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Analytic Review of Modeling Studies of ARV Based PrEP Interventions Reveals Strong Influence of Drug-Resistance Assumptions on the Population-Level Effectiveness

Author

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  • Dobromir Dimitrov
  • Marie-Claude Boily
  • Elizabeth R Brown
  • Timothy B Hallett

Abstract

Background: Four clinical trials have shown that oral and topical pre-exposure prophylaxis (PrEP) based on tenofovir may be effective in preventing HIV transmission. The expected reduction in HIV transmission and the projected prevalence of drug resistance due to PrEP use vary significantly across modeling studies as a result of the broad spectrum of assumptions employed. Our goal is to quantify the influence of drug resistance assumptions on the predicted population-level impact of PrEP. Methods: All modeling studies which evaluate the impact of oral or topical PrEP are reviewed and key assumptions regarding mechanisms of generation and spread of drug-resistant HIV are identified. A dynamic model of the HIV epidemic is developed to assess and compare the impact of oral PrEP using resistance assumptions extracted from published studies. The benefits and risks associated with ten years of PrEP use are evaluated under identical epidemic, behavioral and intervention conditions in terms of cumulative fractions of new HIV infections prevented, resistance prevalence among those infected with HIV, and fractions of infections in which resistance is transmitted. Results: Published models demonstrate enormous variability in resistance-generating assumptions and uncertainty in parameter values. Depending on which resistance parameterization is used, a resistance prevalence between 2% and 44% may be expected if 50% efficacious oral PrEP is used consistently by 50% of the population over ten years. We estimated that resistance may be responsible for up to a 10% reduction or up to a 30% contribution to the fraction of prevented infections predicted in different studies. Conclusions: Resistance assumptions used in published studies have a strong influence on the projected impact of PrEP. Modelers and virologists should collaborate toward clarifying the set of resistance assumptions biologically relevant to the PrEP products which are already in use or soon to be added to the arsenal against HIV.

Suggested Citation

  • Dobromir Dimitrov & Marie-Claude Boily & Elizabeth R Brown & Timothy B Hallett, 2013. "Analytic Review of Modeling Studies of ARV Based PrEP Interventions Reveals Strong Influence of Drug-Resistance Assumptions on the Population-Level Effectiveness," PLOS ONE, Public Library of Science, vol. 8(11), pages 1-9, November.
    • Handle: RePEc:plo:pone00:0080927
    DOI: 10.1371/journal.pone.0080927
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    References listed on IDEAS

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    1. Leigh Johnson & Rob Dorrington & Debbie Bradshaw & Victoria Pillay-Van Wyk & Thomas Rehle, 2009. "Sexual behaviour patterns in South Africa and their association with the spread of HIV: insights from a mathematical model," Demographic Research, Max Planck Institute for Demographic Research, Rostock, Germany, vol. 21(11), pages 289-340.
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    3. Carel Pretorius & John Stover & Lori Bollinger & Nicolas Bacaër & Brian Williams, 2010. "Evaluating the Cost-Effectiveness of Pre-Exposure Prophylaxis (PrEP) and Its Impact on HIV-1 Transmission in South Africa," PLOS ONE, Public Library of Science, vol. 5(11), pages 1-10, November.
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