A New Era in HIV Treatment: Phase 2 Study Shows Promise for Twice-Yearly Injections

For decades, people living with HIV have relied on daily oral medication to maintain viral suppression, but what if a twice-yearly injection could offer the same protection?

A new Phase 2 study, presented at the Conference on Retroviruses and Opportunistic Infections (CROI) 2025, suggests this may soon become a reality.

Researchers from Yale University and other institutions have been investigating a novel combination therapy involving lenacapavir (LEN), a long-acting HIV capsid inhibitor, and two broadly neutralizing antibodies (bNAbs), teropavimab (TAB) and zinlirvimab (ZAB). The study evaluates whether these six-monthly (Q6M) injections could effectively replace daily oral antiretroviral therapy (ART).

This research builds on previous results from the Phase 1b study, which were presented at CROI 2024 in Denver. That earlier trial demonstrated the LEN+TAB+ZAB combination successfully maintained virologic suppression for six months in 18 out of 20 participants. The current Phase 2 study expands on these findings with a larger participant group and a more rigorous assessment of safety and efficacy.

Why This Matters

Adherence to HIV medication remains one of the biggest challenges in long-term treatment. Missing doses can lead to drug resistance and loss of viral suppression. A long-acting injectable regimen could be a game-changer, particularly for individuals who struggle with daily pill regimens, due to stigma, lifestyle, or personal preference.

The Study

The trial enrolled 80 participants, all of whom had maintained undetectable viral loads for at least a year on standard oral ART. The participantswererandomlyassignedintotwogroups:

• 53 participants switched to the injectable regimen (LEN+TAB+ZAB) every six months.
• 27 participants continued their stable oral therapy.

The primary goal was to determine whether those on the injectable regimen maintained viral suppression at week 26, a key milestone for treatment efficacy.

Key Findings

• 96% of participants receiving the injectable combination maintained viral suppression, a rate comparable to those who remained on oral ART.
• Only one participant in the injectable group experienced viral rebound (HIV-1 RNA ≥50 copies/mL).
• No serious side effects or discontinuations due to adverse reactions were reported.
• The most common side effect in the injectable group was mild injection site reactions, such as pain or swelling—similar to other injectable HIV treatments.
• Importantly, no infusion-related reactions occurred with the antibodies TAB and ZAB.

A Step Toward the Future

The results support further exploration of this twice-yearly treatment, as a viable alternative to daily pills. If confirmed in larger trials, this could revolutionize HIV care, making treatment more convenient, discreet and accessible for millions of people worldwide.

The next phase of research will assess long-term efficacy and safety beyond the 26-week mark, with a full year of follow-up data expected soon.

For now, the findings provide hope for a new option in the fight against HIV—one that could offer greater freedom and flexibility for those living with the virus.