liver fibrosis by transient elastography, fibrosis 4, and alanine aminotransferase/platelet ratio index among Asian hepatitis C with and without human immunodeficiency virus infection: role of vitamin D levels.

BACKGROUND AND AIM: Vitamin D insufficiency plays an important role in liver fibrosis in hepatitis C virus (HCV)-infected patients. We assessed liver fibrosis by transient elastography and 25 hydroxy vitamin D [25(OH)D] status in HCV-infected patients, with (HIV/HCV) or without HIV co-infection (HCV) from Thailand. METHODS: Fibrosis stage was defined as mild (< 7.1 kPa); moderate (7.2-9.4 kPa); severe (9.5-14 kPa), and cirrhosis (> 14 kPa). Hypovitaminosis D was defined as 25(OH)D < 30 ng/mL. Logistic regression analyses were used to assess predictors for significant fibrosis. Serum 25(OH) D levels, HCV genotypes (GT), interleukin-28B (IL28B) and HCV-RNA were assessed. RESULTS: A total of 331 HCV and 130 HIV/HCV patients were enrolled (70% male, 35% people who inject drugs [PWIDs]). HCV GT distribution was as follows: GT3 47%, GT1 34%, GT6 17%. IL-28B CC genotype (rs12979860) were found in 88% of HIV/HCV and 85% of HCV. In HCV, liver fibrosis was mild in 56.5%; moderate in 18.4%; severe in 12.4%; and cirrhosis in 12.7%. In HIV/HCV, these figures were 30.6%, 27.8%, 17.6%, and 24.1%, respectively. Patients with significant fibrosis were more often male, older, with HIV infection, hypovitaminosis D, and less likely to be infected with GT6. Factors associated with significant fibrosis by multivariate analysis were HIV infection (adjusted odd ratio [95% confidential interval]: 2.67, 1.20-5.93), P = 0.016, Fib-4 score > 1.45 (6.30, 2.70-14.74), P < 0.001, and hypovitaminosis D (2.48, 1.09-5.67), P = 0.031. GT 6 was less likely to have advanced liver fibrosis (0.17, 0.05-0.65), P = 0.01. CONCLUSIONS: HIV infection, Fib-4 score > 1.45, and hypovitaminosis D are strong and independent predictors for the presence of advanced fibrosis in our HCV-infected patients. These data highlight the urgent need of HCV treatment and vitamin D supplement in resource-limited settings.

Perceptions of inhibitors and facilitators for adhering to hypertension treatment among insured patients in rural Nigeria: a qualitative study.

BACKGROUND: Universal health care coverage has been identified as a promising strategy for improving hypertension treatment and control rates in sub Saharan Africa (SSA). Yet, even when quality care is accessible, poor adherence can compromise treatment outcomes. To provide information for adherence support interventions, this study explored what low income patients who received hypertension care in the context of a community based health insurance program in Nigeria perceive as inhibitors and facilitators for adhering to pharmacotherapy and healthy behaviors. METHODS: We conducted a qualitative interview study with 40 insured hypertensive patients who had received hypertension care for > 1 year in a rural primary care hospital in Kwara state, Nigeria. Supported by MAXQDA software, interview transcripts were inductively coded. Codes were then grouped into concepts and thematic categories, leading to matrices for inhibitors and facilitators of treatment adherence. RESULTS: Important patient-identified facilitators of medication adherence included: affordability of care (through health insurance); trust in orthodox "western" medicines; trust in Doctor; dreaded dangers of hypertension; and use of prayer to support efficacy of pills. Inhibitors of medication adherence included: inconvenient clinic operating hours; long waiting times; under-dispensing of prescriptions; side-effects of pills; faith motivated changes of medication regimen; herbal supplementation/substitution of pills; and ignorance that regular use is needed. Local practices and norms were identified as important inhibitors to the uptake of healthier behaviors (e.g. use of salt for food preservation; negative cultural images associated with decreased body size and physical activity). Important factors facilitating such behaviors were the awareness that salt substitutes and products for composing healthier meals were cheaply available at local markets and that exercise could be integrated in people's daily activities (e.g. farming, yam pounding, and household chores). CONCLUSIONS: With a better understanding of patient perceived inhibitors and facilitators of adherence to hypertension treatment, this study provides information for patient education and health system level interventions that can be designed to improve compliance. TRIAL REGISTRATION: ISRCTN47894401 .

