Discontinuation of standard first-line antiretroviral therapy in a cohort of 1434 Malawian children.

The standard first-line antiretroviral (ART) regimen in Malawi for both adults and children is a fixed-dose combination tablet containing stavudine (d4T), lamivudine (3TC) and nevirapine (NVP). This regimen has been shown to yield satisfactory virologic and immunologic outcomes in children. Published studies have described insights into discontinuation of first-line regimen and toxicities of ART in adults, but similar studies in paediatric populations are lacking. A retrospective cohort study was undertaken to assess reasons for discontinuation of the standard first-line ART regimen (d4T/3TC/NVP) in a paediatric population. In total, 1434 patients met eligibility criteria and were included. The cohort had mean and median age at ART initiation of 4.7 years and 2.9 years, respectively (range: 0.1 months-18.7 years). The gender distribution was 47% female and 53% male. Median follow-up time on ART was 1.8 years (range: 2 weeks-3.9 years). A majority (96.2%) of patients were on the standard first-line ART regimen, while 3.8% (54) were on a different regimen. Twenty-eight patients (2.0%) were on an alternative first-line regimen due to toxicities, 22 patients (1.5%) were on a second-line regimen due to ART failure, and four patients (0.3%) were on a non-standard regimen for other clinical reasons. Of the 28 patients who experienced toxicities requiring ART regimen change, 60.7% (17) were caused by NVP, 39.3% (11) by d4T, and none by 3TC. The median time from first-line ART initiation to alternative first-line ART was two months (range: 10 days-28.1 months); 60.7% of patients on alternative first-line ART were male. Average time on ART until switch to second-line ART regimen was 16.3 months (SD: 9.3 months). The probability of failure after one year on first-line regimen was 1.6% (95% CI: 0.9-2.6). There was no compelling evidence in this cohort, representing approximately 10% of all children on ART in Malawi, to support changing the standard paediatric first-line regimen based on early toxicities or failure. However, experience from the national adult cohort, longer term follow up of the paediatric cohort in this study, emerging data on resistance after single-dose NVP containing mother to child transmission antiretroviral prophylaxis, and new 2009 World Health Organization ART recommendations may influence national policy change to a different first-line regimen.