Targeting Pre-Exposure Prophylaxis Among MSM
Background We aim to identify optimal strategies for deploying pre-exposure prophylaxis among men who have sex with men (MSM) in the United States and Peru to maximize population-level effectiveness in an efficient manner. We use epidemic models to simulate the impact of targeting strategies. Most studies have focused on targeting either the general population or high-risk MSM. Alternative strategies, including serodiscordant couples, may better balance effectiveness and efficiency.
Methods We use dynamic stochastic sexual network models based on exponential-family random graph modeling, parameterized from behavioral surveys of MSM in the United States and Peru. These models represent main partnerships and casual contacts separately, permitting modeling of interventions targeting men whose risk derives from combinations of relational types. We also model varying rates of uptake and adherence to pre-exposure prophylaxis (PrEP). We assess sensitivity of results to risk compensation through increases in condomless casual contacts and condomless sex in main partnerships.
Results Targeting all men who are not exclusively insertive has the largest impact on HIV incidence, but targeting only those with high levels of casual activity yields comparable results using fewer person-years on PrEP. The effect is robust to risk compensation in the United States, but less so in Peru. Targeting serodiscordant main partnerships does not significantly impact incidence, but requires fewer person-years on PrEP per infection averted than other strategies.
Conclusions PrEP could be effective in reducing new infections at the population level in both settings. Serodiscordant partnerships are an attractive component of a targeting program, but targeting should include other high-risk men.
Three decades into the epidemic, HIV in the developed world and much of Latin America remains concentrated among men who have sex with men (MSM). Evidence suggests that incidence is rising among young MSM in the United States. Although great strides have been made in HIV treatment in that time, research on biomedical interventions for prevention has hit frequent roadblocks.
One promising intervention for MSM is pre-exposure prophylaxis (PrEP). PrEP has been evaluated for MSM in a randomized controlled trial in 6 countries, including the United States and Peru. The trial showed significant reductions in HIV acquisition (~44%) for men in the treatment arm, with subgroup analyses suggesting that men with detectable drug levels achieve extremely high rates of protection (~92%). PrEP has been found significantly protective in other populations as well. Continuing follow-up from PrEP trials shows extremely high protection among those with high adherence. Based on these results, implementation studies and projects are planned or underway.
Although these results show great promise for PrEP as an intervention to prevent HIV acquisition, it remains to be seen how demonstrated individual-level efficacy will translate to population-level effectiveness. Evaluating the potential population-level impact of PrEP and how targeting, uptake, adherence, and risk compensation can affect this will help to guide implementation efforts. A number of PrEP implementation models have appeared recently, examining possible population-level reductions in incidence depending on PrEP efficacy or for different targeting strategies. Most use compartmental models of HIV transmission and disease progression, the exception being the microsimulation of Hallett et al. Compartmental models are practically limited in their complexity, as the number of compartments required increases exponentially with the number of variables considered. Microsimulation is a catch-all term for models that track individuals explicitly, as opposed to compartmental models, which are concerned only with rates of movement between states in the population. Ours is a particular type of microsimulation that can account for complex relational structures.
Some of these studies consider MSM in the United States, and 1 models transmission among MSM and transgender women in Peru. These studies model PrEP targeted to either the general population or high-risk men (with risk almost exclusively defined by the number of partners), with a constant rate of protection. Results are mixed; all find a moderate-to-substantial reduction in incidence, but the number of men on treatment needed to achieve that reduction varies. In general, when targeting high-risk men only, efficiency is improved, indicating the central importance of identifying optimal targeting strategies.
Risk compensation is a major concern in HIV prevention, and various studies have suggested that some compensation occurs with different interventions (see Ref. 31 for a review). Since PrEP is a recent development, risk compensation assessments specific to it are not well established. Behavioral data from PrEP clinical trials participants show little evidence of risk compensation, in some cases even after unblinding. This may not reflect behavior changes in practice; however, surveys of MSM in the United States assessing likelihood of PrEP use and associated decision making suggest that a substantial proportion of men would decrease condom use to some extent when taking PrEP, especially, if it is known to be highly effective.
This article models the likely population-level impact of large-scale PrEP rollout among urban MSM populations in the United States and Peru under several different targeting strategies.
Both countries have HIV epidemics concentrated among MSM. It differs from previous work in using a dynamic stochastic network model of contacts, described in Goodreau et al, allowing for greater flexibility in the handling of individual attributes and a more explicit accounting for downstream effects of prevention. We allow for differential protection by adherence level, rather than a single rate of protection for all men on PrEP. This allows us to compare changes in incidence from increasing population coverage by increasing uptake or by increasing adherence of those on PrEP and thus to assess the relative benefit of expending resources on 1 or the other.
We also examine a variety of targeting strategies beyond those already considered in the literature. In particular, we represent main partnerships and casual contacts separately, allowing us to model PrEP interventions that target men whose HIV risk derives from different combinations of these relational types. Finally, we consider levels of risk compensation needed in each relationship type to turn the intervention from beneficial to harmful.
