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Objectives To evaluate the prevalence and characteristics of doravirine resistance and cross-resistance in patients who failed first-line ART in China. Methods From 2014 to 2108, 4132 patients from five provinces were tested for drug resistance by genotypic resistance testing. Drug resistance mutations were assessed using the Stanford HIVdb algorithm Version 9.0. Sequences classified as having low-level, intermediate and high-level resistance were defined as having drug resistance. Results Overall, the prevalence of doravirine and other NNRTIs cross-resistance was 69.5%, with intermediate and high-level resistance accounting for 56.4%. Doravirine resistance highly correlated with efavirenz (r = 0.720) and nevirapine (r = 0.721) resistance and moderately correlated with etravirine (r = 0.637) and rilpivirine (r = 0.692) resistance. The most frequent doravirine-associated resistance mutations were V106M (8.7%), K101E (6.8%) and P225H (5.1%). High-level resistance was mainly due to Y188L (3.2%) and M230L (2.7%). There were significant differences between genotypes and provinces. Compared with CRF01_AE, CRF07_BC (OR = 0.595, 95% CI = 0.546–0.648) and CRF08_BC (OR = 0.467, 95% CI = 0.407–0.536) were associated with lower risks of doravirine resistance. Conversely, genotype A (OR = 3.003, 95% CI = 1.806–4.991) and genotype B (OR = 1.250, 95% CI = 1.021–1.531) were associated with higher risks of doravirine resistance. The risk of doravirine resistance was significantly lower in Xinjiang compared with other provinces. Conclusions In China, the prevalence of doravirine cross-resistance among patients who have failed first-line ART is high. Therefore, doravirine should not be used blindly without genotypic resistance testing and is not recommended for people who have failed first-line NNRTI-based ART.

Introduction: To control the spread of human immunodeficiency virus (HIV) among sero-discordant couples, we explored the HIV seroconversion and its contributing factors. Methodology: We recruited negative partners in HIV sero-discordant couples to established a prospective cohort between January 2010 and June 2015 from areas with severe HIV epidemic in Xinjiang. Follow up once every 3 months, serological tests and risk behavior surveys every 6 months. Variables were screened by LASSO regression and a Cox proportional hazards model was established. Results: A total of 1162 negative partners of sero-discordant couples were recruited. The seroconversion occurred in 42 negative partners during follow-up period, with a seroconversion rate of 2/100 (95% CI = 1.21-2.27), and the median time for seroconversion was 0.92 years. The Cox model showed that frequency of sexual behavior for nearly six months, consistent condom use, knowledge of the transmission route for HIV, a history of sexually transmitted diseases, recent CD4 + T lymphocyte count were all significant contributing factors to the seroconversion in negative partner of HIV sero-discordant couples. In addition, the Cox model was used to evaluate the risk factors of seroconversion for HIV negative partners. Conclusions: The seroconversion rate of HIV negative partners in Xinjiang was lower. The LASSO Cox model may accurately predict the risk of HIV transmission in sero-discordant couples.

Aims Antiretroviral therapy (ART) controls viral replication but cannot eradicate an infected virus and restore the immune response of patients. Materials and methods The gene expression profiles of whole blood, PBMCs, CD4+ and CD8+ T cells were obtained from GSE108297. Coexpression analysis was carried out to evaluate differentially expressed genes (DEGs) between strong and weak responder HIV controllers (HICs). Enrichment analysis was used to explore the biological functions of DEGs. The key genes with common DEGs were screened using the Lasso Cox model. Then, the immune scores of HICs and HAART were calculated by ssGSEA. The content of CD4+ and CD8+ T cells, key genes were verified by flow cytometry, RT-PCR and Western blot analysis. Key findings DEGs were clustered into 24 coexpression modules. DEGs related to general immune responses had the highest correlation with strong responding HICs, while DEGs mainly related to the apoptotic process had the highest correlation with weak responder HICs. The hub genes CD8A and CCT2, as well as the key genes TMEM132C and S100A9, were DEGs in HICs and HARRT. The immune score and flow cytometry showed that CD4+ and CD8+ T cells of HICs were lower than those of HARRT in whole blood. Experiments confirmed the expression of key genes in HICs and HARRT. Significance The key genes identified in this study highlight the strong responder HICs features that to help the immune system control HIV-1 infection. These results will be useful for developing therapeutic targets.

