The “Free by 5” Campaign for Universal, Free Antiretroviral Therapy

The Free by 5 declaration, launched in November 2004, aims to achieve free access for all individuals with HIV to a comprehensive medical package including antiretroviral treatment

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

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

Steady state bioequivalence of generic and innovator formulations of stavudine, lamivudine, and nevirapine in HIV-infected Ugandan adults

Background: Generic antiretroviral therapy is the mainstay of HIV treatment in resource-limited settings, yet there is little evidence confirming the bioequivalence of generic and brand name formulations. We compared the steady-state pharmacokinetics of lamivudine, stavudine and nevirapine in HIV-infected subjects who were receiving a generic formulation (Triomune®) or the corresponding brand formulations (Epivir®, Zerit®, and Viramune®). Methodology/Principal Findings: An open-label, randomized, crossover study was carried out in 18 HIV-infected Ugandan subjects stabilized on Triomune-40. Subjects received lamivudine (150 mg), stavudine (40 mg), and nevirapine (200 mg) in either the generic or brand formulation twice a day for 30 days, before switching to the other formulation. At the end of each treatment period, blood samples were collected over 12 h for pharmacokinetic analysis. The main outcome measures were the mean AUC0–12h and Cmax. Bioequivalence was defined as a geometric mean ratio between the generic and brand name within the 90% confidence interval of 0.8–1.25. The geometric mean ratios and the 90% confidence intervals were: stavudine Cmax, 1.3 (0.99–1.71) and AUC0–12h, 1.1 (0.87–1.38); lamivudine Cmax, 0.8 (0.63–0.98) and AUC0–12h, 0.8 (0.65–0.99); and nevirapine Cmax, 1.1 (0.95–1.23) and AUC0–12h, 1.1 (0.95–1.31). The generic formulation was not statistically bioequivalent to the brand formulations during steady state, although exposures were comparable. A mixed random effects model identified about 50% intersubject variability in the pharmacokinetic parameters. Conclusions/Significant Findings: These findings provide support for the use of Triomune in resource-limited settings, although identification of the sources of intersubject variability in these populations is critical

Neonatal Circumcision for HIV Prevention: Cost, Culture, and Behavioral Considerations

Seth Kalichman discusses a new study that finds neonatal circumcision in Rwanda to be a cost-saving HIV prevention strategy

Steady State Bioequivalence of Generic and Innovator Formulations of Stavudine, Lamivudine, and Nevirapine in HIV-Infected Ugandan Adults

Generic antiretroviral therapy is the mainstay of HIV treatment in resource-limited settings, yet there is little evidence confirming the bioequivalence of generic and brand name formulations. We compared the steady-state pharmacokinetics of lamivudine, stavudine and nevirapine in HIV-infected subjects who were receiving a generic formulation (Triomune®) or the corresponding brand formulations (Epivir®, Zerit®, and Viramune®)., 1.1 (0.95–1.31). The generic formulation was not statistically bioequivalent to the brand formulations during steady state, although exposures were comparable. A mixed random effects model identified about 50% intersubject variability in the pharmacokinetic parameters.These findings provide support for the use of Triomune in resource-limited settings, although identification of the sources of intersubject variability in these populations is critical

The Emergence of HIV Transmitted Resistance in Botswana: “When Will the WHO Detection Threshold Be Exceeded?”

BACKGROUND: The Botswana antiretroviral program began in 2002 and currently treats 42,000 patients, with a goal of treating 85,000 by 2009. The World Health Organization (WHO) has begun to implement a surveillance system for detecting transmitted resistance that exceeds a threshold of 5%. However, the WHO has not determined when this threshold will be reached. Here we model the Botswana government's treatment plan and predict, to 2009, the likely stochastic evolution of transmitted resistance. METHODS: We developed a model of the stochastic evolution of drug-resistant strains and formulated a birth-death Master equation. We analyzed this equation to obtain an analytical solution of the probabilistic evolutionary trajectory for transmitted resistance, and used treatment and demographic data from Botswana. We determined the temporal dynamics of transmitted resistance as a function of: (i) the transmissibility (i.e., fitness) of the drug-resistant strains that may evolve and (ii) the rate of acquired resistance. RESULTS: Transmitted resistance in Botswana will be unlikely to exceed the WHO's threshold by 2009 even if the rate of acquired resistance is high and the strains that evolve are half as fit as the wild-type strains. However, we also found that transmission of drug-resistant strains in Botswana could increase to ∼15% by 2009 if the drug-resistant strains that evolve are as fit as the wild-type strains. CONCLUSIONS: Transmitted resistance will only be detected by the WHO (by 2009) if the strains that evolve are extremely fit and acquired resistance is high. Initially after a treatment program is begun a threshold lower than 5% should be used; and we advise that predictions should be made before setting a threshold. Our results indicate that it may be several years before the WHO's surveillance system is likely to detect transmitted resistance in other resource-poor countries that have significantly less ambitious treatment programs than Botswana

