Yong Xiong

Specific inhibition of HIV-1 replication by short hairpin RNAs targeting human cyclin T1 without inducing apoptosis.

RNA interference (RNAi), a sequence‐specific RNA degradation mechanism mediated by small interfering RNA (siRNA), can be used not only as a research tool but also as a therapeutic strategy for viral infection. We demonstrated that intracellular expression of short hairpin RNA (shRNA) targeting human cyclin T1 (hCycT1), a cellular factor essential for transcription of messenger and genomic RNAs from the long terminal repeat promoter of provirus of human immunodeficiency virus type 1 (HIV‐1), could effectively suppress the replication of HIV‐1. We also showed that downregulation of hCycT1 did not cause apoptotic cell death, therefore, targeting cellular factor hCycT1 by shRNAs may provide an attractive approach for genetic therapy of HIV‐1 infection in the future.

End-stage liver disease: Prevalence, risk factors and clinical characteristics in a cohort of HIV-HCV coinfected Han Chinese

INTRODUCTION Since the advent of combined antiretroviral therapy (cART), liver-related mortality has become the leading cause of non-AIDS-related deaths in human immunodeficiency virus (HIV) infected patients in Western countries. OBJECTIVE To investigate the incidence, mortality and risk factors of end-stage liver disease (ESLD) in HIV and hepatitis C virus (HCV) coinfected former plasma donors (FPDs) and blood recipients (BRs). METHOD A retrospective study was conducted. RESULTS Of 321 HIV-HCV coinfected patients, 42 (13.1%) developed ESLD and 40 (12.5%) died. Factors that were independently associated with ESLD included older age at baseline (Odds ratios [OR]: 2.444, P=0.035), alanine aminotransferase (ALT) greater or equal to 2 (the upper limit of normal [ULN]) at the end of follow-up (OR: 16.460, P=0.000), hepatitis B virus (HBV) (OR: 2.525, P=0.043), CDC stage C (OR: 5.806, P=0.001), duration of cART greater than 5 years (OR: 3.256, P=0.010), and CD4 count greater or equal to 200 cells/mm(3) at the end of follow-up (OR: 0.383, P=0.016). The probability of developing ESLD in HIV-HCV coinfected BRs was significantly higher than in FPDs (P=0.008). Mortality was also significantly higher in HIV-HCV coinfected patients with ESLD than in those without ESLD (P=0.000). CONCLUSION In the cART era, ESLD was common among HIV-HCV coinfected Han Chinese patients and was responsible for reducing patient survival time.

Impact of hepatitis B virus infection on HIV response to antiretroviral therapy in a Chinese antiretroviral therapy center

BACKGROUND Co-infection with hepatitis B virus (HBV) and HIV is common in China; however, the impact of HBV on long-term antiretroviral therapy (ART) outcomes has not been fully characterized. METHODS Patients were classified as being HIV mono-infected (hepatitis B surface antigen (HBsAg)-negative) or HIV/HBV co-infected (HBsAg-positive). The effects of HBV on HIV virological response, changes in CD4 cell counts, hepatotoxicity, and mortality among Chinese patients receiving ART were evaluated. RESULTS The HIV/HBV co-infection rate in our cohort was 9.9% (354/3562). Five hundred and fifty HIV mono-infected and 78 HIV/HBV co-infected individuals fulfilled the inclusion criteria. HIV/HBV co-infected individuals were less likely to achieve HIV-RNA suppression and a CD4 increase than HIV mono-infected individuals at 48 months post-ART. Greater hepatotoxicity and a more rapid occurrence of death were observed in HIV/HBV co-infected subjects. HBV-related mortality accounted for 84.2% (16/19) of the total deaths in HIV/HBV co-infected subjects. CONCLUSIONS HBV co-infection can affect late immunological and virological responses to ART and increase the risk of hepatotoxicity. Mortality due to liver disease was high among HIV/HBV co-infected individuals in this study, despite HBV-active ART. As long as HIV/HBV co-infected persons need anti-HBV therapy, they should be recommended ART that includes agents with activity against both HIV and HBV, regardless of the CD4 cell count level.

Molecular diagnosis of central nervous system opportunistic infections and mortality in HIV-infected adults in Central China