(See the Editorial Commentary by Sugandhi and Harwell on pages 745–6.) Background. The aim of this study was to describe 3-year mortality rates, associated risk factors, and longterm clinical outcomes of children enrolled in China’s national free pediatric antiretroviral therapy (ART) program. Methods. Records were abstracted from the national human immunodeficiency virus (HIV)/AIDS case reporting and national pediatric ART databases for all HIV-positive children ≤15 years old who initiated ART prior to December 2010. Mortality risk factors over 3 years of follow-up were examined using Cox proportional hazards regression models. Life tables were used to determine survival rate over time. Longitudinal plots of CD4 + T-cell percentage (CD4%), hemoglobin level, weight-for-age z (WAZ) score, and height-for-age z (HAZ) score were created using generalized estimating equation models. Results. Among the 1818 children included in our cohort, 93 deaths were recorded in 4022 child-years (CY) of observed time for an overall mortality rate of 2.31 per 100 CY (95% confidence interval [CI], 1.75–2.78). The strongest factor associated with mortality was baseline WAZ score

To understand the misreporting rate regarding the routes of transmission among the reported HIV patients in Yili prefecture of Xinjiang, since 2011.An investigation focusing on the route of transmission among people living with HIV/AIDS was carried out to clarify the responsible reasons for the situation.The overall incorrect reporting rate on the route of transmission was 10.8%.The proportion of heterosexual transmission route was over estimated by 63.8% to 72.0%. However, the proportion of injecting drug was underestimated by 27.5% to 22.2%. The number of cases being confirmed as through heterosexual transmission but incorrectly reported was quite high, contributing 82.6% of all the incorrectly reported cases. Most of the patients that incorrect reported, were moved from injecting drug use to heterosexual transmission, which contributed 79.5% of all the total incorrectly reported cases. Results from multi-factor analysis showed that the risk related to incorrect reporting was 3.64 times in males than in females. People who anticipated to receive HIV testing were 2.23 times more than those who had not. Old-age groups were 3.511, 4.053, 4.415 and 6.524 times higher than those people who were aged below 16 years.The proportion of heterosexual transmission route was over- estimated while the proportion on injecting drug use was underestimated. However, the transmission pattern had changed from injecting drug use at the early epidemic stage, to current sexual transmission mode. We recommended that more attentions should be paid to patients who were males, at older age or those who had no expectation in receiving the HIV testing, during the initial following-up stage.

To analyze the sex specific mortality in HIV/AIDS patients receiving highly active antiretroviral therapy (HAART) and risk factors in Xinjiang Uyghur autonomous region (Xinjiang), and provide evidence for the evaluation of the effect of HAART.A retrospective analysis was conducted on the mortality and survival of 8 061 male cases and 6 001 female cases of HIV infection, who received HAART during July 2004-June 2013 in Xinjiang. The information of the cases were downloaded from national antiretroviral therapy reporting sub-system in national HIV/AIDS reporting system. Cox proportional hazard model was used to identify the risk factors of deaths.The male cases were older and had lower CD4 value at baseline compared with the female cases. The major transmission route was injecting drug use in males, but sexual contact in females. The overall mortality of the male cases was higher than that of the females, which was 10.87/100 person-years during the first three month after receiving HAART, and 7.00/100 person-years two years later in males, but 4.77/100 person-years during the first three month and 3.00/100 person-years two years later in females. The results from Cox analysis showed that the risk factors were the CD4 value at baseline and transmission route. Compared with the cases who had lower CD4 value (CD4200 cells/µl) at baseline, the HR for the cases who had higher CD4 value (CD4≥350 cells/µl) was 4.08 (95% CI: 2.96-5.62) in males and 5.11 (95% CI: 3.16-8.35) in females. Compared with sexual transmission, the HR for IDUs was 1.99 (95% CI: 1.66-2.40) in males and 1.77 (95% CI: 1.24-2.52) in females. The results of cumulative survival analysis showed that in conventional treatment group (CD4350 cells/µl) , the five year survival rates were 81% and 87% for the males and females infected through sexual contact and 66% and 75% for the males and females infected through injecting drug use, and in early treatment group (CD4≥350 cells/µl) , the five year survival rates were 97% and 98% for the males and females infected through sexual contact and 86% and 97% for the males and females infected through injecting drug use.In Xinjiang, the higher mortality in male HIV infection cases receiving HAART was related with lower CD4 value at baseline and higher infection rate through injecting drug use. Besides the weak intention for treatment and poor compliancy would be the deeper risk factors.

