Preexposure prophylaxis-selected drug resistance decays rapidly after drug cessation

Resistance to emtricitabine plus tenofovir disoproxil fumarate (FTC/TDF) or TDF alone used as preexposure prophylaxis (PrEP) has been detected in individuals who initiated PrEP during unrecognized acute HIV infection and, rarely, in PrEP breakthrough infections. PrEP-selected resistance could alter future treatment options, and therefore we sought to determine how long resistance persisted after PrEP cessation.

The Partners PrEP Study was a randomized placebo-controlled trial of FTC/TDF or TDF as PrEP for HIV prevention. We previously reported that PrEP-related mutations (K65R, K70E or M184IV) were detected by 454 sequencing following seroconversion in nine individuals who acquired HIV during the Partners PrEP Study. In the current study, we used 454 sequencing to detect and quantify PrEP-related mutations in HIV RNA-positive plasma samples prior to seroconversion, as well as in plasma from 6, 12, and 24 months after PrEP cessation from these nine individuals.

HIV RNA-positive, antibody-negative samples were available prior to seroconversion for four of nine individuals with resistance detected at seroconversion. In all four cases, K65R, K70E and M184IV were not detected prior to seroconversion, suggesting PrEP-related resistance was selected and not transmitted. All PrEP-selected mutations were no longer detectable by 6 months after PrEP cessation and remained undetectable at 12 and 24 months in the absence of antiretroviral therapy.

Using highly sensitive assays, PrEP-selected resistance in plasma decays below detection by 6 months following drug cessation and remains undetectable for at least 24 months. Even high levels of resistance mutations during acute infection decay rapidly in the absence of ongoing PrEP exposure.