[Show abstract][Hide abstract] ABSTRACT: 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.
[Show abstract][Hide abstract] ABSTRACT: Objectives
. To understand the current risk of HIV infection and transmission and further elucidate the underlying risk factors among men who have sex with men and women (MSMW) in China.
. Following PRISMA guidelines, we conducted a systematic review and meta-analysis of searching through Chinese and English available literature databases between January 2000 and June 2014 to identify articles.
. Thirty-six articles (including 19,730 MSMW and 53,536 MSMO) met the selection criteria and the aggregated results found that MSMW have significantly higher HIV prevalence than MSMO (6.6% versus 5.4%, OR = 1.27, 95% CI = 1.01–1.58). A higher proportion of MSMW had commercial male partners in the past 6 months (18.3% versus 12.2%, OR = 1.56, 95% CI = 1.01–2.42). Additionally, substance use in the past 6 months was significantly more frequent among MSMW than MSMO (alcohol use: 27.1% versus 13.1%, OR = 2.53, 95% CI = 2.14–2.99; illicit drug use: 5.3% versus 2.5%, OR = 2.09, 95% CI = 1.48–2.95).
. A higher proportion of commercial sex and substance use among MSMW may be a potentially indicative factor for significantly higher HIV prevalence compared to MSMO. Targeted interventions should aim at increasing the frequency of HIV/STIs screening and preventing high risk commercial sex and substance use among MSMW to decrease their HIV transmission to the general population.
Full-text · Article · Dec 2015 · BioMed Research International
[Show abstract][Hide abstract] ABSTRACT: During early HIV-1 infection (EHI), the interaction between the immune response and the virus determines disease progression. Although CD1c + myeloid dendritic cells (mDCs) can trigger the immune response, the relationship between CD1c + mDC alteration and disease progression has not yet been defined.
EHI changes in CD1c + mDC counts, surface marker (CD40, CD86, CD83) expression, and IL-12 secretion were assessed by flow cytometry in 29 patients.
When compared with the normal controls, patients with EHI displayed significantly lower CD1c + mDC counts and IL-12 secretion and increased surface markers. CD1c + mDC counts were positively correlated with CD4+ T cell counts and inversely associated with viral loads. IL-12 secretion was only positively associated with CD4+ T cell counts. Rapid progressors had lower counts, CD86 expression, and IL-12 secretion of CD1c + mDCs comparing with typical progressors. Kaplan-Meier analysis and Cox regression models suggested patients with low CD1c + mDC counts (<10 cells/μL) had a 4-fold higher risk of rapid disease progression than those with high CD1c + mDC counts. However, no relationship was found between surface markers or IL-12 secretion and disease progression.
During EHI, patients with low CD1c + mDC counts were more likely to experience rapid disease progression than those with high CD1c + mDC counts.
Full-text · Article · Dec 2015 · BMC Infectious Diseases
[Show abstract][Hide abstract] ABSTRACT: Human Immunodeficiency Virus Type 1 (HIV-1) causes chronic infection characterized by the depletion of CD4+ T lymphocytes and the development of AIDS (Acquired Immunodeficiency Syndrome). Current antiretroviral drugs inhibit viral spread, but they do not lead to a full immune recovery. Hematopoietic stem cells (HSCs) and multipotent hematopoietic progenitor cells (HPCs) give rise to all blood and immune cells, and in HIV infection, hematological abnormalities frequently occur in patients. Here we used bone marrow samples from HIV-1 infected people to study the relationship between the proliferation ability of HSCs/HPCs and peripheral CD4+ T lymphocytes. Three indexes were used to reflect the proliferation ability of HSCs and HPCs: 1) colony-forming units of bone marrow mononuclear cells (BMMCs); 2) amplification of CD34+ cells purified from BMMCs; 3) expression of HOXB4 and HOXA9 in CD34+ cells. We observed a direct correlation between peripheral number of CD4+ T lymphocytes and the HSCs/HPCs proliferation ability in our study. We also compared HIV-infected patients with or without antiretroviral therapy (ART). Our results demonstrated that after ART, CD4+ T cell recovery and HPCs proliferation ability are correlated. Our findings have implications in understanding whether bone marrow (BM)-derived HPCs can supplement for the loss of CD4+ T lymphocytes during HIV-1 infection. Copyright
No preview · Article · Nov 2015 · JAIDS Journal of Acquired Immune Deficiency Syndromes
[Show abstract][Hide abstract] ABSTRACT: Numerous anomalies in B-cell phenotypes and functions have been described in HIV-infected individuals. However, the actual relationship between B cells and disease progression remains unclear. In this study, we investigated B-cell counts/percentages during a 12-month infection period in HIV-infected individuals that eventually developed into typical progressors (TPs) or rapid progressors (RPs). We found, after 12 months of infection, the baseline B-cell counts/percentages correlated positively with CD4
T-cell counts (
) and negatively with HIV viral set points (
). Kaplan-Meier survival analysis showed that high baseline B-cell counts/percentages were associated with a slow CD4-cell decline. B-cell kinetics indicated the baseline B-cell counts/percentages could be factors distinguishing between TPs and RPs. The combination of the baseline B-cell counts and percentages was associated with rapid disease progression (a 80.7% predictive value as measured by the area under the curve). These results indicate that the baseline B-cell counts/percentages might be associated with HIV disease progression.
