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Drug Resistance Acquired During HIV PrEP Rapidly Disappears After Discontinuation

Drug resistance acquired in rare cases of HIV infection occurring while on pre-exposure prophylaxis (PrEP) rapidly disappears once the medication is discontinued, investigators with the Partners PrEP Study Teamreport in the January 2, 2016, edition of AIDS. Use of ultra-sensitive tests performed 6 months after seroconversion and discontinuation of Truvada for PrEP failed to find any remaining resistant virus.

[Produced in collaboration with Aidsmap.com]

"Multiple studies have now shown that the risk of developing resistance from PrEP is very low, but is an important concern for those who initiate PrEP during unrecognized acute infection," authors Julie Weis and colleagues commented. "Our data show that resistance selected in these cases decays rapidly to levels below detection of even highly sensitive assays."

PrEP with tenofovir/emtricitabine (Truvada) or tenofovir (Viread) alone is highly effective at preventing HIV infection. However, resistance to these antiretroviral drugs has been detected in individuals who initiated PrEP during unrecognized acute HIV infection and, very rarely, in patients infected with HIV while taking PrEP. Such resistance could limit future HIV treatment options. It is therefore important to determine if it persists once treatment is withdrawn.

To answer this question, investigators with the Partners PrEP study -- which evaluated the safety and efficacy of PrEP in heterosexual couples in Africa -- designed a longitudinal study involving 9 study participants who had drug-resistant HIV (K65R, K70E, and/or M18IV mutations) detected during HIV seroconversion.

Archived blood samples were tested to see if resistance was transmitted or acquired because of PrEP. Ultra-sensitive assays were used to monitor for resistant strains of virus at 6, 12, and 24 months after cessation of PrEP.

Archived blood samples that were HIV RNA-positive but antibody-negative were available prior to seroconversion for 4 of the 9 patients. None of these individuals had resistance mutations prior to seroconversion, suggesting that resistance was acquired due to taking PrEP rather than being transmitted.

PrEP was stopped immediately upon detection of seroconversion. Ultra-sensitive assays were used to see if resistance persisted after PrEP was withdrawn.

Levels of resistant virus had decayed -- or fallen -- to below the limit of detection in all patients 6 months after PrEP was discontinued and remained undetectable at 12 and 24 months after follow-up.

"PrEP-selected resistance decays rapidly after PrEP cessation," commented the investigators. "By 6 months after seroconversion (after PrEP was discontinued), resistance mutations K65R, K70E and/or M184IV that were present at seroconversion were no longer detected, even with highly sensitive resistance testing."

Only 1 participant started antiretroviral treatment (ART) within 40 months of seroconversion. This patient initiated therapy at month 33, taking a combination of nevirapine/tenofovir/emtricitabine. Viral load was approximately 19,000 copies/mL. At 3 months after starting ART, this individual had an undetectable viral load.

The investigators called for future studies to examine whether PrEP-associated resistance affects subsequent response to treatment.

12/15/15

Reference

Julie F Weis, Jared M Baeten, CO McCoy, et al (Partners PrEP Study Team). Preexposure prophylaxis-selected drug resistance decays rapidly after drug cessation. AIDS 30(1):31-35. January 2, 2016.