Last week, Gilead Sciences, Inc. announced that the U.S. Food and Drug Administration (FDA) has approved Yeztugo (lenacapavir), the company’s injectable HIV-1 capsid inhibitor, for use as pre-exposure prophylaxis (PrEP). Yeztugo is not labeled a “vaccine” but is a pharmaceutical product intended to reduce the risk of acquiring human immunodeficiency virus (HIV) via sexual activity engaged in by adults and adolescents who weigh at least approximately 77 pounds (35 kilograms) and are at high risk for HIV infection.
Yeztugo is the first and only PrEP option in the United States that is administered twice a year. The FDA licensed Yeztugo under an accelerated “Priority Review,1 granting Yeztugo a “Breakthrough Therapy Designation” in October 2024 to help speed up the development and review of the drug based on its potential to offer significant improvement over existing treatments
Other FDA Approved Options for HIV Prevention
Gilead Sciences also manufactures a daily oral PrEP medications under the brand names Truvada and Descovy. Truvada was originally approved by the FDA in 2004, and Descovy received FDA approval in 2016.2 ViiV Healthcare manufactures another injectable PrEP medication called Apretude that was approved by the FDA in 2021. Apretude is taken every two months, following two initial doses given one month apart.3
Although lenacapavir is sometimes compared to a vaccine for HIV, it is not labeled a vaccine. Megan Ranney, MD, MPH, dean of the Yale School of Public Health in New Haven, Connecticut said, “This drug is extraordinary—the closest thing to a vaccine that we have.4
Carlos del Rio, MD, Professor of Medicine in the Division of Infectious Diseases at Emory University School of Medicine and Co-Director at the Emory Center for AIDS Research in Atlanta, Georgia added:
A twice-yearly injection could greatly address key barriers like adherence and stigma, which individuals on more frequent PrEP dosing regimens, especially daily oral PrEP, can face. We also know that, in research, many people who need or want PrEP preferred less frequent dosing.5
Trials Highlight High Efficacy of Yeztugo in Preventing HIV Infection
The FDA approved Yeztugo based on results from two major clinical trials, PURPOSE 1 and PURPOSE 2, conducted by Gilead Sciences. In the PURPOSE 1 trial, which included women in sub-Saharan Africa, none of the 2,134 participants who received the Yeztugo injection every six months contracted HIV. The shot showed strong efficacy and performed better than the daily oral pill Truvada.
In the PURPOSE 2 trial, which included men of different sexual orientations from various regions, only two people who received Yeztugo became infected with HIV, suggesting that 99.9 percent of participants in the Yeztugo group remained HIV free. The injection again proved more effective than daily Truvada. In both studies, Yeztugo demonstrated stronger efficacy than expected based on typical HIV rates in the communities studied.6
Important Safety Guidelines and Risks Associated with Yeztugo
The prescribing information on the FDA’s website requires individuals to be tested for HIV before starting Yeztugo and before each subsequent injection. This precaution is necessary because using Yeztugo in someone with undiagnosed HIV infection can lead to the development of drug-resistant strains of the HIV virus.
Yeztugo is not approved for use in people who are infected with HIV or whose HIV status is unknown. If a person contracts HIV while receiving Yeztugo, they must switch immediately to a full HIV treatment regimen. The medication must be injected under the skin to avoid serious injection site reactions such as ulcers or tissue damage.7
Common side effects of Yeztugo reported in clinical trials include injection site reactions, headaches, and nausea. Yeztugo can interact with certain medications that affect liver enzymes, specifically CYP3A, which play a role in breaking down drugs in the body. Some medications may lower Yeztugo levels, reducing its effectiveness, while others can increase levels of drugs taken alongside Yeztugo, potentially raising the risk of side effects. Those taking Yeztugo are told to inform their healthcare providers about all medications they use before using the product.
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Click here to view References:1 Gilead Sciences. Yeztugo® (Lenacapavir) Is Now the First and Only FDA-Approved HIV Prevention Option Offering 6 Months of Protection. June 18, 2025.
2 Alltucker K. FDA approves new twice-yearly HIV shot. What to know. USA Today June 18, 2025.
3 U.S. Food and Drug Administration. FDA Approves First Injectable Treatment for HIV Pre-Exposure Prevention. Dec. 20, 2021.
4 Phelan M. The Road to Lenacapavir, a Breakthrough HIV Treatment. Aaas.org May. 8, 2025.
5 Gilead Sciences. Yeztugo® (Lenacapavir) Is Now the First and Only FDA-Approved HIV Prevention Option Offering 6 Months of Protection. June 18, 2025.
6 Ibid.
7 U.S. Food and Drug Administration. YEZTUGO® (lenacapavir) tablets, for oral use and YEZTUGO® (lenacapavir) injection, for subcutaneous use. June 2025.
