Qinghai Hu

Syphilis and HIV Seroconversion Among a 12-Month Prospective Cohort of Men Who Have Sex With Men in Shenyang, China

Background: Cross-sectional studies have found a high prevalence of syphilis and HIV infection among men who have sex with men (MSM) in China. Methods: A total of 218 HIV-negative MSM participated in this prospective cohort study. Interviewer-administered questionnaires were completed, and blood samples were obtained for HIV and syphilis testing, both upon enrollment and at 12-month follow-up. Results: Of enrolled participants, 56% (122) were retained for the full 12-month follow-up period. The cohort had an HIV incidence density of 5.4 (95% CI: 2.0–11.3)/100 person-year (PY) and a syphilis incidence density of 38.5(95% CI: 27.7–50.2)/100 PY. Having syphilis (odds ratio [OR]: 11.4, 95% CI: 1.2–104.7) and more than 5 male sexual partners within the past 12 months (OR: 6.5, 95% CI: 1.1–39.8) were independent risk factors for HIV seroconversion (each P < 0.05). Being married (OR: 3.5, 95% CI: 1.4–8.2) and having more than 5 male sexual partners within the past 12 months (OR: 4.7, 95% CI: 2.0–6.2) were risk factors for syphilis seroconversion, while age ≥30 (OR 2.1, 95% CI 0.7–9.5) and having recently engaged in unprotected receptive anal sex (OR: 2.4, 95% CI: 0.7–13.1) were marginally associated with syphilis seroconversion. Conclusion: The high incidence rates of HIV and syphilis in the Shenyang MSM community are significant cause for concern. The seroconversion rate for syphilis, in particular, indicates the high prevalence of high-risk sexual behaviors and the potential for increased HIV transmission. Appropriate interventions that address MSM-specific issues, including stigma, pressures from traditional society, and bisexual behavior, need to be tailored to inform and empower MSM in order to prevent HIV and syphilis in this community.

Recreational Drug Use among Chinese Men Who Have Sex with Men: A Risky Combination with Unprotected Sex for Acquiring HIV Infection

Objective. To investigate the prevalence of recreational drug use and its relationship with HIV infection among Chinese MSM. Methods. A cross-sectional study of 625 MSM was conducted in Shenyang, China. Questionnaires were administered to collect information on recreational drug use and sexual behaviors. Blood specimens were collected to test for HIV and syphilis antibodies. Results. Nearly a quarter (23.2%, 145/625) of participants reported ever using recreational drugs, among which alkyl nitrites (poppers) was the most frequently used drug (19.2%), followed by methylmorphine phosphate (5.1%), methamphetamine (4.0%), and ketamine (0.8%). The overall prevalence of HIV and syphilis was 9.6% and 10.4%, respectively. Multivariate logistic analysis showed that recreational drug use was significantly correlated with age ≤25 year (adjusted odds ratio [aOR] = 1.6, 95% CI, 1.1–2.9), single marital status (aOR = 2.1, 95% CI, 1.2–3.6), and seeking male sexual partners mainly through Internet (aOR = 1.8, 95% CI, 1.8–2.8). Recreational drug use was independently associated with an increased risk of HIV infection (aOR = 3.5, 95% CI, 2.0–6.2). Conclusions. Our study suggests that recreational drug use is popular among Chinese MSM and is associated with significantly increased HIV infection risk. HIV prevention intervention programs should reduce both drug use and risky sexual behaviors in this population.

KIR3DS1/L1 and HLA-Bw4-80I are associated with HIV disease progression among HIV typical progressors and long-term nonprogressors

BackgroundNatural killer (NK) cells have emerged as pivotal players in innate immunity, especially in the defense against viral infections and tumors. Killer immunoglobulin-like receptors (KIRs) – an important recognition receptor expressed on the surface of NK cells – regulate the inhibition and/or activation of NK cells after interacting with human leukocyte antigen (HLA) class I ligands. Various KIR genes might impact the prognosis of many different diseases. The implications of KIR-HLA interaction in HIV disease progression remains poorly understood.MethodsHere, we studied KIR genotypes, mRNA levels, HLA genotypes, CD4+ T cell counts and viral loads in our cohort of Human Immunodeficiency Virus (HIV)-infected individuals, a group that includes HIV long-term nonprogressors (LTNPs) and typical progressors (TPs).ResultsWe found that the frequency of KIR3DS1/L1 heterozygotes with HLA-Bw4-80I gene was much higher in LTNPs than in TPs (P = 0.001) and that the KIR3DL1 homozygotes without HLA-Bw4-80I gene had higher viral loads and lower CD4+ T cell counts (P = 0.014 and P = 0.021, respectively). Our study also confirmed that homozygosity for the HLA-Bw6 allele was associated with rapid disease progression. In addition to the aforementioned results on the DNA level, we observed that higher level expression of KIR3DS1 mRNA was in LTNP group, and that higher level expression of KIR3DL1 mRNA was in TP group.ConclusionsOur data suggest that different KIR-HLA genotypes and different levels of transcripts associate with HIV disease progression.

Genetic and epidemiologic characterization of HIV-1 infection in Liaoning Province, China.

