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Polymorphisms and Mutations in the Reverse Transcriptase Gend of HIV-1 C Isolated from Naive and Treated Batswana Patients F. Doualla-Bell1-3, S. Gaseitsiwe3, T. Peter3, V. Novitsky4, T. Ndung’u3, W. Wester 3, H. Bussman 3, A. Avalos3, N. Ndwapi2, T. Gaolathe 2, H. Moffat2, R. Marlink4, M. A. Wainberg1 and M. Essex4. 3Botswana-Harvard Partnership for HIV Research and Education, 2Infectious Disease Care Clinic; Princess Marina Hospital, Gaborone, Botswana. 4Harvard School of Public Health, Boston, Massachusetts. 1McGill University-AIDS Centre, Lady Davis Institute for Medical Research -Jewish General Hospital-SMD, Montreal, Quebec, Canada Background Little information is available on the impact of genetic diversity of non-B HIV-1 subtypes on antiretroviral (ARV) drug susceptibility. In this study we attempted to determine specific polymorphisms and mutations in the reverse transcriptase (RT) gene from HIV-1C isolated from ARV-naïve or treated Batswana patient plasma. Methods We retrospectively analyzed 17 patients (six ARV-naïve and eleven treated patients) followed at the current Infectious Disease Care Clinic (IDCC) of Princess Marina Hospital (Botswana) between May 2001 and January 2003. Among the eleven ARV-treated patients, 5 started a highly active antiretroviral therapy (HAART) regimen containing ddI/d4T/NVP (4/5 failed) while the 6 others started a CBV/EFV regimen (1/6 failed). At first sign of viral rebound the pol gene of HIV was sequenced and analyzed for the presence of resistance mutations (Viroseq, Applied Biosystems). Results Many polymorphisms on RT were detected in both treated and untreated patients. No mutations associated with resistance were found in unfailed or naïve patients. Primary mutations, associated with 3TC, AZT, ddI, NVP or EFV-resistance, were detected in 5 treated patients in clinical failure: K103N (2/5), Y181C (4/5), K65R (2/5), T69D (1/5), M184V (2/5), V106M (1/5), T215Y and M230L (1/5). The presence of the K166R polymorphism in the background of RT gene mutations seems to delay the emergence of mutations associated with NVP-resistance while the presence of P272A mutation may counteracted this effect. Conclusion Since the beginning of 2002, Batswana have had access to HAART. This study demonstrates for the first time the presence of specific polymorphisms in the RT gene which may change the resistance pattern associated with ARV drugs in Batswana infected with HIV-1 subtype C. |