[Show abstract][Hide abstract] ABSTRACT: Importance:
Current antiretroviral therapy is very effective in suppressing active HIV-1 replication, but does not fully eliminate virally infected cells. The ability of HIV-1 to persist long-term despite suppressive antiretroviral combination therapy represents a perplexing aspect of HIV-1 disease pathogenesis, since most HIV-1 target cells are activated, short-lived CD4 T cells. This study suggests that CD4 T helper cells with Th1/Th17 polarization have a preferential role as a long-term reservoir for HIV-1 infection during antiretroviral therapy, possibly because these cells may imitate some of the functional properties traditionally ascribed to stem cells, such as the ability to persist for extremely long periods of time and to repopulate their own pool size through homeostatic self-renewal. These observations support the hypothesis that HIV-1 persistence is driven by small subsets of long-lasting stem cell-like CD4 T cells that may represent particularly promising targets for clinical strategies aiming at HIV-1 eradication and cure.
Full-text · Article · Sep 2015 · Journal of Virology
[Show abstract][Hide abstract] ABSTRACT: To investigate the relationship between the cognitive impairment and hippocampal morphological and functional change in HIV-seropositive patients.
30 HIV+ patients who complain of memory-decreasing and 15 healthy volunteers were recruited. Performances of learning and memory were assessed using Hopkins Verbal Learning Test-Revised (HVLT-R) and Brief Visuospatial Memory Test-Revised (BVMT-R). Bilateral hippocampal volume, ADC value, FA value and MR spectroscopy variables of bilateral hippocampus and parahippocampus gyrus was detected by 3.0 T MR scanner.
We found significant differences in the all cognitive outcomes but one between HIV+ and HIV-. There was a difference in the ADC value of left parahippocampus gyrus between mild-impairment group and severe-impairment group (p=0.018). We found differences in the Cho, Cho/Cr, NAA/Cr of left hippocampus (p=0.002; p=0.008; p=0.002) and the Cho/Cr of right parahippocampus gyrus (p=0.023) between HIV+ and HIV-, and in the MI of left hippocampus (p=0.003) and the Glx of right hippocampus (p<0.001) between mild-impairment group and severe-impairment group. We found significantly positive correlations between NAA/Cr of left hippocampus and outcomes of HVLT-R, BVMT-R. There were significantly negative correlations between ADC value of hippocampus, parahippocampus gyrus and outcomes of HVLT-R, BVMT-R, and between Cho, Cho/Cr of hippocampus, parahippocampus gyrus and outcomes of HVLT-R, BVMT-R.
The performance of verbal learning and visual memory was significantly decreased in HIV-1 seropositive patients. The cognitive impairment of HIV infection was associated with conductive function and metabolic changes of hippocampus and parahippocampus gyrus in this study.
No preview · Article · Aug 2015 · JAIDS Journal of Acquired Immune Deficiency Syndromes
[Show abstract][Hide abstract] ABSTRACT: In HIV disease course, the decline of peripheral CD4 T-cell count correlates with rapid disease progression. The supply of peripheral naive T cells by the thymus requires precursor T-cell proliferation within the thymus. In the setting of HIV-1 infection, when both naive and memory T cells are progressively depleted, the contribution of thymic dysfunction in CD4 depletion needs to be studied. Previous research has shown that thymic function may also be impaired in HIV-1 infection. However, it is inconclusive regarding whether this impairment occurred at the early time or during the chronic phase. In addition, the relationship between thymic dysfunction and disease progression remains unknown. In this study, we examined the thymic function in 65 HIV-infected individuals. Among them, 17 were in acute phase, 15 were in early chronic phase, 15 were in chronic phase with no ART (antiretroviral therapy), and 18 were on ART. We also included 11 uninfected individuals as controls. We measured the peripheral blood levels of T-cell receptor rearrangement excision circles and PTK7 and CD31 expressions for the frequency of circulating recent thymic emigrants. We observed that the 2 indicators of thymic function, sj/β-TREC and PTK7, seemed to be lower in the chronic infection group than those in the acute and early chronic groups. Both indicators returned to the normal level after ART. However, after 1-year follow-up of patients with early HIV-1 infection, rapid progressors (n = 4) had lower PTK7 and CD31 expressions than chronic progressors (n = 6).
