The 2023 updated report by the U.S. Preventive Services Task Force found that oral tenofovir alafenamide-emtricitabine or injectable cabotegravir were slightly superior to older tenofovir disoproxil fumarate-emtricitabine pre-exposure prophylaxis for HIV prevention.
In 2019, the U.S. Preventive Services Task Force (USPSTF) report confirmed that oral pre-exposure prophylaxis (PrEP) using tenofovir disoproxil fumarate (TDF) alone or in combination with emtricitabine (TDF/FTC) was useful for HIV prevention in high-risk individuals. However, since then, some new options have emerged.
One of the options is tenofovir alafenamide fumarate (TAF), which achieves higher and more sustained intracellular levels and lower serum levels compared to TDF. Additionally, a new drug, cabotegravir, has been introduced, with the benefits of a single injection every 2 months, resulting in higher adherence. Thus, a new and updated systematic review by the USPSTF was published in JAMA in August 2023, answering some key questions and providing updated information.
Benefits of PrEP for HIV Prevention and Quality of Life
The updated report, which included 11 new studies comprising 6 RCTs and 5 diagnostic accuracy studies, found significant risk reduction. Unlike the previous study, this study looked into various population subgroups. It found PrEP effective for multiple population groups. There was no difference in PrEP effectiveness between men and women. PrEP was more effective for men who have sex with men compared to transgender women; however, the difference did not reach statistical significance. PrEP also showed similar effectiveness in Hispanics and non-Hispanics. Higher adherence was associated with better outcomes.
TAF-FTC or Injectable Cabotegravir vs. TDF-FTC
New studies show that TAF-FTC was superior to TDF-FTC in preventing new HIV infections, though the difference was statistically insignificant. However, cabotegravir was superior to oral PrEP regimens due to a much higher adherence rate of 93%, resulting in reduced risk of HIV infection.
Instruments Used for HIV Risk Assessment
No specific self-administered questionnaire was used, and risk assessment was based solely on data from electronic health records and patient interviews. Two studies used computer algorithms for risk assessment in general populations of HIV-uninfected individuals.
PrEP Harm vs. Placebo
The updated systemic review found oral PrEP quite safe, with serious adverse events almost comparable to placebo. There was a small and insignificant withdrawal risk due to adverse events. Serious kidney or gastrointestinal side effects were rare. There was no significant difference between oral PrEP and placebo in syphilis, gonorrhea, chlamydia, and other bacterial sexually transmitted infections.
Harms of Newer Regimens (TAF-FTC or Injectable Cabotegravir) vs. TDF-FTC
There was no difference between TAF-FTC and TDF-FTC in serious adverse events, including kidney events. However, TAF-FTC was less likely to negatively affect bone mineral density and LDL cholesterol levels than TDF-FTC. Severe adverse events with cabotegravir injection were similar to those with TDF-FTC, but cabotegravir was associated with increased weight gain.
The Bottom Line
The updated report demonstrated the superiority of TAF-FTC and injectable cabotegravir to older PrEP regimes using TDF-FTC. The study did report some limitations, such as data heterogeneity and exclusion of non-English trials, though large trials were absent in non-English studies.
Source:
Chou, R., Spencer, H. C., Bougatsos, C., Blazina, I., Ahmed, A. Y., & Selph, S. (2023). Preexposure prophylaxis for the prevention of HIV. JAMA, 330(8), 746. https://doi.org/10.1001/jama.2023.9865
