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Preexposure Prophylaxis Use History in People With Antiretroviral Resistance at Human Immunodeficiency Virus (HIV) Diagnosis: Findings From New York City HIV Surveillance and Partner Services, 2015-2022
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Clinical Infectious Diseases 17 November 2023
The elevated risk of developing drug resistance mutations associated with PrEP during AHI has potential implications for the success of first-line treatment regimens and for the possible persistence of minority variants, increasing the risk of future virologic failure [6, 13].
Only 4% of people in our population with any PrEP use history had evidence of a negative NAT in the 2 weeks before and after PrEP initiation. While our data cannot speak to the overall use of NAT in the context of PrEP screening in NYC, they suggest that in populations at highest risk of HIV infection, complete laboratory testing in conjunction with symptom, exposure, and previous ARV history assessment may not be occurring at optimal levels to rule out AHI before PrEP initiation.
Abstract
Background
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.
Methods
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).
Results
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]).
Conclusions
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.
In conclusion, we found a strong association between PrEP use and the presence of drug resistance at diagnosis in NYC, a setting of high HIV prevalence, regardless of AHI status. Fewer than half of all people with newly diagnosed HIV had a genotype obtained within 30 days of diagnosis. The reasons for this may include lack of drug resistance testing by providers, low VL at the time of testing, and laboratory reporting failure [28]. The proportion of genotypes conducted within 3 months of diagnosis has declined in NYC, from 72% in 2013% to 46% in 2021 [28, 29]. We found that only 4% of people with PrEP use history had evidence of a negative NAT result in the plausible time frame of PrEP screening, revealing missed opportunities for identifying undiagnosed infection. NAT can more confidently rule out AHI in people who may be reluctant to disclose exposure history, whose illness may be mild, nonspecific or asymptomatic, or whose ARV experience may be uncertain. In situations where RNA testing is not feasible owing to cost or time constraints, repeated HIV antigen/antibody testing in the month following PrEP start can decrease PrEP use during undiagnosed infection and facilitate timely transition to fully suppressive ART [22, 30]. In addition, providers should adhere to guidelines recommending baseline genotype resistance testing for everyone with a new HIV diagnosis and follow-up genotyping for people found to have drug resistance at baseline, to assess short- and long-term treatment options [29-32].
The benefits of PrEP outweigh the risk of ADR. HIV infections averted by PrEP would require long-term ART, entailing an estimated annual risk of drug resistance between 5% and 20% [33, 34]. While some studies show that people with PrEP-related resistance went on to become virally suppressed within 6 months of diagnosis [12, 35] and that dolutegravir-based second-line ART regimens have been successful in limiting the effect of M184I/V on ART efficacy [6], others have found a greater risk of virologic nonsuppression with preexisting M184I/V [6]. Longitudinal assessment of people with PrEP-related drug resistance using population level and surveillance data is warranted.
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