NYVAC immunization induces polyfunctional HIV-specific T-cell responses in chronically-infected, ART-treated HIV patients.

We report the results of the Theravac-01 phase I trial, which was conducted to evaluate the safety and immunogenicity of a poxvirus-based vector, NYVAC, expressing Gag, Pol, Nef, and Env from an HIV clade B isolate. NYVAC-B vaccine was injected intra-muscularly into ten HIV-infected patients successfully treated with antiretroviral therapy, twice on day 0 and again at week 4. Safety and immunogenicity were monitored for 48 weeks. HIV-specific T-cell responses following immunization were quantitatively analyzed using an IFN-γ ELISPOT assay and qualitatively characterized for their functional profile (including multiple cytokines secretion plus cytotoxic and proliferation capacity) by polychromatic flow cytometry. Our results indicate that the NYVAC-B vaccine is safe and highly immunogenic, as indicated by increased HIV-specific T-cell responses in virtually all vaccinees. Interestingly, both an expansion of preexisting T-cell responses, and the appearance of newly detected HIV-specific CD4(+) and CD8(+) T-cell responses were observed. Furthermore, immunization mostly induced an increase in Gag-specific T-cell responses. In conclusion, NYVAC-B immunization induces broad, vigorous, and polyfunctional HIV-specific T-cell responses, suggesting that poxvirus-based vaccine regimens may be instrumental in the therapeutic HIV vaccine field.

No treatment versus 24 or 60 weeks of antiretroviral treatment during primary HIV infection: the randomized Primo-SHM trial.

BACKGROUND: The objective of this study was to assess the benefit of temporary combination antiretroviral therapy (cART) during primary HIV infection (PHI). METHODS AND FINDINGS: Adult patients with laboratory evidence of PHI were recruited in 13 HIV treatment centers in the Netherlands and randomly assigned to receive no treatment or 24 or 60 wk of cART (allocation in a 1∶1∶1 ratio); if therapy was clinically indicated, participants were randomized over the two treatment arms (allocation in a 1∶1 ratio). Primary end points were (1) viral set point, defined as the plasma viral load 36 wk after randomization in the no treatment arm and 36 wk after treatment interruption in the treatment arms, and (2) the total time that patients were off therapy, defined as the time between randomization and start of cART in the no treatment arm, and the time between treatment interruption and restart of cART in the treatment arms. cART was (re)started in case of confirmed CD4 cell count < 350 cells/mm(3) or symptomatic HIV disease. In total, 173 participants were randomized. The modified intention-to-treat analysis comprised 168 patients: 115 were randomized over the three study arms, and 53 randomized over the two treatment arms. Of the 115 patients randomized over the three study arms, mean viral set point was 4.8 (standard deviation 0.6) log(10) copies/ml in the no treatment arm, and 4.0 (1.0) and 4.3 (0.9) log(10) copies/ml in the 24- and 60-wk treatment arms (between groups: p < 0.001). The median total time off therapy in the no treatment arm was 0.7 (95% CI 0.0-1.8) y compared to 3.0 (1.9-4.2) and 1.8 (0.5-3.0) y in the 24- and 60-wk treatment arms (log rank test, p < 0.001). In the adjusted Cox analysis, both 24 wk (hazard ratio 0.42 [95% CI 0.25-0.73]) and 60 wk of early treatment (hazard ratio 0.55 [0.32-0.95]) were associated with time to (re)start of cART. CONCLUSIONS: In this trial, temporary cART during PHI was found to transiently lower the viral set point and defer the restart of cART during chronic HIV infection.

Unrecognised tuberculosis at antiretroviral therapy initiation is associated with lower CD4+ T cell recovery.

