Cabotegravir (CAB) and lenacapavir (LEN) both offer high and similar efficacy in reducing the risk for acquiring HIV compared with no PrEP.
Cabotegravir is the first long-acting injectable (LAI) medication approved for pre-exposure prophylaxis (PrEP) to reduce the risk for sexually acquired HIV, based on the HPTN 083 and 084 trials. Also, the recent PURPOSE 1 and 2 trials showed that the investigational LAI PrEP option lenacapavir is efficacious across diverse populations.
In the absence of a head-to-head trial, the investigators conducted an indirect treatment comparison to assess the efficacy and relative clinical value of CAB and LEN.
They conducted a systematic literature review to identify all trials that were relevant to this comparison. Efficacy inputs for the indirect treatment comparison were obtained from published efficacy data from the PURPOSE trials, and derived from published HPTN trial data. CAB and LEN were compared using no PrEP as a common comparator, sourced from the background HIV incidence arm of the PURPOSE trials and the no PrEP arm leveraging previous indirect treatment comparison methods comparing CAB with no PrEP.
The researchers found that the predicted efficacy of CAB versus no PrEP in reducing HIV acquisition risk was high in men who have sex with men (MSM), transgender women (96%), and cisgender women (98%). These results were comparable to the results found in the PURPOSE trials (men and gender-diverse people, 96%; cisgender women, 100%). They estimated the hazard ratio of LEN versus CAB to be 1.04 in MSM and transgender women and 0.00 in cisgender women.
The authors concluded that their results were generally consistent when using oral PrEP as a common comparator when adjusting for differences in adherence. Additional factors associated with these regimens, including the potential for drug-drug interactions and adverse events such as injection site reactions, real-world usage, seroconversion resistance, and patient preference, will be important to consider when assessing clinical value and decision-making.
Reference
IAS 2025. Hawkins Poster exhibition EPLB005.