Abstract and Introduction
Abstract
Background We aim to identify optimal strategies for deploying pre-exposure prophylaxis among men who have sex with men (MSM) in the United States and Peru to maximize population-level effectiveness in an efficient manner. We use epidemic models to simulate the impact of targeting strategies. Most studies have focused on targeting either the general population or high-risk MSM. Alternative strategies, including serodiscordant couples, may better balance effectiveness and efficiency.
Methods We use dynamic stochastic sexual network models based on exponential-family random graph modeling, parameterized from behavioral surveys of MSM in the United States and Peru. These models represent main partnerships and casual contacts separately, permitting modeling of interventions targeting men whose risk derives from combinations of relational types. We also model varying rates of uptake and adherence to pre-exposure prophylaxis (PrEP). We assess sensitivity of results to risk compensation through increases in condomless casual contacts and condomless sex in main partnerships.
Results Targeting all men who are not exclusively insertive has the largest impact on HIV incidence, but targeting only those with high levels of casual activity yields comparable results using fewer person-years on PrEP. The effect is robust to risk compensation in the United States, but less so in Peru. Targeting serodiscordant main partnerships does not significantly impact incidence, but requires fewer person-years on PrEP per infection averted than other strategies.
Conclusions PrEP could be effective in reducing new infections at the population level in both settings. Serodiscordant partnerships are an attractive component of a targeting program, but targeting should include other high-risk men.
Introduction
Three decades into the epidemic, HIV in the developed world and much of Latin America remains concentrated among men who have sex with men (MSM). Evidence suggests that incidence is rising among young MSM in the United States. Although great strides have been made in HIV treatment in that time, research on biomedical interventions for prevention has hit frequent roadblocks.
One promising intervention for MSM is pre-exposure prophylaxis (PrEP). PrEP has been evaluated for MSM in a randomized controlled trial in 6 countries, including the United States and Peru. The trial showed significant reductions in HIV acquisition (~44%) for men in the treatment arm, with subgroup analyses suggesting that men with detectable drug levels achieve extremely high rates of protection (~92%). PrEP has been found significantly protective in other populations as well. Continuing follow-up from PrEP trials shows extremely high protection among those with high adherence. Based on these results, implementation studies and projects are planned or underway.
Although these results show great promise for PrEP as an intervention to prevent HIV acquisition, it remains to be seen how demonstrated individual-level efficacy will translate to population-level effectiveness. Evaluating the potential population-level impact of PrEP and how targeting, uptake, adherence, and risk compensation can affect this will help to guide implementation efforts. A number of PrEP implementation models have appeared recently, examining possible population-level reductions in incidence depending on PrEP efficacy or for different targeting strategies. Most use compartmental models of HIV transmission and disease progression, the exception being the microsimulation of Hallett et al. Compartmental models are practically limited in their complexity, as the number of compartments required increases exponentially with the number of variables considered. Microsimulation is a catch-all term for models that track individuals explicitly, as opposed to compartmental models, which are concerned only with rates of movement between states in the population. Ours is a particular type of microsimulation that can account for complex relational structures.
Some of these studies consider MSM in the United States, and 1 models transmission among MSM and transgender women in Peru. These studies model PrEP targeted to either the general population or high-risk men (with risk almost exclusively defined by the number of partners), with a constant rate of protection. Results are mixed; all find a moderate-to-substantial reduction in incidence, but the number of men on treatment needed to achieve that reduction varies. In general, when targeting high-risk men only, efficiency is improved, indicating the central importance of identifying optimal targeting strategies.
Risk compensation is a major concern in HIV prevention, and various studies have suggested that some compensation occurs with different interventions (see Ref. 31 for a review). Since PrEP is a recent development, risk compensation assessments specific to it are not well established. Behavioral data from PrEP clinical trials participants show little evidence of risk compensation, in some cases even after unblinding. This may not reflect behavior changes in practice; however, surveys of MSM in the United States assessing likelihood of PrEP use and associated decision making suggest that a substantial proportion of men would decrease condom use to some extent when taking PrEP, especially, if it is known to be highly effective.
This article models the likely population-level impact of large-scale PrEP rollout among urban MSM populations in the United States and Peru under several different targeting strategies.
Both countries have HIV epidemics concentrated among MSM. It differs from previous work in using a dynamic stochastic network model of contacts, described in Goodreau et al, allowing for greater flexibility in the handling of individual attributes and a more explicit accounting for downstream effects of prevention. We allow for differential protection by adherence level, rather than a single rate of protection for all men on PrEP. This allows us to compare changes in incidence from increasing population coverage by increasing uptake or by increasing adherence of those on PrEP and thus to assess the relative benefit of expending resources on 1 or the other.
We also examine a variety of targeting strategies beyond those already considered in the literature. In particular, we represent main partnerships and casual contacts separately, allowing us to model PrEP interventions that target men whose HIV risk derives from different combinations of these relational types. Finally, we consider levels of risk compensation needed in each relationship type to turn the intervention from beneficial to harmful.
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