OBJECTIVES: To investigate whether an unrecognised diagnosis of tuberculosis (TB) at the start of antiretroviral therapy (ART) influences subsequent CD4+ T cell (CD4) count recovery in an urban HIV clinic in Uganda. METHODS: In a retrospective cohort study, a multivariable polynomial mixed effects model was used to estimate CD4 recovery in the first 96 weeks of ART in two groups of patients: prevalent TB (started ART while on TB treatment), unrecognised TB (developed TB within 6 months after start ART). RESULTS: Included were 511 patients with a median baseline CD4 count of 57 cells/mm(3) (interquartile range: 22-130), of whom 368 (72%) had prevalent TB and 143 (28%) had unrecognised TB. Compared with prevalent TB, unrecognised TB was associated with lower CD4 count recovery at 96 weeks: -22.3 cells/mm(3) (95% confidence interval -43.2 to -1.5, P = 0.036). These estimates were adjusted for gender, age, baseline CD4 count and the use of zidovudine-based regimen. CONCLUSIONS: Unrecognised TB at the time of ART initiation resulted in impaired CD4 recovery compared with TB treated before ART initiation. More vigilant screening with more sensitive and rapid TB diagnostics prior to ART initiation is needed to decrease the risk of ART-associated TB and sub-optimal immune reconstitution.

Implementation and effect of intensified case finding on diagnosis of tuberculosis in a large urban HIV clinic in Uganda: a retrospective cohort study.

BACKGROUND: Increased detection of tuberculosis (TB) using intensified or active case finding (ICF) is one of the cornerstones of the Stop TB Strategy, and contrasts with passive case finding (PCF) which relies on self-reported symptoms. There is no clear guidance on implementation strategies. We implemented ICF in addition to ongoing PCF in our large urban HIV clinic in July 2010 using a twice-daily announcement screen method by a trained peer educator, asking waiting patients to self-refer to a trained peer supporter for screening of TB symptoms. We sought to determine the associated effect on TB case detection. METHODS: Suspects were investigated by sputum smear, chest X-ray and ultrasound, if indicated. Routinely collected clinical and laboratory data were merged with the ICF register and TB clinic data for patients attending the clinic in 2010. We compared the yield of TB cases (defined as the prevalence of newly diagnosed TB cases in the screened population), the type of TB diagnosed and the total cost per TB case identified (in United States Dollars [USD]) for the period before and after ICF implementation. RESULTS: Of the 20,456 patients who visited the clinic in 2010, 614 were identified as TB suspects, 220 pre-ICF and 394 post-ICF (229 via PCF and 165 via ICF). The proportion diagnosed with TB dropped from 66% to 48% (60% in suspects identified through PCF and 31% through ICF). During the post-ICF period, TB suspects identified through ICF compared to PCF identification were more likely to be female, older, on ART and to have been enrolled in HIV care for a longer duration. The yield of combined PCF and ICF screening was 1.4% pre-ICF and 1.7% post-ICF with a cost per TB case identified of 12.29 USD and 21.80 USD, respectively. CONCLUSIONS: Implementation of ICF in a large HIV clinic yielded more TB suspects and cases, but substantially increased costs and was unable to capture the majority of TB suspects who were referred for diagnosis by clinicians through PCF. The overall yield of TB cases in a mature HIV clinic was low, although targeted screening of those recently enrolled in care may increase the yield.

The spread, treatment, and prevention of HIV-1: evolution of a global pandemic.

The most up-to-date estimates demonstrate very heterogeneous spread of HIV-1, and more than 30 million people are now living with HIV-1 infection, most of them in sub-Saharan Africa. The efficiency of transmission of HIV-1 depends primarily on the concentration of the virus in the infectious host. Although treatment with antiviral agents has proven a very effective way to improve the health and survival of infected individuals, as we discuss here, the epidemic will continue to grow unless greatly improved prevention strategies can be developed and implemented. No prophylactic vaccine is on the horizon. However, several behavioral and structural strategies have made a difference--male circumcision provides substantial protection from sexually transmitted diseases, including HIV-1, and the application of antiretroviral agents for prevention holds great promise.

Development and evaluation of a patient centered cardiovascular health education program for insured patients in rural Nigeria (QUICK - II).

