Polymorphisms and drug resistance analysis of HIV-1 CRF01_AE strains circulating in Fujian Province, China

Abstract

The database of genotypic drug resistance mutations in HIV-1 subtype B circulating in developed industrial countries has been well established; however, little is known regarding the prevalence of genotypic resistance patterns in patients harboring non-subtype-B HIV-1 variants in most Asian countries. To characterize the polymorphisms and emergence of drug-resistance mutations, resistance to antiretroviral drugs in naïve and pretreated patients infected with HIV-1 CRF01_AE isolates in Fujian province, China. HIV-1 pol amplicons from 52 pre- and 14 post-treatment samples were obtained by reverse transcription-polymerase chain reaction (RT-PCR) and sequencing. All of the 14 antiretroviral-treated patients were under a fixed regimen of stavudine (d4T), lamivudine (3TC) and nevirapine (NVP), and they had been on treatment for a mean of 6 months (SD, 4 months). The sequence data were analyzed using the Bioedit software, and the data regarding drug resistance mutations were obtained using the Stanford software ( http://hivdb.stanford.edu ). In comparison with the consensus sequence of B strains, the most common protease polymorphisms in HIV-1 CRF01_AE strains prevailing in Fujian Province, China, were I13V (76.9%), E35D (76.9%), M36I (100%), R41K (98.1%), H69K (90.4%), and L89M (96.2%). Protease mutations between CRF01_AE strains and B' variants prevailing in China were observed. The proportion of substitutions L63P, A71T/V, V77I and I93L in subtype B' sequences was considerably higher than in CRF01_AE viruses, while the proportion of L10I, M36I and K20R/I substitutions in subtype B' sequences was relatively lower than in CRF01_AE strains. A high level of resistance to nucleoside reverse transcriptase inhibitors (NRTIs) (28.6%, 4/14) and non-nucleoside reverse transcriptase inhibitors (NNRTIs) (35.7%, 5/14) was found in treatment-experienced patients. High-level resistance to nevirapine (NVP) and lamivudine (3TC) was found in the stavudine/lamivudine/nevirapine (d4T/3TC/NVP) treatment regimen. The overall drug resistance rate was 42.9% (6/14), the resistance rates to two and to all three drugs under treatment were 14.3% (2/14) and 7.1% (1/14), respectively. This study is the first report on polymorphisms and emergence of drug-resistance mutations in HIV-1 subtype CRF01_AE prevailing in China. These findings provide useful information on global HIV genetic variability and non-B drug resistance.