Outcomes of second‐line antiretroviral therapy among children living with HIV: a global cohort analysis
Open Access
- 15 April 2020
- journal article
- research article
- Published by Wiley in Journal of the International AIDS Society
- Vol. 23 (4), e25477
- https://doi.org/10.1002/jia2.25477
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.Keywords
Funding Information
- National Institutes of Health (UM1AI106716, U01A1069911, N01‐3‐3345, U01AI069924, U01HD052102, U01AI41110, U01AI069923, U01AI096299, U01HD052104, UM1AI068632, HHSN267200800001C, U01AI069919, UM1AI068616, U01AI069907)
- Medical Research Council (MC_UU_12023/26)
- Centers for Disease Control and Prevention (5U62PS223540, 5U2GPS001537)
- Instituto de Salud Carlos III (RD12/0017/0035, RD12/0017/0037)
- European Regional Development Fund
- Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (148522)
- Bristol-Myers Squibb
- GlaxoSmithKline
- Roche
This publication has 25 references indexed in Scilit:
- Relationship between anthropometric indicators and cognitive performance in Southeast Asian school-aged childrenBritish Journal of Nutrition, 2013
- Second-Line Protease Inhibitor-Based Haart after Failing Non-Nucleoside Reverse Transcriptase Inhibitor-Based Regimens in Asian HIV-Infected ChildrenAntiviral Therapy, 2013
- Routine versus clinically driven laboratory monitoring and first-line antiretroviral therapy strategies in African children with HIV (ARROW): a 5-year open-label randomised factorial trialThe Lancet, 2013
- Antiretroviral Drug Resistance Profiles and Response to Second-Line Therapy Among HIV Type 1-Infected Ugandan ChildrenAIDS Research and Human Retroviruses, 2013
- Effectiveness and safety of protease inhibitor‐based regimens in HIV‐infected Thai children failing first‐line treatmentHIV Medicine, 2012
- Virological Response and Resistance Profiles After 18 to 30 Months of First- or Second-/Third-Line Antiretroviral Treatment: A Cross-Sectional Evaluation in HIV Type 1-Infected Children Living in the Central African RepublicAIDS Research and Human Retroviruses, 2012
- Drug Resistance Profiles Among HIV-1–Infected Children Experiencing Delayed Switch and 12-Month Efficacy After Using Second-Line Antiretroviral Therapy: An Observational Cohort Study in Rural ChinaJAIDS Journal of Acquired Immune Deficiency Syndromes, 2011
- First-line antiretroviral therapy with a protease inhibitor versus non-nucleoside reverse transcriptase inhibitor and switch at higher versus low viral load in HIV-infected children: an open-label, randomised phase 2/3 trialThe Lancet Infectious Diseases, 2011
- Virologic Failure and Second-Line Antiretroviral Therapy in Children in South Africa—The IeDEA Southern Africa CollaborationJAIDS Journal of Acquired Immune Deficiency Syndromes, 2011
- A Proportional Hazards Model for the Subdistribution of a Competing RiskJournal of the American Statistical Association, 1999