Strategies for Nevirapine Initiation in HIV‐Infected Children Taking Pediatric Fixed‐Dose Combination “Baby Pills” in Zambia: A Randomized Controlled Trial.

Author(s): Mulenga V, Cook A, Walker AX, Kabamba D, Chijoka C, Ferrier A, Kalengo C, Kityo C, Kankasa C, Burger D, Thomason M, Chintu C, Gibb DX

Affiliation(s): University Teaching Hospital, Lusaka, Zambia; 2Medical Research Council Clinical Trials Unit, London, United Kingdom; 3Joint Clinical Research Center, Kampala, Uganda; and 4Radboud University Nijmegen Medical Center, Nijmegen, the Netherlands.

Publication date & source: 2010-09-24, Clin Infect Dis., [Epub ahead of print]

Background.  Fixed‐dose combination scored dispersible stavudine, lamivudine, and nevirapine minitablets (Triomune Baby and Junior; Cipla Ltd) are simpler and cheaper than liquid formulations and have correct dose ratios for human immunodeficiency virus–infected children. However, they cannot be used for dose escalation (DE) of nevirapine. Methods.  Children were randomized to initiate antiretroviral therapy with full‐dose (FD) nevirapine (Triomune Baby or Junior in the morning and evening) versus DE (half‐dose nevirapine for 14 days [Triomune in the morning and stavudine‐lamivudine {Lamivir‐S} in the evening], then FD), in accordance with World Health Organization weight‐band dosing tables. The primary end point was nevirapine‐related clinical or laboratory grade 3 or 4 adverse events (AEs). Results.  In total, 211 children (median [interquartile range {IQR}] age, 5 [ 2 – 9 ] years; median [IQR] CD4 cell percentage, 13% [8%–18%]) were enrolled and followed up for a median (IQR) of 92 (68–116) weeks. There were 31 grade 3 or 4 AEs that were definitely/probably or uncertainly related to nevirapine in the FD group (18.0 per 100 child‐years), compared with 29 in the DE group (16.5 per 100 child‐years) (incidence rate ratio, 1.09; 95% confidence interval, 0.63–1.87; [Formula: see text]). All were asymptomatic; 11 versus 3 were single grade 3 or 4 elevations in alanine aminotransferase (ALT) or aspartate aminotransferase (AST) levels, all of which resolved without a change in nevirapine dose or interruption. Thirteen (12%) FD versus 2 (2%) DE children had grade 1 (2 in FD) or grade 2 (11 in FD and 2 in DE) rashes. Three (2 in FD and 1 in DE) substituted efavirenz, 3 (FD) continued FD nevirapine, and 9 (8 in FD and 1 in DE) temporarily interrupted nevirapine, followed by successful DE. Predictors of nevirapine rash were older age ([Formula: see text]) and higher CD4 cell count for age ([Formula: see text]). Twenty‐two children died (12 in FD and 10 in DE), 1 FD and 5 DE children at <4 weeks; none were considered to be drug related by independent review. Conclusions.  Rash was more frequent with FD nevirapine, but 88% had no clinical toxicity; elevated AST or ALT levels were transient and resolved spontaneously, suggesting that routine laboratory monitoring has limited value. Dual pediatric stavudine‐lamivudine minitablets are preferred for safe and simple DE; if unavailable, initiating FD Triomune requires timely review for rash, which could be managed by temporary reduction to half‐dose Triomune or efavirenz substitution. Trial registration.  Current Controlled Trials identifier: ISRCTN31084535 .