Identification of associated risk factors for serological distribution of hepatitis B virus via machine learning models.

BACKGROUND: The provincial-level sero-survey was launched to learn the updated seroprevalence of hepatitis B virus (HBV) infection in the general population aged 1-69 years in Chongqing and to assess the risk factors for HBV infection to effectively screen persons with chronic hepatitis B (CHB). METHODS: A total of 1828 individuals aged 1-69 years were investigated, and hepatitis B surface antigen (HBsAg), antibody to HBsAg (HBsAb), and antibody to B core antigen (HBcAb) were detected. Logistic regression and three machine learning (ML) algorithms, including random forest (RF), support vector machine (SVM), and stochastic gradient boosting (SGB), were developed for analysis. RESULTS: The HBsAg prevalence of the total population was 3.83%, and among persons aged 1-14 years and 15-69 years, it was 0.24% and 4.89%, respectively. A large figure of 95.18% (770/809) of adults was unaware of their occult HBV infection. Age, region, and immunization history were found to be statistically associated with HBcAb prevalence with a logistic regression model. The prediction accuracies were 0.717, 0.727, and 0.725 for the proposed RF, SVM, and SGB models, respectively. CONCLUSIONS: The logistic regression integrated with ML models could helpfully screen the risk factors for HBV infection and identify high-risk populations with CHB.

CRF07_BC is associated with slow HIV disease progression in Chinese patients.

HIV subtypes convey important epidemiological information and possibly influence the rate of disease progression. In this study, HIV disease progression in patients infected with CRF01_AE, CRF07_BC, and subtype B was compared in the largest HIV molecular epidemiology study ever done in China. A national data set of HIV pol sequences was assembled by pooling sequences from public databases and the Beijing HIV laboratory network. Logistic regression was used to assess factors associated with the risk of AIDS at diagnosis ([AIDSAD], defined as a CD4 count < 200 cells/µL) in patients with HIV subtype B, CRF01_AE, and CRF07_BC. Of the 20,663 sequences, 9,156 (44.3%) were CRF01_AE. CRF07_BC was responsible for 28.3% of infections, followed by B (13.9%). In multivariable analysis, the risk of AIDSAD differed significantly according to HIV subtype (OR for CRF07_BC vs. B: 0.46, 95% CI 0.39─0.53), age (OR for ≥ 65 years vs. < 18 years: 4.3 95% CI 1.81─11.8), and transmission risk groups (OR for men who have sex with men vs. heterosexuals: 0.67 95% CI 0.6─0.75). These findings suggest that HIV diversity in China is constantly evolving and gaining in complexity. CRF07_BC is less pathogenic than subtype B, while CRF01_AE is as pathogenic as B.

Virological outcomes and drug resistance in Chinese patients after 12 months of 3TC-based first-line antiretroviral treatment, 2011-2012.

OBJECTIVE: To determine the prevalence of virological failure and HIV drug resistance among Chinese patients one year after initiating lamivudine-based first-line antiretroviral treatment. METHODS: A prospective cohort study with follow-up at 12 months was conducted in four urban sentinel sites in China. Antiretroviral naive patients ≥18 years old were recruited. Blood samples were collected for testing CD4 cell count, viral load, and (for samples with HIV-1 RNA ≥1000 copies/ml) genotyping of drug resistance. RESULTS: A total of 513 patients were enrolled in this cohort, of whom 448 (87.3%) were retained at 12 months. The median final CD4 cell count was 313 cells/mm(3), which increased from 192 cells/mm(3) at baseline (P<0.0001). Of the 448 remaining subjects, 394 (87.9%) had successful virological suppression (HIV RNA <1000 copies/ml). Among 54 samples with viral load ≥1000 copies/ml, 40 were successfully genotyped, and 11 were found with detectable HIV drug resistance mutations. Of these, the proportions of drug resistance to NNRTIs, NRTIs and PIs were 100%, 81.8% and 0%, respectively. Injecting drug use (AOR = 0.40, 95% CI: 0.19,0.84; P = 0.0154), CD4 count at baseline ≥350 cells/mm(3) (AOR = 0.32, 95% CI: 0.14,0.72; P = 0.0056), and missed doses in the past month (AOR = 0.30, 95% CI: 0.15,0.60; P = 0.0006) were significantly negatively associated with HIV RNA <1000 copies/ml. CONCLUSIONS: Our study demonstrates effective virological and immunological outcomes at 12 months among these who initiated first-line ART treatment. However, patients infected through drug injection, who missed doses, or with higher CD4 count at baseline are at increased risk for poor virological response.

