Pretreatment HIV drug resistance in adults initiating antiretroviral therapy in China, 2017.

BACKGROUND: After the scale-up of antiretroviral therapy (ART) for HIV infected people, increasing numbers of patients have pretreatment drug resistance (PDR). In this study, the prevalence of PDR was evaluated in adults initiating antiretroviral therapy in China. METHODS: Blood samples were obtained from 1943 patients who initiated antiretroviral therapy (ART) in 2017 from 13 provinces or cities in China. Pol sequences were used to analyze drug resistance and construct transmission networks. Logistic regression model was used to estimate the potential factors associated with PDR. RESULTS: In total, 1711 eligible patients (76.0% male; 87.8% aged ≥ 25 years) were included, of which 117 (6.8%) had PDR. The highest rates of PDR were 12.2% in Liangshan Prefecture of Sichuan and 9.3 and 8.9% in Dehong and Lincang Prefecture of Yunnan. A multivariate logistic regression analysis revealed that PDR was significantly higher among intravenous drug users (adjusted Odds Ratio (aOR) = 2.64, 95% CI: 1.57-4.44) and individuals from Liangshan, Dehong, and Lincang (aOR = 2.04, 95% CI: 1.26-3.30). In total, 754 sequences were used to generate 164 transmission networks. Five transmission networks had two or three sequences containing the same mutations, two networks contained subjects from Liangshan, and one network contained subjects from Dehong. CONCLUSIONS: Overall, the PDR prevalence was moderate, with a particularly high prevalence in areas with severe HIV epidemics. These results indicate the importance of continuous PDR monitoring in patients initiating antiretroviral therapy.

Substance use and HIV-risk behaviors among HIV-positive men who have sex with men in China: repeated measures in a cohort study design.

Global literature revealed that seropositive men who have sex with men (MSM) posed an even higher risk compared to their seronegative counterparts. Identifying risk factors that contribute to HIV-risk behaviors will help to curb the rapid HIV transmission among this group. Our hypothesis was that MSM with substance use were more likely to conduct HIV-risk behaviors, even after accounting for repeated measures. In the current study, we employed a cohort study design by following a group of 367 HIV-positive MSM up to four visits for one year to collect information regarding their sexual behaviors and history of substance use in the past three months. We used Generalized Estimating Equations (GEE) models to account both within- and between-subject variation when assessing associations between substance use and HIV-risk behaviors. A total of 367 MSM were included at the baseline with a mean age of 29.6 years. After accounting for potential confounders and time-varying effects, our models indicated that drug and alcohol use increase HIV risks at the population level by increasing risks of drinking alcohol before sex, having unprotected sex with men and seropositive partners, having more lifetime female sex partners and having a higher number of male sexual partners in the past three months. The current study is one of the first studies with repeated measures to evaluate the association between substance use and sexual risk behaviors among MSM in China. Findings in the current study have several implications for future research. We call for more rigorous study design for future research to better capture changes of risky behaviors among this at-risk population.

Behavioral Risk Profile of Men Who Have Sex with Men in Beijing, China: Results from a Cross-sectional Survey with Randomized Response Techniques.

BACKGROUND: Human immunodeficiency virus (HIV) is spreading rapidly among men who have sex with men (MSM) in China. Anonymous questionnaires or direct interviews have been frequently used to study their behavior. The aim of the study was to describe the behavioral risk profile of the MSM in Beijing using the randomized response techniques (RRTs). METHODS: A cross-sectional survey of sexual behavior among a sample of MSM was conducted in two HIV counseling and testing clinics in Beijing. The survey was carried out with an anonymous questionnaire containing sensitive questions on sexual behavior. To obtain the honest responses to the sensitive questions, three distinctive RRTs were used in the questionnaire: (1) Additive randomized response model for quantitative questions, (2) randomized response model for multiple choice questions, and (3) Simmons randomized response model for binomial questions. Formulae for the point estimate, variance, and confidence interval (CI) were provided for each specific model. RESULTS: Using RRTs in a sample of 659 participants, the mean age at first homosexual encounter was estimated to be 21.7 years (95% CI: 21.2-22.2), and each had sex with about three (2.9, 95% CI: 2.4-3.4) male partners on average in the past month. The estimated rate for consistent condom use was 56.4% (95% CI: 50.1-62.8%). In addition, condom was estimated to be used among 80.0% (95% CI: 74.1-85.9%) of the population during last anal sex with a male partner. CONCLUSIONS: Our study employed RRTs in a survey containing questions on sexual behavior among MSM, and the results showed that RRT might be a useful tool to obtain truthful feedback on sensitive information such as sexual behavior from the respondents, especially in traditional Chinese cultural settings.

