Three models for promoting male circumcision (MC) as a preventative intervention against HIV infection were compared among migrant worker populations in western China.
A cohort study was performed after an initial cross-sectional survey among migrant workers in three provincial level districts with high HIV prevalence in western China. A total of 1,670 HIV seronegative male migrants were cluster-randomized into three intervention models, in which the dissemination of promotional materials and expert- and volunteer-led discussions are conducted in one, two, and three stage interventions. Changes in knowledge of MC, acceptability of MC, MC surgery uptake, and the costs of implementation were analyzed at 6-month and 9-month follow-up visits.
All three models significantly increased the participants’ knowledge about MC. The three-stage model significantly increased the acceptability of MC among participants and led to greatest increase in MC uptake. At the end of follow-up, 9.2% (153/1,670) of participants underwent MC surgery; uptake among the one-, two-, and three-stage models were 4.9%, 9.3%, and 14.6%, respectively. Multivariable Cox regression analysis showed that three-stage model was the most effective method to scale up MC, with RR = 2.0 (95% CI, 1.3-3.1, P=0.002) compared to the on-site session model. The two-stage intervention model showed no significant difference with either the on-site session model (RR=1.5, 95% CI, 0.92-2.4, P=0.12) or three-stage model (P=0.10).
A three-stage intervention with gradual introduction of knowledge led to the significantly increase in MC uptake among migrant workers in western China, and was also the most cost-effective method among the three models.
To determine prevalence, genotypes and predictors of anal human papillomavirus (HPV) among HIV-infected and uninfected men who have sex with men (MSM) in Beijing, China. In 2010–2011, we recruited MSM (age range 18–61; median 28 years) through peer volunteers, and collected demographic/behavioral information via interviewer-administrated questionnaires. Trained health workers collected anal swabs for HPV genotyping by PCR and blood samples for HIV/syphilis serologies . We obtained anal specimens from 212 HIV-infected and 459 HIV-uninfected participants. Among HIV-infected MSM, 82.1% were HPV-infected vs. 57.5% in HIV-uninfected (p<0.01). HIV-infected men had the greatest likelihood of multiple types: 17.9% uninfected; 36.3% with one type; 36.8% with 2–3; 9.0% with >4. Oncogenic HPV prevalence was higher among HIV- infected (61.3%) than uninfected participants (39.7%; p<0.01). HIV-uninfected MSM reporting always using condoms during insertive anal intercourse (past 6 months) were less likely to be HPV-infected (OR=0.49, 95%CI: 0.31–0.77). Among HIV-uninfected MSM, HPV infection was associated with unprotected receptive anal intercourse (past 6 months; OR=1.92, 95%CI: 1.19–3.11) and being forced to have sex (previous year; OR=3.32, 95%CI: 1.10–10.0). Multivariable logistic analysis among HIV infected MSM suggested that unprotected oral intercourse (past 6 months) was associated with HPV (adjusted OR=2.12, 95%CI: 1.00–4.48). Syphilis occurred in 55.8% of HIV-infected/HPV-infected, 50.0% of HIV-infected/HPV-uninfected, 19.6% of HIV-uninfected/HPV-infected, and 13.0% of HIV-uninfected/HPV-uninfected MSM. HPV anal infections were more common among HIV-infected than uninfected MSM in China, including oncogenic and multiple types. Unprotected oral and receptive anal sex were significant HPV risk factors. Promotion of safer sex and HPV vaccination is strongly recommended among MSM.
Human papillomavirus; HIV; syphilis; genotype; men who have sex with men; China
HIV testing is the gateway for prevention and care. We explored factors associated with HIV testing among Chinese men who have sex with men (MSM).
In Chongqing City, we recruited 492 MSM in 2010 using respondent driven sampling in a cross-sectional study. Computer-assisted self-interviews were conducted to collect information on history of HIV testing.
Only 58% of participants reported ever having taken an HIV test. MSM who had a college degree [adjusted odds ratio (AOR): 1.7; 95% confidence interval (CI): 1.2-2.6; P=0.008] were more likely to take a test; those who preferred a receptive role in anal sex were less likely to do so than those with insertive sex preference (AOR: 0.6; 95% CI: 0.35-0.94; P=0.03); those who used condoms with the recent male partner during the past 6 months were more likely to get tested (AOR: 2.87; 95%CI: 1.25-6.62; P=0.01). Principal perceived barriers to testing included: fear of knowing a positive result, fear of discrimination if tested positive, low perceived risk of HIV infection, and not knowing where to take a test. Factors reported to facilitate testing were sympathetic attitudes from health staff and guaranteed confidentiality. Prevalence was high: 11.7% HIV-positive and 4.7% syphilis positive.
