Switching efavirenz to rilpivirine in virologically suppressed adolescents with HIV: a multi-centre 48-week efficacy and safety study in Thailand.

Introduction: Efavirenz (EFV) is commonly used for first-line antiretroviral therapy in children and adolescents with HIV, but is associated with neuropsychiatric and metabolic side effects. Rilpivirine (RPV) is better tolerated, and switching from EFV to RPV in virologically suppressed adults has been safe and efficacious, but data in adolescents are limited. Our primary objective was to describe the 48-week immunologic and virologic outcomes in virologically suppressed adolescents switching from EFV- to RPV-based antiretroviral therapy. Secondary objectives included assessment of neuropsychiatric adverse events, quality of life (QOL) and metabolic profiles while on RPV.

Methods: We conducted an open-label, single-arm, multi-centre study in Thailand in virologically suppressed adolescents aged 12-18 years receiving EFV plus two nucleoside/tide reverse transcriptase inhibitors (NRTIs/NtRTI) for ≥3 months. Participants were switched to an RPV (25 mg) tablet once daily, with the same NRTIs. HIV RNA viral load, CD4 cell count, fasting total cholesterol (TC), triglyceride, glucose, neuropsychiatric adverse events, depression and QOL were assessed over 48 weeks. Data were collected between February 2016 and September 2018.

Results: One hundred and two (52% male) adolescents were enrolled. Median age at entry was 15.5 years (IQR 14.4-17.0), median CD4 count was 664 cells/mm (29.9%); 58% were receiving tenofovir-DF and emtricitabine. At weeks 24 and 48, 96 (94.1%) and 94 (92.2%) participants were virologically suppressed, respectively, with no significant change in CD4 cell counts from baseline. Six (5.9%) participants experienced virologic failure, two of whom had RPV-associated mutations (K101E and Y181C) and a lamivudine-associated mutation (M184V/I). There were significant decreases in TC, triglyceride, high-density lipoprotein (HDL) and low-density lipoprotein (LDL) at weeks 24 and 48 and a significant increase in LDL/HDL ratio at week 48 compared to baseline. No substantial changes in EFV-related symptoms, depression score or health-related QOL were observed over time; however, there was significant improvement in performance-based assessments of executive function at week 24.

Conclusions: A high proportion of adolescents (>92%) remained virologically suppressed up to 48 weeks after switching from EFV to RPV along with no significant change in CD4 cell counts. RPV was well tolerated and associated with improvements in metabolic profiles and executive function.