Abstract

Drug resistance may be acquired in people starting human immunodeficiency virus (HIV) preexposure prophylaxis (PrEP) during undiagnosed infection. Population-based estimates of PrEP-related resistance are lacking. We used New York City surveillance and partner services data to measure the effect of PrEP use (tenofovir disoproxil fumarate/tenofivir alafenamide fumarate with emtricitabine) history on the baseline prevalence of M184I/V mutations in people with HIV diagnosed in 2015-2022. PrEP use was categorized as "recent" (defined as PrEP stopped ≤90 days before diagnosis), "past" (PrEP stopped >90 days before diagnosis), or "no known use." Resistance-associated mutations were determined using the Stanford algorithm. We used log binomial regression to generate the adjusted relative risk (aRR) of M184I/V by PrEP use history in people with or without acute HIV infection (AHI). Of 4246 people with newly diagnosed HIV and a genotype obtained within ≤30 days of diagnosis, 560 (13%) had AHI; 136 (3%) reported recent and 124 (35%) past PrEP use; and 98 (2%) harbored M184I/V. In people with AHI, recent PrEP use was associated with a 6 times greater risk of M184I/V than no known use (aRR, 5.86 [95% confidence interval, 2.49-13.77]). Among people without AHI, the risk of M184I/V in recent users was 7 times that in people with no known use (aRR, 7.26 [95% confidence interval, 3.98-13.24]), and in past users, it was 4 times that in those with no known use (4.46 [2.15-9.24]). PrEP use was strongly associated with baseline M184I/V in New York City, regardless of AHI status. Ordering a nucleic acid test when indicated after assessment of exposure, antiretroviral history, and AHI symptoms can decrease PrEP initiation in people with undetected infection.

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