Association of HLA-A, B, DRB1 alleles and haplotypes with HIV-1 infection in Chongqing, China.

BACKGROUND: The human immunodeficiency virus type 1(HIV-1) epidemic in Chongqing, China, is increasing rapidly with the dominant subtype of CRF07_BC over the past 3 years. Since human leukocyte antigen (HLA) polymorphisms have shown strong association with susceptibility/resistance to HIV-1 infection from individuals with different ethnic backgrounds, a recent investigation on frequencies of HLA class I and class II alleles in a Chinese cohort also indicated that similar correlation existed in HIV infected individuals from several provinces in China, however, such information is unavailable in Chongqing, southwest China. METHODS: In this population-based study, we performed polymerase chain reaction analysis with sequence-specific oligonucleotide probes (PCR-SSOP) for intermediate-low-resolution HLA typing in a cohort of 549 HIV-1 infected individuals, another 2475 healthy subjects from the Han nationality in Chongqing, China, were selected as population control. We compared frequencies of HLA-A, B, DRB1 alleles, haplotypes and genotypes between the two groups, and analyzed their association with HIV-1 susceptibility or resistance. RESULTS: The genetic profile of HLA (A, B, DRB1) alleles of HIV-1 infected individuals from Chongqing Han of China was obtained. Several alleles of HLA-B such as B*46 (P = 0.001, OR = 1.38, 95%CI = 1.13-1.68), B*1501G(B62) (P = 0.013, OR = 1.42, 95%CI = 1.08-1.88), B*67 (P = 0.022, OR = 2.76, 95%CI = 1.16-6.57), B*37 (P = 0.014, OR = 1.93, 95%CI = 1.14-3.28) and B*52 (P = 0.038, OR = 1.64, 95%CI = 1.03-2.61) were observed to have association with susceptibility to HIV-1 infection in this population. In addition, the haplotype analysis revealed that A*11-B*46, A*24-B*54 and A*01-B*37 for 2-locus, and A*11-B*46-DRB1*09, A*02-B*46-DRB1*08, A*11-B*4001G-DRB1*15, A*02-B*4001G-DRB1*04, A*11-B*46-DRB1*08 and A*02-B*4001G-DRB1*12 for 3-locus had significantly overrepresented in HIV-1 infected individuals, whereas A*11-B*1502G, A*11-B*1502G-DRB1*12 and A*33-B*58-DRB1*13 were underrepresented. However, the low-resolution homozygosity of HLA-A, B, DRB1 loci and HLA-Bw4/Bw6 genotypes did not differ significantly between the two groups. CONCLUSION: These results may contribute to the database of HLA profiles in HIV-1 infected Chinese population, consequently, the association of certain HLA alleles with susceptibility or resistance to HIV-1 infection would provide with clues in choosing proper preventive strategies against HIV-1 infection and developing effective HIV-1 vaccines in Chinese population, especially for those in southwest China.

Human leukocyte antigen profile in HIV-1 infected individuals and AIDS patients from Chongqing, China.

