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


OBJECTIVE
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.


METHODS
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 ).


RESULTS
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.


CONCLUSIONS
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.
Liu
J
J
Department of Clinical Laboratory, Shanghai Pulmonary Hospital, Shanghai, China.
Yue
J
J
Wu
S
S
Yan
Y
Y
D000328:Adult; D000595:Amino Acid Sequence / Q000235:genetics; D002681:China / Q000453:epidemiology; D015331:Cohort Studies; D016384:Consensus Sequence; D016208:Databases, Factual; D024921:Drug Resistance, Multiple, Viral / Q000235:genetics*; D005260:Female; D014644:Genetic Variation; D015658:HIV Infections / Q000188:drug therapy* / Q000453:epidemiology; D054303:HIV Reverse Transcriptase / Q000037:antagonists & inhibitors*; D015497:HIV-1 / Q000145:classification / Q000187:drug effects / Q000235:genetics* / Q000302:isolation & purification; D006801:Humans; D019259:Lamivudine / Q000494:pharmacology / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009154:Mutation; D019829:Nevirapine / Q000494:pharmacology / Q000627:therapeutic use; D011110:Polymorphism, Genetic; D015995:Prevalence; D018894:Reverse Transcriptase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017386:Sequence Homology, Amino Acid; D018119:Stavudine / Q000494:pharmacology / Q000627:therapeutic use
D018894:Reverse Transcriptase Inhibitors; D019259:Lamivudine; D019829:Nevirapine; D018119:Stavudine; D054303:HIV Reverse Transcriptase