JAMA Insights: Preexposure Prophylaxis (PrEP) for HIV PDF

Clinical Review & Education JAMA Insights Preexposure Prophylaxis (PrEP) for HIV Matthew A. Spinelli, MD; Kenneth Ngure, MPH, PhD; Monica Gandhi, MD, MPH Preexposure prophylaxis (PrEP) involves use of antiviral medica- venti...

Clinical Review & Education JAMA Insights Preexposure Prophylaxis (PrEP) for HIV Matthew A. Spinelli, MD; Kenneth Ngure, MPH, PhD; Monica Gandhi, MD, MPH Preexposure prophylaxis (PrEP) involves use of antiviral medica- vention efficacy increased to 92% (95% CI, 40%-99%) among those tion for HIV prevention in HIV-negative adults or adolescents at with detectable plasma tenofovir levels (eTable in the Supplement).2 risk for HIV through sex or injection drug use. The United Nations In a pooled analysis from 11 studies (2995 cisgender women with ad- Programme on HIV/AIDS (UNAIDS) recently set a goal for 95% of herence data), TDF/FTC was efficacious for preventing HIV infec- people at risk of HIV (approximately 10 million people worldwide) tion among those who took 4 to 6 doses a week (incidence rate, 0.13 to have access to and use PrEP in 2025, although only 3.5 million [95% CI, 0.02-0.92] infections per 100 person-years).3 In a random- individuals at risk of HIV were receiving PrEP as of 2023. The UNAIDS ized trial of 2413 people who inject drugs in Thailand, those as- 2024 global AIDS update reported no decrease in HIV incidence since signed to receive TDF had 0.35 infections per 100 person-years com- 2021, with an estimated 1.3 million new infections reported globally pared with 0.68 infections per 100 person-years for those assigned in 2023. to receive placebo (P =.01).4 The US Preventive Services Task Force strongly recommends A randomized trial among 5857 MSM and transgender women that clinicians prescribe PrEP to prevent HIV for those at risk. reported that TAF/FTC was noninferior to TDF/FTC in preventing HIV, Several therapies to prevent HIV have been approved in the past 12 with an incidence of 0.16 HIV infections per 100 person-years vs 0.34 years, beginning with daily oral per 100 person-years (rate ratio, 0.47 [95% CI, 0.19-1.15]).5 In a 2024 tenofovir disoproxil fumarate/ randomized clinical trial including 5338 adolescent girls and young Multimedia emtricitabine (TDF/FTC) in 2012. women in South Africa and Uganda, there was no difference in HIV Other currently available PrEP incidence between those receiving TAF/FTC vs TDF/FTC (inci- agents include (1) daily tenofo- dence rate ratio, 1.20 [95% CI, 0.67-2.14]); however, there was gen- Related article and JAMA vir alafenamide (TAF)/FTC (ap- erally low adherence to both TAF/FTC and TDF/FTC, as confirmed Patient Page proved by the US Food and Drug by drug levels.1 Given the lower risk of kidney and bone toxicity com- Administration [FDA] in 2019), pared with TDF/FTC, TAF/FTC may be preferred for individuals at Supplemental content (2) monthly vaginal dapivirine higher risk of kidney injury or osteoporosis. ring (approved by the European The monthly dapivirine vaginal ring is the first effective micro- CME at jamacmelookup.com Medicines Agency in 2020), and bicide for HIV prevention. In a randomized trial of 2629 women aged (3) intramuscular long-acting in- 18 to 45 years in sub-Saharan Africa, those assigned to receive dapi- jectable cabotegravir administered bimonthly (approved by the FDA virine had 3.3 HIV infections per 100 person-years vs 4.5 infections in 2021). Long-acting lenacapavir was shown to be highly effective per 100 person-years among those assigned to receive placebo in preventing HIV in studies performed in 2024,1 although FDA ap- (P =.046).6 The dapivirine ring was added to the World Health proval is pending. None of the PrEP agents investigated to date in- Organization’s HIV prevention guidelines in 2021 and has been ap- terfere with contraception. proved by the European Medicines Agency, but has not yet re- ceived FDA approval. PrEP Indications Cabotegravir, a long-acting antiretroviral administered intra- Individuals at risk of HIV include those with a sexually transmitted muscularly every 8 weeks, demonstrated superiority for preven- infection in the past 6 months, those who have condomless sexual tion of HIV infection compared with TDF/FTC among 4566 MSM intercourse with 1 or more partners who have an unknown HIV sta- and transgender women (0.41% vs 1.2% infected; hazard ratio, tus, and/or those who have a sexual partner living with HIV with an 0.34 [95% CI, 0.18-0.62])7; among 3224 cisgender women, there unsuppressed viral load (not consistently