Background:Although many studies of HIV-1 in China have focused on high-risk injecting drug users and former blood donors in high prevalence regions, little is known about HIV-1 in relatively low prevalence provinces. Here, we compare the epidemiologic and genetic profile of HIV-1 in Liaoning-a low prevalence province-with those identified in Chinas most severely affected provinces. Materials and Methods:Two hundred eight HIV-1-positive subjects from all major cities in Liaoning province were recruited between 2000 and 2008. 2.6 kilobase gag-pol sequences were amplified from plasma viral RNA and sequenced directly. The HIV-1 sequences obtained were analyzed using phylogenetic and recombinant approaches. Results:We have shown that in recent years, although HIV-1 prevalence in Liaoning has remained low, the rate of new infection has increased rapidly, particularly among men who have sex with men and heterosexual risk individuals (together comprising >54% of infected individuals in 2007). Furthermore, phylogenetic analysis has identified all major subtypes/circulating recombinant forms of HIV-1 in Liaoning previously identified in high prevalence provinces. Our study also shows close relationships between HIV-1 subtype/circulating recombinant form and certain risk behaviors. Notably, men who have sex with men and heterosexual risk individuals harbor most divergent strains of HIV-1 from multiple high-risk groups. Conclusions:Our study suggested that HIV-1 continues to spread to the general population through sexual contact; Liaoning, therefore, serves as the critical base for the introduction and spread of HIV-1 in northeast China. We believe the transmission patterns suggested herein will help guide public health workers in reducing further spread of HIV-1 within China.

Identification and Characterization of a Novel HIV-1 Circulating Recombinant Form (CRF59_01B) Identified among Men-Who-Have-Sex-with-Men in China

The HIV-1 epidemic among men-who-have-sex-with-men (MSM) continues to expand in China. A large-scale national survey we conducted on HIV-1 strains among MSM in 11 provinces in China from 2008 to 2013 (n = 920) identified a novel transmission cluster consisting of six strains (0.7%) that belonged to a new circulating recombinant form (designated CRF59_01B). CRF59_01B contains two subtype B segments of U.S.-European origin (in the pol and vpu-env regions) in a CRF01_AE backbone. CRF59_01B is the second CRF (after CRF55_01B) circulating primarily among MSM in China. CRF59_01B occurs at a low frequency (less than 1%), but it was detected in four different provinces/regions in China: Liaoning (northeast China) (n = 3); Hunan (central China) (n = 1); Guangdong (south China) (n = 1); Yunnan (southwest China) (n = 1). One additional recombinant strain was detected in a heterosexual individual in Liaoning province but is not the focus of this paper. Bayesian molecular clock analyses indicate that CRF59_01B emerged as a result of recombination between CRF01_AE and subtype B around the year 2001. The emergence of multiple forms of recombinants and CRFs reflects the ever-increasing contribution of homosexual transmission in Chinas HIV epidemic and indicates an active HIV transmission network among MSM in China.

Higher NK Cell IFN-γ Production is Associated with Delayed HIV Disease Progression in LTNPs

Natural killer (NK) cells are important effectors of the innate immune system that help control viral infections and tumorigenesis. However, the relationship between NK cell function and HIV disease progression remains poorly defined. In this study, we examined the function of NK cells in Chinese patients who were HIV-infected but treatment-naïve. These individuals include primary HIV-infected patients (PHIs), typical progressors (TPs), and long-term nonprogressors (LTNPs). We observed an increase of CD56dim NK cells in PHIs, but the production of interferon-gamma (IFN-γ) and CD107a expression in PHIs were not altered compared with normal control subjects (NCs). However, the NK cells from LTNPs exhibited increased activities in IFN-γ production, CD107a expression and granzyme B change after K562 stimulation compared with NCs. Furthermore, the percentage of IFN-γ+CD107a− NK cells in LTNPs was higher than that in TPs, PHIs and NCs; levels of IFN-γ production in LTNP NK cells exhibited an inverse correlation with viral loads. Similar correlations, however, were not observed in the PHI and TP groups. Taken together, these data demonstrate that enhanced NK cell function may contribute to the control of HIV infection, and increased IFN-γ secretion may be associated with delayed disease progression.

A Large-scale Survey of CRF55_01B from Men-Who-Have-Sex-with-Men in China: implying the Evolutionary History and Public Health Impact.

The HIV-1 epidemic among men-who-have-sex-with-men (MSM) continues to expand in China, involving the co-circulation of several different lineages of HIV-1 strains, including subtype B and CRF01_AE. This expansion has created conditions that facilitate the generation of new recombinant strains. A molecular epidemiologic survey among MSM in 11 provinces/cities around China was conducted from 2008 to 2013. Based on pol nucleotide sequences, a total of 19 strains (1.95%) belonged to the CRF55_01B were identified from 975 MSM in 7 provinces, with the prevalence range from 1.5% to 12.5%. Near full length genome (NFLG) sequences from six epidemiologically-unlinked MSM were amplified for analyzing evolutionary history, an identical genome structure composed of CRF01_AE and subtype B with four unique recombination breakpoints in the pol region were identified. Bayesian molecular clock analyses for both CRF01_AE and B segments indicated that the estimated time of the most recent common ancestors of CRF55_01B was around the year 2000. Our study found CRF55_01B has spread throughout the most provinces with high HIV-1 prevalence and highlights the importance of continual surveillance of dynamic changes in HIV-1 strains, the emergence of new recombinants, and the need for implementing effective prevention measures specifically targeting the MSM population in China.