Genetic Characteristics of CRF01_AE Among Newly Diagnosed HIV-1-Infected 16- to 25-Year Olds in 3 Geographic Regions of Guangxi, China.

The aim of this study was to analyze the distribution of clusters and drug resistance of CRF01_AE among newly diagnosed, treatment-naïve HIV-infected teenagers and young adults in 3 major HIV-affected geographic regions of Guangxi Province, including the cities of Hezhou, Liuzhou, and Nanning. Samples were sequentially collected from newly diagnosed HIV-infected 16- to 25-year olds in these 3 regions from 2009 to 2013. The viral genome was extracted, and the partial pol gene was amplified and sequenced. Phylogenetic analyses were used to determine HIV-1 subtypes and CRF01_AE clusters. Transmitted drug resistance (TDR) mutations were identified using the 2009 WHO list of TDR mutations. A total of 216 sequences were obtained from CRF01_AE strains, which accounted for 83.1% of the 260 genotyped samples, of which 36 were from Hezhou, 147 from Liuzhou, and 33 in Nanning. Most (83.3%, 180/216) were from heterosexuals, followed by injection drug users (5.6%), homosexuals (4.2%), and unknown risk group (6.9%). Based on phylogenetic analyses by the maximum likelihood method, 5 distinct clusters (cluster 1-5) were identified with 213 (98.6%) sequences, whereas 3 (1.4%) sequences were ungrouped. In Hezhou, 88.9% (32/36) of CRF01_AE infections were caused by cluster 2, and 11.1% (4/36) were caused by cluster 1. In Liuzhou, 83.0% (122/147) of the CRF01_AE strains were found in cluster 1, 11.6% (17/147) from cluster 2, 1.4% (2/147) from cluster 3, 2.7% (4/147) from cluster 4, and 0.7% (1/147) from cluster 5. The distribution of CRF01_AE clusters was more even in Nanning than it was in the other 2 regions, with 18.2% (6/33) from cluster 1, 36.3% (12/33) from cluster 2, 9.1% (3/33) from cluster 3, 18.2% (6/33) from cluster 4, and 12.1% (4/33) from cluster 5. The most frequent TDR mutations were M46I (2) in the protease region and Y181C (2) from the reverse transcriptase fragment. Clusters 1 and 2 of CRF01_AE strains were prevalent in Liuzhou and Hezhou, respectively. However, multiple CRF01_AE clusters existed in Nanning. This can be partially explained by the high mobility of laborers in Nanning, the capital city of Guangxi. The prevalence of TDR was low.

High-accuracy identification of incident HIV-1 infections using a sequence clustering based diversity measure.

Accurate estimates of HIV-1 incidence are essential for monitoring epidemic trends and evaluating intervention efforts. However, the long asymptomatic stage of HIV-1 infection makes it difficult to effectively distinguish incident infections from chronic ones. Current incidence assays based on serology or viral sequence diversity are both still lacking in accuracy. In the present work, a sequence clustering based diversity (SCBD) assay was devised by utilizing the fact that viral sequences derived from each transmitted/founder (T/F) strain tend to cluster together at early stage, and that only the intra-cluster diversity is correlated with the time since HIV-1 infection. The dot-matrix pairwise alignment was used to eliminate the disproportional impact of insertion/deletions (indels) and recombination events, and so was the proportion of clusterable sequences (Pc) as an index to identify late chronic infections with declined viral genetic diversity. Tested on a dataset containing 398 incident and 163 chronic infection cases collected from the Los Alamos HIV database (last modified 2/8/2012), our SCBD method achieved 99.5% sensitivity and 98.8% specificity, with an overall accuracy of 99.3%. Further analysis and evaluation also suggested its performance was not affected by host factors such as the viral subtypes and transmission routes. The SCBD method demonstrated the potential of sequencing based techniques to become useful for identifying incident infections. Its use may be most advantageous for settings with low to moderate incidence relative to available resources. The online service is available at http://www.bioinfo.tsinghua.edu.cn:8080/SCBD/index.jsp.

