Optimal uses of antiretrovirals for prevention in HIV-1 serodiscordant heterosexual couples in South Africa: a modelling study

Abstract

Background: Antiretrovirals have substantial promise for HIV-1 prevention, either as antiretroviral treatment (ART) for HIV-1-infected persons to reduce infectiousness, or as pre-exposure prophylaxis (PrEP) for HIV-1-uninfected persons to reduce the possibility of infection with HIV-1. HIV-1 serodiscordant couples in long-term partnerships (one member is infected and the other is uninfected) are a priority for prevention interventions. Earlier ART and PrEP might both reduce HIV-1 transmission in this group, but the merits and synergies of these different approaches have not been analyzed.

Methods and findings: We constructed a mathematical model to examine the impact and cost-effectiveness of different strategies, including earlier initiation of ART and/or PrEP, for HIV-1 prevention for serodiscordant couples. Although the cost of PrEP is high, the cost per infection averted is significantly offset by future savings in lifelong treatment, especially among couples with multiple partners, low condom use, and a high risk of transmission. In some situations, highly effective PrEP could be cost-saving overall. To keep couples alive and without a new infection, providing PrEP to the uninfected partner could be at least as cost-effective as initiating ART earlier in the infected partner, if the annual cost of PrEP is <40% of the annual cost of ART and PrEP is >70% effective.

Conclusions: Strategic use of PrEP and ART could substantially and cost-effectively reduce HIV-1 transmission in HIV-1 serodiscordant couples. New and forthcoming data on the efficacy of PrEP, the cost of delivery of ART and PrEP, and couples behaviours and preferences will be critical for optimizing the use of antiretrovirals for HIV-1 prevention. Please see later in the article for the Editors' Summary.

Figure 1. The impact of different PrEP interventions on HIV infections in the couple.

(A, D) The proportion of infections averted by age 50 (relative to a baseline strategy with no PrEP intervention) for four PrEP strategies (see Table 2). (B, E) The expected mean years on PrEP (blue boxes) and years on ART averted (yellow boxes) for each of the four PrEP interventions (after discounting). (C, F) The expected cost per infection averted for each of the four PrEP interventions: the pink boxes reflect the lower PrEP cost estimates (and the higher ART cost estimates) and the blue boxes reflect the higher PrEP cost estimates (and the lower of ART cost estimates). In (A–F), the boxes shows a “feasible” range of results, which corresponds to a functional effectiveness of PrEP ranging between 50% and 80%. The assumptions used about the couple's behaviour are: (A–C) “partners in prevention” assumptions and (D–F) the “more typical couples” assumptions (see main text for details). Figure S2 shows the analysis repeated for alternative types of couples. (Summary of strategies from Table 2: I, always PrEP; II, PrEP prior to ART with 1-y overlap; III, PrEP prior to ART (no overlap); IV, PrEP during conception/pregnancy.)

Figure 2. Comparison of PrEP versus earlier ART initiation for keeping couples “alive and HIV free at 50.”

The relative cost of PrEP to ART (vertical axis) and the effectiveness of PrEP (horizontal axis) are varied and the shaded region indicates the conditions where a PrEP intervention (PrEP used up to the moment that their infected partner starts treatment (at CD4<350 cells/µl)) is at least as cost-effective as earlier initiation of ART (at CD4<500 cells/µl) at allowing couples to be “alive and HIV-1 free at 50.” The dark shaded region corresponds to the “partners in prevention” assumptions about couples' behaviour and the lighter shaded region corresponds to “more typical couples” behaviour assumptions. Alternative analyses are presented where different assumptions about ART initiation and couples' behaviour are made (Figure S3) and where the comparison is based on savings of QALYs (Figure S4).