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Polymorphism and drug selected mutations of reverse transcriptase gene in 102 HIV-1 infected patients living in China.

Research paper by Li L Liu, Hong Zhou HZ Lu, Mireille M Henry, Catherine C Tamalet

Indexed on: 21 Aug '07Published on: 21 Aug '07Published in: Journal of Medical Virology



Abstract

Few data are available for genotypic patterns within human immunodeficiency virus-1 (HIV-1) reverse transcriptase (RT) in drug-naive patients and RT inhibitor (RTI) treated patients in China. This study aimed at characterizing the polymorphism of RT HIV-1 in the absence of drug treatment and to identify known and unknown mutations emerging under RTI selective pressure. The HIV-1 RT gene from 21 drug-naive patients and 81 RTI treated patients from three provinces in China was analyzed. Most patients (>80%) received a triple regimen including stavudine (d4T) plus didanosine (ddI) and nevirapine (NVP), or d4T plus lamivudine (3TC) and efavirenz (EFV), or zidovudine (AZT) +ddI + NVP. In untreated patients, four highly polymorphic positions were found (122, 200, 207, and 211). In treated patients, two patterns of resistance associated mutations (RAMs) were observed: (1) K65R (9.8%), L74V (7.4%), M184V (7.4%), Q151M (5%), and thymidine analogue mutations (TAMs) (9.3%) including T215Y (5.5%), in patients who underwent ddI + d4T + NVP. (2) T215Y (23%), M184V (20%), and TAMs (15.4%) in patients receiving d4T + 3TC + EFV. In all cases, a high prevalence of non-nucleoside RTIs (NNRTI) RAMs (41.9%) was found. Four RTI suspected new RAMs were described at position 142, 221, 224, and 228. An association between H221Y and L228H/R with Y181C was noted. These data highlight the predominant spread of NNRTI RAM in China, depict the specific genotypic pattern of RTI selected mutations in China, and suggest the association of newly described mutations with RTI therapy.