Background: Cabotegravir (CAB) and rilpivirine (RPV) are under development as long-acting (LA) injectable nanosuspensions. LATTE-2 was designed to select an intramuscular (IM) regimen of CAB LA + RPV LA and to evaluate safety and efficacy of 2-drug IM ART, relative to 3-drug oral ART (CAB + ABC/3TC) to maintain viral suppression of HIV-1.
Methods: Phase 2b, multicentre, parallel group, open-label study in ART-naïve HIV infected adults. Enrolled patients with plasma HIV-1 RNA < 50 c/mL during the 20-week Induction Period on daily oral CAB 30 mg + ABC/3TC were randomized 2:2:1 to IM CAB LA + RPV LA every 4 weeks (Q4W), every 8 weeks (Q8W), or oral CAB + ABC/3TC (PO) in the Maintenance Period (MP). Dosing regimens were evaluated according to antiviral activity, protocol defined virologic failure (PDVF), and safety at the pre-specified Week 48 endpoint in MP (ITT Maintenance Exposed (ME)).
Results: 309 patients were enrolled (ITT-Exposed): 91% male, 20% non-white, and 19%>100,000 c/mL HIV-1 RNA. 286 pts were randomized into the MP. At Week 48, 92% (Q8W), 91% (Q4W), and 89% (PO) remained suppressed (ITT-ME). More patients on Q8W (5%), relative to Q4W (< 1%) and PO (0%) had HIV-1 RNA >50 c/mL at Week 48; 5/6 Q8W patients subsequently achieved HIV-1 RNA < 50 c/mL. Three ME patients had PDVF during MP (PO [W8]; Q8W [W4, W48]); one with NNRTI/INI mutations (Q8W[W48]). Grade 1/2 injection site pain occurred commonly, median duration 3 days, < 1% ISR withdrawals. MP SAEs occurred in IM (7%) and PO (5%), none drug-related.

Week 48 Outcomes
[Week 48 Outcomes]

Conclusions: Both Q8W and Q4W IM dosing demonstrated good virologic response rates and were generally well tolerated through 48 weeks. Q4W dosing resulted in modestly lower rates of virologic non-response than Q8W. Q4W dosing was chosen for progression into phase 3 studies while Q8W and Q4W remain under evaluation within LATTE-2.