Indirect Treatment Comparison of the Efficacy of Long-Acting Injectable Cabotegravir Compared With Lenacapavir for HIV Pre-exposure Prophylaxis

INTRODUCTION: Long-acting injectable cabotegravir (hereafter referred to as cabotegravir) is the first long-acting injectable approved for pre-exposure prophylaxis (PrEP) based on the HPTN 083 and 084 trials. Long-acting injectable lenacapavir (hereafter referred to as lenacapavir) was approved for PrEP based on the PURPOSE 1 and 2 trials. In the absence of a head-to-head trial, we conducted an indirect treatment comparison (ITC) to assess efficacy of lenacapavir versus cabotegravir in reducing the risk of HIV acquisition. METHODS: A systematic literature review identified all relevant trials. Efficacy inputs for this ITC were derived from re-adjudicated data from the injection phase of the HPTN trials or published data from the PURPOSE trials. The ITC was performed using 2 network approaches: (1) using no PrEP and (2) using daily oral tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) as common comparators, with adjustments accounting for differing levels of adherence to TDF/FTC across trials. Sensitivity analyses were also performed using data from both the oral lead-in and injection phases of the HPTN trials. RESULTS: Both network approaches estimated high and comparable efficacy of cabotegravir and lenacapavir. Using no PrEP (network approach 1), the base case estimated hazard ratio (95% CrI) of lenacapavir versus cabotegravir was 1.04 (0.19, 5.69) in men who have sex with men and transgender women and 0.00 (0.00, 3.21) in cisgender women. Predicted efficacy (95% CrI) rates of cabotegravir versus no PrEP were high in men who have sex with men and transgender women 96% (90%, 98%)] and cisgender women [98% (89%, 100%)] in the HPTN trials, which were comparable to the PURPOSE trials [men and gender-diverse people, 96% (82%, 99%); cisgender women, 100%(96%,100%)]. Sensitivity analyses confirmed these findings. CONCLUSION: Based on this ITC, cabotegravir and lenacapavir offer similar and high efficacy in preventing HIV acquisitions compared with no PrEP or TDF/FTC. Graphical abstract and video abstract available for this article.