Objective To investigate the association of blood transfusion volume with early death among recipients with known duration of infection in rural central China. Methods From January 1, 1999 to December 30, 2003, 76 individuals with duration of blood transfusion who met the study criterion had been found to be infected in the HIV/AIDS notified system in rural of Yuncheng Prefecture of Shanxi Province, China. A retrospective study was conducted to investigate Socio-demographic characteristics, transfusion volume, and mortality. Cox' proportional hazard regression model was used to analyze the data. Results By December 30, 2003, among 76 subjects with transfusion-acquired HIV infection, 24 recipients had died. Mortality rate and median survival was 45.64 and 8.3 per 1000 person years, respectively. Transfusion volume (HR=3.12, 95% CI: 1.18～8.25; P=0.0218) was significantly associated with mortality in recipients in the multiply Cox' proportional hazard regression model. Conclusions This study suggests that more units of transfusion in recipients with known duration of HIV infection can influence time to death in recipients in China.

Objective To explore the impact of broad antigen HLA-Bw4 on disease progression in HIV-1 infected subjects. Methods Three hundred and forty subjects chronically infected with HIV-1 and 69 HIV-1 negative subjects were recruited and HLA-B alleles were typed with sequence-based high resolution typing assay. HLA-Bw genotypes of these HIV-1 infected subjects were determined and their association with CD4+ T cell counts and viral loads were analyzed. Results Sixty-five HLA-B alleles were detected in HIV-1 positive subjects. Subjects with Bw4 (Bw4 homozygotes and Bw4Bw6 heterozygotes ) had higher CD4+ T cell counts ( P = 0. 004 ) and lower plasma viral load ( P = 0.003 ) than subjects without Bw4 ( Bw6 homozygotes). When compared with HIV-1 postive subjects with CD4+ T cell counts above 500 celis/μl, those with CD4+ T cell counts below 500 cells/μl were observed with decreased percentage of Bw4Bw6 heterozygote ( P =0.0002) and increased percentage of Bw6 homozygotes ( P < 0. 0001 ). There is no significant difference in CD4+ T cell counts between Bw4 homozygotes and Bw4Bw6 heterozygote, but lower viral loads were observed in Bw4Bw6 heterozygotes( P = 0. 037 ). Conclusion HLA-Bw4 can confer pretective effects on H1V-1 infected subjects by maintaining higher CD4+ T cell counts and lower viral load, the mechanism behind this effect need further exploration.

Objective:To study the amino acid and codon usage profile of HIV-1 Env gene in donors whose serum exhibit highly broad cross-neutralizing activity. Methods:The samples were divided into highly broad cross-neutralizing activity group (hBCN + group) and non-highly broad cross-neutralizing activity group (hBCN - group) based on whether the neutralization breadth was higher than 90% or not. Full-length Env genes were amplified by single genome amplification (SGA) method from patients′ plasma samples, and the characteristics of Env sequences in hBCN + group were compared with hBCN - group. The correspondence analysis (COA) on relative amino acid usage (RAAU), adaptability to host based on similarity index D( A, B) and relative synonymous codon usage (RSCU) values of Env genes (hBCN + and hBCN -) with respect to human host RSCU were analyzed. Results:Correspondence analysis showed that the RAAU data of hBCN + group and hBCN - group were distributed along the two main axes to form two relatively separated clusters, indicating that the Env genes of the two groups had relatively unique amino acid usage patterns; the similarity index calculation results showed that hBCN + group (0.097) was lower than the hBCN - group (0.102), in addition, the Env gene of the hBCN + group had less frequency of similarly selected codons with human host system compared to hBCN - group. Conclusions:Env genes in hBCN + group and hBCN - group may have relatively unique amino acid usage patterns, and virus strains in hBCN + group are less adaptable to the host than those in hBCN - group.

