Background: Long-acting (LA) injectable nanosuspensions of cabotegravir (CAB) and rilpivirine (RPV) are being developed. At the LATTE-2 W32 primary endpoint, response rates were statistically comparable between injectable every 4 weeks (Q4W), injectable every 8 weeks (Q8W) LA arms and daily oral CAB 30 mg + ABC/3TC (PO) dosing.
Methods: Phase 2b, multicenter, parallel group, open-label study in ART-naïve HIV infected adults. Patients with plasma HIV-1 RNA < 50 c/mL during the 20-week Induction Period on once daily oral CAB + ABC/3TC were randomized 2:2:1 to IM CAB LA + RPV LA Q4W, Q8W or PO in the Maintenance Period (MP). Evaluations included; antiviral activity < 50 c/mL (FDA snapshot analysis), protocol defined virologic failure (PDVF), and safety at the pre-specified W96 secondary 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 patients were randomized into the MP. At W96, 94% (Q8W), 87% (Q4W) and 84% (PO) remained suppressed (ITT-ME). Three ME patients had PDVF through W96; two Q8W (one at W4 and one at W48 with NNRTI/INI mutations) and one PO at W8. SAEs occurred in 10% (Q8W), 10% (Q4W) and 13% (PO) patients, none were drug related. Excluding injection site reactions (ISRs), 2% (Q8W) 4% (Q4W) and 2% (PO) reported drug-related AEs ≥ grade 3. Only two patients had ISRs leading to discontinuation through W96. Majority of ISRs were mild/moderate pain and discomfort with < 1% of ISRs classified severe. Emergent lab abnormalities ≥ Grade 3 occurred in 19% (Q8W), 29% (Q4W) and 21% (PO).
Conclusions: LA injectable 2-drug therapy given either Q8W or Q4W IM demonstrated high rates of virologic response and was well tolerated through 96 weeks. Difference in virologic success between Q8W and Q4W is primarily due to non-virologic reasons. Phase 3 studies are evaluating Q4W dosing.