Impact along the HIV pre-exposure prophylaxis "cascade of prevention" in western Kenya: a mathematical modelling study

• Type of Material: Article
• Authors: Anna Bershteyn, NYU Grossman School of Medicine; Monisha Sharma, Institute for Disease Modeling, Bellevue WA; Adam N Akullian, Institute for Disease Modeling, Bellevue WA; Kathryn Peebles, University of Washington; Supriya Sarkar, Emory University; Scott R Braithwaite, NYU Grossman School of Medicine; Edinah Mudimu, University of South Africa
• Language: English
• Date: 2020-06-01
• Publisher: JOHN WILEY & SONS LTD
• Publication Version: Final Published Version
• Copyright Statement: © 2020 The Authors. Journal of the International AIDS Society published by John Wiley & Sons Ltd on behalf of the International AIDS Society.
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1002/jia2.25527
• Title of Journal or Parent Work: JOURNAL OF THE INTERNATIONAL AIDS SOCIETY
• Volume: 23
• Issue: S3
• Start Page: e25527
• End Page: e25527
• Grant/Funding Information: AB and ANA received funding from the Global Good Fund. MS received funding from NIMH K01MH115789. The funders had no role in the study design, analysis, interpretation of data, or the decision to submit the paper for publication.
• Keywords: mathematical modelling; MEN; HIV prevention; Science & Technology; sub-Saharan Africa; cascade; WOMEN; Immunology; Life Sciences & Biomedicine; Infectious Diseases; Kenya; pre-exposure prophylaxis; TRANSMISSION; PREP
• Research Categories: Health Sciences, Epidemiology; Health Sciences, Medicine and Surgery

Abstract

Introduction: Over one hundred implementation studies of HIV pre-exposure prophylaxis (PrEP) are completed, underway or planned. We synthesized evidence from these studies to inform mathematical modelling of the prevention cascade for oral and long-acting PrEP in the setting of western Kenya, one of the world’s most heavily HIV-affected regions. Methods: We incorporated steps of the PrEP prevention cascade – uptake, adherence, retention and re-engagement after discontinuation – into EMOD-HIV, an open-source transmission model calibrated to the demography and HIV epidemic patterns of western Kenya. Early PrEP implementation research from East Africa was used to parameterize prevention cascades for oral PrEP as currently implemented, delivery innovations for oral PrEP, and future long-acting PrEP. We compared infections averted by PrEP at the population level for different cascade assumptions and sub-populations on PrEP. Analyses were conducted over the 2020 to 2040 time horizon, with additional sensitivity analyses for the time horizon of analysis and the time when long-acting PrEP becomes available. Results: The maximum impact of oral PrEP diminished by over 98% across all prevention cascades, with the exception of long-acting PrEP under optimistic assumptions about uptake and re-engagement after discontinuation. Long-acting PrEP had the highest population-level impact, even after accounting for possible delays in product availability, primarily because its effectiveness does not depend on drug adherence. Retention was the most significant cascade step reducing the potential impact of long-acting PrEP. These results were robust to assumptions about the sub-populations receiving PrEP, but were highly influenced by assumptions about re-initiation of PrEP after discontinuation, about which evidence was sparse. Conclusions: Implementation challenges along the prevention cascade compound to diminish the population-level impact of oral PrEP. Long-acting PrEP is expected to be less impacted by user uptake and adherence, but it is instead dependent on product availability in the short term and retention in the long term. To maximize the impact of long-acting PrEP, ensuring timely product approval and rollout is critical. Research is needed on strategies to improve retention and patterns of PrEP re-initiation.