How Much Do We Know about Drug Resistance Due to PrEP Use? Analysis of Experts' Opinion and Its Influence on the Projected Public Health Impact

• Published in: PloS one Vol. 11; no. 7; p. e0158620
• Main Authors: Dimitrov, Dobromir T, Boily, Marie-Claude, Hallett, Timothy B, Albert, Jan, Boucher, Charles, Mellors, John W, Pillay, Deenan, van de Vijver, David A M C
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 08.07.2016; Public Library of Science (PLoS)
• Subjects: Anti-HIV Agents - therapeutic use; Antiretroviral agents; Antiretroviral drugs; Biological activity; Biology and Life Sciences; Complications and side effects; Computer simulation; Controlled conditions; Demographic aspects; Drug resistance; Drug Resistance, Viral; Drug therapy; Emergence; Emtricitabine; Health aspects; HIV; HIV Infections - drug therapy; Human immunodeficiency virus; Humans; Infections; Mathematical models; Medicin och hälsovetenskap; Medicine and Health Sciences; Microbial drug resistance; Models, Theoretical; Mutation; Patient outcomes; Pre-Exposure Prophylaxis; Prophylaxis; Public Health; Randomized Controlled Trials as Topic; Research and Analysis Methods; Reversion; Risk factors; Surveys; Tenofovir; Virology; United Kingdom; Sweden; United States > US; Netherlands
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0158620

Randomized controlled trials reported that pre-exposure prophylaxis (PrEP) with tenofovir and emtricitabine rarely selects for drug resistance. However, drug resistance due to PrEP is not completely understood. In daily practice, PrEP will not be used under the well-controlled conditions available in the trials, suggesting that widespread use of PrEP can result in increased drug resistance. We surveyed expert virologists with questions about biological assumptions regarding drug resistance due to PrEP use. The influence of these assumptions on the prevalence of drug resistance and the fraction of HIV transmitted resistance was studied with a mathematical model. For comparability, 50% PrEP-coverage of and 90% per-act efficacy of PrEP in preventing HIV acquisition are assumed in all simulations. Virologists disagreed on the following: the time until resistance emergence (range: 20-180 days) in infected PrEP users with breakthrough HIV infections; the efficacy of PrEP against drug-resistant HIV (25%-90%); and the likelihood of resistance acquisition upon transmission (10%-75%). These differences translate into projections of 0.6%- 1% and 3.5%-6% infected individuals with detectable resistance 10 years after introducing PrEP, assuming 100% and 50% adherence, respectively. The rate of resistance emergence following breakthrough HIV infection and the rate of resistance reversion after PrEP use is discontinued, were the factors identified as most influential on the expected resistance associated with PrEP. Importantly, 17-23% infected individuals could virologically fail treatment as a result of past PrEP use or transmitted resistance to PrEP with moderate adherence. There is no broad consensus on quantification of key biological processes that underpin the emergence of PrEP-associated drug resistance. Despite this, the contribution of PrEP use to the prevalence of the detectable drug resistance is expected to be small. However, individuals who become infected despite the use of PrEP should be closely monitored due to higher risk of virological failure when initiating antiretroviral treatment in the future.