The HIV testing rate among MSM in Chongqing is still low, though MSM prevalence is high compared to other Chinese cities. MSM preferring receptive anal sex are less likely to get testing and perceive having lower HIV risk. Along with expanded education and social marketing, a welcoming and non-judgmental environment for HIV testing is needed.
Human immunodeficiency virus; syphilis; men who have sex with men; HIV testing; respondent driven sampling; China
To evaluate the effect of risk reduction interventions on HIV knowledge, attitudes and behaviors among men who have sex with men (MSM) in China.
We performed a systematic review and meta-analysis of HIV risk reduction intervention studies among Chinese MSM. The summary difference of standardized mean differences (SMD) between both study arms or between pre- and post-intervention assessments were defined as the effect size (ES); ES was calculated using standard meta-analysis in random effects models.
Thirty-four eligible studies were included in the analysis, including two randomized clinical trials (RCT), six quasi-experimental studies, six pre-and-post intervention studies, and twenty serial cross-sectional intervention studies. These studies showed an increase in consistent condom use with any male sexual partners (mean ES, 0.46; 95% confidence interval [CI], 0.35–0.56), with regular sexual partners (mean ES, 0.41; 95% CI, 0.18–0.63), and casual sexual partners (mean ES, 0.52; 95% CI, 0.24–0.79). The analysis of ten studies that measured the impact on uptake of HIV testing also showed a positive result (mean ES, 0.55; 95% CI, 0.38–0.71). The risk reduction interventions also improved HIV/AIDS-related knowledge (mean ES, 0.77; 95% CI, 0.60–0.94) and attitudes (mean ES, 1.35; 95% CI, 0.91–1.79), but did not reduce prevalence of HIV (mean ES, 0.23; 95% CI, 0.02–0.45) and syphilis infections (mean ES, −0.01; 95% CI, −0.19–0.17). There was significant heterogeneity among these studies.
On aggregate, HIV risk reduction interventions were effective in reducing risky behaviors and improving knowledge and attitudes among Chinese MSM, but were not associated with a change in the prevalence of HIV and syphilis. Future studies should use incidence as definitive study outcome.
The vaccinia virus TianTan (VTT) has been modified as an HIV vaccine vector in China and has shown excellent performance in immunogenicity and safety. However, its adverse effects in immunosuppressed individuals warrant the search for a safer vector in the following clinic trails. In this study, we deleted the C7L and K1L genes of VTT and constructed six recombinant vaccinia strains VTT△C7L, VTT△K1L, VTT△C7LK1L, VTKgpe△C7L, VTKgpe△K1L and VTT△C7LK1L-gag. The pathogenicity and immunogenicity of these recombinants were evaluated in mouse and rabbit models. Comparing to parental VTT, VTT△C7L and VTT△K1L showed significantly decreased replication capability in CEF, Vero, BHK-21 and HeLa cell lines. In particular, replication of VTT△C7LK1L decreased more than 10-fold in all four cell lines. The virulence of all these mutants were decreased in BALB/c mouse and rabbit models; VTT△C7LK1L once again showed the greatest attenuation, having resulted in no evident damage in mice and erythema of only 0.4 cm diameter in rabbits, compared to 1.48 cm for VTT. VTKgpe△C7L, VTKgpe△K1L and VTT△C7LK1L-gag elicited as strong cellular and humoral responses against HIV genes as did VTKgpe, while humoral immune response against the vaccinia itself was reduced by 4-8-fold. These data show that deletion of C7L and K1L genes leads to significantly decreased virulence without compromising animal host immunogenicity, and may thus be key to creating a more safe and effective HIV vaccine vector.
We report here the first novel HIV-1 second-generation intercirculating recombinant form 61_BC (inter-CRF61_BC), composed of two established CRFs (CRF07_BC and CRF08_BC), in China. CRF61_BC is the first CRF found among the heterosexual population in two different regions in China, suggesting the increasing significance of heterosexual transmission of HIV in China.
