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Background Previously reported post hoc multivariable analyses exploring predictors of confirmed virologic failure (CVF) with cabotegravir + rilpivirine long-acting (CAB + RPV LA) were expanded to include data beyond week 48, additional covariates, and additional participants. Methods Pooled data from 1651 participants were used to explore dosing regimen (every 4 or every 8 weeks), demographic, viral, and pharmacokinetic covariates as potential predictors of CVF. Prior dosing regimen experience was accounted for using 2 populations. Two models were conducted in each population—baseline factor analyses exploring factors known at baseline and multivariable analyses exploring baseline factors plus postbaseline model-predicted CAB/RPV trough concentrations (4 and 44 weeks postinjection). Retained factors were evaluated to understand their contribution to CVF (alone or in combination). Results Overall, 1.4% (n = 23/1651) of participants had CVF through 152 weeks. The presence of RPV resistance-associated mutations, human immunodeficiency virus-1 subtype A6/A1, and body mass index ≥30 kg/m2 were associated with an increased risk of CVF (P <.05 adjusted incidence rate ratio), with participants with ≥2 of these baseline factors having a higher risk of CVF. Lower model-predicted CAB/RPV troughs were additional factors retained for multivariable analyses. Conclusions The presence of ≥2 baseline factors (RPV resistance-associated mutations, A6/A1 subtype, and/or body mass index ≥30 kg/m2) was associated with increased CVF risk, consistent with prior analyses. Inclusion of initial model-predicted CAB/RPV trough concentrations (≤first quartile) did not improve the prediction of CVF beyond the presence of a combination of ≥2 baseline factors, reinforcing the clinical utility of the baseline factors in the appropriate use of CAB + RPV LA. [ABSTRACT FROM AUTHOR]

Background Cabotegravir (CAB) and rilpivirine (RPV) are under development as a novel long-acting (LA) regimen for maintenance of HIV virologic suppression. Pooled Week 48 data from pivotal Phase 3 trials demonstrated noninferiority of CAB LA + RPV LA vs. current antiretroviral regimen (CAR) on the primary endpoint, proportion of subjects with HIV-1 RNA ≥50 c/mL (1.9% and 1.7%, respectively). Adherence to dosing visits, use of oral dosing (bridging) to cover planned missed injections and injection tolerability were examined for subjects in the ATLAS and FLAIR studies. Methods Virologically suppressed subjects (HIV-1 RNA < 50 c/mL) were randomized to switch to CAB LA + RPV LA or to continue CAR. On-time injections occurred Q4 weeks within a + 7-day dosing window of the projected dosing date. Adherence to LA therapy was calculated as the number of on-time injection visits divided by the number of expected dosing visits through Week 48. Injection visits outside the pre-specified window and missed injection visits with/without the use of oral dosing were quantified. Injection tolerability was assessed via adverse event reporting. Results A total of 14,682 injections of CAB and RPV were administered to 581 subjects during 6,920 injection visits. 98% of injection visits took place within the allowed ±7-day dosing window with 3,194 (46%) on the projected dosing date. Forty-six (<1%) injection visits were early and 106 (2%) were late. Oral bridging was used in 16 subjects overall; 8 planned missed injection visits were successfully covered, with no change to virologic suppression status. No subject with HIV-1 RNA ≥ 50 c/mL at Week 48 had missed/late injection visits. 25% (3,663/14,682) of injections were associated with local injection site reactions (ISRs). The most common ISR was pain (3,087/3,663 = 84%). Most ISRs were grade 1–2 (99%), short duration (median 3 days), with few associated discontinuations (<1%). Conclusion Subjects receiving CAB LA + RPV LA demonstrated high rates of adherence to injection visits through week 48, with 98% of injections occurring within the ±7-day dosing window. Oral bridging with CAB and RPV was an effective strategy for maintaining viral load suppression to cover missed injection visits. Injections were well-tolerated with few associated discontinuations. Disclosures All Authors: No reported Disclosures. [ABSTRACT FROM AUTHOR]