Indirect Comparison Shows Apretude and Yeztugo Have Similar Efficacy | IAS 2025

Apretude (cabotegravir) and the recently approved Yeztugo (lenacapavir) have similar efficacy in reducing HIV acquisition risk compared with no pre-exposure prophylaxis (PrEP), finds an indirect comparison presented as a poster at the International AIDS Society meeting in Kigali, Rwanda.

The analysis was sponsored by ViiV Healthcare, the manufacturer of Apretude, which is a long-acting cabotegravir indicated to reduce the risk of getting HIV-1 in adults and adolescents. It is given by injection by a healthcare professional every two months, after two initial injections in the first month. When it was approved in December 2021, it was the first long-acting injectable PrEP medication.

Gilead Sciences’ lenacapavir (now with the brand name Yeztugo) was approved by the FDA on June 18 as both an oral tablet and as a subcutaneous injection as a twice-yearly option for PrEP.

Laure Dupont-Benjamin, Ph.D.

Researchers in this analysis — led by Laure Dupont-Benjamin, Ph.D., director, of global health outcomes at ViiV Healthcare — conducted a systematic literature review to identify all relevant trials for this comparison. They assessed efficacy data for the two therapies compared with no use of PrEP.

Researchers specifically reviewed the data from the HPTN 083 and 084 trials, which led to Apretude’s approval, and the PURPOSE 1 and 2 trials, which were conducted with Yeztugo.

The predicted efficacy of Apretude compared with no PrEP in reducing HIV acquisition risk was 96% in men who have sex with men (MSM) and transgender women and 98% in cisgender women. In the PURPOSE trials, the predicted efficacy of Yeztugo compared with no PrEP was 95% in men/gender-diverse people and 100% in cisgender women. Researchers of the indirect comparison study also found similar efficacy for both products when compared with oral PrEP.

“Additional factors associated with these regimens, including the potential for drug-drug interactions and adverse events (e.g., injection site reactions), real-world usage, seroconversion resistance, and patient preference, will be important to comprehensively assess clinical value and assist with decision-making,” researchers noted.

Approximately 1.2 million people in the United States have HIV, according to the 2022 Centers for Disease Control and Prevention (CDC). There is currently no cure for HIV or AIDS.

Increasing access to PrEP is one of the key initiatives of Ending the HIV Epidemic in the U.S., which aims to reduce the number of new HIV infections by 90% by 2030. However, only 36% of people who would benefit from PrEP were accessing it, a CDC estimate shows.