To study the dynamics of HIV drug resistance (HIVDR) and its association with virologic and immunologic failure as well as mortality among patients on combination antiretroviral therapy (cART) in China.
We recruited 365 patients on cART in two rural Chinese counties in 2003–2004 and followed them every 6 months until May 2010.
Virologic failure, HIVDR, immunologic failure and death were documented. We used Kaplan–Meier and the proportional hazards models to identify the timing of the events, and risk factors for mortality.
At the end of study, patients had been followed for 1974.3 person-years, a median of 6.1 years. HIVDR mutations were found in 235 (64.4%) patients and 75 died (20.5%, 3.8/100 person-years). Median time from cART to detection of virologic failure was 17.5 months, to HIVDR 36.6 months and to immunologic failure 55.2 months (≈18-month median interval between each adverse milestone). Being male, having a baseline CD4+ cell count of less than 50 cells/μl and HIVDR were associated with higher mortality. Patients who developed HIVDR in the first year of treatment had higher mortality than those developing HIVDR later (adjusted hazard ratio 1.90, 95% confidence interval 1.01–3.48).
HIVDR was common and was associated with higher mortality among Chinese patients on cART, particular when HIVDR was detected early in therapy. Our study reinforces the importance of improving patient adherence to cART in order to delay the emergence of HIVDR and obviate the need to switch to costly second-line drug regimens too early.
antiretroviral therapy; China; cohort; drug resistance; immunologic failure; mortality; virologic failure
Objective. To investigate the association of serum sTREM-1 with myocardial dysfunction in patients with severe sepsis. Methods. A total of 85 patients with severe sepsis were divided into severe sepsis group (n = 40) and septic shock group (n = 45). Serum levels of sTREM-1, NT-proBNP, APACHE II score, SOFA score, cardiac index, cardiac function index, global ejection fraction, and left ventricular contractility index were measured on days 1, 3, and 7 after admission to ICU. Results. Serum sTREM-1 levels of patients with septic shock were significantly higher than those with severe sepsis on days 1, 3, and 7. Serum sTREM-1 was positively correlated with APACHE II scores, SOFA scores, and NT-proBNP. However, The sTREM-1 level was markedly negatively correlated with CI, CFI, GEF, and dP/dt max, respectively. Multiple logistic regression analysis showed that sTREM-1 was independent risk factor to NT-proBNP increasing. The optimal cut-off point of sTREM-1 for detecting patients with myocardial dysfunction was 468.05 ng/mL with sensitivity (80.6%) and specificity (75.7%). There is no difference in TREM-1-mRNA expression between the two groups. Conclusions. Serum sTREM-1 is significantly associated with myocardial dysfunction and may be a valuable tool for determining the presence of myocardial dysfunction in patients with severe sepsis.
To develop an effective HIV vaccine strategy that can induce cross-reactive neutralizing antibody.
Codon-optimized gp140 and gp145 env genes derived from HIV-1cn54, a CRF07 B′/C recombinant strain, were constructed as DNA and recombinant Tiantan vaccinia (rTV) vaccines. The effect of heterologous immunization with gp140 and gp145 was tested in mice and guinea pigs. T cell responses were detected using the IFN-γ ELISPOT assay. A panel of primary isolates of clade B′ and B′/C HIV-1 and TZM-bl cells was used to determine the neutralizing activity of immunized sera.
The neutralizing antibodies (NAbs) induced by the heterologous immunogen immunization neutralized all HIV-1 B′ and B′/C primary isolates in the guinea pig model. Gp145 and gp140 heterologous prime-boost induced the best neutralizing antibody response with a broad neutralizing spectrum and the highest titer of 1:270 at 6 weeks after the last inoculation. However, the T cell response to HIV-1 peptides was significantly weaker than the gp145+gp145 homologous prime-boost.
This heterologous prime-boost immunization strategy could be used to design immunogen-generating broad neutralizing antibodies against genetic variance pathogens.
HIV; vaccine; neutralizing antibody; heterologous prime-boost immunization
Early detection of HIV infection enables timely care and treatment. However, many men who have sex with men (MSM) remain unaware of their HIV status because they do not or are unable to access HIV testing services. Oral fluid HIV rapid tests have the potential to increase HIV testing. This study is the first to evaluate willingness to use the oral fluid test among MSM in China.
