Purpose of review

To discuss progress and challenges in the development of antiretroviral regimens that combine broadly neutralizing antibodies (bNAbs) and long-acting (LA) small-molecule antiretroviral drugs (ARVs).

Recent findings

Data are extremely limited, with results from only a single phase 1a clinical trial reported to date. That study, a combination of lenacapavir plus the bNAbs teropavimab and zinlirvimab, maintained viral suppression over 26 weeks in 18 of 20 participants. A second pilot study, ACTG A5357, which tests the safety and virologic efficacy of the combination of LA injectable cabotegravir with the bNAb VRC07-523LS is fully enrolled; results are expected in the second half of 2023.

Summary

The development of regimens that combine bNAbs and LA ARVs has been challenging. Both agents need similar half-lives in order to harmonize dosing schedules. In addition, the need to perform bNAb susceptibility testing to assure activity of the bNAb in order to protect against the risk of developing resistance to the LA ARV has slowed enrollment into trials and poses substantial logistical challenges to widespread adoption of these combinations should they prove safe and effective. Improvements in manufacture that reduce the cost of goods and advances in delivery systems are needed to ensure equitable access to these regimens.