Objective To analyze characteristics of Nef-specific T lymphocyte responses in Chinese HIV-1 recombinant subtype B/C infectors. Methods 19 HIV-1 recombinant subtype B/C infectors infected within 1 year, 40 chronic infectors infected for more than 3 years were enrolled in this cohort study. Elispot assay was used to observe HIV-1 specific T lymphocyte responses in HIV-1 recombinant subtype B/C infectors. Results Nef-specific T lymphocyte responses of interferon-gamma secretion were identified in 15 Chinese HIV-1 recombinant subtype B/C infectors infected within 1 year. The specific T lymphocytes were mainly targeted at four peptides which span from Nef 83 to 135: EVA7081.1, EVAT081.5, EVA7081.6 and EVAT081.48. Responses were identified in 29(75. 2%) infectors with more than 3 years of infection and the specific T lymphocytes were mainly targeted at three peptides which span from Nef 63 to 101 : EVA7081.43, EVA7081.44, EVAT081.45, EVA7081.47, EVA7081.48 and EVA7081.49. The average magnitude of response in infectors with less than 1 year of infection was 284. 13 SFC/106 PBMC. The average magnitude of response in infectors with more than 3 years of infection was 152. 44 SFC/106 PBMC. There was a significant difference between the two groups (U = 91. 000, P = 0. 002). Conclusions HIV-1recombinant subtype B/C infectors at different stages of diseases (less than 1 year and more thank 3 years) can recognize central region of Nef. The magnitude of Nef-specific IFN-γ secretion T lymphocyte responses in this cohort gradually decrease with disease progression.

Objective To analyze the character of Pol-specific T lymphocyte responses and identify immunodominant region recognized in Chinese HIV-1 recombinant subtype B/C infectors at different stages of diseases. Methods Eleven Chinese HIV-1 recombinant subtype B/C infectors infected in 18 months, 25 which infected time more than 3 years and 10 HIV-1-seronegative healthy individuals were enrolled. HIV-1-specific T lymphocyte responses were analyzed by an IFN-γ ELISPOT assay against 249 overlapping peptides spanning HIV-1 Pol protein in the present study. Results Pol-specific T lymphocyte responses of IFN-γsecretion were identified in 8 (72.73%) out of 11 infectors infected in 18 months, the specific T lymphocytes are mainly targe-ted at six peptides which amino acid position from Pol 481 to 631 in reverse transcriptase region: Pol5581, Pol5582, Pol5587, Pol5609, Pol5610 and Pol5615. There was a negative correlation between the breadth of re-sponse and peripheral CD4+ T cell count (P=0.0212, r=-0.762) ; Responses were identified in 15 (60%) out of 25 chronic infectors, the specific T lymphocytes are mainly targeted at four peptides which amino acid po-sition from Pol 241 to 295: Pol5521, Pol5525, Pol5526, Pol5531 and another peptide: Pol5638 which amino acid position from Pol 708 to 722 in reverse transcriptase region. There was a positive correlation between the magnitude of Pol-specific IFN-γ secretion T lymphocyte responses and plasma viremia (P = 0.006 95 , r = 0.660) . None of the seronegative healthy individuals gave the positive responses. Conclusion Chinese HIV-1 recombinant subtype B/C infectors at different stages of diseases mainly recognized different re-gions of Pol.

Objective To analyze character of Nef-specific T lymphocyte responses in Chinese HIV-1 recombinant subtype C/B' and subtype B' infectors and to identify the common immunodominant re-gions recognized by these infectors. Methods Fifty-nine HIV-1 recombinant subtype C/B' infectors and 27 subtype B' infectors were tested by IFN-γ enzyme linked immunospot (ELISPOT) assay using HIV-1 C/B' Nef overlapping peptides. Results Nef-specific T-cell responses of IFN-γ secretion were identified in 44 (74.58%) out of 59 HIV-1 recombinant subtype C/B' infectors. Ten peptides, EVA7081.1,5, 6, 7,43, 44, 45, 47, 48, 49 were mainly recognized. Amino acid position was from Nef63 to 115 and 117 to 139. Twenty of 27 (74.07%) HIV-1 subtype B' infectors recognized peptides. EVA7081.1,2, 43 and 49 were mainly recognized. Amino acid position was from Nef 63 to 77 and 87 to 119. There was no correlation be-tween the Nef-specific IFN-production of HIV-1-specific T cells responses and viral load or CD4 T cell count in both subtype infectors. Conclusion The immunodominant regions, from Nef63 to 77 and 87 to 115 were recognized by both Chinese HIV-1 recombinant subtype C/B' infectors and subtype B' infectors. These re-gions could be used in design of vaccine.

