PrEP and Drug Resistance: Cause for Concern?

PrEP and Drug Resistance: Cause for Concern?

With a continually increasing number of people beginning to take the drug Truvada as pre-exposure prophylaxis (PrEP) to prevent HIV, some have raised concerns that this might lead to more opportunities for drug resistant strains of HIV to develop. Drug resistance that develops while a person is on PrEP would limit treatment options for those who subsequently become -- or are unknowingly -- infected with a drug-resistant strain. A recent study in the Journal of Infectious Diseases tempers concern over drug-resistance caused by PrEP, with evidence that worrisome mutations -- while discovered -- appear to be rare.

"We know from using medications to prevent HIV transmission from mother-to-child, that resistance can occur in those that become infected despite the medication's use," explains Dara Lehman, PhD, of the Fred Hutchinson Cancer Research Center, and lead author of the study.

That's why she and her colleagues set out to find evidence of drug resistance in participants enrolled in the Partners PrEP Study, a large-scale, randomized, placebo-controlled study of PrEP efficacy for serodiscordant couples. Of the study's 4,747 participants, 26 people who took PrEP tested positive for HIV after the study began. Among these participants, the researchers used an assay -- "454 sequencing" -- to detect four HIV mutations known to cause resistance to emtricitabine (FTC) or tenofovir disoproxil fumarate (TDF), the two drugs in the PrEP combination pill Truvada.

Out of the 26 people who seroconverted during the study and were on PrEP, five ended up developing strains of the virus with mutations associated with resistance to either FTC or TDF, at a frequency high enough to be clinically significant. People who seroconverted during the study were significantly more likely to develop a strain of HIV resistant to PrEP when treated with PrEP versus treated with placebo. And among people who were assigned to active study drug, people were more likely to develop HIV with a PrEP-related resistance mutation when the levels of TDF in their plasma samples were detectable versus undetectable.

Despite these statistically significant findings, Lehman explains that the amount of drug resistance they detected was "actually quite low." She adds that, "This is really encouraging in terms of the ability to use PrEP on a broader scale. It's important to remember that if you take PrEP, and if you're adherent, it's actually a very effective prevention method. You don't have to worry about resistance if you don't get infected."

She and her colleagues estimate that 123 new infections were prevented over the course of the Partners PrEP Study, and comment in the paper that the five cases of drug resistance that emerged "should be weighed against the number of HIV infections averted."

This excerpt was cross-posted with the permission of Read the full article.