Efficacy, Safety, and Durability of Long-Acting Cabotegravir and Rilpivirine in Adults With Human Immunodeficiency Virus Type 1 Infection: 5-Year Results From the LATTE-2 Study

Abstract

Background In the LATTE-2 phase IIb study, long-acting (LA) injectable cabotegravir + rilpivirine dosed every 8 weeks (Q8W) or 4 weeks (Q4W) demonstrated comparable efficacy with daily oral antiretroviral therapy (ART) through 96 weeks in ART-naive adults with HIV-1. Here we report efficacy, tolerability, and safety of cabotegravir + rilpivirine LA over ~5 years. Methods After 20 weeks of oral cabotegravir + abacavir/lamivudine, participants were randomized to cabotegravir + rilpivirine LA Q8W or Q4W or continue oral ART through the 96-week maintenance period. In the extension period through Week 256, participants continued their current LA regimen (randomized Q8W/Q4W groups) or switched from oral ART to Q8W or Q4W LA therapy (extension-switch groups). Endpoints assessed included proportion of participants with HIV-1 RNA <50 copies/mL (Snapshot algorithm) and adverse events (AEs). Results At Week 256, 186 (81%) of 230 participants in randomized Q8W/Q4W groups and 41 (93%) of 44 participants in extension-switch groups had HIV-1 RNA <50 copies/mL. No protocol-defined virologic failures occurred after Week 48. Injection-site reactions infrequently resulted in discontinuation (4 [2%] and 1 [2%] participants in randomized Q8W/Q4W and extension-switch groups, respectively). Three participants in randomized Q8W/Q4W groups experienced drug-related serious AEs, including 1 fatal serious AE (Q4W group); none occurred in extension-switch groups. Of 25 participants with AEs leading to withdrawal, 20 were in the randomized Q4W group; no AE leading to withdrawal occurred in >1 participant. Conclusions Cabotegravir + rilpivirine LA exhibited long-term efficacy and tolerability, demonstrating its durability as maintenance therapy for HIV-1 infection (ClinicalTrials.gov, NCT02120352).

A new paradigm for antiretroviral delivery: long-acting cabotegravir and rilpivirine for the treatment and prevention of HIV

“…Phase 2b studies of long-acting CAB and RPV, LATTE [9] and LATTE-2 [10], were described in a previous review [11]. Since then, the 5-year results of the LATTE-2 study were published, demonstrating reassuring long-term durability of the injectable regimen in the phase 2b trial [12 ▪ ]. These initial studies provided proof of concept that the two-drug oral regimen of CAB and RPV effectively maintained viral suppression of HIV-1 and informed the recently completed phase 3 clinical trials of this long-acting ART strategy.…”

Long-acting injectable antiretroviral therapy: will it change the future of HIV treatment?

“…In the extension period through week 256, the oral ART group was offered to switch to either the Q4W group or the Q8W group at week 96. 5 After 256 weeks, 81% of patients in the randomized Q8W/Q4W groups and 93% of patients in the group switch from oral to Q8W/Q4W groups had HIV RNA levels <50 copies/mL. Twenty-five patients had adverse effects leading to withdrawal and 20 of these patients were in the Q4W groups.…”

Development and Evaluation of Dissolving Microarray Patches for Co-administered and Repeated Intradermal Delivery of Long-acting Rilpivirine and Cabotegravir Nanosuspensions for Paediatric HIV Antiretroviral Therapy

“…Phase 2: Evaluation of Plasma Pharmacokinetics of RPV and CAB Following Multiple Repeated MAP Applications The second (Phase 2) in vivo study evaluated the ability of MAPs to reproducibly maintain therapeutic plasma levels following multiple repeated MAP applications over a period of 42 d and further examined the effect of an IM loading dose of ARV LA NS. This experiment was set up to loosely correlate to the doses used in IM LA ARV clinical trials and to that of the newly marketed Cabenuva LA injection [34].…”