Adverse events associated with abacavir use in HIV-infected children and adolescents: a systematic review and meta-analysis. Issue 2 (February 2016)

• Record Type: Journal Article
• Authors: Jesson, Julie; Dahourou, Désiré L; Renaud, Françoise; Penazzato, Martina; Leroy, Valériane
• Is Part Of: Lancet. Volume 3:Issue 2(2016)
• Page Start: e64
• Page End: e75
• Publication Date: 2016-02
• Subjects: HIV (Viruses) -- Periodicals; HIV infections -- Periodicals; AIDS (Disease) -- Periodicals; 616.9792
• DOI: 10.1016/S2352-3018(15)00225-8
• Languages: English
• ISSNs: 2405-4704

Abstract

Summary: Background: Concerns exist about the toxicity of drugs used in the implementation of large-scale antiretroviral programmes, and documentation of antiretroviral toxicity is essential. We did a systematic review and meta-analysis of adverse events among children and adolescents receiving regimens that contain abacavir, a widely used antiretroviral drug. Methods: We searched bibliographic databases and abstracts from relevant conferences from Jan 1, 2000, to March 1, 2015. All experimental and observational studies of HIV-infected patients aged 0–18 years who used abacavir, were eligible. Incidence of adverse outcomes in patients taking abacavir (number of new events in a period divided by population at risk at the beginning of the study) and relative risks (RR) compared with non-abacavir regimens were pooled with random effects models. Findings: Of 337 records and 21 conference abstracts identified, nine studies (eight full-text articles and one abstract) collected information about 2546 children, of whom 1769 (69%) were on abacavir regimens. Among children and adolescents taking abacavir, hypersensitivity reactions (eight studies) had a pooled incidence of 2·2% (95% CI 0·4–5·2); treatment switching or discontinuation (seven studies) pooled incidence was 10·9% (2·1–24·3); of grade 3–4 adverse events (six studies) pooled incidence was 9·9% (2·4–20·9); and adverse events other than hypersensitivity reaction (six studies) pooled incidence was 21·5% (2·8–48·4). Between-study inconsistency was significant for all outcomes (p<0·0001 for all inconsistencies). Incidence of death (four studies) was 3·3% (95% CI 1·5–5·6). In the three randomised clinical trials with comparative data, no increased risk of hypersensitivity reaction (pooled RR 1·08; 95% CI 0·19–6·15), grade 3 or 4 events (0·79 [0·44–1·42]), or death (1·72 [0·77–3·82]) was noted for abacavir relative to non-abacavir regimens. None of the reported deaths were related to abacavir. Interpretation: Abacavir-related toxicity occurs early after ART initiation and is manageable. Abacavir can be safely used for first-line or second-line antiretroviral regimens in children and adolescents, especially in sub-Saharan Africa were HLA B5701 genotype is rare. Funding: WHO.