Has the phasing out of stavudine in accordance with changes in WHO guidelines led to a decrease in single-drug substitutions in first-line antiretroviral therapy for HIV in sub-Saharan Africa?

This version is the Accepted Manuscript and is published in final edited form as: AIDS. 2017 January 02; 31(1): 147–157. doi:10.1097/QAD.0000000000001307OBJECTIVE: We assessed the relationship between phasing out stavudine in first-line antiretroviral therapy (ART) in accordance with WHO 2010 policy and single-drug substitutions (SDS) (substituting the nucleoside reverse transcriptase inhibitor in first-line ART) in sub-Saharan Africa. DESIGN: Prospective cohort analysis (International epidemiological Databases to Evaluate AIDS-Multiregional) including ART-naive, HIV-infected patients aged at least 16 years, initiating ART between January 2005 and December 2012. Before April 2010 (July 2007 in Zambia) national guidelines called for patients to initiate stavudine-based or zidovudine-based regimen, whereas thereafter tenofovir or zidovudine replaced stavudine in first-line ART. METHODS: We evaluated the frequency of stavudine use and SDS by calendar year 2004-2014. Competing risk regression was used to assess the association between nucleoside reverse transcriptase inhibitor use and SDS in the first 24 months on ART. RESULTS: In all, 33 441 (8.9%; 95% confience interval 8.7-8.9%) SDS occurred among 377 656 patients in the first 24 months on ART, close to 40% of which were amongst patients on stavudine. The decrease in SDS corresponded with the phasing out of stavudine. Competing risks regression models showed that patients on tenofovir were 20-95% less likely to require a SDS than patients on stavudine, whereas patients on zidovudine had a 75-85% decrease in the hazards of SDS when compared to stavudine. CONCLUSION: The decline in SDS in the first 24 months on treatment appears to be associated with phasing out stavudine for zidovudine or tenofovir in first-line ART in our study. Further efforts to decrease the cost of tenofovir and zidovudine for use in this setting is warranted to substitute all patients still receiving stavudine

Programme science methodologies and practices that address ‘FURRIE’ challenges : examples from the field

Introduction “Programme science” deploys scientific methods to address questions that are a priority to support the impact of public health programmes. As such, programme science responds to the challenges of making such studies: 1) feasible to undertake, 2) useful, 3) rigorous, 4) real-world-relevant, 5) informative, and undertaken by, 6) equitable partnerships. We use the acronym ‘FURRIE’ to describe this set of six challenges. We discuss selected HIV/STI programme science case studies to illustrate how programme science rises to the FURRIE challenges. Discussion One way in which programme science is made more feasible is through the analysis and interpretation of data collected through service delivery. For some questions, we need to augment these data through methods that reach potential clients of services who have not accessed services or been lost to follow up. Process evaluation can enhance the usefulness of programme science by studying implementation processes, programme-client interactions and contextual factors. Ensuring rigor by limiting bias and confounding in the real world context of programme science studies requires methodological innovation. Striving for scientific rigor can also have the unintended consequence of creating a gap between what happens in a study, and what happens in the “real-world”. Community-led monitoring is one approach to grounding data collection in the real-world experience of clients. Evaluating complex, context-specific strategies to strengthen health outcomes in a way that is informative for other settings requires clear specification of the intervention packages that are planned and delivered in practice. Programme science provides a model for equitable partnership through co-leadership between programmes, researchers and the communities they serve. Conclusions Programme science addresses the FURRIE challenges, thereby improving programme impact and ultimately health outcomes and health equity. The adoption and adaptation of the types of novel programme science approaches showcased here should be promoted within and beyond the HIV/STI field

Multi-stakeholder consensus on a target product profile for an HIV cure

Developing a cure for HIV is a global priority. Target product profiles are a tool commonly used throughout the drug development process to align interested parties around a clear set of goals or requirements for a potential product. Three distinct therapeutic modalities (combination therapies, ex-vivo gene therapy, and in-vivo gene therapy) for a target product profile for an HIV cure were identified. Using a process of expert face-to-face consultation and an online Delphi consultation, we found a high degree of agreement regarding the criteria for the optimum target product profile. Although the minimum attributes for a cure were debated, the broad consensus was that an acceptable cure need not be as safe and effective as optimally delivered antiretroviral therapy. An intervention that successfully cured a reasonable fraction of adults would be sufficient to advance to the clinic. These target product profiles will require further discussion and ongoing revisions as the field matures

