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Objective:To investigate the prevalence of pretreatment drug resistance and the genetic polymorphism of CRF08_BC strains among HIV-1 patients in China.Methods:This cross-sectional survey involved the plasma samples of HIV patients in a national pretreatment HIV drug resistance survey conducted in 2018. RNA was extracted from the samples. The fragments containing protease and partial reverse transcriptase (PR/RT) regions were obtained and sequenced. Drug resistance was analyzed using Stanford HIVdb Program. Differences in polymorphic mutations between drug-resistant and non-drug-resistant HIV-1 strains were analyzed by Chi-square test or Fisher′s exact test. The association between drug-resistant and polymorphic mutations was evaluated using CorMut R package. Molecular transmission networks were constructed using HIV-TRACE software. Results:Totally 465 partial pol sequences were obtained from individuals with CRF08_BC infection in 25 provinces and cities. The total pretreatment drug resistance rate was 17.8% (83/465). The pretreatment drug resistance rates to non-nucleoside reverse transcriptase inhibitors (NNRTIs), nucleoside reverse transcriptase inhibitors (NRTIs) and protease inhibitors (PIs) were 16.6% (77/465), 1.1% (5/465) and 0.9% (4/465), respectively. The resistance rate to rilpivirine (RPV) was the highest (15.7%, 73/465). The most common mutation was E138A (11.6%, 54/465). There were six polymorphic mutations (S162C, K102Q, T200A, V179E, I202V, T200M) that co-variated with E138A. The molecular transmission network showed that patients infected with CRF08_BC strains carrying the resistant mutations at position E138 mainly gathered in clusters in Yunnan and Sichuan, and the highest degree of connection was in Lincang, Yunnan. Conclusions:In China, HIV-1 CRF08_BC-infected patients showed a high rate of pretreatment resistance to one of the second-generation NNRTIs, namely RPV. Further researches were warranted to evaluate the impacts of co-mutations of the E138A mutation and polymorphic sites on HIV resistance and replicative capacity.
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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.
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Objective@#To explore HIV-1 drug resistance and influencing factors among people living with HIV/AIDS before antiretroviral therapy in Liangshan Yi Autonomous Prefecture (Liangshan).@*Methods@#Between January 1 and June 30, in both 2017 and 2018, a cross-sectional survey was conducted in Liangshan HIV-1 pol sequences were gathered and analyzed according to WHO Guidelines on HIV drug resistance surveillance of 2014. Both HyPhy 2.2.4 and Cytoscape 3.6.1 software were used to analyze the drug resistant strains of HIV-1 transmission network.@*Results@#A total of 464 people living with HIV/AIDS was recruited. The proportion of HIV-1 CRF07_BC subtype was 88.6% (411/464), with HIV-1 drug resistance rate was 9.9% (46/464). The HIV-1 drug resistance rates of non-nucleoside reverse transcriptase inhibitors (NNRTI), nucleoside reverse transcriptase inhibitors(NRTI) and protease inhibitors (PI) were 6.7% (31/464), 1.9% (9/464) and 0.4% (2/464) respectively. New recombinant strains of HIV-1 URF_01BC subtype was independently clustered according to the drug resistant mutation sites. Results from the multivariate logistic analysis showed that injected drug users group had higher risk on HIV-1 drug resistance (aOR=3.03, 95%CI:1.40-6.54) than heterosexual group among people living with HIV/AIDS.@*Conclusions@#HIV-1 drug resistance rate had already been in a high level before antiretroviral therapy was in place. The newly identified recombinant strains of HIV-1 URF_01BC subtype were independently clustered according to the drug resistant mutation sites. It was necessary to strengthen the prevention of the HIV-1 drug resistant strains transmission.