A cross-sectional study was conducted in Beijing from July to October, 2012. Data were collected by self-administered questionnaires.
Of 262 who participated in the survey, 223(85.1%) reported that they were willing to use the oral fluid HIV rapid test. Willingness to use the oral fluid test was associated with higher education (adjusted odds ratio (AOR): 2.40, 95% confidence interval (CI): 1.13–5.10), lack of unprotected anal intercourse (UAI) with male partners in the past one month (AOR: 2.38; 95% 95%CI: 1.15–4.95), having taken more than 4 HIV tests (AOR: 3.54; 95%CI:1.52–8.28), and having ever heard of the oral fluid HIV rapid test from gay friends or gay organizations (AOR: 3.24, 95%CI: 1.40–7.51). Among those who expressed willingness to use the oral fluid HIV rapid test, the median amount of money they were willing to pay was 8 dollars. Among the 39 participants who were unwilling to use the oral fluid test, 79.5% (31/39) expressed concerns about the accuracy of the oral fluid HIV rapid test results and 17.9%(7/39) reported that they were not familiar with the oral fluid test and did not know how to use such a test.
A high proportion of MSM in Beijing appear to be willing to use the oral fluid HIV rapid test. Appropriate cost and education measures could help improve acceptance of the oral fluid test.
It is generally believed that CD8+ cytotoxic T lymphocytes (CTLs) play a critical role in limiting the replication of human immunodeficiency virus type 1 (HIV-1) and in determining the outcome of the infection, and this effect may partly depend on which HIV product is preferentially targeted. To address the correlation between HIV-1-specific CTL responses and virus replication in a cohort of former plasma donors (FPDs), 143 antiretroviral therapy naive FPDs infected with HIV-1 clade B' strains were assessed for HIV-1-specific CTL responses with an IFN-γ Elispot assay at single peptide level by using overlapping peptides (OLPs) covering the whole consensus clade B proteome. By using a Spearman's rank correlation analysis, we found that the proportion of Gag-specific CTL responses among the total virus-specific CTL activity was inversely correlated with viral loads while being positively correlated to CD4 counts, as opposed to Pol- and Env-specific responses that were associated with increased viral loads and decreased CD4 counts. In addition, Vpr-specifc CTL responses showed a similar protective effect with Gag responses, but with a much lower frequency of recognition. Significantly, we also observed an association between HLA-A*30/B*13/Cw*06 haplotype and lower viral loads that was probably due to restricted Gag-specific CTL responses. Thus, our data demonstrate the prominent role of Gag-specific CTL responses in disease control. The advantage of HLA-A*30/B*13/Cw*06 haplotype in viral control may be associated with the contribution of Gag-specific CTL responses in the studied individuals.
human immunodeficiency virus type 1; cytotoxic T lymphocytes; human leukocyte antigen class I; Gag
Despite the worldwide eradication of smallpox in 1979, the potential bioterrorism threat from variola virus and the ongoing use of vaccinia virus (VACV) as a vector for vaccine development argue for continued research on VACV. In China, the VACV Tiantan strain (TT) was used in the smallpox eradication campaign. Its progeny strain is currently being used to develop a human immunodeficiency virus (HIV) vaccine. Here we sequenced the full genomes of five TT clones isolated by plaque purification from the TT (752-1) viral stock. Phylogenetic analysis with other commonly used VACV strains showed that TT (752-1) and its clones clustered and exhibited higher sequence diversity than that found in Dryvax clones. The ∼190 kbp genomes of TT appeared to encode 273 open reading frames (ORFs). ORFs located in the middle of the genome were more conserved than those located at the two termini, where many virulence and immunomodulation associated genes reside. Several patterns of nucleotide changes including point mutations, insertions and deletions were identified. The polymorphisms in seven virulence-associated proteins and six immunomodulation-related proteins were analyzed. We also investigated the neuro- and skin- virulence of TT clones in mice and rabbits, respectively. The TT clones exhibited significantly less virulence than the New York City Board of Health (NYCBH) strain, as evidenced by less extensive weight loss and morbidity in mice as well as produced smaller skin lesions and lower incidence of putrescence in rabbits. The complete genome sequences, ORF annotations, and phenotypic diversity yielded from this study aid our understanding of the Chinese historic TT strain and are useful for HIV vaccine projects employing TT as a vector.
