Identifying Key Drivers of the Impact of an HIV Cure Intervention in Sub-Saharan Africa

The Journal of Infectious Diseases MAJOR ARTICLE Identifying Key Drivers of the Impact of an HIV Cure Intervention in Sub-Saharan Africa Andrew N. Phillips,1 Valentina Cambiano,1 Paul Revill,3 Fumiyo Nakagawa,1 Jens D. Lundgren,4 Loveleen Bansi-Matharu,1 Travor Mabugu,5 Mark Sculpher,3 Geoff Garnett,7 Silvija Staprans,7 Stephen Becker,11 Joseph Murungu,6 Sharon R. Lewin,9,10 Steven G. Deeks,8 and Timothy B. Hallett 2 1 Research Department of Infection & Population Health, UCL, 2Department of Infectious Disease Epidemiology, Imperial College London, and 3Centre for Health Economics, University of York, United Kingdom; 4Department of Infectious Diseases, Rigshospitalet, University of Copenhagen, Denmark; 5University of Zimbabwe, and 6Ministry of Health and Child Care, Harare, Zimbabwe; 7Bill & Melinda Gates Foundation, Seattle, Washington; 8San Francisco General Hospital Medical Center, California; 9The Peter Doherty Institute for Infection and Immunity, University of Melbourne, and 10Department of Infectious Diseases, Alfred Hospital and Monash University, Melbourne, Australia; and 11Independent Consultant in HIV Global Health, Yountville, California Research is ongoing into developing an intervention that would allow human immunodeficiency virus (HIV)–infected individuals to have prolonged, and perhaps permanent, viral suppression in the absence of therapy (“remission” or “cure”). We refer to this as antiretroviral therapy (ART)–free viral suppression [1– 8]. The implications of this research for sub-Saharan Africa, where most persons with HIV live, are as yet unclear, and any such intervention requires consideration in the context of resource-constrained public health approaches to treatment and prevention. Knowing what properties are likely to be required of such an intervention for it to be cost-effective or cost saving in low-income, high–HIV prevalence settings (ie, a “target product profile”) is important to enable focusing of research, clinical development and delivery approaches. In the current study, we sought to identify some basic product and delivery attributes within a framework of a global policy Received 23 December 2015; accepted 21 March 2016; published online 30 March 2016. Correspondence: A. N. Phillips, Research Department of Infection & Population Health, UCL, Rowland Hill Street, London NW3 2PF, UK (). The Journal of Infectious Diseases® 2016;214:73–9 © The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs licence (http://creativecommons.org/licenses/by-nc-nd/ 4.0/), which permits non-commercial reproduction and distribution of the work, in any medium, provided the original work is not altered or transformed in any way, and that the work is properly cited. For commercial re-use, contact . DOI: 10.1093/infdis/jiw120 agenda. We addressed the following research questions. First, what would be the predicted impact of an intervention to induce sustained ART-free HIV suppression in low-income countries in sub-Saharan Africa, in terms of death rates, HIV incidence, and disability-adjusted life years (DALYs)? Second, under what conditions, particularly those relating to efficacy and cost, would such an intervention represent a cost-effective approach, within the context of continued expansion in access to ART? METHODS Model and Context We assess these questions in the context of a generalized HIV epidemic with ongoing ART rollout using a model that has been informed by, and calibrated to, data from Zimbabwe [9–19]. We used the HIV Synthesis transmission model, an individualbased stochastic model of heterosexual HIV transmission, progression, and treatment in adults that has been described elsewhere ([20–23]; see Supplementary Material). Each simulation run generates time-updated longitudinal “data” over time for a population from 1989, such that the overall characteristics in terms of age, sex, sexual risk behavior, and HIV status resemble those of the entire adult population of Zimbabwe (HIV positive and negative). Transmission of HIV is modeled, with the HIV status of each (condomless sex) partner being sampled, along with viral load status of HIV-positive partners. For persons who have become infected with HIV, the variables for Impact of an HIV Cure in Sub-Saharan Africa • JID 2016:214 (1 July) • 73 Background. It is unknown what properties would be required to make an intervention in low income countries that can eradicate or control human immunodeficiency virus (HIV) without antiretroviral therapy (ART) cost-effective. Methods. We used a model of HIV and ART to investigate the effect of introducing an ART-free viral suppression intervention in 2022 using Zimbabwe as an example country. We assumed that the intervention (cost: $500) would be accessible for 90% of the population, be given to those receiving effective ART, have sufficient efficacy to allow ART interruption in 95%, with a rate of viral rebound of 5% per year in the first 3 months, and a 50% decline in rate with each successive year. Results. An ART-free viral suppression intervention with these properties would result in >0.53 million disability-adjusted-lifeyears averted over 2022–2042, with a reduction in HIV program costs of $300 million (8.7% saving). An intervention of this efficacy costing anything up to $1400 is likely to be cost-effective in this setting. Conclusions. Interventions aimed at curing HIV infection have the potential to improve overall disease burden and to reduce costs. Given the effectiveness and cost of ART, such interventions would have to be inexpensive and highly effective. Keywords. HIV; cure; economic evaluation; model; antiretroviral therapy. Table 1. Model Outputs of Status in 2025 and 2035 for Persons Starting ART in 2015a in male circumcision uptake and no introduction of preexposure prophylaxis. AFVS Intervention We envisaged an intervention that would induce AFVS, either by activating and killing latently infected cells and thus depleting the reservoir to zero or close to zero or by enhancing longterm immune control of a durable reservoir, with or without reservoir reduction. We assume that the intervention is introduced in 2022 and that 90% of persons in the country would have access to the intervention should they fulfill the eligibility criteria (50% in sensitivity analysis, which is perhaps more realistic if the intervention requires intravenous administration). We assume that the eligibility criteria for the intervention is an undetectable viral load for ≥6 months and a CD4 cell count >500 cells/µL. We consider that an AFVS intervention would most likely be started in those in whom ART had initially been used to reduce replicating virus. We assume that the AFVS intervention would be administered for 6 months (while ART is continued). We assume that 95% of those given the AFVS inter (...truncated)