Genotype and phenotype patterns of drug-resistant HIV-1 subtype B' (Thai B) isolated from patients failing antiretroviral therapy in China.
Many AIDS patients in China who received free-of-charge antiretroviral therapeutics, including nucleoside reverse transcriptase inhibitors (NRTIs) and nonnucleoside reverse transcriptase inhibitors (NNRTIs), showed significant life improvement. Increasing numbers of patients, however, are experiencing antiretroviral therapy failure due to the emergence of drug-resistant viruses. The aim of this study was to investigate the genotypic and phenotypic drug resistance patterns of HIV-1 subtype B' variants, which are prevalent in China, in order to rationally design more efficient anti-HIV-1 regimens for future treatment of AIDS patients. 13 out of 16 patients (81%) who were treated with two NRTIs (ddI, and d4T or AZT) and one NNRTI (NVP) exhibited high resistance to NVP, 8 of them with a >1,000 IC50 fold increase. Five codons (101, 103, 108, 181, and 190) were involved in the NVP-resistant mutations, and K103N and Y181C mutations were predominant in these isolates. Fifteen isolates were resistant to at least one of the NRTIs, with high resistance to AZT (>10 IC50 fold increase) and intermediate resistance to d4T or ddI (approximately 4 IC50 fold increase). More than 10 codons were involved in the NRTI-resistant mutation and located in two regions (M41-V75 and T215-K219) of the reverse transcriptase. Concordance between the genotype and phenotype patterns for both NRTIs and NNRTI were detected in a majority of the isolates, suggesting that phenotypic resistance is predictable from genotyping assays, which are faster and less expensive than phenotypic assay. Because NVP and AZT can induce high resistances in these patients, these two drugs should be replaced with others more effective NNRTIs and NRTIs.
Ma
Liying
L
State Key Laboratory for Infection Diseases Prevention and Control, National Center for AIDS/STD Control and Prevention (NCAIDS), Chinese Center for Disease Control and Prevention (China CDC), People's Republic of China.
Sun
Jianping
J
Xing
Hui
H
Si
Xuefeng
X
Yuan
Lin
L
Guo
Yanfang
Y
Cheng
Hua
H
Shao
Yiming
Y
D019380:Anti-HIV Agents / Q000494:pharmacology* / Q000627:therapeutic use; D023241:Antiretroviral Therapy, Highly Active; D002681:China; D024882:Drug Resistance, Viral / Q000235:genetics*; D005838:Genotype; D015658:HIV Infections / Q000188:drug therapy / Q000453:epidemiology / Q000821:virology*; D015497:HIV-1 / Q000187:drug effects* / Q000235:genetics; D010641:Phenotype
D019380:Anti-HIV Agents