HIV/AIDS is currently the leading cause of infectious disease mortality around the world. Since many alleles and/or haplotypes of HLA have been reported to be associated with progressive HIV infection, more detailed information on the HLA profile in HIV-1 infected individuals in Chongqing, southwest China would facilitate further understanding of HIV-1 infection, help AIDS vaccine design and the planning of effective preventive strategies. In this study, we performed 4-digit resolution HLA-A, B, DRB1 genotyping of 759 HIV-1 seropositive individuals using PCR-SSO methods. Six alleles were found at more than 10% high frequency: A*1101, A*0201, A*2402, B*4601, B*4001 and DRB1*0901. The most common 2- and 3-locus haplotypes were A*0201-B*4601, A*1101-B*4001, A*1101-B*4601, A*3303/1-B*5801, A*0201-B*4601-DRB1*0901, A*1101-B*4601-DRB1*0901 and A*3303/1-B*5801-DRB1*0301. 690 HIV-1 seropositive individuals with records of CD4 counts were divided into two groups: an AIDS patient group comprising 216 subjects with AIDS-defining symptoms and CD4 counts below 200 cells/mm(3) and an asymptomatic, HIV seropositive group of 474 subjects with a stable CD4 count of no less than 200 individuals. In the AIDS patient group, A*3303/1 and B*5801 alleles and the A*3303/1-B*5801 haplotype were significantly underrepresented as compared to the HIV-infected group, whereas A*1101-B*4001, A*1101-B*1502, A*2402-B*4801 haplotypes and five common haplotypes from two groups were significantly overrepresented. HLA-A or B and HLA-Bw6-Bw6 homozygotes were also overrepresented in the AIDS patients group. Our observations suggest that the presence of the B*3501 allele, A*2402-B*4801, common 2-locus and 3-locus haplotypes, HLA-A or B and Bw6-Bw6 homozygosity may predict a poor disease outcome in HIV-1 infection. However, HIV-1 infected individuals who have B*5801 alleles, A*3303/1-B*5801 haplotype and are heterozygous for Bw4-Bw6 are more likely to be resistant to progression of AIDS in this Chinese population.

HIV-1 incidence estimates using IgG-capture BED-enzyme immunoassay from surveillance sites of injection drug users in three cities of China.

OBJECTIVE: To detect recent infection in injection drug users (IDU) using the HIV-1 subtypes B, E, and D IgG-capture enzyme immunoassay (BED-CEIA) and estimate HIV-1 incidence in the IDU population in three cities of China. DESIGN: HIV-1-positive samples from IDU surveillance sentinel sites were collected for BED-CEIA, including 215 from city C (2001-2006), 433 from city D (2005), and 912 from city E (2000-2003). All 1560 samples were confirmed HIV positive with Western blot or alternative strategy. METHODS: HIV-1 incidence was calculated with BED-CEIA statistics software. RESULTS: City C: Annualized HIV-1 incidence among IDU of surveillance sentinel sites was 0.57-0.93% from 2000 to 2001, and approximately 1.0% from 2004 to 2006. City D: In IDU surveillance sentinel sites in 2005, the HIV-1 incidence was estimated to be 9.6%, whereas the incidence in all drug users was 2.1%. City E: IDU sentinel surveillance indicated a slight decrease in HIV-1 incidence from 9.2% in 2000 to 7.9% in 2003. CONCLUSION: The HIV-1 incidence in IDU in city C was stable and relatively low. In contrast, there is a high HIV-1 incidence among IDU in cities D and E. The adjusted BED-CEIA estimated incidence rates indicate clearly that interventions must be strengthened continuously in IDU, especially in two Chinese cities.

[Application of BED-CEIA to estimate the human immunodeficiency virus prevalence among injecting drug users in Chongqing municipality].

OBJECTIVE: To estimate the human immunodeficiency virus (HIV-1) prevalence of injecting drug users (IDUs) in Chongqing city. METHODS: To apply BED-capture enzyme immunoassay (CEIA) which was based on the principle of HIV-antibody varies as the disease progress, in order to estimate both the HIV incidence and prevalence of IDUs from two IDUs surveillance sites in Chongqing. RESULTS: During the research period, 4711 serum samples were tested by ELISA and 130 were HIV-1 positive, confirmed by Western blot. The prevalence of IDUs surveillance site A from 1999 to 2006 were 0.73%, 2.02%, 1.54%, 2.96% and 2.80%, and the incidence rates were 0.57%, 0.93%, 0,1.24% and 1.68% respectively. The prevalence of IDUs surveillance site B appeared to be 4.21%, 9.96%, 8.13%, and the incidence rates were 0.95%, 1.04% and 0.90% respectively, from 2004 to 2006. CONCLUSION: Many of the IDUs HIV carriers in Chongqing had been infected for long time, and the incidence rates among them were steady, keeping at the same level for 1-2 years. Promotion on intervention for IDUs had produced certain effects but more attention still needs to be paid.