Abstract
INTRODUCTION: The efficacy of long-acting injectable cabotegravir (hereafter referred to as cabotegravir) versus daily oral tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) for pre-exposure prophylaxis (PrEP) was demonstrated in two phase 3 randomized controlled trials (RCTs), HPTN 083 and HPTN 084. As these trials did not have a no-PrEP group, this analysis aimed to perform an indirect treatment comparison (ITC) of cabotegravir versus no PrEP via the common comparator of oral TDF/FTC. METHODS: A systematic literature review identifying trials of oral or both oral and injectable PrEP reporting HIV acquisition and oral PrEP adherence, measured by detectable TDF/FTC plasma levels, was conducted (November 1, 2023). Heterogeneity in oral TDF/FTC adherence level between trials was expected to confound ITC estimates; therefore, a meta-regression of adherence and resulting oral PrEP effectiveness, or reduction in HIV acquisition, was incorporated into an ITC using a joint Bayesian model framework. RESULTS: The analysis included ten RCTs. The meta-regression showed a strong relationship between oral TDF/FTC adherence and effectiveness. The predicted effectiveness of oral TDF/FTC versus no PrEP was greater for HPTN 083 (77%) compared with HPTN 084 (47%), reflecting the higher level of adherence observed in HTPN 083 (86%) compared with HPTN 084 (56%). Based on the ITC, the predicted effectiveness of cabotegravir versus no PrEP was similar for both populations investigated in HPTN 083 (92%) and HPTN 084 (93%). CONCLUSIONS: The ITC of cabotegravir versus no PrEP predicted similar estimates of cabotegravir effectiveness in the HPTN 083 and 084 trials, suggesting a very high level of efficacy despite differences in population, setting, underlying rate of HIV acquisition, and oral TDF/FTC adherence. These estimates support the generalizability of the cabotegravir results from both HPTN trials to other populations and regions than those in which these trials were conducted. Graphical abstract available for this article.