Indirect Treatment Comparison (ITC) of Cabotegravir Long Acting (CAB-LA) for Pre-Exposure Prophylaxis (PREP) Versus No Prep for HIV Prevention

OBJECTIVES: The efficacy of CAB-LA for PrEP vs oral TDF/FTC as PrEP has been demonstrated in two phase 3 randomized controlled trials (RCTs), HPTN 083 (men who have sex with men and transgender women) and HPTN 084 (cisgender women). The aim of this analysis was to perform an ITC of CAB-LA vs no PrEP via the common comparator of TDF/FTC.

METHODS: A systematic literature review to identify RCTs of oral/injectable PrEP reporting HIV acquisition and oral PrEP adherence, measured by detectable TDF/FTC plasma levels, was conducted (01-Nov-2023). Heterogeneity between trials in levels of adherence to TDF/FTC as PrEP was expected to confound ITC estimates; therefore, the ITC of CAB-LA vs no PrEP was conducted, including a meta-regression of adherence using a joint Bayesian model framework.

RESULTS: The analysis included 9 RCTs. The meta-regression showed a strong relationship between adherence and effectiveness (posterior predictive P value <0.01). There were no obvious deviations from this trend according to location or study population. The predicted effectiveness of TDF/FTC vs no PrEP was greater for HPTN 083 (74.64%) compared with HPTN 084 (46.03%), reflecting the higher level of adherence observed in HTPN 083 compared with HPTN 084. Based on the ITC, the predicted effectiveness of CAB-LA vs no PrEP was similar for HPTN 083 (91.10%) and HPTN 084 (92.52%).

CONCLUSIONS: Similar estimates of effectiveness for CAB-LA vs no PrEP were seen in the HPTN 083 and 084 studies, indicating a high level of efficacy despite the differences in the population, setting, underlying rate of HIV acquisition, and adherence to TDF/FTC. This would support the generalizability of the results of the HPTN 083 and 084 trials of CAB-LA to other populations and geographies not studied. The variation in adherence to TDF/FTC appears to explain to a large degree the heterogeneity observed in results from PrEP studies.