BACKGROUND:In resource-limited settings holding regimens, such as lamivudine monotherapy (LM), are used to manage HIV-positive children failing combination antiretroviral therapy (cART) to mitigate the risk of drug resistance developing, whilst adherence barriers are addressed or when access to second- or third-line regimens is restricted. We aimed to investigate characteristics of children placed on LM and their outcomes. METHODS:We describe the characteristics of children (age 90 days we describe their immunologic outcomes on LM and their immunologic and virologic outcomes after resuming cART. FINDINGS:We included 228 children in our study. At LM start their median age was 12.0 years (IQR 7.3-14.6), duration on cART was 3.6 years (IQR 2.0-5.9) and median CD4 count was 605.5 cells/μL (IQR 427-901). Whilst 110 (48%) had no prior protease inhibitor (PI)-exposure, of the 69 with recorded PI-exposure, 9 (13%) patients had documented resistance to all PIs. After 6 months on LM, 70% (94/135) experienced a drop in CD4, with a predicted average CD4 decline of 46.5 cells/μL (95% CI 37.7-55.4). Whilst on LM, 46% experienced a drop in CD4 to