To investigate gay identity status of men who have sex with men(MSM) in Xinjiang, and analyze its association with sexual behaviors.From May to August in 2013, an anonymous questionnaire survey with convenience sampling was conducted among MSM in Urumqi, Kashgar, Aksu and Yining cities of Xinjiang. Those who were ≥ 16 years of age and claimed to have male-to-male sex behaviors were eligible for the survey. A total of 1 467 participants were recruited. Chi square analysis was performed for examining the association between ego-identity, social-identity and relevant sexual behaviors. Selected variables associated with ego-identity, social-identity in the univariate analysis were subsequently assessed in a multivariate analysis using logistic regression.The MSM with positive ego-identity accounted for 44.7% (656/1 467), and positive social-identity accounted for 29.1% (427/1 467). For ego-identity, Uyghur MSM were less positive than Han MSM (OR (95%CI) was 0.43 (0.32-0.58) ) ; those who were over 20 years of age when accepting their sexual orientation were less positive than those who were younger than 20 years of age when accepting their sexual orientation (OR (95%CI) was 0.61 (0.47-0.80) );and homosexuals were more positive than bisexuals (OR (95%CI) was 1.98 (1.50-2.61) ). For social-identity, Hui MSM were less positive than Han MSM (OR (95%CI) was 0.61 (0.42-0.88) ); those whose education level was higher than college were less positive than those with junior high education (OR (95%CI) was 0.60 (0.40-0.89) ); famers/herdsmen were more positive than students (OR (95%CI) was 4.17 (2.13-8.17) ); the divorced/widowed were more positive than the singles (OR (95%CI) was 2.40 (1.34-4.29) ); those who were over 20 years of age when accepting their sexual orientation were less positive than those who were younger than 20 years of age when accepting their sexual orientation (OR (95%CI) was 0.59 (0.44-0.81) ). Among the MSM with negative ego-identity and negative social-identity, the proportion of planning to get married with women was 66.8% (267/400) and 76.5% (306/400), respectively, which were higher than those with positive ego-identity (33.2% (133/400)) and positive social-identity (23.5% (94/400)) ; their proportion of intending to have offspring was 62.0% (287/463) and 73.4% (340/463), respectively, which were higher than those with positive ego-identity and social-identity (38.0% (176/463), 26.6% (123/463)) (χ(2) = 39.61 and 7.90, respectively, both P values were0.05). Among the MSM with negative social-identity, the proportion of looking for male sexual partners in toilets or parks was 18.1% (188/1 040), in bathhouse or sauna was 17.3% (180/1 040), and through internet was 82.0% (853/1 040), which were higher than those with positive social-identity (8.9% (38/427), 9.8% (42/427) and 61.6% (263/427)) (χ(2) = 66.78, P0.01).In 2013, the gay identity of MSM in Xinjiang was relatively poor, and the factors associated with it included ethnicity, occupation, marital status and education level. The MSM with negative identity tended to involve in risk sexual behaviors, and had increased risk of HIV infection.

To explore the temporal genetic variation of human immunodeficiency virus type 1 CRF07_BC and reconstruct its epidemic in Xinjiang, China, we studied 216 C2–V4 fragments of env genes sampled from 1996 to 2008. Phylogenetic analysis indicates that the viruses prevailing in Xinjiang form a large monophyletic cluster and may have originated from a common ancestor. The epidemic in Xinjiang was probably established around 1995 (95 % confidence interval, 1994–1996). We noted an increased diversity of CRF07_BC over time, with a rapid evolutionary rate we estimated to be 8.3×10−3 substitutions per site per year in the env gene. After 5–6 years of the epidemic (1997–2002), the transmission rate of CRF07_BC in Xinjiang slowed down, although CRF07_BC infection remained at a high prevalence.

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.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.HIV-1 incidence was calculated with BED-CEIA statistics software.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.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.