PMID- 20868279
OWN - NLM
STAT- MEDLINE
DCOM- 20110118
LR  - 20211020
IS  - 1537-6591 (Electronic)
IS  - 1058-4838 (Linking)
VI  - 51
IP  - 9
DP  - 2010 Nov 1
TI  - Strategies for nevirapine initiation in HIV-infected children taking pediatric 
      fixed-dose combination "baby pills" in Zambia: a randomized controlled trial.
PG  - 1081-9
LID - 10.1086/656628 [doi]
AB  - 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; P = .74). 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 (P = .003) and higher CD4 cell count 
      for age (P = .03). 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 .
FAU - Mulenga, V
AU  - Mulenga V
AD  - University Teaching Hospital, Lusaka, Zambia.
FAU - Cook, A
AU  - Cook A
FAU - Walker, A S
AU  - Walker AS
FAU - Kabamba, D
AU  - Kabamba D
FAU - Chijoka, C
AU  - Chijoka C
FAU - Ferrier, A
AU  - Ferrier A
FAU - Kalengo, C
AU  - Kalengo C
FAU - Kityo, C
AU  - Kityo C
FAU - Kankasa, C
AU  - Kankasa C
FAU - Burger, D
AU  - Burger D
FAU - Thomason, M
AU  - Thomason M
FAU - Chintu, C
AU  - Chintu C
FAU - Gibb, D M
AU  - Gibb DM
LA  - eng
SI  - ISRCTN/ISRCTN31084535
GR  - MC_U122886353/MRC_/Medical Research Council/United Kingdom
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Clin Infect Dis
JT  - Clinical infectious diseases : an official publication of the Infectious Diseases 
      Society of America
JID - 9203213
RN  - 0 (Anti-HIV Agents)
RN  - 2T8Q726O95 (Lamivudine)
RN  - 99DK7FVK1H (Nevirapine)
RN  - BO9LE4QFZF (Stavudine)
RN  - EC 2.6.1.1 (Aspartate Aminotransferases)
RN  - EC 2.6.1.2 (Alanine Transaminase)
SB  - IM
MH  - Alanine Transaminase/blood
MH  - Anti-HIV Agents/*administration & dosage/*adverse effects
MH  - Antiretroviral Therapy, Highly Active/*methods
MH  - Aspartate Aminotransferases/blood
MH  - Chemical and Drug Induced Liver Injury
MH  - Child
MH  - Exanthema/chemically induced
MH  - HIV Infections/*drug therapy
MH  - Humans
MH  - Lamivudine/administration & dosage
MH  - Nevirapine/*administration & dosage/*adverse effects
MH  - Stavudine/pharmacology
MH  - Zambia
EDAT- 2010/09/28 06:00
MHDA- 2011/01/19 06:00
CRDT- 2010/09/28 06:00
PHST- 2010/09/28 06:00 [entrez]
PHST- 2010/09/28 06:00 [pubmed]
PHST- 2011/01/19 06:00 [medline]
AID - 10.1086/656628 [doi]
PST - ppublish
SO  - Clin Infect Dis. 2010 Nov 1;51(9):1081-9. doi: 10.1086/656628.