[Genetic characteristics of viral quasispecies of HIV-1 CRF07_BC among intravenous drug users].

To explore the genetic characteristics of viral quasispecies in HIV-1 CRF07_BC infections among intravenous drug users (IDU), the gp120 fragments of HIV-1 env gene were amplified from plasma samples collected from 6 CRF07_BC infected persons using single genome amplification and sequencing (SGA/ SGS) method, and 11 to 28 sequences were obtained from these samples, respectively, A neighbor-joining phylogenetic tree was reconstructed to describe the genetic characteristics of viral quasispecies. The Simplot, segments' phylogenetic trees and diversity plots based on average pairwise distance (APD) were used to identify the recombination events between quasispecies. The SGA sequences derived from single specimen formed a large monophyletic cluster in the neighbor-joining phylogenetic tree and showed the complex topologic structures of viral quasispecies. Of the 6 CRF07_BC infected patients, only one possessed the high genetic homogeneity, whereas the other five individuals showed high heterogeneity, with two to four subclusters inside the monophyletic cluster for each specimen. In addition, the recombinant events were identified among viral quasispecies from 3 cases. The results show SGA technique and phylogenetic analyses are useful tool to investigate the intrahost CRF07_BC gp120 complex quasispecies variation and high genetic diversity.

[Loss to follow-up and associated factors in a cohort study among men who have sex with men].

OBJECTIVE: To explore the associated factors on loss to follow-up among men who have sex with men (MSM) in a prospective cohort study. METHODS: We recruited eligible HIV-negative MSM at baseline in eight cities from June to October 2009. Interviewer-administrated questionnaire and blood testings for HIV, syphilis and human simplex virus type 2, were accomplished upon enrollment, 6-month and 12-month follow-up visits in the program. Loss to follow-up was recorded at each visit in this cohort. Univariate and multivariate statistical analysis were conducted to examine the associated factors on loss to follow-up. RESULTS: A total of 3196 eligible MSM were enrolled at the baseline study. During one year of follow-up, 894 (28.0%) of them dropped out thoroughly while 2302 (72.1%) showed up at least on one visit. Factors as MSM who were at age 25 or younger, resided locally less than 1 year, being unemployed, self-recognized as heterosexuality or bisexuality, never taking HIV testing in the past year, having had sex with women in the past 6 months etc., were more likely to withdraw from the follow-up visits. Conclusion Age, length of residency, sex orientation and history of HIV testing were associated with the loss of follow-up among MSM cohort in our study. These factors should be considered in this kind of study design in the future.

[Study on the incidence of HIV and associated risk factors through a prospective cohort among men who have sex with men in Beijing, China].

