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Monthly injected cabotegravir/rilpivirine
noninferior to oral DTG at 48 weeks
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Conference on Retroviruses and Opportunistic Infections (CROI), March 4-7, 2019, Seattle
Mark Mascolini
Monthly injections of cabotegravir plus rilpivirine (CAB+RPV) maintained HIV control at the same high rate as a daily pill containing dolutegravir, abacavir, and lamivudine (DTG/ABC/3TC) through week 48 of the international FLAIR trial [1]. The international ATLAS trial comparing a switch to monthly CAB+RPV versus a continued effective integrase inhibitor, protease inhibitor, or nonnucleoside had a similar high 48-week virologic suppression rate in both study arms [2].
The investigational integrase inhibitor CAB comes in oral and intramuscular injected forms with half-lives of about 40 hours and 40 days. The nonnucleoside rilpivirine has about a 50-hour half-life in its oral formulation and a 90-day half-life in its injectable formulation. Injected every 4 to 8 weeks in the LATTE-2 trial, long-acting CAB+RPV maintained viral loads below 50 copies in most people for more than 3 years. FLAIR and ATLAS are phase 3 pivotal trials of CAB+RPV for maintenance of initial antiretroviral therapy (FLAIR) and as a switch regimen in people successfully treated with oral antiretrovirals (ATLAS).
FLAIR is a randomized open-label trial aiming to test the virologic noninferiority of injected CAB+RPV versus oral DTG/ABC/3TC [1]. The 629 previously untreated participants took single-tablet oral DTG/ABC/DTC for 20 weeks. Those who reached a confirmed viral load below 50 copies got randomized to continue this oral regimen or switch to oral CAB plus RPV for 4 weeks, then to CAB+RPV injected once monthly.
Median baseline age stood at 34 in both groups, 11% were 50 or older, and 22% were women. Twenty percent of participants in both groups had an initial viral load above 100,000 copies, and median baseline CD4 counts stood at 437 with CAB+RPV and 452 with DTG/ABC/3TC.
A week-48 snapshot analysis determined that 93.6% randomized to CAB+RPV and 93.3% randomized to the oral combination had a viral load below 50 copies. This result established the virologic noninferiority of CAB+RPV at week 48 (adjusted difference -0.4, confidence interval -2.8 to +2.1). At 48 weeks 6 people (2.1%) randomized to CAB+RPV and 7 (2.5%) randomized to DTG/ABC/3TC had a viral load at or above 50 copies. Four people (1.4%) stopped CAB+RPV and 3 (1.1%) stopped the oral combination for lack of efficacy.
Nine people quit the CAB+RPV arm because of an adverse event, compared with 4 stopping DTG/ABC/3TC for that reason (3% versus 1%). Researchers recorded 1 drug-related serious adverse event (knee monoarthritis) in the CAB+RPV group and none in the DTG arm. About 29% of CAB+RPV shots resulted in injection site reactions, which were usually mild and lasted for a median of 3 days. Two people dropped out of the study because of injection site reactions. Among 259 surveyed participants, 257 (99%) preferred injected CAB+RPV to previous oral therapy.
ATLAS enrolled people with viral suppression on a standard triple-drug regimen and randomized 308 to continue that regimen and 308 to switch to once-monthly injected CAB+RPV (after a 4-week lead-in with oral CAB+RPV) [2]. A week-48 snapshot analysis determined that 92.5% randomized to CAB+RPV and 95.5% randomized to continue their standard oral regimen had a viral load below 50 copies. That result confirmed the virologic noninferiority of switching to CAB+RPV (difference 0.6, confidence interval -1.2 to 2.5). Three people (1.0%) stopped CAB+RPV for lack of efficacy, compared with 2 (0.6%) who stopped their oral antiretrovirals for that reason.
Ten adverse events led to withdrawal in the CAB+RPV group versus 5 in the comparison arm (3% versus 2%). No drug-related serious adverse events arose. Injection site reactions caused 4 of the 10 adverse event withdrawals from the CAB+RPV arm.
References
1. Orkin C, Arasteh K, Hernandez-Mora MG, et al. Long-acting cabotegravir + rilpivirine for HIV maintenance: FLAIR week 48 results. Conference on Retroviruses and Opportunistic Infections (CROI). March 4-7, 2019. Seattle. Abstract 140LB.
2. Swindells S, Andrade-Villanueva JF, Richmond GJ, et al. Long-acting cabotegravir + rilpivirine as maintenance therapy: ATLAS week 48 results. Conference on Retroviruses and Opportunistic Infections (CROI). March 4-7, 2019. Seattle. Abstract 139.
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