Background CSF PCR is the standard diagnostic technique used in resource-rich settings to detect pathogens of the CNS infection. However, it is not currently used for routine CSF testing in China. Knowledge of CNS opportunistic infections among people living with HIV in China is limited. Methods Intensive cerebrospiral fluid (CSF) testing was performed to evaluate for bacterial, viral and fungal etiologies. Pathogen-specific primers were used to detect DNA from cytomegalovirus (CMV), herpes simplex virus (HSV), varicella-zoster virus (VZV), Epstein-Barr virus (EBV), human herpesvirus 6 (HHV-6) and John Cunningham virus (JCV) via real-time polymerase chain reaction (PCR). Results Cryptococcal meningitis accounted for 63.0% (34 of 54) of all causes of meningitis, 13.0% (7/54) for TB, 9.3% (5/54) for Toxoplasma gondii. Of 54 samples sent for viral PCR, 31.5% (17/54) were positive, 12 (22.2%) for CMV, 2 (3.7%) for VZV, 1 (1.9%) for EBV, 1 (1.9%) for HHV-6 and 1 (1.9%) for JCV. No patient was positive for HSV. Pathogen-based treatment and high GCS score tended to have a lower mortality rate, whereas patients with multiple pathogens infection, seizures or intracranial hypertension showed higher odds of death. Conclusion CNS OIs are frequent and multiple pathogens often coexist in CSF. Cryptococcal meningitis is the most prevalent CNS disorders among AIDS. The utility of molecular diagnostics for pathogen identification combined with the knowledge provided by the investigation may improve the diagnosis of AIDS related OIs in resource-limited developing countries, but the cost-efficacy remains to be further evaluated.BackgroundCSF PCR is the standard diagnostic technique used in resource-rich settings to detect pathogens of the CNS infection. However, it is not currently used for routine CSF testing in China. Knowledge of CNS opportunistic infections among people living with HIV in China is limited.MethodsIntensive cerebrospiral fluid (CSF) testing was performed to evaluate for bacterial, viral and fungal etiologies. Pathogen-specific primers were used to detect DNA from cytomegalovirus (CMV), herpes simplex virus (HSV), varicella-zoster virus (VZV), Epstein-Barr virus (EBV), human herpesvirus 6 (HHV-6) and John Cunningham virus (JCV) via real-time polymerase chain reaction (PCR).ResultsCryptococcal meningitis accounted for 63.0% (34 of 54) of all causes of meningitis, 13.0% (7/54) for TB, 9.3% (5/54) for Toxoplasma gondii. Of 54 samples sent for viral PCR, 31.5% (17/54) were positive, 12 (22.2%) for CMV, 2 (3.7%) for VZV, 1 (1.9%) for EBV, 1 (1.9%) for HHV-6 and 1 (1.9%) for JCV. No patient was positive for HSV. Pathogen-based treatment and high GCS score tended to have a lower mortality rate, whereas patients with multiple pathogens infection, seizures or intracranial hypertension showed higher odds of death.ConclusionCNS OIs are frequent and multiple pathogens often coexist in CSF. Cryptococcal meningitis is the most prevalent CNS disorders among AIDS. The utility of molecular diagnostics for pathogen identification combined with the knowledge provided by the investigation may improve the diagnosis of AIDS related OIs in resource-limited developing countries, but the cost-efficacy remains to be further evaluated.

Long-term Follow-up of Patients Triply Infected with HIV and Hepatitis B and C Viruses in a Comprehensive Hospital in Central China

Summary The clinical characteristics of patients triply infected with HIV, HBV and HCV are notable. From January 2005 to June 2014, a total of 115 cART-naive HIV/HBV/HCV infected individuals were studied and 91 of them were followed-up consecutively after cART with 3TC. After cART with 3TC, the HBV-DNA positive rate decreased from 37.4% (43/115) to 9.9% (9/91) (P<0.001), whereas the HCV-RNA positive rate increased from 53.9% (62/115) to 70.3% (64/91) (P=0.016), and HCV-RNA level increased from 3.52 log10 copies/ml to 4.81 Log10 copies/ml (P=0.012). The occurrence of end-stage liver diseases (ESLDs) increased from 6.1% (7/115) to 18.7% (17/91) (P=0.005), and the occurrence of HCV-related ESLDs increased from 0.9% (1/115) to 14.3% (13/91) (P=0.001) whereas the proportion of HBV-related ESLDs decreased from 85.7% (6/7) to 23.5% (4/17) (P=0.005). Along with the initiation of 3TC-based cART, HCV-related liver diseases have become the leading challenge among HIV/HBV/HCV infectied patients. This article is protected by copyright. All rights reserved.

Five-year follow-up observation of HIV prevalence in serodiscordant couples.

OBJECTIVES To evaluate the rate of HIV seroconversion and the related risk factors among HIV discordant couples in Hubei Province, China. METHODS HIV seroconversion rates and associated factors in discordant couples were identified during 2010-2012, based on existing data collected in serological and behavioral surveys between 2005 and 2007. RESULTS At baseline, HIV transmission had occurred in 505 out of 1258 couples and the annual rate of HIV transmission was 6.3% in the absence of an intervention (40.14% after HIV exposure for 6.4 years). Five out of 753 discordant couples were found to have seroconverted during the 5-year follow-up observation after the implementation of interventions. Factors independently associated with HIV seroconversion included an HIV viral load >1000 copies/ml (odds ratio (OR) 18.706, 95% confidence interval (CI) 1.577-221.926), the index partner being on antiretroviral therapy (OR 0.019, 95% CI 0.002-0.180), and condom use in the past 6 months (OR 0.194, 95% CI 0.021-0.795). CONCLUSIONS HIV-negative partners in serodiscordant couples were at risk of HIV infection if the index partner did not receive any intervention. It is strongly advised that existing interventions are used, such as couples consultations, condom use, and antiretroviral treatment, to minimize the risk of HIV transmission.