OBJECTIVE: To investigate the dynamic change and associated risk factors of HIV sero-conversion rate in Beijing. METHODS: 809 sero-negative men who have sex with men (MSM) were recruited in the cohort from August to December in 2009. HIV sero-antibody, medicinal examination and behavior questionnaire interview were carried out every six months. RESULTS: 962 MSM with overall baseline prevalence of HIV infection as 6.34% (61/962) together with 809 sero-negative MSM, were enrolled in the cohort. Of the 809 sero-negative participants, 95.1% (769/ 809), 85.5% (692/809) and 71.0% (574/809) of them were retained in the 6-month, 12-month and 18-month follow-up visits, with 19, 29 and 17 of them became HIV sero-conversion at 6-month, 12-month, and 18-month follow-up visits and the HIV incidence rates appeared to be 5.47, 12.37 and 6.86 per 100 person-years respectively. The HIV incidence was 7.59 per 100 person-years in the 18 months follow-up visit. Factors including: younger than 25-years old (HR = 2.32, 95%CI: 1.39 - 3.87), having more than 8 MSM partners (HR = 2.50, 95%CI: 1.49 - 4.20), less than 2000¥ every month income (HR = 1.76, 95%CI: 1.05 - 2.95), having more than 4 homosexual partners in the last six months (HR = 3.50, 95%CI: 2.11 - 5.81), showing phimosis and redundant prepuce (HR = 2.47, 95%CI: 1.50 - 4.07) as well as positive syphilis test (HR = 2.62, 95%CI: 1.53 - 4.49) etc., were significantly associated with HIV incidence. CONCLUSION: High HIV incidence was shown among MSM in Beijing and had spread fast in this population, calling for more favorable prevention measures to be taken.

[The prevalence of HIV-1 drug resistance and associated factors in AIDS patients receiving HAART in Zhecheng county, Henan province].

OBJECTIVE: To understand the prevalence of HIV-1 drug resistance and its main factors in AIDS patients receiving to HAART in Zhecheng county, Henan province. METHODS: By cross-sectional survey, 378 AIDS patients who had received the national free antiretroviral therapy from July 2003 to March 2009 in Zhecheng county of Henan were selected. All recruits were interviewed and blood samples were collected. HIV-1 viral loads were measured by real-time polymerase chain reaction, HIV genotypic resistance was determined by an in-house polymerase chain reaction to amplify the HIV-1 pol gene region. RESULTS: Among 378 subjects receiving antiretroviral therapy, the prevalence of successful viral suppression was 42.9% (162/378), and HIV-1 drug resistance was detected in 47.1% (178/378) patients. The rate of resistance-associated mutations to non-nucleotide reverse transcriptase inhibitors (NNRTIs), nucleotide reverse transcriptase inhibitors (NRTIs) and protease inhibitors (PIs) was 46.6% (176/378), 37.8% (143/378) and 1.9% (7/378), respectively. Multivariate logistic regression analysis showed that the main risk factors associated with the prevalence of drug resistance included drug non-adherence (ratio of on-time drug intake in the past month < 90%:≥ 90% = 64.5% (40/62):43.7% (138/316), OR = 2.3, 95%CI: 1.3 - 4.1), and initiation of anti-retroviral therapy (ART) with didanosine (DDI) (ART with DDI:ART with lamivudine (3TC) = 53.3% (137/257):33.9% (41/121), OR = 2.3, 95%CI = 1.1 - 4.5). CONCLUSION: The prevalence of HIV-1 drug resistance among ART patients in Zhecheng county of Henan was high. Drug non-adherence and initiation of ART with DDI were the main factors of drug resistance.

[Analysis on the relationship between condom social norms and unprotected anal intercourse among men who have sex with men in Beijing].

OBJECTIVE: To understand the prevalence of and factors associated with unprotected anal intercourse (UAI) among men who have sex with men (MSM) in Beijing. METHODS: Five hundred MSM were recruited for a survey using Respondent Driven Sampling (RDS) method, from September to October in 2009. A computer-assisted, interviewer-administered questionnaire was used to gather information including demographics, sexual behaviors and condom use social norms (a scaled number). Variables were evaluated by using RDSAT and SAS software. RESULTS: Mean age of the participants was 30.6 years, with 96.0% of them as Han ethnicity and 68.5% having had at least high school or higher education level. 72.8% of them were unmarried, with 61.7% of them identified themselves as homosexual, 61.2% had > 1 male partners in the past six months, and the prevalence of UAI was 42.0%. Significant bivariate predictors of UAI would include condom use social norms score, role for anal sex with male sex partner, number of male sexual partners in the past 6 months and amount of alcohol consumed. In multivariable analysis, UAI was associated with a higher condom use social norms score (AOR = 1.2, 95%CI: 1.1 - 1.3), receptive anal intercourse (AOR = 2.0, 95%CI: 1.3 - 3.2) and drinking alcohol more than 3 times per month in the past 12 months (AOR = 1.6, 95%CI: 1.1 - 2.5). CONCLUSION: The prevalence of UAI was high in the MSM community in Beijing, suggesting that efforts should be targeting on how to make the condom use a social norm and being promoted.

