Date Published: July 7, 2017
Publisher: Public Library of Science
Author(s): Haseena Cassim, Kennedy Otwombe, Erica Lazarus, Afaaf Liberty, Glenda E. Gray, Oppel B. W. Greeff, Avy Violari, Graciela Andrei.
The current World Health Organization guideline for first line antiretroviral therapy (ART) in HIV-infected children recommends the use of abacavir and lamivudine as nucleoside backbones and no longer includes stavudine. We compared treatment outcomes with abacavir (ABC) versus stavudine (d4T) in a cohort of HIV-1 infected children 6 and 12 months after antiretroviral therapy was initiated.
This was a retrospective case-cohort study, using programmatic data from children enrolled in the Paediatric Wellness Programme at the Perinatal HIV Research Unit in Soweto, South Africa between 2005 and 2013. Children on abacavir/stavudine who had initiated ART at age <3 years with a regimen including lamivudine and lopinavir/ritonavir and had at least one 6 or 12 month viral load result were eligible. All ABC cases identified were matched for age at ART initiation and gender to eligible d4T controls (1:2). Outcomes analysed at 6 and 12 months post ART initiation included virological failure, mortality, immunological failure and anthropometry. Chi-square tests compared categorical measures while Kruskal-Wallis compared continuous measures. We identified 57 eligible ABC cases and selected 114 matched d4T controls. Overall, 57% were females and 89% started treatment at age <1year. The median age at ART initiation was 3.11 (IQR: 1.98–6.05) months. There was no difference in the proportion of children virologically suppressed between the groups at 6 (ABC 54.5% vs. d4T 67.0%, p = 0.125) and 12 (ABC 66.7% vs. d4T 71.6%, p = 0.53) months post ART-initiation. The proportion of children with adherence levels >90% for ABC and d4T were similar too (95% in ABC vs. 86% in d4T, p = 0.10). The proportion of children who died over 12 months was 3.5% in the ABC and 7.9% in the d4T group (p = 0.27). Similarly, the anthropometric measures were comparable.
It is reassuring that in the short term, in this group of patients, the treatment outcomes were similar.
The management of paediatric HIV is accompanied by an abundance of challenges ranging from making the diagnosis, to the unwillingness of inexperienced clinicians in facing the challenge of paediatric HIV, to finding a suitable palatable formulation for children. It is not surprising then, according to the 2013 World Health Organization (WHO) progress report, that even though 630 000 children received treatment in 2012 compared to 566 000 in 2011, the percentage increase in children younger than 15 years receiving antiretroviral treatment (ART) was considerably less than the increase achieved amongst adults (11 vs 21%) . Despite improvements in the prevention of mother to child transmission of HIV (PMTCT), there were still an estimated 2.6 million children under 15 years of age living with HIV in 2014 of whom only about 31% (800 000) were receiving antiretroviral therapy (ART) . This paediatric treatment gap has been noted by the Joint United Nations Programme on HIV/AIDS (UNAIDS) and with improvements in early infant diagnosis, access to ART, and paediatric drug formulations, the global plan aims to increase paediatric ART coverage with the 90-90-90 treatment goal (90% of people living with HIV to know their HIV status, 90% of people who know their status to access HIV treatment and 90% of people on HIV treatment to achieve viral suppression) by 2020 .
We identified 57 eligible ABC cases and selected 114 matched d4T controls for a total sample of 171 children (56.7% female; 89.5% under 1 year of age at time of ART initiation) with a median age of 3.11 (IQR: 1.98–6.05) months (Table 1). Pre-ART, more children in the ABC group had viral load < 100,000 copies/ml (17.9% vs. 2.8%, p = 0.0013) and were catergorised as WHO stage 1 or 2 (86% vs 63.1%, p = 0.002) compared with the d4T group. However, the CD4% was similar between the groups. Children in the ABC group also had better median WAZ (-1.15 vs. -1.88, p = 0.0009) and WLZ (0.28 vs. -0.50, p = 0.0002) relative to d4T. Our analysis showed that overall there was no difference in virological, immunological or clinical outcomes between children receiving ABC or d4T based ART in Soweto, South Africa. The rate of decline of the viral load amongst the groups was also similar. ABC and d4T based ART regimens are equally efficacious in young children in Soweto when adherence is good. Children with lower pre-ART anthropometric values experience more remarkable catch-up growth. It is reassuring that, at least in the short term, in this group of patients, the treatment outcomes were similar between those taking ABC compared to d4T-containing regimens. Source: http://doi.org/10.1371/journal.pone.0180645