Antiretroviral drug resistance among HIV-1 infected children failing treatment.
High levels of HIV-1 replication occur following perinatal infection and antiretroviral drugs may not fully suppress viral load during the early years of childhood. Adherence to treatment may also be difficult among children. These two factors will contribute to development of drug resistance but limited paediatric data are available. This study has, therefore, evaluated the prevalence of drug resistance among children and assessed the contribution of adherence to failing therapy. Samples from 26 children who had experienced virological failure to antiretroviral therapy were tested for drug resistance using the Visible Genetics TRUGENE trade mark HIV-1 genotyping assay. HIV-1 subtype was determined using a peptide-based EIA and drug adherence determined by physician assessment. Twenty-four children were black African, 23 of whom were infected with a non-B subtype. HIV RNA sequence data was obtained for 21 of the 26 children; at treatment failure resistance mutations were detected in the protease gene of 7 (33%) and the reverse transcriptase gene of 19 (90%). A lower proportion of children had evidence of drug resistance at nadir and no resistance mutations were detected prior to treatment. Genotypic resistance was common in those treated with lamivudine (10/11, 91%), nevirapine (6/8, 75%), and zidovudine (7/11, 64%). The prevalence of mutations was lower among those receiving other nucleoside reverse transcriptase inhibitors and protease inhibitors. In 50% of children, drug adherence was >90%. Antiretroviral drug resistance was common among this group of children failing therapy, the majority of whom were infected with non-B subtypes of HIV-1. As adherence to treatment was low in 50%, this was likely to be an important contributory factor.
Mullen
Jane
J
Virology Section, Department of Infection, Guy's, King's and St Thomas' School of Medicine, King's College, London, UK.
Leech
Susan
S
O'Shea
Siobhan
S
Chrystie
Ian L
IL
Du Mont
Gillian
G
Ball
Colin
C
Sharland
Michael
M
Cottam
Fiona
F
Zuckerman
Mark
M
Rice
Philip
P
Easterbrook
Philippa
P
D000293:Adolescent; D019380:Anti-HIV Agents / Q000494:pharmacology* / Q000627:therapeutic use; D002648:Child; D002675:Child, Preschool; D024882:Drug Resistance, Viral; D004359:Drug Therapy, Combination; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000453:epidemiology / Q000821:virology; D016333:HIV Protease / Q000235:genetics; D054303:HIV Reverse Transcriptase / Q000235:genetics; D015497:HIV-1 / Q000145:classification / Q000187:drug effects* / Q000235:genetics; D006801:Humans; D007223:Infant; D008297:Male; D010349:Patient Compliance; D018894:Reverse Transcriptase Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D017211:Treatment Failure
D019380:Anti-HIV Agents; D018894:Reverse Transcriptase Inhibitors; D054303:HIV Reverse Transcriptase; D016333:HIV Protease