[Incidence and risk factors of HIV and syphilis seroconversion among men who have sex with men in Beijing].

OBJECTIVE: To study the incidence and risk factors of HIV and syphilis seroconversion among men who have sex with men (MSM) in Beijing. METHODS: A total of 550 MSM were recruited on the basis of community and followed up after 6 and 12 months in Beijing. Each subject was investigated by only one investigator at one time to collect information on demographics and behaviors. Blood samples were collected to test HIV and syphilis seroconversion. ELISA was used for screening test, west blotting (WB) and Particle agglutination were used for confirmatory test. RESULTS: A total of 550 MSM investigated, among which 4.5% (25/550) were HIV-positive and 29.3% (161/550) were syphilis-positive. For 525 HIV-negative MSM, 87.0% (457/525) retained during the 12-month investigation. Seroincidence for HIV and syphilis were 3.37/100 person-years (95%CI = 1.66 - 5.08) and 9.32/100 person-years (95%CI = 5.87 - 12.77) respectively. HIV seroconversions for those who performed and did not perform rectal douching after homosexual anal intercourse in the past 3 months were 7.11/100 and 0.76/100 person-years respectively. Multivariate Cox regression analysis revealed that rectal douching after homosexual anal intercourse in the past 3 months (HR = 9.23, 95%CI = 2.08 - 40.88) was significantly associated with HIV seroconversion. Syphilis seroconversions for those who met male sex partners in parks, public washrooms or bathhouses in the past 3 months were 41.77/100 and 7.97/100 person-years respectively. Syphilis seroconversions for those who performed and did not perform rectal douching after homosexual anal intercourse in the past 3 months were 16.17/100 and 4.92/100 person-years respectively. In the past 3 months, meeting male sex partners in parks, public washrooms or bathhouses (HR = 4.67, 95%CI = 1.77 - 12.34) and performing rectal douching after homosexual anal intercourse (HR = 3.09, 95%CI = 1.40 - 6.83) were significantly associated with syphilis seroconversion. CONCLUSION: The seroconversions of HIV and syphilis during the follow-up visits in this MSM cohort study in Beijing were very serious, and that the associated factors for seroconversions were rectal douching after homosexual anal intercourse and meeting male sex partners in parks, public washrooms or bathhouses.

[Drug resistance and associated factors on HIV in Liangshan prefecture, Sichuan province].

OBJECTIVE: To investigate the HIV drug resistance among HIV/AIDS patients who had received highly active antiretroviral treatment (HAATR) in Liangshan prefecture and related factors. METHODS: This investigation was conducted from August to October 2010. Data on epidemiology, treatment, CD4(+) T cell, viral load and drug resistance tests were collected. RESULTS: 233 (73.50%) had a viral load of < 1000 copy/ml, with the median CD4(+) T cell count as 329 cell/µl. 26 samples appeared to be drug resistant, with the rate as 8.20%. Among 84 patients with antiviral therapy failure, the overall drug resistance rate was 30.95% (26/84). While 24 (28.57%) were resistant to non-nucleoside reverse transcriptase inhibitor (NNRTI) drugs. Among nucleoside reverse transcriptase inhibitors (NRTI), 7 (8.33%) were resistant. 1 (1.19%) had protease inhibitor (PI) resistance mutations identified. Factors that significantly associated with drug resistance would include: being injecting drug users (AOR = 3.37, 95%CI: 1.06 - 10.66, P = 0.0390), having had chronic diarrhea > 1 month (AOR = 8.38, 95%CI: 1.87 - 37.69, P = 0.0055), having had CD4(+) T cell < 200 (AOR = 3.48, 95%CI: 1.29 - 9.39, P = 0.0139), being residents from Butuo area (AOR = 17.68, 95%CI: 4.97 - 62.86, P < 0.0001). When comparing with other areas, data from Butuo showed that people who carried Yi ethnicity (AOR = 17.35, 95%CI: 2.01 - 149.73, P = 0.0095) and were literate (having had primary or higher levels of education) (AOR = 0.18, 95%CI: 0.08 - 0.42, P < 0.0001), being married or having cohabited relations (AOR = 8.17, 95%CI: 2.35 - 28.39, P = 0.001) were found to be less adherent (AOR = 0.05, 95%CI: 0.02 - 0.13, P < 0.0001) to the treatment. CONCLUSION: Successful antiviral outcomes were seen among those AIDS patients under treatment, in Liangshan prefecture. Resistance rates were significantly different in regions. For IDUs, enforcement on subjects including prevention on drug resistance, adherence to HAART and treatment for drug addiction should be strengthened and programs being integrated.

