Objectives: HIV pre-exposure prophylaxis (PrEP) may change serosorting patterns. We examined the influence of serosorting on the population-level HIV transmission impact of PrEP, and how impact could change if PrEP users stopped serosorting. Design: We developed a compartmental HIV transmission model parameterized with bio-behavioural and HIV surveillance data among MSM in Canada. Methods: We separately fit the model with serosorting and without serosorting [counterfactual; sero-proportionate mixing (random partner-selection proportional to availability by HIV status)], and reproduced stable HIV epidemics with HIV-prevalence 10.3–24.8%, undiagnosed fraction 4.9–15.8% and treatment coverage 82.5–88.4%. We simulated PrEP-intervention reaching stable pre-specified coverage by year-one and compared absolute difference in relative HIV-incidence reduction 10 years post-intervention (PrEP-impact) between models with serosorting vs. sero-proportionate mixing; and counterfactual scenarios when PrEP users immediately stopped vs. continued serosorting. We examined sensitivity of results to PrEP-effectiveness (44–99%; reflecting varying dosing or adherence levels) and coverage (10–50%). Results: Models with serosorting predicted a larger PrEP-impact than models with sero-proportionate mixing under all PrEP-effectiveness and coverage assumptions [median (interquartile range): 8.1% (5.5–11.6%)]. PrEP users’ stopping serosorting reduced PrEP-impact compared with when PrEP users continued serosorting: reductions in PrEP-impact were minimal [2.1% (1.4–3.4%)] under high PrEP-effectiveness (86–99%); however, could be considerable [10.9% (8.2–14.1%)] under low PrEP effectiveness (44%) and high coverage (30–50%). Conclusion: Models assuming sero-proportionate mixing may underestimate population-level HIV-incidence reductions due to PrEP. PrEP-mediated changes in serosorting could lead to programmatically important reductions in PrEP-impact under low PrEP-effectiveness. Our findings suggest the need to monitor sexual mixing patterns to inform PrEP implementation and evaluation.
BackgroundPre-exposure prophylaxis (PrEP) with antiretrovirals is an efficacious and effective intervention to decrease the risk of HIV (human immunodeficiency virus) acquisition. Yet drug and delivery costs prohibit access in many jurisdictions. In the absence of guidelines for the synthesis of economic evaluations, we developed a protocol for a systematic review of economic evaluation studies for PrEP by drawing on best practices in systematic reviews and the conduct and reporting of economic evaluations. We aim to estimate the incremental cost per health outcome of PrEP compared with placebo, no PrEP, or other HIV prevention strategies; assess the methodological variability in, and quality of, economic evaluations of PrEP; estimate the incremental cost per health outcome of different PrEP implementation strategies; and quantify the potential sources of heterogeneity in outcomes.MethodsWe will systematically search electronic databases (MEDLINE, Embase) and the gray literature. We will include economic evaluation studies that assess both costs and health outcomes of PrEP in HIV-uninfected individuals, without restricting language or year of publication. Two reviewers will independently screen studies using predefined inclusion criteria, extract data, and assess methodological quality using the Philips checklist, Second Panel on the Cost-effectiveness of Health and Medicines, and the International Society for Pharmacoeconomics and Outcomes Research recommendations. Outcomes of interest include incremental costs and outcomes in natural units or utilities, cost-effectiveness ratios, and net monetary benefit. We will perform descriptive and quantitative syntheses using sensitivity analyses of outcomes by population subgroups, HIV epidemic settings, study designs, baseline intervention contexts, key parameter inputs and assumptions, type of outcomes, economic perspectives, and willingness to pay values.DiscussionFindings will guide future economic evaluation of PrEP strategies in terms of methodological and knowledge gaps, and will inform decisions on the efficient integration of PrEP into public health programs across epidemiologic and health system contexts.Systematic review registrationPROSPERO CRD42016038440.Electronic supplementary materialThe online version of this article (10.1186/s13643-018-0710-0) contains supplementary material, which is available to authorized users.
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