HPTN 071 (PopART): A Cluster-Randomized Trial of the Population Impact of an HIV Combination Prevention Intervention Including Universal Testing and Treatment: Mathematical Model

Abstract

BackgroundThe HPTN 052 trial confirmed that antiretroviral therapy (ART) can nearly eliminate HIV transmission from successfully treated HIV-infected individuals within couples. Here, we present the mathematical modeling used to inform the design and monitoring of a new trial aiming to test whether widespread provision of ART is feasible and can substantially reduce population-level HIV incidence.Methods and FindingsThe HPTN 071 (PopART) trial is a three-arm cluster-randomized trial of 21 large population clusters in Zambia and South Africa, starting in 2013. A combination prevention package including home-based voluntary testing and counseling, and ART for HIV positive individuals, will be delivered in arms A and B, with ART offered universally in arm A and according to national guidelines in arm B. Arm C will be the control arm. The primary endpoint is the cumulative three-year HIV incidence.We developed a mathematical model of heterosexual HIV transmission, informed by recent data on HIV-1 natural history. We focused on realistically modeling the intervention package. Parameters were calibrated to data previously collected in these communities and national surveillance data.We predict that, if targets are reached, HIV incidence over three years will drop by >60% in arm A and >25% in arm B, relative to arm C. The considerable uncertainty in the predicted reduction in incidence justifies the need for a trial. The main drivers of this uncertainty are possible community-level behavioral changes associated with the intervention, uptake of testing and treatment, as well as ART retention and adherence.ConclusionsThe HPTN 071 (PopART) trial intervention could reduce HIV population-level incidence by >60% over three years. This intervention could serve as a paradigm for national or supra-national implementation. Our analysis highlights the role mathematical modeling can play in trial development and monitoring, and more widely in evaluating the impact of treatment as prevention.

Why the proportion of transmission during early-stage HIV infection does not predict the long-term impact of treatment on HIV incidence

“…This finding has generated interest in understanding the population-level impact of HIV treatment on reducing the rate of new HIV infections in generalized epidemic settings (4). Research, including mathematical modeling (5-10), implementation research (11), and major randomized controlled trials (12)(13)(14), are focused on how ART provision might be expanded strategically to maximize its public health benefits (15, 16).One concern is that if a large fraction of HIV transmission occurs shortly after a person becomes infected, before the person can be diagnosed and initiated on ART, this will limit the potential impact of HIV treatment on reducing HIV incidence (9,17,18). Data suggest that persons are more infectious during a short period of "early infection" after becoming infected with HIV (19-22), although there is debate about the extent, duration, and determinants of elevated infectiousness (18, 23).…”

“…This finding has generated interest in understanding the population-level impact of HIV treatment on reducing the rate of new HIV infections in generalized epidemic settings (4). Research, including mathematical modeling (5-10), implementation research (11), and major randomized controlled trials (12)(13)(14), are focused on how ART provision might be expanded strategically to maximize its public health benefits (15, 16).…”

Effectiveness of combination packages for HIV-1 prevention in sub-Saharan Africa depends on partnership network structure: a mathematical modelling study

“…Is this sort of behavioural change possible? Variations in concurrency within West Africa and across SSA suggest that alternative behavioural norms can become established, 28 but even small changes to sexual behaviour over a sustained time may be challenging, especially compared with a one-time circumcision surgery. 29 Assuming no behavioural change, our study suggested that targeting MMC should depend on epidemiological context.…”

Innovative Strategies for Scale up of Effective Combination HIV Prevention Interventions in Sub-Saharan Africa

“…For example, the HPTN 071/PopART model estimates a 60 % reduction in HIV incidence when compared to current standard care. This impact is importantly dependent on high coverage of ART aligned to the UNAIDS Fast-Track Targets [24,25].…”