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.

© The Author(s) 2021. Published by Oxford University Press on behalf of Infectious Diseases Society of America.

Figures

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.