Since the emergence of drug-resistant mutants has limited the efficacy of non-nucleoside reverse transcriptase inhibitors (NNRTIs), it is essential to develop new antivirals with better drug-resistance and pharmacokinetic profiles. Here we designed and synthesized a series of 1-[(2-benzyloxyl/alkoxyl)methyl]-5-halo-6-aryluracils, the HEPT analogues, and evaluated their biological activity using Nevirapine and 18 (TNK-651) as reference compounds. Most of these compounds, especially 6b, 7b, 9b, 11b and 7c, exhibited highly potent anti-HIV-1 activity against both wild-type and NNRTI-resistant HIV-1 strains. The compound 7b, that had the highest selectivity index (SI = 38,215), is more potent than Nevirapine and 18. These results suggest that introduction of halogen at the C-5 position may contribute to the effectiveness of these compounds against RTI-resistant variants. In addition, m-substituents on the C-6 aromatic moiety could significantly enhance activity against NNRTI-resistant HIV-1 strains. These compounds can be further developed as next-generation NNRTIs with improved antiviral efficacy and drug-resistance profile.
HIV-1; Non-nucleoside reverse transcriptase inhibitors (NNRTIs); Drug-resistance
Buprenorphine/naloxone (BUP/NX) is not licensed for use in China or Thailand and there was little clinical experience with this drug combination in these countries at the inception of HIV Prevention Trial Network (HPTN) 058, a randomized trial comparing risk reduction counseling combined with either short-term or long-term medication assisted treatment with BUP/NX to prevent HIV infection and death among opioid-dependent injectors.
We conducted a safety phase that included the first 50 subjects enrolled at each of the three initial study sites (N=150). Clinical and laboratory assessments were conducted at baseline and weekly for the first 4 weeks. Changes in laboratory parameters were estimated with random effects models.
BUP/NX was well tolerated by study subjects and opioid withdrawal scores decreased substantially during the 3-day induction. Two participants experienced grade 3 clinical adverse events, which were categorized as probably not related to the study drug. Grade 2 or 3 increases in alanine aminotransferase (ALT) occurred in 25 (17%) subjects. The magnitude of ALT increase over 4-week follow-up was strongly associated with baseline ALT elevation.
In Chinese and Thai opioid-dependent injectors, we found BUP/NX to be effective in reducing opioid withdrawal symptoms and safe during short-term use. ALT increases were observed over 4-week-follow-up, which are consistent with reports from Western populations. Long-term safety and efficacy evaluations are indicated.
buprenorphine/naloxone; injection drug use; opioid dependence; HIV prevention; risk reduction counseling; safety; hepatic toxicity
We assessed HIV prevalence and associated behaviors and risk factors among men who have sex with men (MSM) in Beijing, China. Five hundred MSM were recruited for a biological and behavioral survey using respondent-driven sampling (RDS) in 2009. Serologic specimens were tested for markers of HIV and syphilis infection. A computer-assisted personal interview (CAPI) administered questionnaire gathered information including demographic characteristics, sexual behaviors, HIV testing, and social norms concerning condom use. The adjusted HIV prevalence was 8.0%, syphilis 22.0%. HIV testing and disclosure was low; only 39.3% had HIV tested in the past 12 months, 49.7% knew their own HIV status and 22.8% knew their last male partner's HIV status. HIV infection was associated with syphilis, ever having sex with a woman, not knowing the HIV status of the most recent male partner, and never buying condoms in the past 12 months. Stronger endorsement of positive social norms around condom use strongly and predicted lower prevalence of HIV infection. Compared to surveys of similar design in the recent past, HIV continues to spread rapidly among Beijing's MSM. Our results identify points of intervention that, if addressed in time, may still alter the course of the epidemic including the promotion of HIV testing and partner disclosure, syphilis control and particularly changing social norms around condom use.
