Objective:
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.
Methods:
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.
Results:
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.
Conclusion:
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.
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