BACKGROUND: In Sub Saharan Africa, the incidence of hypertension and other modifiable cardiovascular risk factors is growing rapidly. Poor adherence to prescribed prevention and treatment regimens by patients can compromise treatment outcomes. Patient-centered cardiovascular health education is likely to improve shortcomings in adherence. This paper describes a study that aims to develop a cardiovascular health education program for patients participating in a subsidized insurance plan in Nigeria and to evaluate the applicability and effectiveness in patients at increased risk for cardiovascular disease. DESIGN: The study has two parts. Part 1 will develop a cardiovascular health education program, using qualitative interviews with stakeholders. Part 2 will evaluate the effectiveness of the program in patients, using a prospective (pre-post) observational design. SETTING: A rural primary health center in Kwara State, Nigeria. POPULATION: For part 1: 40 patients, 10 healthcare professionals, and 5 insurance managers. For part 2: 150 patients with uncontrolled hypertension or other cardiovascular risk factors after one year of treatment. INTERVENTION: Part 2: patient-centered cardiovascular health education program. MEASUREMENTS: Part 1: Semi-structured interviews to identify stakeholder perspectives. Part 2: Pre- and post-intervention assessments including patients' demographic and socioeconomic data, blood pressure, body mass index and self-reporting measures on medication adherence and perception of care. Feasibility of the intervention will be measured using process data. OUTCOMES: For program development (part 1): overview of healthcare professionals' perceptions on barriers and facilitators to care, protocol for patient education, and protocol implementation plan.For program evaluation (part 2): changes in patients' scores on adherence to medication and life style changes, blood pressure, and other physiological and self-reporting measures at six months past baseline. ANALYSIS: Part 1: content analytic technique utilizing MAXQDA software. Part 2: univariate and multilevel analysis to assess outcomes of intervention. DISCUSSION: Diligent implementation of patient-centered education should enhance adherence to cardiovascular disease prevention and management programs in low income countries. TRIAL REGISTRATION: ISRCTN47894401.

Cardiovascular disease prevention in rural Nigeria in the context of a community based health insurance scheme: QUality Improvement Cardiovascular care Kwara-I (QUICK-I).

BACKGROUND: Cardiovascular diseases (CVD) are a leading contributor to the burden of disease in low- and middle-income countries. Guidelines for CVD prevention care in low resource settings have been developed but little information is available on strategies to implement this care. A community health insurance program might be used to improve patients' access to care. The operational research project "QUality Improvement Cardiovascular care Kwara - I (QUICK-I)" aims to assess the feasibility of CVD prevention care in rural Nigeria, according to international guidelines, in the context of a community based health insurance scheme. DESIGN: prospective observational hospital based cohort study. SETTING: a primary health care centre in rural Nigeria. STUDY POPULATION: 300 patients at risk for development of CVD (patients with hypertension, diabetes, renal disease or established CVD) who are enrolled in the Hygeia Community Health Plan. MEASUREMENTS: demographic and socio- economic data, physical and laboratory examination, CVD risk profile including screening for target organ damage. MEASUREMENTS will be done at 3 month intervals during 1 year. Direct and indirect costs of CVD prevention care will be estimated. OUTCOMES: 1) The adjusted cardiovascular quality of care indicator scores based on the "United Kingdom National Health Services Quality and Outcome Framework". 2) The average costs of CVD prevention and treatment per patient per year for patients, the clinic and the insurance company. 3) The estimated net health care costs of standard CVD prevention care per quality-adjusted life year gained. ANALYSIS: The primary outcomes, the score on CVD quality indicators and cost data will be descriptive. The quality scores and cost data will be used to describe the feasibility of CVD prevention care according to international guidelines. A cost-effectiveness analysis will be done using a Markov model. DISCUSSION: Results of QUICK-I can be used by policy makers and professionals who aim to implement CVD prevention programs in settings with limited resources. The context of the insurance program will provide insight in the opportunities community health insurance may offer to attain sustainable chronic disease management programs in low resource settings. TRIAL REGISTRATION: This protocol has been registered at ISRCTN, ID number: ISRCTN47894401.

Long-term voluntary counseling and testing (VCT) uptake dynamics in a multicountry HIV workplace program in sub-Saharan Africa.

High uptake of HIV voluntary counseling and testing (VCT) services is important for the success of HIV workplace programs in sub-Saharan Africa. From 2001 onwards, Heineken, a multinational brewing company, implemented a comprehensive HIV prevention and treatment program for employees and their dependents of its African subsidiaries. Confidential in-house VCT is part of this program. VCT uptake dynamics over time, and factors associated with early uptake were studied. Between September 2001 and December 2007, 9723 adult beneficiaries were tested for HIV in 14 company sites in five African countries. Three hundred and seventy (3.8%) of tested persons were infected with HIV-1. During the first 12 months 1412 tests were done, compared to 8311 tests in the subsequent years. The annual average uptake of testing among eligible persons varied between 15 and 32%. The coverage was higher among female compared to male employees, and higher among female compared to male spouses. Distinct peaks in uptake were linked to specific local events. HIV-1 infected persons were significantly more likely to be tested in the early period. The proportion of HIV-1 infected persons among testees was 8.8% in the first 12 months compared to 3.0% in the subsequent period (p<0.001). HIV-1 infected persons diagnosed in the early period were in a more advanced clinical stage, and had a significantly lower CD4 count than those tested later (median CD4 count 227 vs. 314 cells/microl; p=0.002). In this workplace program, HIV-1 infected individuals came earlier for an HIV test than uninfected people, and people with advanced infection came earlier than those with less advanced disease. Employees' spouses are harder to reach than employees and extra efforts should be undertaken to reach them as well. Uptake of HIV testing can be actively influenced by educational or promotional activities.

