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 Long-Acting Antiretroviral Treatment Enabling Trial 2 (LATTE-2) phase 2b study, long-acting (LA) injectable cabotegravir + rilpivirine dosed every 8 weeks (Q8W) or every 4 weeks (Q4W) demonstrated comparable efficacy with daily oral antiretroviral therapy (ART) through 96 weeks in ART-naive adults with human immunodeficiency virus type 1 (HIV-1). Here we report efficacy, tolerability, and safety of cabotegravir + rilpivirine LA over approximately 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 of 230 (81%) participants in randomized Q8W/Q4W groups and 41 of 44 (93%) participants in extension-switch groups had HIV-1 RNA <50 copies/mL. No protocol-defined virologic failures occurred after week 48. Injection wsite 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.Clinical Trials Registration. NCT02120352.

Keywords: cabotegravir; integrase strand transfer inhibitor; long-acting; nonnucleoside reverse transcriptase inhibitor; rilpivirine.

Figure 1.

Study design (A) and participant disposition through week 256 (B). ^aOral rilpivirine 25 mg once daily was added from week –4 to day 1.  ^bParticipants received a loading dose of cabotegravir 800 mg (two 2-mL injections) + rilpivirine 900 mg (one 3-mL injection) LA on day 1 and a second loading dose of cabotegravir 600 mg (one 3-mL injection) LA at week 4 before starting every-8-week dosing at week 8.  ^cParticipants received a loading dose of cabotegravir 800 mg (two 2-mL injections) + rilpivirine 600 mg (one 2-mL injection) LA on day 1 and started every-4-week dosing at week 4.  ^dOptimized loading doses were cabotegravir 600 mg (one 3-mL injection) + rilpivirine 900 mg (one 3-mL injection) LA. ^eReasons for discontinuation have been previously reported [9]. Abbreviations: AE, adverse event; ART, antiretroviral therapy; c/mL, copies per milliliter; HIV-1, human immunodeficiency virus type 1; IM, intramuscular; LA, long acting; NNRTI, nonnucleoside reverse transcriptase inhibitor; Q4W, every 4 weeks; Q8W, every 8 weeks; QD, once daily; RAM, resistance-associated mutation.

Figure 2.

Virologic outcomes at week 256 by United States Food and Drug Administration Snapshot algorithm. ^aParticipants in extension-switch groups switched to cabotegravir + rilpivirine long-acting at week 100. Abbreviations: c/mL, copies per milliliter; IM, intramuscular; Q4W, every 4 weeks; Q8W, every 8 weeks.