Does PrEP Induce Drug Resistance?

Article

Resistance development has been minimal under the controlled high adherence conditions of clinical trials. However, real-world adherence is less consistent.

High-risk behaviors for both HIV infection and inappropriate medication use tend to overlap.

Patients with poor adherence are most likely to contract HIV despite pre-exposure prophylaxis (PrEP) and also experience rapid antiretroviral therapy (ART) resistance. Meanwhile, patients with poor follow-up may fail to refill PrEP and forget to undergo periodic HIV testing.

Individual mutations eliminate the activity of tenofovir and emtricitabine—both of which are present in the PrEP product, Truvada. Highly active ART (HAART) uses at least 3 medications with different resistance mechanisms to prevent therapeutic failure. However, PrEP uses only 1 or 2 ART ingredients. Thus, PrEP could potentially induce drug resistance in patients who contract HIV and don’t escalate therapy to HAART promptly after infection.

Expert opinion differs widely concerning the rate of resistance emergence, infectiousness, efficacy of PrEP against resistant strains, and disease progression of infected patients.

In a recent survey, expert virologists predicted an infected patient could develop resistance within 20 to 180 days with consistent PrEP use. Half of the virologists believed weekly PrEP use (instead of daily, as indicated) has a weak effect on drug resistance, and 1 in 6 suggested rapid resistance development.

Their mathematical models suggested HIV-infected patients with 50% PrEP adherence develop resistance in 17% to 24% of cases, while 13% to 33% of those who take PrEP weekly experience resistance formation.

PrEP-induced resistance can reduce transmission risk compared with wild-type virus strains. Some of the expert virologists believed resistant strains are transmitted 10% to 60% less often in the weeks following infection, and 5% to 30% less often a year later.

PrEP is 90% effective against wild-type HIV, but predicted to be only 25% to 80% effective against resistant viruses. In 3 of 5 mathematical models, PrEP was <30% effective. Providers should reconsider PrEP if a patient has known contacts (eg, a spouse) with a resistant strain.

All surveyed virologists agreed PrEP doesn’t affect disease progression without HAART initiation, and PrEP patients are 25% to 55% less likely to achieve viral suppression within 1 year of diagnosis and HAART initiation.

Notably, all US Department of Health and Human Services HIV guideline-recommended HAART regimens (as of July 2016) contain tenofovir and emtricitabine.

Expert opinion fills gaps in evidence-based care regarding PrEP-induced drug resistance. Providers should advise PrEP patients to regularly take their medication, not share it with sex partners, and undergo periodic HIV testing to mitigate resistance development.

Reference

Dimitrov DT, et al. 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. PLOS One. 2016 Jul;11(7):e0158620.

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