Maximising HIV prevention by balancing the opportunities of today with the promises of tomorrow: a modelling study

Abstract

Background: Many ways of preventing HIV infection have been proposed and more are being developed. We sought to construct a strategic approach to HIV prevention that would use limited resources to achieve the greatest possible prevention impact through the use of interventions available today and in the coming years.

Methods: We developed a deterministic compartmental model of heterosexual HIV transmission in South Africa and formed assumptions about the costs and effects of a range of interventions, encompassing the further scale-up of existing interventions (promoting condom use, male circumcision, early antiretroviral therapy [ART] initiation for all [including increased HIV testing and counselling activities], and oral pre-exposure prophylaxis [PrEP]), the introduction of new interventions in the medium term (offering intravaginal rings, long-acting injectable antiretroviral drugs) and long term (vaccine, broadly neutralising antibodies [bNAbs]). We examined how available resources could be allocated across these interventions to achieve maximum impact, and assessed how this would be affected by the failure of the interventions to be developed or scaled up.

Findings: If all interventions are available, the optimum mix would place great emphasis on the following: scale-up of male circumcision and early ART initiation with outreach testing, as these are available immediately and assumed to be low cost and highly efficacious; intravaginal rings targeted to sex workers; and vaccines, as these can achieve a large effect if scaled up even if imperfectly efficacious. The optimum mix would rely less on longer term developments, such as long-acting antiretroviral drugs and bNAbs, unless the costs of these reduced. However, if impossible to scale up existing interventions to the extent assumed, emphasis on oral PrEP, intravaginal rings, and long-acting antiretroviral drugs would increase. The long-term effect on the epidemic is most affected by scale-up of existing interventions and the successful development of a vaccine.

Interpretation: With current information, a strategic approach in which limited resources are used to maximise prevention impact would focus on strengthening the scale-up of existing interventions, while pursuing a workable vaccine and developing other approaches that can be used if further scale-up of existing interventions is limited.

Funding: Bill & Melinda Gates Foundation.

Figure 1

Effect achievable with the full range of interventions (A) The impact and cost of all possible interventions (grey dots), with the frontier highlighted (blue line). The medium scale-up scenario (purple dot), the optimum allocation point on the frontier with the same cost (green dot), and the maximum scale-up scenario (red dot) are highlighted. (B) Trajectory of HIV incidence in 15–49-year-olds, 2016–50, for the constant scale-up, medium scale-up, optimum allocation, and maximum scale-up scenarios. (C) The level of scale-up for each intervention in the optimum allocation scenario. (D) The distribution of costs by intervention type, 2016–50, in the optimum allocation scenario. VMMC=voluntary medical male circumcision. ART=antiretroviral therapy. PrEP=pre-exposure prophylaxis. IVR=intravaginal ring. LA-ARVs=long-acting antiretrovirals. bNAbs=broadly neutralising antibodies.

Figure 2

The level of scale-up for each intervention in the optimum allocation scenario, under different assumptions for the availability of interventions (see table 2) Scenario A, all interventions available; scenario B, as A without LA-ARVs or bNAbs; scenario C, as A without vaccine; scenario D, as A without vaccine, LA-ARVs, or bNAbs; scenario E, all interventions available, condom use limited to constant level; scenario F, all interventions available, condom use, VMMC, and early ART limited to constant levels. VMMC=voluntary medical male circumcision. ART=antiretroviral therapy. PrEP=pre-exposure prophylaxis. IVR=intravaginal ring. LA-ARVs=long-acting antiretrovirals. bNAbs=broadly neutralising antibodies.

Figure 3

Maximum impact (HIV infections averted 2016–50) achievable with the resources implied in the medium scenario, under different assumptions for the availability of interventions (see table 2) Scenario A, all interventions available; scenario B, as A without long-acting antiretrovirals or broadly neutralising antibodies; scenario C, as A without vaccine; scenario D, as A without vaccine, long-acting antiretrovirals, or broadly neutralising antibodies; scenario E, all interventions available, condom use limited to constant level; scenario F, all interventions available, condom use, voluntary medical male circumcision, and early antiretroviral therapy limited to constant levels.