Objective To explore the polymorphism of HLA class I alleles of HIV-infected former plasma donors and to investigate its impact on HIV-1 viral load in central China.Methods 106 subjects chronically infected with HIV-1 were recruited and HLA class I alleles were genotyped with PCR-SSP assay.HLA class I genotypes and haplotypes were determined and their association with plasma viral loads were analyzed.Gag-specific CTL responses were detected by an IFN-λ EUSPOT assay by using overlapping peptides,and their association with plasma viral loads were also analyzed.Results Subjects homozygous at HLA class I locus had higher plasma viral loads(P=0.0098);HLA-A*30,-B*13,-Cw*06,-Cw*14 alleles and HLA-A*30/B*13/Cw*06 haplotype were associated with lower plasma viral loads(P=0.0004,0.0103,0.0058,0.0371 and 0.0006);an inverse correlation between p2p7p1p6-specific CTL responses and viral loads in subjects with HLA-A*30/B*13/Cw*06 haplotype as well as an inverse correlation between p17-specific CTL responses and viral loads in subjects with HLA-Cw*14 allele were observed.Conclusion HLA-A*30,-B*13,-Cw*06,-Cw*14 alleles and HLA-A*30/B*13/Cw*06 haplotype were associated with lower plasma viral loads and Gag-specific CTL responses restricted by these HLA alleles may contribute to the protection.

Objective　To understand the impact of early and timely treatment and initial antiviral treatment regimen on mortality and attrition of antiretroviral therapy. Methods A retrospective cohort study was conducted using download data on antiretroviral therapy for HIV-infected patients in Liuzhou City, Guangxi Province, from the database of the Basic Information System for AIDS Control and Prevention (BISAC) from 2010 to 2020. The Cox proportional risk regression model was used to analyze the influencing factors of mortality and attrition. Results A total of 15 713 infected patients were included, including 53.4% aged 18-<50 years, 69.4% male, 61.0% farmer, 75.1% CD4 count <350 cells /μL before initial antiviral treatment, the overall mortality rate was 4.30/100 person-years, and the overall attrition was 2.42/100 person-years. The results of Cox regression analysis showed that the influencing factors of mortality were pretreatment CD4 counts of 350-<500 cells/μL(AHR=0.72, 95%CI: 0.63-0.81) and ≥500 cells/μL (AHR= 0.64, 95%CI: 0.55-0.76); duration from diagnosis to initial antiviral treatment 91-180 days (AHR=1.25, 95%CI: 1.08-1.45), 181-365 days (AHR=1.26, 95%CI: 1.08-1.47), and ≥365 days (AHR=1.26, 95%CI: 1.11-1.44); initial antiviral treatment regimens of D4T+3TC+EFV/NVP (AHR=1.47, 95%CI: 1.32-1.63) and AZT/D4T/TDF+3TC+LPV/r (AHR=1.73, 95%CI: 1.50-1.99). Factors affecting attrition were pretreatment CD4 counts of 350-499 cells/μL (AHR=1.32, 95%CI: 1.16-1.50) and ≥500 cells/μL (AHR=1.28, 95%CI: 1.10-1.50); interval from HIV positivity confirmation to initial dosing ≥365 days (AHR=1.21, 95%CI: 1.04-1.40), initial antiviral treatment regimens of TDF+3TC+NVP (AHR=1.32, 95%CI: 1.13-1.55), AZT+3TC+EFV/NVP (AHR=1.43, 95%CI: 1.26-1.62) and AZT/D4T/TDF+3TC+LPV/r (AHR=1.33, 95CI%: 1.06-1.67). Conclusions　Early and timely treatment and the initial antiviral treatment regimen of TDF+3TC+EFV have good efficacy, but attention should be paid to the high risk of attrition of HIV-infected people with high CD4 count before treatment.

