An efficient tool for surveying CRF01_AE HIV type 1 resistance in Thailand to combined stavudine-lamivudine-nevirapine treatment: mutagenically separated PCR targeting M184I/V

• Published in: AIDS research and human retroviruses Vol. 23; no. 12; p. 1461
• Main Authors: Saeng-Aroon, Siriphan, Yoshida, Lay Myint, Ariyoshi, Koya, Taguchi, Masataka, Pathipvanich, Panita, Rojanawiwat, Archawin, Matsuda, Masakazu, Kannagi, Mari, Sawanpanyalert, Pathom, Sugiura, Wataru, Auwanit, Wattana
• Format: Journal Article
• Language: English
• Published: United States 01.12.2007
• Subjects: Anti-HIV Agents - pharmacology; Anti-HIV Agents - therapeutic use; Drug Resistance, Multiple, Viral - genetics; Drug Therapy, Combination; HIV Infections - drug therapy; HIV Infections - virology; HIV-1 - drug effects; HIV-1 - genetics; Humans; Lamivudine - pharmacology; Lamivudine - therapeutic use; Mutation; Nevirapine - pharmacology; Nevirapine - therapeutic use; Polymerase Chain Reaction - economics; Polymerase Chain Reaction - methods; Sensitivity and Specificity; Stavudine - pharmacology; Stavudine - therapeutic use; Thailand; Thailand
• ISSN: 0889-2229
• DOI: 10.1089/aid.2007.0042

Under programs organized by the government of Thailand, HIV-1-infected patients have been treated since 2002 with several regimens, including a tablet known as GPOvir, which contains lamivudine, stavudine, and nevirapine. The aim of this study was to establish an effective assay, based on mutagenically separated PCR (MS-PCR), with the goal of surveying GPOvir-resistant HIV-1 cases. To determine the target mutation point for the assay, we analyzed the patterns of acquired drug resistance in plasma samples from GPOvir-failed cases. Of 428 HIV-1-infected individuals treated with GPOvir at Lampang Hospital in northern Thailand from 2002 to 2004, 66 had detectable viral loads after 3 months of treatment. The HIV-1 sequences of these 66 GPOvir-failed cases and 55 pre-GPOvir baseline samples were analyzed. The most prevalent drug resistance mutation among the samples was the lamivudine resistance M184I/V mutation. Based on this finding, we developed a new MS-PCR assay to detect the M184I/V mutation, and evaluated the assay performance for detecting GPOvir-resistant CRF01_AE cases. Comparing the results of M184I/V MS-PCR and sequence analyses, we found a concordance rate of 95% and an overall sensitivity of the M184I/V MS-PCR for detecting GPOvir-resistant cases of 79%. Considering the relatively low price of the assay, approximately $12.50 per sample, M184I/V MS-PCR may be a candidate for monitoring a large number of GPOvir-treated patients, particularly in developing nations.