Transmission reduction, health benefits, and upper-bound costs of interventions to improve retention on antiretroviral therapy: a combined analysis of three mathematical models

Abstract

Background: In this so-called treat-all era, antiretroviral therapy (ART) interruptions contribute to an increasing proportion of HIV infections and deaths. Many strategies to improve retention on ART cost more than standard of care. In this study, we aimed to estimate the upper-bound costs at which such interventions should be adopted.

Methods: In this combined analysis, we compared the infections averted, disability-adjusted life-years (DALYs) averted, and upper-bound costs of interventions that improve ART retention in three HIV models with diverse structures, assumptions, and baseline settings: EMOD in South Africa, Optima in Malawi, and Synthesis in sub-Saharan African low-income and middle-income countries (LMICs). We modelled estimates over a 40-year time horizon, from a baseline of Jan 1, 2022, when interventions would be implemented, to Jan 1, 2062. We varied increment of ART retention (25%, 50%, 75%, and 100% retention), the extent to which interventions could be targeted towards individuals at risk of interrupting ART, and cost-effectiveness thresholds in each setting.

Findings: Despite simulating different settings and epidemic trends, all three models produced consistent estimates of health benefit (ie, DALYs averted) and transmission reduction per increment in retention. The range of estimates was 1·35-3·55 DALYs and 0·12-0·20 infections averted over the 40-year time horizon per additional person-year retained on ART. Upper-bound costs varied by setting and intervention effectiveness. Improving retention by 25% among all people receiving ART, regardless of risk of ART interruption, gave an upper-bound cost per person-year of US$2-6 in Optima (Malawi), $43-68 in Synthesis (LMICs in sub-Saharan Africa), and $28-180 in EMOD (South Africa). A maximally targeted and effective retention intervention had an upper-bound cost per person-year of US$93-223 in Optima (Malawi), $871-1389 in Synthesis (LMICs in sub-Saharan Africa), and $1013-6518 in EMOD (South Africa).

Interpretation: Upper-bound costs that could improve ART retention vary across sub-Saharan African settings and are likely to be similar to or higher than was estimated before the start of the treat-all era. Upper-bound costs could be increased by targeting interventions to those most at risk of interrupting ART.

Funding: Bill & Melinda Gates Foundation.

Figure 1

Projections of HIV incidence (A), prevalence (B), and mortality (C) with improvements to ART retention EMOD, Optima, and Synthesis model projections of HIV incidence per 100 person-years among adults aged 15 years and older (A), HIV prevalence among adults aged 15 years and older (B), and HIV deaths per 100 people living with HIV per year (C). Graphs show baseline projections with no intervention to improve ART retention and improved retention so that treatment interruption rates decrease by 25%, 50%, 75%, or 100% at the start of 2022 (grey vertical dashed lines). ART=antiretroviral therapy. EMOD=EMOD-HIV. LMICs=low-income and middle-income countries. Optima=Optima HIV. Synthesis=HIV Synthesis.

Figure 2

Health benefits (A) and transmission reduction (B) per additional person-year retained on ART with improved retention, representing a maximally targeted retention intervention Model estimates from EMOD, Optima, and Synthesis showing the ratios of DALYs averted (A) and HIV infections averted (B) per additional person-year retained on ART, with annual discounting of 0%, 3%, and 6%, at different levels of improvement in ART retention (25–100%). Inverting these numbers provides estimates of the number needed to treat, where the number treated is the additional number of individuals on ART compared with the no intervention scenario (ie, those who would have interrupted ART without improvement to retention). ART=antiretroviral therapy. DALYs=disability-adjusted life-years. EMOD=EMOD-HIV. Optima=Optima HIV. Synthesis=HIV Synthesis.

Figure 3

Health benefits (A) and transmission reduction (B) per total person-years on ART with improved retention, representing a minimally targeted retention intervention Model estimates from EMOD, Optima, and Synthesis showing the ratios of DALYs averted (A) and HIV infections averted (B) to total person-years on ART with annual discounting of 0%, 3%, and 6%, at different levels of improvement in ART retention (25–100%). Inverting these numbers provides estimates of the number needed to treat, where the number treated is the total number of individuals on ART, regardless of whether or not the intervention changed the retention status. ART=antiretroviral therapy. DALYs=disability-adjusted life-years. EMOD=EMOD-HIV. Optima=Optima HIV. Synthesis=HIV Synthesis.