Explaining Adherence Success in Sub-Saharan Africa: An Ethnographic Study

Using ethnographic data from Nigeria, Tanzania, and Uganda, Norma Ware and colleagues examine why levels of adherence to HIV/AIDS drugs are so much higher in sub-Saharan Africa than in North America

Excellent Adherence to Antiretrovirals in HIV+ Zambian Children Is Compromised by Disrupted Routine, HIV Nondisclosure, and Paradoxical Income Effects

INTRODUCTION: A better understanding of pediatric antiretroviral therapy (ART) adherence in sub-Saharan Africa is necessary to develop interventions to sustain high levels of adherence. METHODOLOGY/PRINCIPAL FINDINGS: Adherence among 96 HIV-infected Zambian children (median age 6, interquartile range [IQR] 2,9) initiating fixed-dose combination ART was measured prospectively (median 23 months; IQR 20,26) with caregiver report, clinic and unannounced home-based pill counts, and medication event monitoring systems (MEMS). HIV-1 RNA was determined at 48 weeks. Child and caregiver characteristics, socio-demographic status, and treatment-related factors were assessed as predictors of adherence. Median adherence was 97.4% (IQR 96.1,98.4%) by visual analog scale, 94.8% (IQR 86,100%) by caregiver-reported last missed dose, 96.9% (IQR 94.5,98.2%) by clinic pill count, 93.4% (IQR 90.2,96.7%) by unannounced home-based pill count, and 94.8% (IQR 87.8,97.7%) by MEMS. At 48 weeks, 72.6% of children had HIV-1 RNA <50 copies/ml. Agreement among adherence measures was poor; only MEMS was significantly associated with viral suppression (p = 0.013). Predictors of poor adherence included changing residence, school attendance, lack of HIV disclosure to children aged nine to 15 years, and increasing household income. CONCLUSIONS/SIGNIFICANCE: Adherence among children taking fixed-dose combination ART in sub-Saharan Africa is high and sustained over two years. However, certain groups are at risk for treatment failure, including children with disrupted routines, no knowledge of their HIV diagnosis among older children, and relatively high household income, possibly reflecting greater social support in the setting of greater poverty

Transitioning the COVID-19 response in the WHO African region: a proposed framework for rethinking and rebuilding health systems

The onset of the pandemic revealed the health system inequities and inadequate preparedness, especially in the African continent. Over the past months, African countries have ensured optimum pandemic response. However, there is still a need to build further resilient health systems that enhance response and transition from the acute phase of the pandemic to the recovery interpandemic/preparedness phase. Guided by the lessons learnt in the response and plausible pandemic scenarios, the WHO Regional Office for Africa has envisioned a transition framework that will optimise the response and enhance preparedness for future public health emergencies. The framework encompasses maintaining and consolidating the current response capacity but with a view to learning and reshaping them by harnessing the power of science, data and digital technologies, and research innovations. In addition, the framework reorients the health system towards primary healthcare and integrates response into routine care based on best practices/health system interventions. These elements are significant in building a resilient health system capable of addressing more effectively and more effectively future public health crises, all while maintaining an optimal level of essential public health functions. The key elements of the framework are possible with countries following three principles: equity (the protection of all vulnerable populations with no one left behind), inclusiveness (full engagement, equal participation, leadership, decision-making and ownership of all stakeholders using a multisectoral and transdisciplinary, One Health approach), and coherence (to reduce the fragmentation, competition and duplication and promote logical, consistent programmes aligned with international instruments)