Increasing evidence indicates that antibody-dependent cellular cytotoxicity (ADCC) contributes to the control of HIV/SIV infection. However, little is known about the ADCC function of natural killer (NK) cells in non-human primate model. Here we demonstrated that ADCC function of NK cells was significantly compromised in chronic SIV/SHIV infection, correlating closely with the expression of FcγRIIIa receptor (CD16) on NK cells. CD32, another class of IgG Fc receptors, was identified on NK cells with higher expression in the infected macaques and the blockade of CD32 impacted the ability of NK cells to respond to antibody-coated target cells. The inhibition of matrix metalloproteases (MMPs), a group of enzymes normally involved in tissue/receptor remodeling, could restore NK cell-mediated ADCC with increased CD16 expression on macaque NK cells. These data offer a clearer understanding of NK cell-mediated ADCC in rhesus macaques, which will allow us to evaluate the ADCC repertoire arising from preclinical vaccination studies in non-human primates and inform us in the future design of effective HIV vaccination strategies.
Highly active antiretroviral therapy (HAART) has significantly decreased mortality among Chinese HIV patients. However, emerging HIV drug resistance (HIVDR) poses a growing threat to the long-term success and durability of HAART.
Three cross-sectional surveys were conducted across the country from 2004 to 2006, respectively. Patients completed a questionnaire and provided blood for CD4 cell count, HIV viral load (VL), and HIV resistance genotyping. Factors associated with HIVDR were identified by logistic regression.
3667 unique patients were included across the three surveys. Among 2826 treatment-experienced patients, median duration of treatment was 17.4 (IQR 8.6–28.4) months and HIVDR was identified in 543 (19.2%). Factors significantly associated with HIVDR included ART drug distribution location, CD4 cell count, initial HAART regimen, self-reported medication adherence, and province.
Virologic failure increased over time on therapy but a significant proportion of patients in failure had no resistance mutations identified, suggesting that treatment adherence is suboptimal and must be emphasized. Due to the significantly higher risk of HIVDR in certain provinces, additional steps to reduce HIVDR should be taken.
HIV-1 subtype B’ isolates have been predominantly circulating in China. Their intra- and inter-subtype neutralization sensitivity to autologous and heterologous plasmas has not been well studied.
Twelve HIV-1 B’ clinical isolates obtained from patients were tested for their intra- and inter-subtype neutralization sensitivity to the neutralization antibodies in the plasmas from patients infected by HIV-1 B’ and CRF07_BC subtypes, respectively. We found that the plasmas from the HIV-1 B’-infected patients could potently neutralize heterologous viruses of subtype B’ with mean ID50 titer (1/x) of about 67, but they were not effective in neutralizing autologous viruses of subtype B’ with mean ID50 titer (1/x) of about 8. The plasmas from HIV-1 CRF07_BC-infected patients exhibited weak inter-subtype neutralization activity against subtype B’ viruses with ID50 titer (1/x) is about 22. The neutralization sensitivity of HIV-1 B’ isolates was inversely correlated with the neutralizing activity of plasmas from HIV-1 B’-infected patients (Spearman’s r = −0.657, P = 0.020), and with the number of potential N-glycosylation site (PNGS) in V1-V5 region (Spearman’s r = −0.493, P = 0.034), but positively correlated with the viral load (Spearman’s r = 0.629, P = 0.028). It had no correlation with the length of V1-V5 regions or the CD4+ T cell count. Virus AH259V has low intra-subtype neutralization sensitivity, it can be neutralized by 17b (IC50: 10μg/ml) and 447-52D (IC50: 1.6μg/ml), and the neutralizing antibodies (nAbs) in plasma AH259P are effective in neutralizing infection by the primary HIV-1 isolates with different subtypes with ID50 titers (1/x) in the range of 32–396.
These findings suggest that the HIV-1 subtype B’ viruses may mutate under the immune pressure, thus becoming resistant to the autologous nAbs, possibly by changing the number of PNGS in the V1-V5 region of the viral gp120. Some of primary HIV-1 isolates are able to induce both intra- and inter-subtype cross-neutralizing antibody responses.
HIV-1 subtype B’; Clinical isolates; Neutralization sensitivity
Host immunogenetic factors such as HLA class I polymorphism are important to HIV-1 infection risk and AIDS progression. Previous studies using high-resolution HLA class I profile data of Chinese populations appeared insufficient to provide information for HIV-1 vaccine development and clinical trial design. Here we reported HLA class I association with HIV-1 susceptibility in a Chinese Han and a Chinese Uyghur cohort.
