Recently, antiretroviral drugs have been shown to dramatically reduce the risk of onward transmission from infected individuals (as ART) and also to reduce the risk of acquisition for uninfected individuals in stable relationships with infected partners (as Pre-Exposure Prophylaxis (PrEP)). This has raised many questions about how to harness these important findings for HIV prevention. One particular focus has been on stable sero-discordant couples (where one partner is infected and the other is uninfected), which are a recognised focus for HIV prevention efforts and studies of both early ART and PrEP have been conducted among this group. Given that treatment is already provided to individuals when they reach certain clinical thresholds and that there is a movement towards providing treatment earlier, we posed two questions: 1) What would the impact and cost-effectiveness of PrEP be for sero-discordant couples in the context of ART being provided to the infected partner along current clinical guidelines? 2) What is the most effective use of antiretroviral drugs to avert HIV infections and keep individuals alive for as long as possible?
We used an individual-based micro simulation model of serodiscordant heterosexual couples in South Africa to investigate these questions. The model included transmission of HIV-1, disease progression, use of ART, ageing, conception and pregnancies. The model was parameterised using data from the Partners in Prevention HSV/HIV Transmission study. Throughout the analysis two sets of behavioural assumptions were used: ‘Partners in Prevention couples’ (based on data from the Partners in Prevention study) and ‘More typical couples’ (assuming lower levels of condom use, more external partners and more unprotected sex with external partners). This was done in recognition of the fact that the couples observed in trials may or may not have similarities to the couples that would test together and be eligible for this kind of intervention in actual programmes.
First, we examined the impact of PrEP use by the uninfected partner before their infected partner started treatment. The highest impact, in terms of percentage of infections averted, is obtained when PrEP is used at all times by the uninfected partner after diagnosis of HIV in the infected partner, irrespective of ART use by the infected partner. Up to 59% of infections among couples could be averted with this strategy of PrEP use, assuming a PrEP effectiveness of 80% and the level of risk observed in Partners in Prevention couples. Strategies whereby PrEP is discontinued once the infected partner initiates ART result in a lower impact, with 49% of infections averted — but this was much more cost-effective. In fact, if PrEP is used in that way and the couples are at a high risk of becoming infected, using PrEP could reduce future costs as many individuals would then not become infected and require ART.
Next we compared using PrEP for the uninfected partner to earlier ART for the infected partner and attempted to identify the characteristics of PrEP that would be required for it to be at least as effective as providing earlier ART to the infected partner. For couples like those in the Partners in Prevention study, PrEP would be at least as cost-effective, at keeping couples ‘alive and HIV free at 50’ as earlier ART if its effectiveness was over 75% and the annual cost was less than 40% that of ART. In the trials, the upper estimates of effectiveness of oral PrEP did reach this level, and cost estimates do suggest PrEP would be substantially cheaper than ART, so this might be achievable, providing that couples using PrEP in real programs benefit from the same level of effectiveness as observed in the trials.
In summary, the evidence of efficacy of antiretroviral-based prevention might provide the best opportunity for reducing HIV infections. For sero-discordant couples, a key risk group for HIV transmission, the combination of both PrEP and ART may be a cost-effective way to reduce infections. However, there will certainly be many other considerations besides cost-effectiveness that inform decision-making for HIV treatment initiation and provision of PrEP in couples, including equitable access to medications and the preferences of the couples themselves.