Drug resistance in the Chinese National Pediatric Highly Active Antiretroviral Therapy Cohort: implications for paediatric treatment in the developing world.
China's National Pediatric ART Program began in 2005, in which 32 ART-experienced and 51 antiretroviral therapy (ART)-naïve children received paediatric formulations of (zidovudine or stavudine) plus lamivudine plus (nevirapine or efavirenz). Reverse transcriptase sequencing and analysis was performed on plasma samples with >1000 HIV copies/mL after one year of treatment. Thirty-four samples were sequenced. Nearly all patients had nucleoside reverse transcriptase inhibitor and non-nucleoside reverse transcriptase inhibitor mutations. High/intermediate resistance was found to lamivudine/emtricitabine in 31 patients; to didanosine, abacavir, stavudine and zidovudine in 18 patients; and to tenofovir in 11 patients. All had high-level resistance to nevirapine; all but one had high/intermediate-level resistance to efavirenz. Viral load was the only cohort characteristic significantly associated with developing resistance. Resistance to zidovudine, stavudine and tenofovir was more common in ART-experienced versus ART-naïve patients (P = 0.02-0.05). Drug resistance is high in this cohort. Second-line therapy will require additional ART strategies and options, which are currently unavailable in most developing settings.
Zhang
F
F
National Center for AIDS/STD Control and Prevention/Chinese Center for Disease Control and Prevention, China.
Haberer
J
J
Wei
H
H
Wang
N
N
Chu
A
A
Zhao
Y
Y
Zhao
H
H
D000293:Adolescent; D019380:Anti-HIV Agents / Q000494:pharmacology / Q000627:therapeutic use; D002648:Child; D002681:China / Q000453:epidemiology; D015331:Cohort Studies; D003906:Developing Countries; D024882:Drug Resistance, Viral / Q000235:genetics; D004359:Drug Therapy, Combination; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000453:epidemiology / Q000821:virology; D054303:HIV Reverse Transcriptase / Q000235:genetics; D015497:HIV-1 / Q000187:drug effects* / Q000201:enzymology / Q000235:genetics; D006801:Humans; D008297:Male; D009154:Mutation; D009313:National Health Programs; D015995:Prevalence; D018894:Reverse Transcriptase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D019562:Viral Load
D019380:Anti-HIV Agents; D018894:Reverse Transcriptase Inhibitors; C514824:reverse transcriptase, Human immunodeficiency virus 1; D054303:HIV Reverse Transcriptase