The Molecular Epidemiology Of Human Immunodeficiency Virus Type I (HIV-1) And HIV-1 Drug Resistant Genotype In Central China

1. HIV-1 epidemic in paid blood donors (PBDs) in central China-Henan and Hubei provinces.To investigate the genetic background of HIV-1 strains among infected paid blood donors (PBD) in Henan and Hubei of Central China, we performed a molecular epidemiological study based on blood samples collected from 2000 to 2004. Of 69 PBDs, accounting for 92% of total Henan and Hubei samples, 45 were from 15 geographic locations in Henan and 14 from 7 in Hubei. HIV-1 gag fragments and env fragment from some of the samples were sequenced. Viral sequences were phylogenetically analyzed in comparison to reference sequences in the HIV database. We found that PBDs from geographically distant regions in Henan and Hubei harbored a group of genetically closely related HIV-1 B' strains. There were no distinct viral clusters based on geographic proximity. And further analysis of env fragment and pol fragment sequences also got the same result-B' appeared to be dominant HIV-1 genotype among PBDs in Central China. Our data indicated that 1) the AIDS epidemic caused by paid blood donation is not restricted in certain villages in Henan but rather spreading out in other provinces in Central China; 2) HIV-1 B' strains dictate the AIDS epidemic among PBDs in Henan and Hubei provinces, in contrast with the epidemics among intravenous drug users, sex transmitters in otherprovinces; 3) It is likely that the introduction of B' viruses into Henan from Yunan have occurred before the formation of multiple mosaic HIV-1 strains-07_BC and ()8_BC CRF-in Dehong, Yunnan.2. HIV-1 Drug resistant genotype before and after antiretroviral therapy (ART) in ChinaTo understand the prevalence and distribution of HIV-1 drug resistant genotypes before the initiation of antiretroviral therapy in China, we conducted a cross-sectional study on 175 subjects found in 13 provinces including Henan, Hubei, Beijing, Xinjiang, Shenzhen, Yunnan, Guangdong, Hebei, Shanxi, Anhui, Fujian, Guangxi, Shanghai. These subjects represent different risk populations such as paid blood donors (PBDs), intravenous drug users (IDUs), sexual contact transmitters (ST), blood recipients (BR) and vertical transmitters (VTs). Multiple clones of HIV-1 protease and reverse transcriptase genes were amplified and sequenced from each study subject. The sequence data were then subjected to genetic analysis. Of the 175 subjects studied, we identified multiple HIV-1 subtypes including B' (n=122), B (n=19), 07_BC (n=16), 08_BC (n=7), C (n=2), and 01_AE (n=7). Consistent to our previous findings, B' dominates the population of PBDs (63/63) in Henan and Hubei. Moreover, drug resistant mutations/substitutions were found in 98.9% study subjects. These mutations, however, represent mainly secondary mutations (173/175) with only a relatively small percentage of the primary mutations (31/175). The frequencies of protease mutations were found to be significantly different between subtype B and non-B strains: K20R/I (2.1% versus 11.4%, p=0.012), M36I (7.1% versus 60.0%, p=0.000), L63P (92.9% versus 74.3%, p=0.002), A71V/T (25.7% versus 2.9%, p=0.003) and V77I (97.1% versus 5.7%, p=0.000). L63P, V77I, and I93L are more frequently found in subtype B viruses whereas mutation site combined with M36I co-occurred more in non-B viruses. Similar difference was also found in reverse transcriptase, such as V106I (11.4% versus none, p=0.036). The geographic distribution of the transmitting viruses was also investigated. In summary, mutations or substitutions associated with drug resistance were identified in our study subjectsdistributed in almost every province or city. Mutations with high frequency might suggest the active transmission of these kinds of drug resistant viruses. This study has established a basis for the monitoring of HIV-1 drug resistant genotypes in study areas. Our findings will also help the assessment of optimal treatment for patients who receive antiretroviral therapy.As the large scale of anti-HlV-l therapy has been launched from August of 2003 to July of 2004 in Hubei province of China. Many HIV-1 infected paid blood donors (PBDs) in Hubei have been treated by highly active antiretroviral therapy (HAART, mainly combination of zidovudine, stavudine, didanosine, nevirapine and efavirenz). To monitor the treatment effect and provide guide to the physicians for their choice of antiretroviral drugs, we continued our drug resistant genotyping research in Hubei province.We collect specimens randomly from 74 individuals treated with antiretroviral drugs from Aug. 2003 to Dec. 2004. After months of therapy, primary resistance mutations were found from 32 out of 74 patients (43.2%). The mutation sites were K65R, M184V/I, K103N, V106A, V108I, Y181C, Y188L/C and G190A. Nineteen (55.9%) Of the 32 patients, 15patients' plasma viral load were detected, ranging from 3.59xl03 to 1.48xl06copies/ml. Our findings demonstrated that more drug resistant HIV-1 strains have been emerging overtime since the initiation of antiretroviral therapy. And the resistance strains might have transmitted in a group of people. Since there are only limited drug regimens available to patients in China, our data strongly urge the need for strengthening the antiretroviral therapy management.