[Analysis of gag-specific IFN-gamma secretion responses in HIV-1 B/C recombinant infectors].

OBJECTIVE: To characterize the Gag-Specific T lymphocyte responses and identify immunodominant region recognized in Chinese HIV-1 recombinant subtype B/C infectors. METHODS: 10 antiretroviral treatment (ART) naive HIV-1 recombinant subtype B/C infectors with infected time in 1 year, 25 ART-naive infectors with infected time > 3 years and 10 HIV-1-seronegative healthy individuals were enrolled. HIV-1-specific T lymphocyte responses were analyzed by an IFN-gamma Elispot assay against 123 overlapping peptides spanning HIV-1 Gag protein in the present study. RESULTS: Gag-specific T lymphocyte responses of interferon-gamma secretion were identified in 8(8/10) Chinese HIV-1 recombinant subtype B/ C infectors with infected time in 1 year, the specific T lymphocytes are mainly targeted at five seperated peptides. Responses were identified in 17(68%) infectors with infected time more than 3 years, the specific T lymphocytes are mainly targeted at one peptide in p17 and six in p24. There was obviously positive correlation (P = 0.0318, r = 0.519) between the magnitude of responses and viremia in infectors infected time > 3 years. The magnitude of response in infectors infected in 1 year was significantly higher than group infected time > 3 years (P = 0.021). None of healthy individuals produced positive responses. CONCLUSIONS: HIV-1 recombinant subtype B/C Infectors at different stages of diseases recognize different region of gag.

HIV-specific IL-2(+) and/or IFN-γ(+) CD8(+) T cell responses during chronic HIV-1 infection in former blood donors.

OBJECTIVE: Conflicting data have been generated from previous studies to determine which kind of relationship exists between HIV-1 specific CD8 Tcell responses and HIV-1 viral load or CD4 count over the course of infection. In this study, 153 HIV-1 infected LTNPs were enrolled to investigate the role of HIV-1 specific CD8 T-cell responses in chronic HIV-1 infection among HIV-1 infected former blood donors. METHODS: The patients were stratified into three groups according to CD4 count: CD4≥500 cells/µL; 350 cells/µL≤CD4<500 cells/µL; CD4<350 cells/µL. PBMCs were isolated from the patients' anticoagulated blood samples. IL-2 and IFN-γ secretions of CD 8 T cells against 17 HIV-1 consensus B full peptide pools were analyzed by using ICS assay. RESULTS: An overall inverse correlation were observed between CD4 count and plasma viral load. Although no significant difference was observed during the comparisons of frequency/breadth of HIV-1 specific CD8 T cell responses, CD4 count stratification analysis showed that different correlation pattern existed in three strata: as for patients whose CD4 counts were less than 350 cells/µL, no significant correlations were identified between frequency/breadth of HIV-1 specific CD8 T cell responses and CD4 count/viral load; as for patients whose CD4 counts ranged from 350 cells/µL to 500 cells/µL, significant correlation was only observed between the response breadth of IL-2+IFN-γ+ CD8 T cells and CD4 count; however, as for patients whose CD4 counts were more than 500 cells/µL, direct correlations were identified between IL-2+IFN-γ+/IL-2+/IFN-γ+ CD8 T cells and viral load or CD4 count. CONCLUSIONS: Universal consistent inverse correlation was only indentified between CD4 count and viral load. The relationship between HIV-1 specific CD8 T cell responses and CD4 count/viral load varied in different CD4 strata, which showed that better preserved CD4 T cells were correlated with better CD8 T cell functions.