Objective: To explore drug resistance of different viral loads, and investigate the relationship between drug resistance and CD4⁺T cell counts in patients with HIV antiretroviral therapy (ART) in China from 2003 to 2015. Methods: Data were extracted from the Chinese National HIVDR Surveillance database from 2003 to 2015. For this study, the data collected were as follows: having received ART for ≥12 months; 18 years or older; demographic characteristics, information of ART, CD4⁺T cell counts, viral load (VL) and HIV drug resistance of a total of 8 362 patients were collected. Multi-variables non-conditional logistic regression model was used to study the relationship between viral load, HIV drug resistance and CD4⁺T cell counts. Results: Participants with age of (41.8±10.5) years were enrolled in this study. Among them, 59.9% (5 009 cases) were men. The percentage of CD4⁺T cell counts <200 cells/μl in the total population was 17.9% (1 496 cases), the highest was in VL ≥1 000 copies/ml with drug resistance, which was 43.0% (397/923) , followed by VL 50-999 copies/ml with drug resistance, which was 31.1% (69/222), and the lowest was in VL 50-999 copies/ml without drug resistance 13.2% (273/2 068). Compared to VL 50-999 copies/ml without drug resistance, VL<50 copies/ml, VL 50-999 with drug resistance, VL≥1 000 copies/ml without drug resistance, and VL ≥1 000 copies/ml with drug resistance, the OR (95%CI) of CD4 <200 cells/μl were 0.9 (0.7-1.0), 3.2 (2.3-4.4), 2.6 (2.1-3.2), and 4.9 (4.0-5.9), respectively. Among 222 patients with VL 50-999 and HIVDR, the most frequent antiretroviral drugs were EFV and NVP, both of which were NNRTI, and whose percentage both were 94.1% (209 cases). The most frequent mutations were M184V/I (NNRTI), and the percentage was 26.1% (58 cases). The second one was K103N (NNRTI), and the percentage was 22.5% (50 cases). The percentage of V32L/E (PI) and V82A (PI) were lower, they were 0.9% (2 cases) and 0.5% (1 case) respectively. Conclusion Decreased CD4⁺T cell counts were associated with HIV drug resistance at low viraemia. In the case of low viral load, the most vulnerable were the NNRTI antiviral drugs such as EFV and NVP.

Objective:To understand influencing factors on the deaths of HIV/AIDS patients receiving antireviral treatment in Butuo county of Liangshan Yi Autonomous Prefecture (Liangshan) from 2010 to 2019, to provide data for drug replacement and sustainable antiviral treatment strategy.Methods:A matched case-control study was used to collect basic and follow-up information on AIDS death patients receiving antiviral treatment in Butuo county of Liangshan from 2010 to 2019. The control group was formed by sampling twice the number of cases. The logistic regression model was used to analyze the risk factors affecting mortality.Results:In 3 355 patients of HIV/AIDS treated with antiviral therapy, 1 179 cases in the death group and 2 176 cases in the control group. Including 81.34% were 30-49 years old, 69.09％males, 99.55% Yi nationality, 91.12% were married or cohabitated, 95.77% had junior high school education or below, and 88.41% peasants. Amultivariate logistic stepwise regression model showed that among the death risk factors, age ≥50 years old was 5.08 times (95% CI:3.05-8.48) that of the 18-29, female was 0.70 times (95% CI: 0.52-0.94) than male, the transmission rate of intravenous drug use was 1.43 times (95% CI: 1.06-1.91) that of heterosexual transmission, CD4 +T lymphocyte (CD4) count ≥350 cells/μl before treatment was 0.38 times (95% CI: 0.30-0.48) that of CD4 <200 cells/μl before treatment, the most recent antiviral treatment regimen containing LPV/r was 0.04 times (95% CI: 0.01-0.18) than that of stavudine (d4T) + lamivudine (3TC) + nevirapine (NVP)/efavirenz (EFV) regimen, drug resistance was 3.40 times (95% CI: 2.13-5.42) of non-drug resistance, non-viral load and non-drug resistance test results were 12.98 times (95% CI: 10.28-16.40) of non-drug resistance. Conclusions:Age, gender, transmission route, CD4 before treatment, the latest antiviral treatment program, and drug resistance test after antiviral therapy were the influencing factors of HIV/AIDS death in Butuo county. It is necessary to expand the coverage of viral load and drug resistance test to change the antiviral therapeutic schedule scientifically and carry out publicity and education on the compliance of patients with antiviral treatment and medical staff training in order to reduce the mortality of patients with antiviral treatment.