No preview · Article · Aug 2015 · JAIDS Journal of Acquired Immune Deficiency Syndromes
[Show abstract][Hide abstract] ABSTRACT: Aims: To evaluate the prevalence and associated factors of reduced bone mineral density (BMD) among antiretroviral therapy (ART) naive HIV-infected male patients in China. Methods: We compared BMD between HIV-infected male patients and healthy controls. Risk factors of reduced BMD were studied using multivariable linear regression. Results: Reduced BMD rate of chronic HIV infection patients was higher. HIV infection was independently associated with decreased BMD after adjusting for demographic factors. Older age, lower BMI and men who have sex with men (MSM) were revealed as the risk factors of lower BMD in HIV-infected male patients. Conclusion: Reduced BMD rate of HIV-infected patients was high. Policies are needed for prevention and treatment.
[Show abstract][Hide abstract] ABSTRACT: Background
Recent upsurge of new HIV infections among men who have sex with men (MSM) is a major concern in China. Paucity of national-level information regarding the burden and predictors of this progressive epidemic of new infections called for a multi-centric, comprehensive investigation to determine incidence and prevalence of HIV infections (both early and established) and their predictors.
Methods and findings
In a multi-center cross-sectional study with a prospective component, 4496 eligible, consenting (written) MSM were recruited (non-response=0.22%), interviewed and undergone tests for HIV (Wesern blot(WB) and BED HIV-1 capture enzyme immunoassay IgG captured EIA(BED-CEIA) were jointly used to determinealong with HIV early(recent) or/and established case differentiationinfection), syphilis and herpes simplex virus-2 (HSV-2), in seven cities of China (Shanghai, Nanjing, Changsha, Zhengzhou, Ji’nan, Shenyang and Kunming) between June 2012 and June 2013.
Majority participants were aged ≤35 years (77.52%), migrants (60.27%), never married (69.79%), receptive during anal sex (70.52%) %) and found partners mainly through internet (67.94%). Only 8.47% got circumcised, 27.85% did not use condom during last anal sex, 28.32% used recreational drugs and 15.46% reported anal bleeding post intercourse.
HIV prevalence was 9.9% ( [95% Confidence Intervals (CI) =4.0 %-13.913.9 %] %). Among HIV cases 41.89% were recently infected, with HIVand incidence was of 8.90/100 Person-Years (95%CI =7.62-10.17). Among HIV cases 41.89% were recently infected. Prevalence for HSV-2 and syphilis were 11.9512.50% and 8.47%, respectively. Among HIV cases 41.89% were recently infected.
Compared to respective reference groups, higher odds of recent acquisition of HIV was associated with sexual debut during 16-25 years (aOR=3.20, 95%CI =1.01-10.22), playing receptive role (aOR=2.62, 95%CI =1.38-3.08), having multiple male partners (aOR=1.54, 95%CI =1.12-2.13), recreational drug use (aOR=1.98, 95%CI =1.39-2.80), anal bleeding (aOR=1.73, 95%CI =1.14-2.60) and having syphilis (aOR=3.08, 95%CI =2.04-4.67) or HSV-2 (aOR=2.43, 95%CI =1.58-3.73).
High rate of early HIV infection is potentially resulting in progressive deterioration of the overall HIV situation epidemic among MSM in China. Targeted interventions to address high-risk MSM including those having later sexual debut, receptive role, multiple partners, history of recreational drug use, syphilis or HSV-2 infection and anal bleeding seemed to be the need of the hour.
[Show abstract][Hide abstract] ABSTRACT: Genome-wide association studies (GWASs) have revealed several genetic loci associated with HIV-1 outcome following infection (e.g., HLA-C at 6p21.33) in multi-ethnic populations with genetic heterogeneity and racial/ethnic differences among Caucasians, African-Americans, and Hispanics. To systematically investigate the inherited predisposition to modulate HIV-1 infection in Chinese populations, we performed GWASs in three ethnically diverse HIV-infected patients groups (i.e., HAN, YUN, and XIN, N = 538). The reported loci at 6p21.33 was validated in HAN (e.g., rs9264942, P = 0.0018). An independent association signal (rs2442719, P = 7.85 × 10(-7), HAN group) in the same region was observed. Imputation results suggest that haplotype HLA-B*13:02/C*06:02, which can partially account for the GWAS signal, is associated with lower viral load in Han Chinese. Moreover, several novel loci were identified using GWAS approach including the top association signals at 6q13 (KCNQ5, rs947612, P = 2.15 × 10(-6)), 6p24.1 (PHACTR1, rs202072, P = 3.8 × 10(-6)), and 11q12.3 (SCGB1D4, rs11231017, P = 7.39 × 10(-7)) in HAN, YUN, and XIN groups, respectively. Our findings imply shared or specific mechanisms for host control of HIV-1 in ethnically diverse Chinese populations, which may shed new light on individualized HIV/AIDS therapy in China.
