Intramuscular cabotegravir (CAB) and rilpivirine (RPV) long-acting (LA) has been evaluated in two Phase 3 studies, ATLAS (NCT02951052) and FLAIR (NCT02938520), which demonstrated noninferiority of CAB+RPV LA dosed every 4 weeks (Q4W) to daily oral standard of care (SoC), and the Phase 3b study ATLAS-2M (NCT03299049), demonstrating noninferiority of CAB+RPV LA dosed every 8 weeks (Q8W) to Q4W. Tenofovir disoproxil fumarate (TDF) is associated with renal/bone toxicities and improvements in renal/bone markers have been reported after cessation of TDF regimens. We present data from Week (W) 48 of ATLAS and ATLAS-2M examining changes in renal markers and bone turnover markers.
Data from ATLAS and ATLAS-2M were stratified by baseline (BL) TDF use. Efficacy and safety outcomes including changes in renal markers (urine protein-to-creatinine ratio [UPCR] and urine albumin-to-creatinine ratio [UACR]) and bone turnover markers (bone-specific alkaline phosphatase, osteocalcin, procollagen 1 N-terminal propeptide [P1NP], type 1 collagen C telopeptides [CTx]) were assessed. For ATLAS-2M participants who transitioned from LA therapy in ATLAS, only data from ATLAS were included. W48 efficacy endpoints were proportion with plasma HIV-1 RNA ?50 c/mL and <50 c/mL. Changes in bone markers were only available for ATLAS participants.
In total, 1270 participants were included in the analysis; 665 were receiving TDF at BL and 605 were receiving non-TDF regimens. BL characteristics and outcomes at W48 are presented in Table 1. Within strata, the proportions with HIV-1 RNA ?50 c/mL and <50 c/mL were comparable across arms. Participants switching from TDF regimens to CAB+RPV LA experienced reductions in UPCR, compared with small increases observed among those switching from or continuing non-TDF regimens. Participants continuing TDF regimens had greater increases in UPCR (mean % UPCR change from BL: TDF: Q8W, –13.2; Q4W, –17.5; SoC, 79.3; non-TDF: Q8W, 10.0; Q4W, 5.4; SoC, 12.0). In ATLAS, there were greater reductions in bone turnover markers in participants switching from TDF to CAB+RPV LA compared with other groups (mean change from BL in P1NP and CTx [?g/L]: TDF: Q4W: –23.7, –0.14; SoC: –12.4, 0.01; non-TDF: Q4W: –8.1, 0.06; SoC: –6.4, 0.07).
Participants switching from TDF to CAB+RPV LA experienced improvements in renal markers and bone turnover markers. These results support the therapeutic potential of CAB+RPV LA.
