Understanding Adolescent Anti-Retroviral Therapy Use in the BREATHER-Plus Trial: Qualitative Findings From South Africa and Uganda.

INTRODUCTION: The BREATHER-Plus trial was an open-label, randomized non-inferiority trial comparing weekends off antiretroviral therapy (ART) (short cycle therapy [SCT]) with daily oral ART (continuous therapy [CT]) for adolescents aged 12-19 years. We present findings from the qualitative sub-study on the factors influencing trial participants' decisions to take/not take ART in accordance with their randomized arm. METHODS: Qualitative data collection was conducted in South Africa and Uganda from December 2022 to July 2024 using in-depth interviews (IDIs) and focus group discussions (FGDs). We purposively recruited 29 trial participants (14 SCT/15 CT arm) to take part in IDIs in South Africa. From the trial sites in both countries, 47 trial participants, 17 non-trial participants, 15 caregivers and 16 healthcare providers took part in FGDs. Data collection with trial participants focused on adherence to SCT compared to daily ART; the acceptability of SCT and the experience of taking part in the trial. All FGDs explored the feasibility of SCT and preferences for alternative approaches to accessing therapy. Data were analysed thematically. RESULTS: Both IDI and FGD data showed that the opportunity to have weekends off from treatment was welcomed by participants, caregivers and healthcare providers. However, the understanding of "2 days off" treatment was interpreted flexibly by some participants. Trial participants in both arms described their fluctuating adherence practices both prior to and during the trial. The introduction of SCT as a possibility through the trial prompted some to talk about previously concealed missed doses. Participants reported that they only mentioned missed doses in the clinic if they had a raised viral load result or had returned to the clinic with too many pills. Many participants relied on their viral load result to confirm that non-adherent behaviour was not problematic. CONCLUSIONS: Our findings offer insights into the factors that shape ART adherence among adolescents living with HIV. Adherence is not a static behaviour but a socially embedded and relational practice, shaped by adolescents' interpretations of treatment, interpersonal relationships and the structure of care environments. Regimen modification alone does not resolve the broader social and emotional challenges adolescents face.