The Polymorphism Of HIV-1Vpr Gene And Its Clinical Significances Among Chinese HIV-1Infected Patients

[Objective]To discuss the molecular epidemiologcal characteristic of HIV-1subtypes and HIV-1Vpr gene diversity and its Clinical significances among Chinese HIV-1infected patients.[Methods]The patients were screened from antiretroviral therapy cohort of the national11th Five-year Plan in Chinese treatment-naive HIV/AIDS patients. We assessed the different influencing factors of AIDS disease progression (including gender, age, ethnicity, sexual transmission mode, the baseline CD4+T lymphocyte count, baseline HIV viral load). HIV RNA were extracted from plasma samples of total323patients, and the Vpr gene were amplified by RT-PCR and nested-PCR. Using Contig Express software, Bioedit5.0software, the United States Alamos National Laboratory Los Alamos site HIV databases, Clustal W software, Mega4.1software, we constructed the phylogenetic trees to confirm the virus subtype. We compared the two results of virus subtype which were genotyped by vpr gene and env/gag gene, analyzed the deduced amino acid sequence. We collected and calculated the clinical data at baseline and the end of48weeks’ combined antiretroviral therapy (including gender, age, transmission mode, CD4+T lymphocyte count, HIV viral load, serum creatinine, estimated glomerular filtration rate (eGFR) and clearance of creatinine). We described the molecular epidemiologcal characteristic of HIV-1subtypes and identified the characteristics of the polymorphism of HIV-1Vpr gene and its clinical significances among Chinese HIV-1infected patients.[Results]1. The molecular epidemiologcal characteristic of HIV-1subtypes among Chinese HIV-1infected patientsMost of the Chinese HIV-1infected patients are male accounted for74.7%. Patients with age18to49years old accounted for87.0%. The majority subtype was CRF01_AE accounted for46%. There were other subtypes including subtype BC(28%)(CRF07_BC(19%), CRF08_BC(9%))、subtype B(23%)、subtype CRF03_AB(2%) and subtype C(1%). The subtype CRF01_AE was mainly distributed in Beijing, Shanghai, and Guangzhou. Subtype BC (CRF07_BC、CRF08_BC) were mainly distributed in Yunnan. Subtype B was mainly distributed in Henan. Sexually-transmitted population accounts for83.0%Chinese HIV-1infected patients, which included43.0%homosexual transmitted patients and38.3%heterosexual transmitted patients. The ratio is roughly1:1between homosexual and heterosexual transmission patterns. The spread of subtype CRF01_AE is mainly through homosexual transmission. Subtype B predominates in patients through Blood transmission. The co-infection prevalence of HIV-1and HBV is15.0%and of HIV-1and HCV is11.3%among Chinese HIV-1infected patients. The co-infection prevalence of HIV-1and HCV was much higher in patients infected with subtype B (26.5%) than others (P=0.000). Comparing the methods for identifying the subtypes of HIV-1when HIV-1env/gag gene was used to analyze, the consistence of results is up to94%, and it is an accurate, simple, convenient and cost savings method when HIV-1Vpr gene was used to analyze.2. The impact of different HIV-1subtypes on clinical effect of antiretroviral treatmentAt baseline, patients infected with subtype CRF01_AE have a lower CD4+T lymphocyte count than others (P=0.007). At the end of48weeks, the results that the CD4+T lymphocyte count increased and plasma HIV-1viral load significantly decreased, were found among patients infected with subtype CRF01_AE, subtype CRF07_BC, CRF08_BC and subtype B, but there were no significant difference according to HIV-1subtype in the clinical effect of antiretroviral treatment.3. HIV-1Vpr gene diversity and its Clinical significances among Chinese HIV-1infected patientsThe conservative sites of HIV-1Vpr took41.7%in the whole deduced amino acid residues among Chinese HIV-1infected patients. The mutation sites distributed more dispersed. The occurrence of viriation in the C-term was more obvious than that in the N-term. In the77th position,81.7%of the300amino acid sequences were glutamine (Q), which differ from overseas reports most of them were Arginine (R). Among Chinese HIV-1infected patients, Vpr R85P and Q86G have been associated with a lower CD4+T lymphocyte count and a higher plasma HIV-1viral load at baseline (P<0.05). Vpr A89G has been associated with a lower CD4+T lymphocyte count at baseline and at the end of48weeks (P<0.05). Vpr I84L has been associated with a lower plasma HIV-1viral load at baseline and a higher CD4+T lymphocyte count at the end of48weeks (P<0.05). Vpr E55A has been associated with a higher CD4+T lymphocyte count at baseline (P=0.038)。[Conclusions]This study proposed that it is convenient and feasible we when use phylogenetic trees of Vpr gene to confirm the HIV-1subtypes among Chinese HIV-1infected patients. The majority of Chinese HIV-1infected patients are male. CRF01_AE is a predominant HIV-1subtype in Chinese HIV-1infected patients. Sexual transmission is the main route of transmission. The ratio is roughly equal between homosexual and heterosexual transmission patterns. Patients infected with CRF01_AE are associated with fast progression to AIDS. This study finds no significant difference in the clinical effect of antiretroviral treatment among patients infected with different HIV-1subtypes. Among Chinese HIV-1infected patients, the mutation frequency of Vpr R77Q is higher than overseas reports. Vpr R85P and Q86G, A89G may be associated with a fast progression to AIDS. However, Vpr E55A may be associated with a slow progression to AIDS.This study not only revealed the molecular epidemiologcal characteristic of HIV-1subtypes and HIV-1Vpr gene diversity and its clinical significances among Chinese HIV-1infected patients, but also could guide the disease surveillance, assist the HIV-1vaccine development and provide potential treatments.