Our cohort included 327 Han and 161 Uyghur ethnic individuals. Each cohort included HIV-1 seropositive and HIV-1 seronegative subjects. Four-digit HLA class I typing was performed by sequencing-based typing and high-resolution PCR-sequence specific primer. We compared the HLA class I allele and inferred haplotype frequencies between HIV-1 seropositive and seronegative groups. A neighbor-joining tree between our cohorts and other populations was constructed based on allele frequencies of HLA-A and HLA-B loci. We identified 58 HLA-A, 75 HLA-B, and 32 HLA-Cw distinct alleles from our cohort and no novel alleles. The frequency of HLA-B*5201 and A*0301 was significantly higher in the Han HIV-1 negative group. The frequency of HLA-B*5101 was significantly higher in the Uyghur HIV-1 negative group. We observed statistically significant increases in expectation-maximization (EM) algorithm predicted haplotype frequencies of HLA-A*0201-B*5101 in the Uyghur HIV-1 negative group, and of Cw*0304-B*4001 in the Han HIV-1 negative group. The B62s supertype frequency was found to be significantly higher in the Han HIV-1 negative group than in the Han HIV-1 positive group.
At the four-digit level, several HLA class I alleles and haplotypes were associated with lower HIV-1 susceptibility. Homogeneity of HLA class I and Bw4/Bw6 heterozygosity were not associated with HIV-1 susceptibility in our cohort. These observations contribute to the Chinese HLA database and could prove useful in the development of HIV-1 vaccine candidates.
Pakistan is experiencing a growing HIV epidemic. Antiretroviral drugs (ARV) have been smuggled into the country and available without prescription since the early 1990s, but are now provided free of cost by the government. We assessed the prevalence of HIV-1, drug resistance, and subtype distributions. Blood specimens were collected from HIV-1-infected participants registered in Sindh Province on dry blood spot (DBS) cards in 2008. Pol, protease, and partial reverse transcriptase regions were sequenced after reverse transcriptase PCR (RT-PCR). HIV-1 subtype was assigned by phylogenetic analysis. Primary drug resistance was analyzed by the Calibrated Population Resistance (CPR) tool using the Stanford Surveillance Drug Resistance Mutation (SDRM) major mutation list. Out of 100 blood samples collected, 42 were suitable for testing. Out of 42, 11 were ARV-receiving and 31 ARV-naive patients. Among them, 24 were injection drug users (IDUs), four immigrants, two hijras (male transvestites), two men who have sex with men (MSM), four prisoners, one female sex workers, two spouses of HIV-infected persons, and four from the general population. ARV resistance among naive patients was 2/31 (6.5%) and 36.4% (4/11) among ARV-experienced patients making an overall resistance of 14.2%. HIV-1 subtype A1 was the predominant subtype found in 35/42 (83.3%) followed by CRF35_AD and C, 6.5% each. Subtype D and G were found in one (2.4%) each. A significant proportion of Pakistani HIV patients has ARV drug resistance. Physicians treating patients should consider the magnitude of drug resistance while selecting regimens, and address drug adherence aggressively.
The increasing prevalence of human immunodeficiency virus type 1 (HIV-1) subtype C infection worldwide calls for efforts to develop a relevant animal model for evaluating AIDS candidate vaccines. In China, the prevalent HIV strains comprise a circulating recombinant form, BC (CRF07_BC), in which the envelope belongs to subtype C. To evaluate potential AIDS vaccines targeting Chinese viral strains in nonhuman primate models, we constructed a simian-human immunodeficiency virus (SHIV) carrying most of the envelope sequence of a primary HIV-1 clade C strain isolated from an HIV-positive intravenous drug user from YunNan province in China. Infection of six Chinese rhesus macaques with SHIV-CN97001 resulted in a low level of viremia and no significant alteration in CD4+ T-lymphocyte counts. To determine whether in vivo adaptation would enhance the infectivity of SHIV-CN97001, the parental infectious strain was serially passaged through eight Chinese rhesus macaques. The hallmarks of SHIV infectivity developed gradually, as shown by the increasingly elevated peak viremia with each passage. These findings establish that the R5-tropic SHIV-CN97001/Chinese rhesus macaque model should be very useful for evaluation of HIV-1 subtype C vaccines in China.
