PrEP Use in Persons With Undetected HIV Infections Contributes to Resistance

With antimicrobial resistance at the top of the World Health Organization’s top 10 global health threats of 2019, it’s only natural that resistance is also at top of mind for those on the frontlines of the HIV epidemic.

The success of pre-exposure prophylaxis (PrEP) in keeping HIV-negative individuals from becoming infected has now triggered fears of possible drug resistance linked to prescribing the prevention treatment to persons with an undiagnosed HIV infection.

Investigators from the New York City Department of Health and Mental Hygiene culled data from cases assigned for partner services from November 2015 to August 2017 in New York City to examine the viral resistance profile and determine rates of mutations in recently diagnosed persons (< 12 months) with a recent history of PrEP (emtricitabine [3TC] [M184I/V/IV/MV] and tenofovir disoproxil fumarate [TDF] [K65R]) use. The team compared acute HIV infection, negative nucleic acid amplification tests (NAAT), and prevalence of viral resistance in pre-diagnosis PrEP users and those who had never taken PrEP before.

The findings were presented in an oral abstract session at the Annual Conference on Retroviruses and Opportunistic Infections (CROI 2019) on March 6, 2019.

Of 3721 persons with a recent HIV diagnosis, 95 (3%) reported pre-diagnosis PrEP use, due either to insufficient HIV screening or screening during the window period between exposure and infection. The median length of PrEP exposure pre-diagnosis was 3 months.

Pre-diagnosis PrEP users were more likely to be diagnosed with acute HIV infection (33% vs 9%, p<0.0001) and were more likely than never-users to have negative NAAT pre-diagnosis (33% vs 4%, p<0.0001).

Investigators analyzed genotypes from 75% of pre-diagnosis PrEP users and 62% of never-users and found that M184I/V/IV/MV was significantly more prevalent among pre-diagnosis PrEP users than never-users (26% vs 2%, p-value <0.0001). Four persons exhibited K65R mutations, none of whom were pre-diagnosis PrEP users.

“Persons with a history of pre-diagnosis PrEP use were significantly more likely to have

resistance mutations to 3TC. There were no signature TDF mutations (K65R) detected among pre-diagnosis PrEP users,” the investigators concluded. “Our findings stress the importance of screening regularly to reduce the likelihood of PrEP start during undetected HIV infection in order to reduce the risk of inducing drug resistance.”

The study, “Impact of PrEP on Drug Resistance and Acute HIV Infection, New York City, 2015-2017,” was presented on Wednesday, March 6, 2019, at CROI 2019 in Seattle, Washington.