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Objective@#To analyze the change trend of HIV genetic subtypes and compare the first CD4+T cell counts of newly diagnosed HIV infected patients in Liuzhou from 1998 to 2012, and provide a reference for AIDS prevention and control.@*Methods@#Newly diagnosed HIV-infected patients from 1998 to 2012 in Liuzhou were selected through national HIV/ADIS comprehensive response information management system. Their plasma samples were used for RNA gene extraction, amplification, sequencing and genotyping. Coharan-Armitage trend test was used to analyze the ratio trend of genetic subtypes and phylogenetic clusters of HIV and Wilcoxon Rank Sum Test was used to compare the first CD4+T cell counts (CD4) of the different subtype HIV infected patients.@*Results@#A total of 1 877 newly diagnosed HIV infected patients were included in the study. From 1998 to 2012, the proportions of CRF01_AE and CRF01_AE (Cluster 1) increased from 78.4% (76/97) to 91.5% (1 441/1 574), from 63.9% (62/97) to 74.0% (1 164/1 574), and the proportion of CRF07_BC decreased from 17.5% (17/97) to 4.6% (72/1 574), respectively (Z=4.632, P<0.001; Z=2.455, P=0.014; Z=-5.943, P<0.001). The median and interquartile range of the first CD4 of the patients infected with subtype CRF01_AE (Cluster 1), CRF01_AE (Cluster 2), CRF07_BC and CRF08_BC were 230 (83-375), 215 (48-351), 365 (254-503) and 334 (206-479) cell/μl, respectively. The first CD4 levels of the patients infected with subtype CRF01_AE (Cluster 1) or CRF01_AE (Cluster 2) were significantly lower than those of CRF07_BC (Z=-4.795, P<0.001; Z=-4.238, P<0.001).@*Conclusion@#The genetic subtypes of HIV were mainly CRF01_AE in newly diagnosed HIV-infected patients and this subtype proportion was in increase and the first CD4 levels of the patients were low in Liuzhou during 1998 to 2012.
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Objective To investigate the effect of baseline CD4+T cell count (CD4) on drop-out of antiretroviral therapy (ART) in HIV infected persons.Methods Retrospective cohort was conducted in this study.HIV infected persons aged≥ 18 years and receiving free ART for the first time in Guangxi Zhuang Autonomous Region (Guangxi) from 2008 to 2015 were selected from the antiretroviral treatment database of National Comprehensive HIV/AIDS Information System,with follow-up conducted till May 30,2016.Cause-specific Cox proportional hazard models were used to evaluate effect of different CD4 on the drop-out of ART in the HIV infected persons.Results A total of 58 502 eligible study participants were included in this retrospective cohort study.The average drop-out ratio was 4.8/100 person-years.After controlling the following baseline covariates:age,sex,marital status,route of HIV infection,WHO clinical stage before ART,initial/current ART regiment,ART regiment adjustment,and year of initiating ART for potential confounding,the adjusted HR of drop-out for HIV infected persons with 200-cells/μl,351-cells/μl and ≥500 cells/μl were 1.110 (95％CI:1.053-1.171,P＜0.001),1.391 (95％CI:1.278-1.514,P＜0.001) and 1.695 (95％CI:1.497-1.918,P＜ 0.001),respectively,in risk for drop-out compared with those with baseline CD4 ＜200 cells/μ 1.Among the HIV infected persons,56.0％ (1 601/2 861) of drug withdrawal was due to poor compliance with medication.Conclusions With the increase of baseline CD4 when initiating ART,the risk for the drop-out in HIV infected persons increased significantly.To further reduce the drop-out of ART,it is important to take CD4 into account in initiating ART and to strengthen the health education on treatment compliancy and training for healthcare providers.
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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.
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Objective To investigate the effect of baseline CD4+T cell count (CD4) on drop-out of antiretroviral therapy (ART) in HIV infected persons.Methods Retrospective cohort was conducted in this study.HIV infected persons aged≥ 18 years and receiving free ART for the first time in Guangxi Zhuang Autonomous Region (Guangxi) from 2008 to 2015 were selected from the antiretroviral treatment database of National Comprehensive HIV/AIDS Information System,with follow-up conducted till May 30,2016.Cause-specific Cox proportional hazard models were used to evaluate effect of different CD4 on the drop-out of ART in the HIV infected persons.Results A total of 58 502 eligible study participants were included in this retrospective cohort study.The average drop-out ratio was 4.8/100 person-years.After controlling the following baseline covariates:age,sex,marital status,route of HIV infection,WHO clinical stage before ART,initial/current ART regiment,ART regiment adjustment,and year of initiating ART for potential confounding,the adjusted HR of drop-out for HIV infected persons with 200-cells/μl,351-cells/μl and ≥500 cells/μl were 1.110 (95％CI:1.053-1.171,P＜0.001),1.391 (95％CI:1.278-1.514,P＜0.001) and 1.695 (95％CI:1.497-1.918,P＜ 0.001),respectively,in risk for drop-out compared with those with baseline CD4 ＜200 cells/μ 1.Among the HIV infected persons,56.0％ (1 601/2 861) of drug withdrawal was due to poor compliance with medication.Conclusions With the increase of baseline CD4 when initiating ART,the risk for the drop-out in HIV infected persons increased significantly.To further reduce the drop-out of ART,it is important to take CD4 into account in initiating ART and to strengthen the health education on treatment compliancy and training for healthcare providers.
