Drug resistance in human immunodeficiency virus type-1 infected Zambian children using adult fixed dose combination stavudine, lamivudine, and nevirapine.
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.
Gupta
Ravindra K
RK
Division of Infection and Immunity, University College London Medical School, London, United Kingdom. rebmrag@ucl.ac.uk
Ford
Deborah
D
Mulenga
Veronica
V
Walker
A Sarah
AS
Kabamba
Desire
D
Kalumbi
Moxmalama
M
Grant
Paul R
PR
Ferrier
Alexander
A
Pillay
Deenan
D
Gibb
Diana M
DM
Chintu
Chifumbe
C
D019943:Amino Acid Substitution / Q000235:genetics; D019380:Anti-HIV Agents / Q000008:administration & dosage* / Q000494:pharmacology; D018791:CD4 Lymphocyte Count; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D016903:Drug Monitoring; D024882:Drug Resistance, Viral; D005260:Female; D005500:Follow-Up Studies; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology; D015497:HIV-1 / Q000187:drug effects* / Q000302:isolation & purification; D006801:Humans; D019259:Lamivudine / Q000008:administration & dosage* / Q000494:pharmacology; D008297:Male; D020125:Mutation, Missense; D019829:Nevirapine / Q000008:administration & dosage* / Q000494:pharmacology; D011446:Prospective Studies; D018119:Stavudine / Q000008:administration & dosage* / Q000494:pharmacology; D017211:Treatment Failure; D019562:Viral Load; D014764:Viral Proteins / Q000235:genetics; D015024:Zambia
D019380:Anti-HIV Agents; D014764:Viral Proteins; D019259:Lamivudine; D019829:Nevirapine; D018119:Stavudine