PMID- 20508547 OWN - NLM STAT- MEDLINE DCOM- 20101104 LR - 20211020 IS - 1532-0987 (Electronic) IS - 0891-3668 (Linking) VI - 29 IP - 8 DP - 2010 Aug TI - Drug resistance in human immunodeficiency virus type-1 infected Zambian children using adult fixed dose combination stavudine, lamivudine, and nevirapine. PG - e57-62 LID - 10.1097/INF.0b013e3181e47609 [doi] AB - BACKGROUND: There are few medium-term virologic data in children from resource-limited settings taking adult fixed-dose-combination antiretroviral therapy (cART) without viral load monitoring. METHODS: CHAP2 (Children with HIV Antibiotic Prophylaxis 2) is a prospective cohort of Zambian children using d4T/3TC/NVP adult Triomune30 dosed according to WHO guidelines. RESULTS: A total of 103 children (19 with previous antiretroviral therapy) had follow-up >6 months. Median age at cART initiation was 8 years (IQR, 6-12) and CD4 8% (4-12). At 24 months, CD4% had increased by a median of 15% (7-25). For 74 children viral load was known/inferred: 51 of 74 (69%) had viral load <50 copies/mL (45 of 63 [71%] with no previous cART, 6 of 11 [55%] with previous cART; difference P = 0.30); 22 of 74 (30%) had viral load >1000 copies/mL. Of 26 children with resistance data, 25 (96%) had NNRTI resistance; 22 (84%) had M184V; 2 (8%) had Q151M; and 1 (4%) each had K65R, L74V, or K70E. Eight (31%) had > or =1 TAM. Those failing virologically with a genotypic sensitivity score of 0 for first-line therapy had a somewhat smaller increase in CD4% from baseline compared with those failing therapy with a genotypic sensitivity score >0 (+3 vs. +8, P = 0.13), and had somewhat lower CD4% at initiation of cART (2 vs. 11, P = 0.09). In 6 children with >1 resistance test, the estimated rate of accumulation of TAMs was 0.59/yr (95% confidence interval: 0.22-1.29). CONCLUSIONS: Twenty-four month virologic responses to cART were good. However, the rate of TAM accumulation in those with rebound was higher than reported in Western adult cohorts, and there was some indication of a detrimental effect of high level resistance on CD4% change from baseline. FAU - Gupta, Ravindra K AU - Gupta RK AD - Division of Infection and Immunity, University College London Medical School, London, United Kingdom. rebmrag@ucl.ac.uk FAU - Ford, Deborah AU - Ford D FAU - Mulenga, Veronica AU - Mulenga V FAU - Walker, A Sarah AU - Walker AS FAU - Kabamba, Desire AU - Kabamba D FAU - Kalumbi, Moxmalama AU - Kalumbi M FAU - Grant, Paul R AU - Grant PR FAU - Ferrier, Alexander AU - Ferrier A FAU - Pillay, Deenan AU - Pillay D FAU - Gibb, Diana M AU - Gibb DM FAU - Chintu, Chifumbe AU - Chintu C LA - eng GR - MC_U122886353/MRC_/Medical Research Council/United Kingdom GR - WT081772MA/WT_/Wellcome Trust/United Kingdom PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - Pediatr Infect Dis J JT - The Pediatric infectious disease journal JID - 8701858 RN - 0 (Anti-HIV Agents) RN - 0 (Viral Proteins) RN - 2T8Q726O95 (Lamivudine) RN - 99DK7FVK1H (Nevirapine) RN - BO9LE4QFZF (Stavudine) SB - IM MH - Amino Acid Substitution/genetics MH - Anti-HIV Agents/*administration & dosage/pharmacology MH - CD4 Lymphocyte Count MH - Child MH - Child, Preschool MH - Cohort Studies MH - Drug Monitoring MH - *Drug Resistance, Viral MH - Female MH - Follow-Up Studies MH - HIV Infections/*drug therapy/virology MH - HIV-1/*drug effects/isolation & purification MH - Humans MH - Lamivudine/*administration & dosage/pharmacology MH - Male MH - Mutation, Missense MH - Nevirapine/*administration & dosage/pharmacology MH - Prospective Studies MH - Stavudine/*administration & dosage/pharmacology MH - Treatment Failure MH - Viral Load MH - Viral Proteins/genetics MH - Zambia EDAT- 2010/05/29 06:00 MHDA- 2010/11/05 06:00 CRDT- 2010/05/29 06:00 PHST- 2010/05/29 06:00 [entrez] PHST- 2010/05/29 06:00 [pubmed] PHST- 2010/11/05 06:00 [medline] AID - 10.1097/INF.0b013e3181e47609 [doi] PST - ppublish SO - Pediatr Infect Dis J. 2010 Aug;29(8):e57-62. doi: 10.1097/INF.0b013e3181e47609.