W96 ATLAS results boost therapeutic potential of LA cabotegravir-rilpivirine as HIV-1 maintenance

The monthly injectable regimen comprising the INSTI* cabotegravir and the NNRTI** rilpivirine long-acting (CAB+RPV LA) maintained virological suppression (ie, plasma HIV-1 RNA <50 copies/mL) in almost all participants of the phase III ATLAS*** trial who entered the extension phase, according to the 96-week analysis presented at HIV Glasgow 2020.

In the week 48 analysis of ATLAS, the monthly injectable CAB+RPV LA regimen was noninferior to a three-drug daily oral ART for adults living with HIV-1. [N Engl J Med 2020;382:1112-1123]

“The [current] longer-term efficacy, safety and tolerability data, in addition to patient preference data, complement the positive results collected at week 48 and support the therapeutic potential of injectable CAB+RPV LA treatment in people living with HIV-1,” said the researchers. "LA injectable therapies [may] address some challenges associated with daily oral antiretroviral therapy (ART; eg, pill fatigue, drug/food interactions, stigma and suboptimal adherence).”

In the 52-week maintenance phase of ATLAS, 705 virologically suppressed patients (median age 42 years, 67 percent male) who were exposed to ART were randomized 1:1 to either continue with their daily oral ART regimen or switch to the monthly injectable CAB+RPV LA therapy. Following which, participants could opt to transition to ATLAS-2M^#, enter an extension phase, or withdraw from the trial. Those who entered the extension phase at week 52 (n=52) either continued the monthly injectable CAB+RPV LA therapy (LA arm) or switched from the oral to the injectable regimen (switch arm). A 4-week oral lead-in phase with CAB+RPV preceded the switch in both the maintenance and the extension phases. [HIV Glasgow, abstract P006]

At the week-96 assessment of the extension-phase data, almost all participants in both LA and switch arms (100 percent and 97 percent) maintained virological suppression. Only one patient in the switch arm had HIV-1 RNA ≥50 copies/mL. Moreover, there were no participants with confirmed virologic failure (ie, two consecutive HIV-1 RNA ≥200 copies/mL).

The LA and switch arms had similar rates of adverse events (AEs) leading to withdrawal (2 vs 1), drug-related AEs leading to withdrawal (one in each arm), and serious AEs (two in each arm). The most common drug-related AE was injection site reactions (ISRs; n=154 [LA] and 238 [switch]), which were mostly mild (n=134 and 184, respectively) in severity and were of short duration (median duration 3 days).

Excluding ISRs, the most common AEs were nasopharyngitis, headache, upper respiratory tract infection, and diarrhoea. Most drug-related AEs were grade 1/2, and occurred at a frequency of <1 percent.

“Overall treatment satisfaction for the LA arm participants remained at a high level through week 96, with large improvements from baseline across all timepoints,” said the researchers. Moreover, all 27 participants in the switch arm who responded to the questionnaire at week 96 expressed that they preferred LA therapy over the daily oral regimen.