Resistance to PrEP can occur

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Recent data suggest that resistance to pre-exposure prophylaxis, while rare, can occur with both treatment initiation during acute seronegative infection and in pre-exposure prophylaxis breakthrough infections. “Ours is the first study to indicate that, although antiretroviral resistance selected by PrEP is rare, resistance can occur both in settings of PrEP exposure during unrecognized acute infection and in breakthrough infections and that it may be more common with [Truvada (FTC/TDF; emtricitabine/tenofovir disoproxil fumarate, Gilead Sciences)] than [tenofovir] alone,” Dr Dara A Lehman of the University of Washington and colleagues write in a Healio report.

The phase 3 randomised study examined HIV-uninfected partners of 4,747 HIV-serodiscordant couples in Kenya and Uganda assigned FTC/TDF, TDF, or placebo. HIV RNA was measured to estimate the time frame of HIV infection. Resistance mutations were identified through sequencing of plasma samples. The researchers said 122 HIV seroconversions occurred during the study, of which 25 patients had received FTC/TDF, 39 had received TDF alone, and 58 had received placebo.

Among those with PrEP use detected during or after infection (n = 26), five were drug resistant. Resistance was more frequent in the FTC/TDF arm compared with the TDF-only arm (57% vs. 5.3%; P = .01), Lehman and colleagues wrote, adding that this was likely due to the FTC-associated mutation M184IV. Of these cases, three had unrecognized acute infection at PrEP randomization, and two were HIV negative at enrollment.

The relative protection of receiving TDF alone vs FTC/TDF was 0.67 (95% CI, 0.39-1.17). Additional evidence that TDF may fail more frequently when used without FTC was the greater rate of drug detection among TDF PrEP seroconverters (49%), compared with FTC/TDF PrEP seroconverters (25%), the researchers wrote – 71% of participants assigned to the active arm used their medications consistently.

“Our highly sensitive resistance testing with 454 sequencing technology confirms previous findings with consensus sequencing that resistance was highest in those with unrecognized acute infection at PrEP initiation, suggesting that careful screening is important in PrEP implementation,” the researchers wrote.

Full Healio report
Journal of Infectious Diseases abstract


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