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PrEP Use and HIV Incidence Among Youth At-Risk for HIV Infection in Los Angeles and New Orleans: Findings From ATN 149
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Nov 1 2023
Reducing the discontinuation of PrEP is an important strategy for lowering seroconversion. To date, much attention has been focused on the uptake of PrEP. This paper has shown that HIV incidence rates can be higher for discontinuous PrEP users who cycle on and off PrEP over 24 months. These discontinuous users experience higher seroconversion rates than PrEP nonusers or continuous PrEP users. Providing PrEP users with prescriptions for more than 1 month at a time could reduce the “hassle” of continuing PrEP. LAI could also address treatment discontinuation because of monthly refills, but at higher cost and clinic attendance burden. More broadly, reducing clinical burdens for PrEP continuation, such as less-frequent clinic visits, telehealth visits, mail-based home HIV/STI testing, and longer-acting injectable formulations are warranted to realize the promise of PrEP in reducing new HIV infections.
In coming years, with the increased use of generic Truvada and possible reductions in the price of LAI PrEP agents, such as cabotegravir, the lack of cost-effectiveness of LAI PrEP12 may change. Furthermore, longer-lasting injectable PrEP could significantly reduce the risks of discontinuation. Nevertheless, our results suggest that only starting someone on PrEP without mechanisms in place for continuous use is not sufficient for averting new HIV infections. Previous research has documented that taking 4 or more oral doses of PrEP in a week provides good protection against acquiring HIV.16,17 Only a small share of the youth in this study was able to continue using PrEP between each 4-month visit, despite reporting high levels of daily adherence when they were taking it. Thus, the measures of adherence commonly used may not address the most relevant margin. Therefore, this paper introduced a novel measure of adherence—consistent use of PrEP over time. Inconsistent users had a greater incidence rate than consistent users.
Although the focus of many analyses of adherence has been on adherence to a daily oral medication schedule, equally important are longer durations of maintaining use from month to month. A number of studies have documented short durations of PrEP treatment. Among young black men in Georgia who initiated PrEP, 16% discontinued PrEP before 90 days, and 46% discontinued it later. The median duration of PrEP use was 122 days.24 The problem is not unique to the U.S. Early discontinuation of PrEP is also an issue in Australia10 and Belgium.25Barriers to remaining on PrEP include substance use, mental health conditions, housing loss, and difficulty accessing PrEP because of the time and costs of clinic visits. Low self-perceived risk, younger age, and cannabis use also predicted discontinuation.18

Expanding HIV pre-exposure prophylaxis (PrEP) use is key to goals for lowering new HIV infections in the U.S. by 90% between 2022 and 2030. Unfortunately, youth aged 16-24 have the lowest PrEP use of any age group and the highest HIV incidence rates.
To examine the relationship between HIV seroconversion and PrEP uptake, adherence, and continuity, we used survival analysis and multivariable logistic regression on data of 895 youth at-risk for HIV infection enrolled in Adolescent Trials Network for HIV Medicine protocol 149 in Los Angeles and New Orleans, assessed at 4-month intervals over 24 months.

The sample was diverse in race/ethnicity (40% Black, 28% Latine, 20% White). Most participants (79%) were cis-gender gay/bisexual male but also included 7% transgender female and 14% trans masculine and nonbinary youth. Self-reported weekly PrEP adherence was high (98%). Twenty-seven participants acquired HIV during the study. HIV incidence among PrEP users (3.12 per 100 person year [PY]) was higher than those who never used PrEP (2.53/100 PY). The seroconversion incidence was highest among PrEP users with discontinuous use (3.36/100 PY). If oral PrEP users were adherent using 2-monthly long-acting injectables, our estimate suggests 2.06 infections per 100 PY could be averted.
Discontinuous use of PrEP may increase risk of HIV acquisition among youth at higher risk for HIV infection and indications for PrEP. Thus, to realize the promise of PrEP in reducing new HIV infections, reducing clinical burdens for PrEP continuation are warranted.

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