Abstract
BACKGROUND: Long-acting cabotegravir and rilpivirine is the first intramuscular injectable antiretroviral treatment regimen recommended for maintenance of virological suppression in adults living with HIV-1. We report acceptability and tolerability outcomes in adolescents during 48 weeks of treatment with this regimen. METHODS: In this analysis of the phase 1/2, multicentre, open-label, non-comparative trial conducted at 18 sites across Botswana, South Africa, Thailand, Uganda, and the USA, 144 adolescents (weight ≥35 kg) with HIV-1 were enrolled to receive long-acting intramuscular cabotegravir and rilpivirine and 140 completed 48 weeks of treatment. Participant-reported acceptability and tolerability outcomes were a Faces Scale assessment of pain at each injection, preferred treatment method, and Quality of Life Inventory (PedsQL) at baseline and across 48 weeks of treatment for participants in Botswana, South Africa, Thailand, Uganda, and the USA. USA-based participants completed a Medication Satisfaction Questionnaire (SMSQc-Teen; after week 24), assessing their satisfaction with the all-intramuscular versus their previous oral regimen. A subset of eight adolescents and three parents or caregivers in the USA underwent in-depth interviews after a minimum of 24 weeks on study. This study is registered with ClinicalTrials.gov, NCT03497676. FINDINGS: Between July 26, 2021, and Aug 27, 2022, 44 of 55 adolescents who participated in cohort 1 and 100 of 115 screened study-naive adolescents were enrolled in cohort 2. 70 (49%) participants were male and 74 (51%) were female. 144 adolescents completed study questionnaires; 11 adolescents and parents completed in-depth interviews. At weeks 8, 24, and 48, 138 (97%) of 142, 139 (99%) of 141, and 140 (100%) of 140 participants, respectively, preferred intramuscular injections over oral treatment. Pain was more frequent with intramuscular rilpivirine than with cabotegravir (more pain than "hurts little bit" at all timepoints: 51-62% for rilpivirine vs 12-14% for cabotegravir). Health-related quality of life was high across all timepoints (overall median 94·6 [IQR 84·8-97·8] at baseline vs 93·5 [82·6-97·8] at 48 weeks). The 19 (100%) participants who completed the SMSQc-Teen reported higher satisfaction with the all-intramuscular regimen than with previous oral regimen. In the subset of individuals who underwent in-depth interviews, a prominent theme was reduced stress between parents and adolescents with the initiation of intramuscular antiretrovirals. INTERPRETATION: Acceptability and tolerability of intramuscular cabotegravir-rilpivirine remained high through to 48 weeks of treatment, suggesting that this long-acting intramuscular treatment approach is well received by diverse populations of adolescents with HIV across multiple settings. FUNDING: National Institutes of Health and ViiV Healthcare.