[Study on the relationship between behavioral factors, psychological status and HIV infection among men who have sex with men in Beijing.].

OBJECTIVE: To study the prevalence and risk factors of human immunodeficiency virus (HIV) among men who have sex with men (MSM) in Beijing. METHODS: A sample of 550 MSM was recruited between March and June in 2008 in Beijing. Interviewer-administered interviews were conducted to collect information on demographics and behaviors. Blood samples were collected to test for HIV, syphilis, HBsAg and HCV infections. Chi-square test and logistic regression model were used to identify risk factors associated with HIV infection. RESULTS: Of the 550 eligible MSM surveyed, HIV prevalence appeared to be 4.5% (25/550). Data from multivariate logistic regression analysis demonstrated that factors as reporting unprotected anal intercourse with causal male sexual partners in the last month (chi(2) = 11.381, P = 0.001), rectal douching after homosexual anal intercourse in the past three months (chi(2) = 5.326, P = 0.021), feeling sad in the last month (chi(2) = 8.809, P = 0.003) were significantly associated with HIV infection. CONCLUSION: Health education on safer sex behavior and mental health care should be taken to hinder the speed of HIV transmission among MSM.

[Genetic variation of gag gene in HIV-1 subtype B infections from Henan and Shanxi provinces of China].

The 109 whole blood samples were collected from HIV-1 infected former blood donors in Henan and Shanxi. The RNA templates were extracted from plasma and used for the full gag gene amplification and sequencing. The sequences were divided into 3 groups according to sampling year. The Entropy software was used to identify the amino acids with composition difference among different groups of amino acid sequences. The results showed that there existed 8 and 13 amino acid sites with the statistical significance difference, respectively, in sequences in year 2004 and 2005, compared to those in 2002. Among them, there existed 5 amino acid sites in two groups. Of 16 amino acid sites, the increasing polymorphism and the decreasing polymorphism along the sampling year were observed in 10 and 6 amino acid sites respectively. Of 10 sites with increased polymorphism, 8 sites were located in the CTL epitopes recognized and presented by the main HLA alleles existed in Chinese population. The 6 sites with decreasing polymorphism all existed in main domains of Gag proteins.

Complete human immunodeficiency virus-1 specific T lymphocyte response to Chinese human immunodeficiency virus-1 B/C chronic infectors.

OBJECTIVE: To characterize the human immunodeficiency virus (HIV) -specific T lymphocyte responses and identify the immunodominant regions in Chinese HIV-1 recombinant subtype B/C chronic infectors at complete genome level. METHODS: Twenty-five HIV-1B/C recombinant chronic infectors were screened for their specific T lymphocyte responses to a panel of peptides corresponding to the complete HIV-1 subtype B genome by gamma interferon ELISPOT assay. Kruskal-Wallis nonparametric analysis of variance was used to test significant differences across gene regions, and Tukey pairwise analysis was used to identify differences between gene regions. Spearman rank correlation was used to assess the relation between responses. Results The order of recognized frequencies of specific T lymphocyte responses to HIV proteins was Nef>Vpr>Gag>Pol>Vpu>Env>Rev>Vif>Tat. When adjusted for protein length, Nef, Vpr, Gag, and Pol were the most intensely targeted proteins and the central region of Nef, Gag p24, Pol RT, and Vpr was most frequently recognized. No significant correlation was observed between the magnitude of IFN-gamma production of HIV-l-specific T lymphocyte responses and plasma viremia, breadth of response and CD4 counts. Conclusion The central region of Nef, Gag p24, Pol RT, and Vpr is most frequently targeted in HIV-1 B/C recombinants chronic infectors. HIV-l-specific T lymphocyte responses and plasma viremia or CD4 counts play no protective role at complete genome level in these infectors.