The Different Progression Characteristics Among Chinese Sexually-transmitted HIV/AIDS Patients And Related Influencing Factors Study

[Objective]:To study the various characteristics of disease progression from HIV infection to AIDS among Chinese treatment-naive sexually-transmitted HIV/AIDS patients with CD4+ T cells below 350cells/μl, and assess the host and virological factors associated with disease progression.[Methods]:The patients were screened from a cohort of treatment-naive HIV/AIDS patients of the national 11th-five-year-plan and the follow-up outpatients from Clinic of Infectious Diseases, Peking Union Medical College hospital (PUMCH). The including criteria were:1) 18-65 years old; 2) Patients were found to be HIV-seropositive by standard serum enzyme-linked immunosorbent assay (ELISA) and Western blotting analysis; 3) sexually-transmitted; 4) the definite time on positive HIV antibody; 5) the time of HIV infection were relatively clear; 6) CD4+T cells≤350cells/μl; 7) treatment-naive. The excluding criteria were:1) in the acute stage; 2) the possibility of mixed transmitted infection. Rapid progressors (RP) were defined if the time from HIV seroconversion to AIDS was≤5 years; all other patients were defined as non-rapid progressors (NRP). We assessed various influencing factors of disease progression, including gender, age, ethnicity, sexual transmission mode, the baseline CD4+T lymphocyte count and baseline HIV viral load. Genomic DNA was extracted and analyzed on HLA-A, HLA-B, HLA-C, HLA-DRB1 alleles. The allele distribution was compared between RP group and NRP as well in order to evaluate different HLA polymorphism among different HIV/AIDS disease progression.35 patients were selected from two different groups (approximately by 1:1). HIV RNA was also extracted and the env (V3-V4), gag and pol were sequenced. Using Contig Express software, Bioedit 7.0 software, the United States Alamos National Laboratory Los Alamos site HIV databases, RIP program, Mega5.0 software and geno2pheno [coreceptor] software, we constructed the phylogenetic trees of HIV subtype, calculated the genetic divergence of HIV and predicted the viral tropism.[Results]:1,Total 282 patients were included. The trends of disease progression after HIV infection were fast in Chinese sexually-transmitted untreatable HIV/AIDS whose CD4+T cells had dropped below 350 cells/μl. The median time from HIV infection to the set of the CD4+ T cells below 350 cells/μl was 3.46 years (95% Cl:3.19～3.74). The median time from HIV infection to onset of AIDS was 3.40 years (95% Cl:2.88～3.93).2,The RP population accounted for 69.1% of whole 282 patients. The median time from HIV infection to onset of AIDS were 2.43 years (95% Cl:2.22～2.64) and 6.84 years (95% Cl:6.43～7.24) for RP and NRP, respectively.3,MSM accounts for majority of sexually-transmitted population. It was also a risk factor for disease progression (RR=1.732,95% Cl:1.360～2.205, P=0.000).4～The HLA typing results showed Chinese Han ethnic HIV/AIDS patients had highly polymorphic alleles of HLA molecules. HLA-A*02 allele may promote disease progression in HIV infection (OR=1.797,95%CI:1.128～2.862, P=0.014). The HLA-B*51 allele may delay disease progression in HIV infection (OR=0.379,95% Cl:0.157～0.914, P=0.031).5,Different subtypes of HIV-1 were found in 35 cases of sexually-transmitted HIV/AIDS, and the majority was CRF01_AE (51.4%). However, there was no difference between RP and NRP group. Among 15 patients with subtype CRF01_AE infection from Beijing, the changing trend of gene divergence on V4 region was different from other regions, and it was also different between RP and NRP group. The cell tropism predictions from 32 patients showed that the majority strains were CCR5 tropic (78.1%). CXCR4 tropic strains only occurred when patients' CD4+T cells were≤200cells/μl, which suggested that CXCR4 tropic viruses may be related to progression to AIDS stage.[Conclusions]:This is the first study to discuss the fast trends of progression of treatment-naive sexually-transmitted HIV/AIDS patients with CD4+T cells below 350cells/μl in China. MSM, HLA-A*02 allele maybe the risk factors to promote disease progression in HIV infection, and HLA-B*51 allele may delay HIV disease progression, and there were potential virological changes. This study not only revealed the different virological and immunological pathogenesis of different AIDS progressors, but also could guide the disease surveillance, aid potential treatments and assist vaccine development.