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<p><b>OBJECTIVE</b>To understand the efficacy of antiviral therapy on prevention of HIV transmission and to assess the feasibility of treatment-as-prevention strategy in public health practice, among sero-discordant couples in Guangxi Zhuang autonomous region (Guangxi).</p><p><b>METHODS</b>Data was gathered through the AIDS prevention and control information system in Guangxi from January 1, 2008 to December 31, 2014, on HIV sero-discordant couples. Time-dependent Cox Model was used to analyze the efficacy of antiviral treatment.</p><p><b>RESULTS</b>A total of 7 694 sero-discordant couples were followed and 394 appeared positive from those negative spouses. The overall HIV positive seroconversion rate was 2.5 (2.2-2.7) /100 person-year. The HIV positive sero-conversion rates were 4.3 (3.7-4.8) /100 person-year in the untreated cohort and 1.6 (1.4-1.9) per 100 person-year in the treated cohort. Rate of HIV transmission declined by 51% in the treated cohort (HR=0.49, 95%CI: 0.40-0.60) but appeared as 45% (AHR=0.55, 95%CI:0.43-0.69) after adjusting for factors as sex, age, education, marital status, occupation, transmission route and baseline CD4(+)T lymphocyte cell count. The rate of reduction in transmission was significant among couples in which the HIV-positive spouses showing the following features as: aged ≥25 years, married, farmers, with educational level of junior high school or below, baseline CD4(+)T lymphocyte cell count <500 cells/mm(3) and infection was through heterosexual intercourse.</p><p><b>CONCLUSION</b>Antiviral therapy as a prevention strategy among sero-discordant couples seemed feasible and effective in Guangxi. Expansion of the coverage on antiviral therapy would reduce the spread of HIV in married couples.</p>
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Adult , Humans , Antiviral Agents , Therapeutic Uses , CD4 Lymphocyte Count , China , Feasibility Studies , HIV Infections , HIV Seronegativity , HIV Seropositivity , Heterosexuality , Socioeconomic Factors , Spouses , Treatment OutcomeABSTRACT
<p><b>OBJECTIVES</b>To investigate the incidence of syphilis infection and to determine the risk factors related to syphilis infection among young men who had sex with men (YMSM), which were documented for developing effective intervention to prevent sexually transmitted diseases among YMSM.</p><p><b>METHODS</b>A cohort study was conducted in 8 cities (Beijing, Shanghai, Kunming,Guiyang, Chongqing, Chengdu, Urumqi and Nanning) from May to December, 2009. A total of 1 037 syphilis-negative YMSM aged 18-25 were enrolled in the cohort and the two follow-up surveys were carried out every six months. The contents of study included sociodemographic characteristics, HIV-related knowledge, sexual behavior and condom use in the 6 months prior to survey. All participants were tested for syphilis with whole blood specimens. Chi-square test was used to compare demographic characteristics of participants in baseline with those of two follow-up, and Cox regression analysis was used to identify risk factors associated with syphilis infection.</p><p><b>RESULTS</b>The rates of participants in 6, 12 months follow-up surveys was 79.85% (828/1 037) and 82.16% (852/1 037) respectively.39 syphilis seroconversions were found in the 12 months follow-up survey. Cumulative observed person-years during follow-up time was 1 106.67. The syphilis incidence rate was 3.5%. The Multivariate Cox regression analysis showed that the education of senior high school (senior high school vs some college or higher, RR = 2.19, 95% CI:1.21-3.98), bisexual orientation (bisexual orientation vs homosexual orientation, RR = 2.19, 95% CI:1.21-3.97), score of HIV/AIDS knowledge <8 (score of HIV/AIDS knowledge <8 vs knowledge = 8, RR = 2.39, 95%CI:1.35-4.21), had two and more sexual partners and inconsistent condom use in the past 6 months (inconsistent condom use vs consistent condom use, RR = 3.10, 95% CI:1.39-6.91) were significantly associated with syphilis seroconversion in the 12-month period.</p><p><b>CONCLUSIONS</b>The syphilis incidence was high and risk behaviors were common among YMSM of China.</p>
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Adolescent , Adult , Humans , Male , Young Adult , China , Epidemiology , Cohort Studies , Homosexuality, Male , Risk Factors , Risk-Taking , Syphilis , EpidemiologyABSTRACT
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.
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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.
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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.
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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.
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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.
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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.