Outcomes of second‐line antiretroviral therapy among children living with HIV: a global cohort analysis

Abstract

Introduction Limited data describe outcomes on second‐line antiretroviral therapy (ART) among children globally. Our objective was to contribute data on outcomes among children living with HIV after initiation of second‐line ART in the context of routine care within a large global cohort collaboration. Methods Patient‐level data from 1993 through 2015 from 11 paediatric HIV cohorts were pooled. Characteristics at switch and through two years of follow‐up were summarized for children who switched to second‐line ART after starting a standard first‐line regimen in North America, Latin America, Europe, Asia, Southern Africa (South Africa & Botswana) and the rest of sub‐Saharan Africa (SSA). Cumulative incidences of mortality and loss to follow‐up (LTFU) were estimated using a competing risks framework. Results Of the 85,389 children on first‐line ART, 3,555 (4%) switched to second‐line after a median of 2.8 years on ART (IQR: 1.6, 4.7); 69% were from Southern Africa or SSA and 86% of second‐line regimens were protease inhibitor‐based. At switch, median age was 8.4 years and 50% had a prior AIDS diagnosis. Median follow‐up after switch to second‐line ranged from 1.8 years in SSA to 5.3 years in North America. Median CD4 counts at switch to second‐line ranged from 235 cells/mm3 in SSA to 828 cells/mm3 in North America. Improvements in CD4 counts were observed over two years of follow‐up, particularly in regions with lower CD4 counts at second‐line switch. Improvements in weight‐for‐age z‐scores were not observed during follow‐up. Cumulative incidence of LTFU at two years was <5% in all regions except SSA (7.1%) and Southern Africa (7.4%). Risk of mortality was <3% at two years of follow‐up in all regions, except Latin America (4.9%) and SSA (5.5%). Conclusions Children switched to second‐line ART experience CD4 count increases as well as low to moderate rates of LTFU and mortality within two years after switch. Severe immune deficiency at time of switch in some settings suggests need for improved recognition and management of treatment failure in children.

Clinical, immunologic and virologic outcomes of children and adolescents receiving second line anti-retroviral therapy in two referral hospitals in Addis Ababa, Ethiopia

“…The study also showed that 5 out of 75 participants (6.7%) had been lost to follow-up. This mimicked the cumulative incidence of loss to follow-up (LTFU) at the end of 2 years of follow-up among similar cohorts in sub-Saharan Africa (7.1%) versus less than 5% globally, reported by the Collaborative Initiative for Paediatric HIV Education and Research (CIPHER) Global Cohort Collaboration [ 26 ].…”

Development and emerging trends of drug resistance mutations in HIV: a bibliometric analysis based on CiteSpace

“…In addition, TAF-containing regimens have been demonstrated to be a not-to-be-ignored strategy for children ( O'Rourke et al, 2023 ). When second-line ART is begun in children, their CD4+ T lymphocyte count increases, and their mortality and loss to follow-up decrease ( Collaborative Initiative for Paediatric HIV Education and Research (CIPHER) Global Cohort Collaboration, 2020 ). Consequently, treating drug resistance in children is positively impacted by prompt medication modifications.…”