Clade C; Passage; Rhesus macaques; SHIV
(1) To assess the HIV incidence rate among men who have sex with men (MSM) in a large cohort study in Beijing, China and (2) to identify sociodemographic and behavioural risk factors of HIV seroconversion among MSM in Beijing, China.
A prospective cohort study.
Baseline and follow-up visits were conducted among MSM in Beijing, China.
A cohort of 797 HIV-seronegative MSM was recruited from August to December 2009, with follow-up occurring after 6 and 12 months.
Primary and secondary outcome measures
At baseline and follow-up visits, participants reported sociodemographic and sexual behaviour information, and were tested for HIV, herpes simplex virus-2 (HSV-2) and syphilis with whole blood specimens. Cox regression analysis was used to identify factors associated with HIV seroconversion.
Most study participants (86.8%) were retained by the 12-month follow-up. The HIV, HSV-2 and syphilis incidence rates were 8.09 (95% CI 6.92 to 9.26), 5.92 (95% CI 5.44 to 6.40) and 8.06 (95% CI 7.56 to 8.56) cases per 100 person-years, respectively. HIV seroconversion was significantly associated with being <25 years old, having <12 years of education, having >1 male sex partner in the past 6 months, and being syphilis positive or HSV-2 positive.
The HIV incidence among MSM in Beijing is serious. Interventions and treatment of sexually transmitted diseases (STD) should be combined with HIV control and prevention measures among MSM.
The mannose-sensitive hemagglutination pilus strain of Pseudomonas aeruginosa (PA-MSHA) has been shown to trigger naïve immune responses through the activation of monocytes, macrophages, natural killer cells (NK cells) and antigen presenting cells (APCs). Based on the hypothesis that PA-MSHA activates natural immunity through the Toll-like receptor (TLR) pathway, we scanned several critical TLR pathway molecules in mouse splenocytes using high-throughput real-time QRT-PCR and co-stimulatory molecule in bone marrow-derived dendritic cells (BMDCs) following in vitro stimulation by PA-MSHA. PA-MSHA enabled activation of the TLR pathway mediated by NF-κB and JNK signaling in splenocytes, and the co-stimulatory molecule CD86 was up-regulated in BMDCs. We then assessed the adjuvant effect of PA-MSHA for HIV-1 DNA vaccines. In comparison to DNA inoculation alone, co-inoculation with low dosage of PA-MSHA enhanced specific immunoreactivity against HIV-1 Env in both cellular and humoral responses, and promoted antibody avidity maturation. However, high doses of adjuvant resulted in an immunosuppressive effect; a two- or three-inoculation regimen yielded low antibody responses and the two-inoculation regimen exhibited only a slight cellular immunity response. To our knowledge, this is the first report demonstrating the utility of PA-MSHA as an adjuvant to a DNA vaccine. Further research is needed to investigate the exact mechanisms through which PA-MSHA achieves its adjuvant effects on innate immune responses, especially on dendritic cells.
China is experiencing a dynamic HIV/AIDS epidemic. While serology based surveillance systems have reported the spread of HIV/AIDS, detailed tracking of its transmission in populations and regions is not possible without mapping it at the molecular level. We therefore conducted a nationwide molecular epidemiology survey across the country.
HIV-1 genotypes were determined from 1,408 HIV-positive persons newly diagnosed in 2006. The prevalence of each genotype was estimated by weighting the genotype’s prevalence from each province- and risk-specific subpopulation with the number of reported cases in the corresponding subgroups in that year.
CRF07_BC (35.5%), CRF01_AE (27.6%), CRF08_BC (20.1%), and subtype B' (9.6%) were the four main HIV-1 strains in China. CRF07_BC and CRF08_BC were the primary drivers of infection among injecting drug users in northeastern and southeastern China, respectively, and subtype B' remained dominant among former plasma donors in central China. In contrast, all four strains occurred in significant proportions among heterosexuals nationwide, pointing to an expansion of the HIV-1 epidemic from high-risk populations into the general population. CRF01_AE also replaced subtype B as the principal driver of infection among men-who-have-sex-with-men.
Our study provides the first comprehensive baseline data on the diversity and characteristics of HIV/AIDS epidemic in China, reflecting unique region- and risk group-specific transmission dynamics. The results provide information critical for designing effective prevention measures against HIV transmission.