Plasma concentrations of generic lopinavir/ritonavir in HIV type-1-infected individuals.

BACKGROUND: Generic drugs can contribute to access to treatment for HIV-infected patients. However quality and safety remains an issue of concern. Therefore, we evaluated minimal plasma concentrations and short-term safety of a generic lopinavir/ritonavir 200/50 mg tablet formulation. METHODS: In a single-centre prospective pilot study, patients receiving protease-inhibitor-based antiretroviral treatment were switched to a generic lopinavir/ritonavir tablet at the standard dose (400/100 mg twice daily). Minimum drug concentrations (C(min)) of lopinavir and ritonavir were performed before switching (in 16 patients who were on Kaletra((R)) soft-gel capsules) and after 4 weeks (in all patients). Plasma levels of lopinavir and ritonavir were determined by a validated HPLC method. Either the Wilcoxon signed-rank or Mann-Whitney U test was used to compare the groups. RESULTS: A total of 37 patients (18 females) were included in the study. Two stopped their study medications prematurely because of intolerance. The median (interquartile range) lopinavir C(min) was 7.2 mg/l (5.8-8.3) and no patients had subtherapeutic levels <1.0 mg/l. No significant difference of lopinavir C(min) levels was found between Kaletra((R)), and the generic product (P=0.224). By contrast, the C(min) of generic ritonavir was higher (P=0.012). Food did not affect the drug levels. Mild gastrointestinal complaints were reported in 12 patients. CONCLUSIONS: The generic lopinavir/ritonavir tablet showed C(min) plasma concentrations similar to what is described for the branded product, with good stability, independent of food intake. These data support the efforts in scaling up access to generic second-line treatment in middle- and low-income countries.

Mortality and morbidity among HIV type-1-infected patients during the first 5 years of a multicountry HIV workplace programme in Africa.

BACKGROUND: This study aimed to evaluate the effectiveness of an HIV workplace programme in sub-Saharan Africa. METHODS: The international brewing company, Heineken, introduced an HIV workplace programme in its African subsidiaries in 2001. Beneficiaries from 16 sites in 5 countries were eligible. HIV type-1 (HIV-1)-infected individuals were assessed clinically and immunologically, and started highly active antiretroviral therapy (HAART) if they had AIDS or had a CD4+ T-cell count <300 cells/microl. In this cohort, study patients were followed-up for vital status, new AIDS events, CD4+ T-cell count and haemoglobin. RESULTS: Over the first 5 years of the programme, 431 adults were found to be HIV-1-infected. The mortality rate among those not yet taking HAART was 2.6 per 100 person-years of observation (pyo). By October 2006, 249 patients had started HAART at a median CD4+ T-cell count of 170 cells/microl; 59 (23.7%) patients were in CDC stage C. Among patients on HAART, 25 died and 7 were lost to follow-up. The mortality rate was 3.7 per 100 pyo overall, 14 per 100 pyo in the first 16 weeks and 2.5 per 100 pyo thereafter (P < 0.0001). At 4 years after start of treatment, 89% of patients were known to be alive. The CD4+ T-cell count increased by a median of 153 and 238 cells/microl after 1 and 4 years of HAART, respectively. CONCLUSIONS: In this HIV workplace programme in sub-Saharan Africa, long-term high survival was achieved.

Safety and efficacy of once-daily nevirapine dosing: a multicohort study.