Multi-stakeholder consensus on a target product profile for an HIV cure

Developing a cure for HIV is a global priority. Target product profiles are a tool commonly used throughout the drug development process to align interested parties around a clear set of goals or requirements for a potential product. Three distinct therapeutic modalities (combination therapies, ex-vivo gene therapy, and in-vivo gene therapy) for a target product profile for an HIV cure were identified. Using a process of expert face-to-face consultation and an online Delphi consultation, we found a high degree of agreement regarding the criteria for the optimum target product profile. Although the minimum attributes for a cure were debated, the broad consensus was that an acceptable cure need not be as safe and effective as optimally delivered antiretroviral therapy. An intervention that successfully cured a reasonable fraction of adults would be sufficient to advance to the clinic. These target product profiles will require further discussion and ongoing revisions as the field matures

The case for an HIV cure and how to get there

In light of the increasing global burden of new HIV infections, growing financial requirements, and shifting funding landscape, the global health community must accelerate the development and delivery of an HIV cure to complement existing prevention modalities. An effective curative intervention could prevent new infections, overcome the limitations of antiretroviral treatment, combat stigma and discrimination, and provide a sustainable financial solution for pandemic control. We propose steps to plan for an HIV cure now, including defining a target product profile and establishing the HIV Cure Africa Acceleration Partnership (HCAAP), a multidisciplinary public-private partnership that will catalyse and promote HIV cure research through diverse stakeholder engagement. HCAAP will convene stakeholders, including people living with HIV, at an early stage to accelerate the design, social acceptability, and rapid adoption of HIV-cure products

Mitigating the effects of COVID-19 on HIV treatment and care in Lusaka, Zambia: A before-after cohort study using mixed effects regression

Introduction The Zambian Ministry of Health (MoH) issued COVID-19 mitigation guidance for HIV care immediately after the first COVID-19 case was confirmed in Zambia on 18 March 2020. The Centre for Infectious Disease Research in Zambia implemented MoH guidance by: 1) extending antiretroviral therapy (ART) refill duration to 6 multi-month dispensation (6MMD) and 2) task-shifting communication and mobilisation of those in HIV care to collect their next ART refill early. We assessed the impact of COVID-19 mitigation guidance on HIV care 3 months before and after guidance implementation. Methods We reviewed all ART pharmacy visit data in the national HIV medical record for PLHIV in care having ≥1 visit between 1 January - 30 June 2020 at 59 HIV care facilities in Lusaka Province, Zambia. We undertook a before-after evaluation using mixed-effects Poisson regression to examine predictors and marginal probability of early clinic return (pharmacy visit >7 days before next appointment), proportion of late visit (>7 days late for next appointment) and probability of receiving a 6MMD ART refill. Results A total of 101 371 individuals (64% female, median age 39) with 130 486 pharmacy visits were included in the analysis. We observed a significant increase in the adjusted prevalence ratio (4.63; 95% CI 4.45 to 4.82) of early return before compared with after guidance implementation. Receipt of 6MMD increased from a weekly mean of 47.9% (95% CI 46.6% to 49.2%) before to 73.4% (95% CI 72.0% to 74.9%) after guidance implementation. The proportion of late visits (8-89 days late) was significantly higher before (18.8%, 95% CI17.2%to20.2%) compared with after (15.1%, 95% CI13.8%to16.4%) guidance implementation. Conclusions Timely issuance and implementation of COVID-19 mitigation guidance involving task-shifted patient communication and mobilisation alongside 6MMD significantly increased early return to ART clinic, potentially reducing interruptions in HIV care during a global public health emergency

The revolving door of HIV care: revising the service delivery cascade to achieve the UNAIDS 95-95-95 goals

Peter Ehrenkranz and co-authors present a cyclical cascade of care for people with HIV infection, aiming to facilitate assessment of outcomes