Safety and efficacy of abacavir for treating infants, children, and adolescents living with HIV: a systematic review and meta-analysis.

BACKGROUND: Abacavir is a nucleoside reverse transcriptase inhibitor recommended in paediatric HIV care. We assessed the safety and efficacy profile of abacavir used in first, second, or subsequent lines of treatment for infants, children, and adolescents living with HIV to inform 2021 WHO paediatric ART recommendations. METHODS: In this systematic review and meta-analysis, we included observational and experimental studies conducted in infants aged 0-1 year, children aged 1-10 years, and adolescents aged 10-19 years living with HIV; with data on safety or efficacy, or both, of abacavir-based antiretroviral therapy (ART); published in English or French between Jan 1, 2009, and Oct 1, 2020, plus an updated search to incorporate studies published between Oct 1, 2020, and May 15, 2022. Studies could be non-randomised or non-comparative and include patients who are treatment-naive or those who previously received abacavir (only if abacavir was combined with other ART). Case studies, studies in adults aged 18 years or older, and those assessing the effect of maternal ART exposure were excluded. We extracted data related to study identifier, study design, study period, setting, population characteristics, ART treatment, and safety (any hypersensitivity reaction, death, grade 3 or 4 adverse events, treatment discontinuation, any other morbidities, and serious adverse events), and efficacy outcomes (HIV viral load and CD4 counts reported at 6 and 12 months after ART initiation). Using random-effect models, we estimated weighted pooled incidence and relative risk (RR) of outcomes. The protocol is published in PROSPERO (CRD42022309230). FINDINGS: Of 1777 records identified, 1475 (83%) were screened after removing duplicates and a further 1421 (96%) were excluded. Of 54 full-text articles assessed for eligibility, 33 (61%) were excluded. Four records were identified from grey literature plus one duplicate from database searching, resulting in 24 studies included (two randomised controlled trials, one single-arm trial, 12 prospective cohorts, seven retrospective cohorts, and two cross-sectional studies). 19 studies described safety data and 15 described efficacy data. 18 (75%) studies were conducted in ART-naive participants. The risk of bias was considered moderate to high for most studies, and all outcomes had significant between-study heterogeneity. Data from 24 265 participants were included, of whom 7236 (30%) received abacavir. Abacavir hypersensitivity reaction was reported in nine (38%) studies, with an incidence ranging from 0·00% to 8·26% (I2=85%; p<0·0001). The incidence of death (reported in seven studies) following abacavir treatment varied from 0·00% to 5·49% (I2=58%; p=0·026). Viral suppression (<400 copies per mL) varied from 50% to 70% at 6 months (I2=92%, p<0·0001) and from 57% to 78% at 12 months (I2=88%, p<0·0001). INTERPRETATION: Toxic effects due to abacavir use remain rare and manageable. Despite scarce data on efficacy, this meta-analysis supports the use of abacavir as a preferred first-line regimen for infants and children living with HIV. FUNDING: WHO.

Impact of knowledge, attitudes, and sociocultural factors on school enrollment of children with epilepsy in Gabon.

PURPOSE: Perceptions, beliefs and culture influence attitude towards epilepsy in sub-Saharan Africa. Misconceptions on epilepsy contribute to the persistence of negative attitudes in children with epilepsy particularly on their school enrollment. The aim of the study was to assess knowledge, attitudes, and sociocultural factors affecting schooling of children with epilepsy in Gabon. METHODS: Teachers and health workers from two urban and four rural localities of Gabon were assessed using a self-administered questionnaire. RESULTS: Overall 1310 subjects filled the survey questionnaire, including 813 teachers and 497 health workers. Knowledge on risk factors and suggestive signs of childhood epilepsy were globally poor. Misconceptions on etiology of epilepsy were significant with contagiousness (27.5%) and demonic possession (16.0%) representing the major prevalent idea about the origin of epilepsy in children. Attitudes of teachers and health workers towards schooling of children with epilepsy were positive (85.0%). However, more than half recommended enrollment of these children in specialized school programs. In multivariate analysis, education level (OR = 1.40; 95% confidence interval 1.01-1.81) and marital status (OR = 1.62; 95% confidence interval 1.18-2.22) were sociocultural factors likely to affect chances of school enrollment of children with epilepsy. CONCLUSION: Understanding the influence of socio-cultural factors surrounding school enrollment of children with epilepsy could enhance public awareness campaigns about epilepsy and to improve school integration of these children.