Full-text · Article · Jun 2015 · Scientific Reports
[Show abstract][Hide abstract] ABSTRACT: The data from apparently healthy individuals with thalassemia has been demonstrated to have an effect on the reference intervals for the erythrocyte indices in areas with a high incidence of thalassemia.
Six clinical centers screened apparently healthy individuals using a questionnaire and a physical examination. Then, the qualified reference individuals were selected by hematological indices and a genotypic thalassemia diagnosis. Statistical comparisons were conducted for the erythrocyte reference intervals in the Chinese population with and without thalassemia. The constituent ratios and the mean (SD) of erythrocyte indices according to the thalassemia genotype were calculated. The relationship between the MCV values and the thalassemia genotype was also estimated.
4,636 reference individuals were included using hematological indices and genotypic thalassemia screening. The results of the erythrocyte reference intervals for individuals in Guangzhou with thalassemia demonstrated that the RBC, MCV, and MCH values significantly differed by gender compared with other regions (p < 0.01). In contrast, for individuals without thalassemia, the results tended to be similar and clinically acceptable. In addition, the results of the erythrocyte indices revealed significant differences among α-thalassemia patients, β-thalassemia patients, and the control group.
Apparently healthy individuals with thalassemia in the high prevalence zone of thalassemia could not be excluded by the questionnaire, physical examination or laboratory indices (Fe < 6 μmol/L, Hb < 90 g/L). The screening of genotypic thalassemia based on the MCV or MCH values to exclude unqualified individuals is the most effective way to obtain accurate and reliable reference intervals for the erythrocyte indices.
No preview · Article · May 2015 · Clinical laboratory
[Show abstract][Hide abstract] ABSTRACT: The Kaposi's sarcoma-associated herpesvirus (KSHV)-encoded latent nuclear antigen LANA plays an essential role in viral episome maintenance. LANA also contributes to DNA replication and tumorigenesis during latency. Recent studies suggested that LANA was involved in regulation of SUMOylation which results in chromatin silencing. To examine the pleiotropic effects of LANA protein on host cell gene expression, we utilized MS analysis to identify cellular proteins associated with the SUMO-Interacting Motif of LANA (LANA(SIM) ). In addition to the 6 bands identified as substantially associated with LANA(SIM) , 151 proteins were positively identified by MS/MS analysis. Compared with previous proteomic analysis of the N- and C- truncated mutants of LANA (LANA(NC) ), our results revealed that a complex of specific proteins with relatively high SUMOylation and SIM motifs are associated with LANA(SIM) . Intriguingly, consistent with our previous report that identified KAP1 as a key component, the in-vitro SUMO-2 modified isoform has a substantially higher affinity with LANA(SIM) than the SUMO-1 modified isoform. Moreover, via cluster and pathway analysis, we proposed a hypothetical model for the LANA(SIM) regulatory circuit involving aberrant SUMOylation of cell cycle (particular mitotic), DNA unwinding and replication, and pre-mRNA/mRNA processing-related proteins. This study provides a SUMOylated and non-SUMOylated proteome profile of LANA(SIM) -associated complex, and facilitates our understanding that viral-mediated gene regulation through SUMOylation is important for KSHV persistence and pathogenesis. This article is protected by copyright. All rights reserved.
This article is protected by copyright. All rights reserved.
[Show abstract][Hide abstract] ABSTRACT: Co-signaling molecules have been demonstrated to regulate regulatory T cells' (Tregs) function during human immunodeficiency virus (HIV) infection. A recently reported co-signaling molecule called herpes virus entry mediator (HVEM), a member of the tumor necrosis factor receptor family, can both enhance and inhibit the immune response. HVEM was also reported to enhance the suppressive function of regulatory T cells in mice. However, it remains unknown whether HVEM can regulate Treg function in HIV-infected patients or whether HVEM affects HIV disease progression. In this study, we found that the blockage of the HVEM could weaken Tregs' suppressive activity to effector T cells (Teffs). HVEM expression is reduced during the asymptomatic phase of HIV infection and fairly predictive of the recovery of CD4+T-cells in response to highly active anti-retroviral therapy (HAART), more so than nadir CD4+T-cell count or viral load. Taken together, these findings demonstrate the importance of HVEM in relation to Treg function and HIV disease progression, which would have therapeutic implications and provide insight into the pathogenesis of acquired immune deficiency syndrome (AIDS).
No preview · Article · Apr 2015 · Current HIV research