BACKGROUND: Nevirapine (NVP) is often prescribed once daily in clinical practice in combination with a once daily nucleoside backbone. We investigated the relationship of NVP dosing with safety and efficacy. METHODS: Patients from the Dutch AIDS Therapy Evaluation in the Netherlands (ATHENA) cohort study, Canadian HAART Observational Medical Evaluation and Research (HOMER) cohort and Swiss HIV Cohort Study (SHCS) using NVP-based combination therapy either once daily or twice daily were included. Risk factors for discontinuing NVP because of hypersensitivity reactions (HSRs) were investigated using multivariate logistic regression. Risk factors for virological failure 96 weeks after NVP initiation were identified using logistic regression and Cox models. RESULTS: Of 5,636 patients (774 once daily and 4,862 twice daily), 268 (4.8%) discontinued NVP because of HSR between 2 and 18 weeks. Logistic regression showed that, compared with patients with detectable HIV type-1 (HIV-1) RNA starting twice-daily NVP, there was a significantly higher risk of discontinuation of once-daily NVP because of HSR in patients with detectable HIV-1 RNA at the start of NVP (odds ratio [OR] 1.52; P=0.04), whereas the risk was actually significantly lower in patients starting once-daily NVP with undetectable HIV-1 RNA (OR 0.44; P=0.04). Cox models showed that risk of virological failure was not different for twice- versus once-daily NVP in treatment-naive patients (twice-daily versus once-daily hazard ratio [HR] 1.01; P=0.95), treatment-experienced patients experiencing treatment failure (twice-daily versus once-daily HR 1.22; P=0.30) or patients with undetectable HIV-1 RNA simplifying treatment with NVP (twice-daily versus once-daily HR 1.29; P=0.30). CONCLUSIONS: Initiation of a once-daily NVP-based regimen in patients with suppressed viraemia carries a low risk of treatment-limiting HSR. Once- or twice-daily NVP-based regimens appear to have similar antiretroviral efficacy.

Discontinuation of nevirapine because of hypersensitivity reactions in patients with prior treatment experience, compared with treatment-naive patients: the ATHENA cohort study.

BACKGROUND: Recommendations that nevirapine (NVP) should be avoided in female individuals with CD4 cell counts >250 cells/microL and in male individuals with CD4 cell counts >400 cells/microL are based on findings in treatment-naive patients. It is unclear whether these guidelines also apply to treatment-experienced patients switching to NVP-based combination therapy. METHODS: Patients in the ATHENA cohort study who had used NVP-based combination therapy were included. We identified patients who discontinued NVP-based combination therapy because of hypersensitivity reactions (HSRs; rash and/or hepatotoxicity) within 18 weeks after starting such therapy. We grouped patients according to their CD4 cell count at the start of NVP-based combination therapy (current CD4 cell count) as having a high CD4 cell count (for female patients, >250 cells/microL; for male patients, >400 cells/microL) or a low CD4 cell count. Treatment-experienced patients were further subdivided according to the last available CD4 cell count before first receipt of antiretroviral therapy (ART; pre-ART CD4 cell count) using the same criteria. Risk factors for HSR were assessed using multivariate logistic regression. RESULTS: Of 3752 patients receiving NVP-based combination therapy, 231 patients (6.2%) discontinued NVP therapy because of HSRs. Independent risk factors included female sex and Asian ethnicity. Having an undetectable viral load (VL) at the start of NVP therapy was associated with reduced risk of developing an HSR (adjusted odds ratio [OR], 0.52; 95% confidence interval [CI], 0.38-0.71). Pretreated patients with low pre-ART and high current CD4 cell counts and a detectable VL when switching to NVP-based combination therapy had a significantly higher risk of developing an HSR, compared with treatment-naive patients who started NVP therapy with low CD4 cell counts (adjusted OR, 1.87; 95% CI, 1.11-3.12); pretreated patients with low pre-ART CD4 cell counts who switched to NVP therapy with a high current CD4 cell count and an undetectable VL did not have an increased risk of developing an HSR (adjusted OR, 1.03; 95% CI, 0.66-1.61). CONCLUSIONS: Treatment-experienced patients who start NVP-based combination therapy with low pre-ART and high current CD4 cell counts and an undetectable VL have a similar likelihood for discontinuing NVP therapy because of HSRs, compared with treatment-naive patients with low CD4 cell counts. This suggests that NVP-based combination therapy may be safely initiated in such patients. However, in similar patients with a detectable VL, it is prudent to continue to adhere to current CD4 cell count thresholds.