Cabotegravir (CAB), an HIV INSTI and rilpivirine (RPV), an HIV NNRTI are both 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 the safety and efficacy of 2-drug IM ART, relative to 3-drug oral ART (CAB + ABC/3TC) when used to maintain viral suppression in HIV-1 infected adults.
Phase 2b, multicentre, parallel group, open-label study in ART-naïve HIV infected adults. Enrolled patients that had a plasma HIV-1 RNA <50 c/mL during the 20-week Induction Period (IP) with 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 remained on oral CAB + ABC/3TC (PO) in the Maintenance Period (MP). The primary endpoints evaluated antiviral activity by FDA snapshot algorithm, protocol defined virologic failure, and safety at a pre-specified 32 wks in MP (ITT Maintenance Exposed (ME)).
309 pts were enrolled and treated (ITT-E): 91% male, 20% non-white, and 19%>100,000 c/mL HIV-1 RNA. After 20 wks of IP, 91% of pts achieved HIV-1 RNA <50 c/mL by snapshot and 286 pts were randomized to maintenance therapy. In the MP, 95% (Q8W) and 94% (Q4W) of pts maintained HIV-1 RNA <50 c/mL at W32 compared to 91% on PO (ITT-ME). Two pts had consecutive HIV-1 RNA >200 c/ml during MP (PO [1 at W8]; Q8W [1 at W4]), both without NRTI, NNRTI, or INSTI resistance. The most common drug-related AE was injection site pain (92% on IM arms) with 99% of injection site reactions (ISRs) being mild (82%) or moderate (17%). ISRs lasted a median of 3 days, decreased in frequency following the first injection, and led to 2 pt (<1%) withdrawals. Most common non-ISR AEs during MP were nasopharyngitis (20%), diarrhea (12%) and headache (14%) on IM arms and nasopharyngitis (25%), headache (7%), and diarrhea (5%) on PO CAB. SAEs during MP occurred in 6% of IM pts and 5% PO pts, none drug related, with 1 unrelated death (seizure [Q4W]). Nine pts withdrew from MP due to AEs; Q8W (2%), Q4W (5%) and PO (2%). Treatment emergent lab abnormalities ≥ Grade 3 occurred in 16% of IM pts and 14% of PO pts during MP.
Q8W and Q4W CAB LA + RPV LA as 2-drug injectable maintenance therapy demonstrated comparable antiviral activity to daily oral CAB + ABC/3TC through 32 weeks in virologically suppressed pts. Injectable CAB LA + RPV LA were generally well tolerated. LATTE-2 results support continued development of this novel treatment regimen.