Increase of RT-related transmitted drug resistance in non-CRF01_AE among HIV type 1-infected men who have sex with men in the 7 cities of China.

Objectives:To elucidate new features in the prevalence of HIV-1 transmitted drug resistance (TDR) in men who have sex with men (MSM) in China. Methods:A total of 441 HIV-1–positive subjects were recruited from high-risk MSM populations in 7 cities across China between 2012 and 2013. Nucleotide sequences of 1.1-kb pol-RT regions were amplified and sequenced from 367 of the 441 samples. Phylogenetic and genetic drug-resistant analyses were performed. Results:The overall distribution of HIV-1 genotypes was as the following: CRF01_AE, 52.3%; CRF07_BC, 33.2%; 01/B recombinants, 6.0%; subtype B (United States–European), 3.8%; subtype B′, 3.8%; and CRF08_BC, 0.8%. About 91.3% of the sequences clustered together. An overall 4.6% TDR rate was found. Reverse transcriptase (RT)-related TDR reached 2.7%. TDR of 2.2% was detected in protease region. Most of RT-related TDRs were detected in non-CRF01_AE subtypes (90.0%, 9/10), including T215A/S, K101E, K103N, V106M, and E138G. Most of the strains with TDRs (88.2%, 15/17) were presented in the clusters. TDR strains against non-nucleoside reverse transcriptase inhibitors in non-CRF01_AE subtypes also formed some subclusters (70.0%, 7/10). One CRF07_BC subject with K103N in Kunming had a very close genetic distance with one that received highly active antiretroviral therapy locally (bootstrap = 99%). Two CRF55_01B subjects carrying K103N in Changsha and Nanjing also had a very close genetic distance (bootstrap = 100%). Conclusions:RT-related TDR of non-CRF01_AE became the main TDR among MSM in China. There is an increasing trend and a potential transmission risk for the RT-related TDR among MSM throughout China. Some TDRs could have already been transmitted among different cities. Intervention efforts should be strengthened among MSM to prevent further transmission of HIV and the proliferation of the strains with TDR.

Associations of HLA class I antigen specificities and haplotypes with disease progression in HIV-1-infected Hans in Northern China.

The human leukocyte antigen (HLA) allele frequencies, which differ among various ethnic populations, may result in population-specific effects on HIV-1 disease progression. No large-scale study has yet been conducted on the Chinese population. In this study, HLA class I antigen specificities were determined in a cohort including 105 long-term non-progressors (LTNPs) and 321 typical progressors (TPs), who were recruited from HIV-1-infected Northern Han Chinese, to determine the associations between certain HLA types and HIV-1 disease progression. The frequencies of HLA class I specificities and haplotypes among the two groups were compared using binary logistic stepwise regression. Results showed that HLA-A(∗)30-B(∗)13-C(∗)06 (OR = 0.387, P = 0.019) and B(∗)67 (OR = 0.134, P = 0.005) were associated with a long-term non-progressing condition, and C(∗)01 (OR = 2.539, P = 0.050) was overrepresented in TPs after adjusting for non-genetic factors (sex, age, the location of patients, HIV subtype and the route of infection). The influence of HLA homozygosity on HIV disease progression was also analyzed. However, homozygosity at HLA-A, HLA-B or HLA-C conferred no observable disadvantage in our study population (P = 0.730, 0.246 and 0.445, respectively). These findings suggest that the hosts genetics make important contributions to HIV viral control and may help to develop peptide-based vaccines for this population.

HIV Related High Risk Behaviors and Willingness to Participate in HIV Vaccine Trials among China MSM by Computer Assisted Self-Interviewing Survey

Background. The number of new HIV infections among MSM of China is rapidly increasing in recent years and behavioral interventions have had limited effectiveness. To control the HIV pandemic may lie in an HIV vaccine. This study examined the factors associated with willingness to participate (WTP) in HIV vaccine clinical trials among China MSM. Methods. A cross-sectional survey was carried out among MSM from three cities in northeast China. Questionnaires pertaining to MSM risk behavior and WTP in HIV vaccine trials were administered through computer assisted self-interviewing (CASI). Results. A total of 626 MSM participated in this survey. 54.8% had occasional male partners and 52.2% always used condoms with male sex partners. HIV prevalence was 5.0%. 76.7% were WTP in a preventive HIV vaccine clinical trial. Results showed that HIV vaccination is a means of protection for spouses and family; family support to participate in vaccine trials and desire for economic incentives were significantly associated with WTP. Conclusions. There was a high proportion of WTP in HIV vaccine trials among Chinese MSM. The high HIV prevalence and high proportion of risky sexual behavior indicate that Liaoning MSM are potential candidates for HIV vaccine trials.