The role of autophagy in THP-1 macrophages resistance to HIV- vpr-induced apoptosis.

Macrophages are resistant to cell death and are one of HIV reservoirs. HIV viral protein Vpr has the potential to promote infection of and survival of macrophages, which could be a highly significant factor in the development and/or maintenance of macrophage viral reservoirs. However, the impact of vpr on macrophages resistance to apoptosis is yet to be comprehended. Autophagy is a cell survival mechanism under stress state. In this study, we investigated whether autophagy is involved in macrophages resistant to vpr-induced apoptosis. Using the THP1 macrophages, we studied the interconnection between macrophages resistance to apoptosis and autophagy. We found that vpr is able to trigger autophagy in transfected THP-1 macrophages confirmed by electron microscopy (EM) and western blot analysis, and inhibition of autophagy with 3MA increased vpr-induced apoptosis. The results indicate that autophagy may be responsible for maintenance of macrophage HIV reservoirs.

Hepatitis B virus mutation may play a role in hepatocellular carcinoma recurrence: A systematic review and meta-regression analysis.

BACKGROUND AND AIMS: A number of studies have confirmed that antiviral therapy with nucleotide analogs (NAs) can improve the prognosis of hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) after curative therapy. However, what factors affected the prognosis of HBV-HCC after removal of the primary tumor and inhibition of HBV replication? A meta-regression analysis was conducted to explore the prognostic factor for this subgroup of patients. METHODS: MEDLINE, EMBASE, Web of Science, and Cochrane library were searched from January 1995 to February 2014 for clinical trials evaluating the effect of NAs on the prognosis of HBV-HCC after curative therapy. Data were extracted for host, viral, and intervention information. Single-arm meta-analysis was performed to assess overall survival (OS) rates and HCC recurrence. Meta-regression analysis was carried out to explore risk factors for 1-year OS rate and HCC recurrence for HBV-HCC patients after curative therapy and antiviral therapy. RESULTS: Fourteen observational studies with 1284 patients met the inclusion criteria. Influential factors for prognosis of HCC were mainly baseline HBeAg positivity, cirrhotic stage, advanced Tumor-Node-Metastasis (TNM) stage, macrovascular invasion, and antiviral agent type. The 1-year OS rate decreased by more than four times (coefficient -4.45, P<0.001) and the 1-year HCC recurrence increased by more than one time (coefficient 1.20, P=0.003) when lamivudine was chosen for HCC after curative therapy, relative to entecavir for HCC. CONCLUSIONS: HBV mutation may play a role in HCC recurrence. Entecavir or tenofovir, a high genetic barrier to resistance, should be recommended for HBV-HCC patients.

KDM4C represses liver fibrosis by regulating H3K9me3 methylation of ALKBH5 and m6A methylation of snail1 mRNA.

OBJECTIVE: We aimed to disclose the molecular mechanism of snail1 in liver fibrosis. METHODS: Carbon tetrachloride (CCl4) was used to induce a liver fibrosis model in mice whereby serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels were evaluated, and liver pathological alternations were assessed. Rat hepatic stellate cells (HSC-T6) were irritated with transforming growth factor (TGF)-ß1, followed by assessment of cell viability and migration. The levels of snail1, ALKBH5, and lysine specific demethylase 4C (KDM4C) were quantified by immunohistochemistry, western blot, or reverse transcription-quantitative polymerase chain reaction, in addition to α-smooth muscle actin (SMA), anti-collagen type I α1 (COL1A1), vimentin, and E-cadherin. Photoactivatable ribonucleoside-enhanced crosslinking and immunoprecipitation and RNA stability were evaluated to determine the relationship between ALKBH5 and snail1. Changes in KDM4C-bound ALKBH5 promoter and enrichment of histone H3 lysine 9 trimethylation (H3K9me3) at the ALKBH5 promoter were determined using chromatin immunoprecipitation. RESULTS: In fibrosis mice, snail1 was upregulated while ALKBH5 and KDM4C were downregulated. KDM4C overexpression reduced serum ALT and AST levels, liver injury, and α-SMA, COL1A1 and VIMENTIN expressions but increased E-cadherin expression. However, the aforementioned trends were reversed by concurrent overexpression of snail1. In HSC-T6 cells exposed to TGF-ß1, ALKBH5 overexpression weakened cell viability and migration, downregulated α-SMA, COL1A1 and VIMENTIN, upregulated E-CADHERIN, and decreased m6A modification of snail1 and its mRNA stability. KDM4C increased ALKBH5 expression by lowering H3K9me3 level, but inhibited HSC-T6 cell activation by regulating the ALKBH5/snail1 axis. CONCLUSION: KDM4C decreases H3K9me3 methylation to upregulate ALKBH5 and subsequently inhibits snail1, ultimately impeding liver fibrosis.

Hepatitis B virus infection in patients with Wilson disease: A large retrospective study.

BACKGROUND: Wilson disease (WD) is the most common genetic metabolic liver disease. Some studies have shown that comorbidities may have important effects on WD. Data on hepatitis B virus (HBV) infection in patients with WD are limited. AIM: To investigate the prevalence and clinical impact of HBV infection in patients with WD. METHODS: The clinical data of patients with WD were analyzed retrospectively, and the data of patients with concurrent WD and HBV infection were compared with those of patients with isolated WD. RESULTS: Among a total of 915 WD patients recruited, the total prevalence of current and previous HBV infection was 2.1% [95% confidence interval (CI): 1.2%-3.0%] and 9.2% (95%CI: 7.3%-11.1%), respectively. The main finding of this study was the identification of 19 patients with concurrent WD and chronic hepatitis B (CHB) infection. The diagnosis of WD was missed in all but two patients with CHB infection. The mean delay in the diagnosis of WD in patients with concurrent WD and CHB infection was 32.5 mo, which was significantly longer than that in patients with isolated WD (10.5 mo). The rates of severe liver disease and mortality in patients with concurrent WD and CHB infection were significantly higher than those in patients with isolated WD (63.1% vs 19.3%, P = 0.000 and 36.8% vs 4.1%, P < 0.001, respectively). Binary logistic regression analysis revealed a significantly higher risk of severe liver disease at the diagnosis of WD in patients with current HBV infection [odds ratio (OR) = 7.748; 95%CI: 2.890-20.774; P = 0.000)] or previous HBV infection (OR = 5.525; 95%CI: 3.159-8.739; P = 0.000) than in patients with isolated WD. CONCLUSION: The total prevalence of current HBV infection in patients with WD was 2.1%. The diagnosis of WD in CHB patients is usually missed. HBV infection is an independent risk factor for severe liver disease in WD patients. The diagnosis of WD should be ruled out in some patients with CHB infection.

[Cellular HIV DNA quantitative testing and its significance in Chinese AIDS patients during 48 weeks' highly-active antiretroviral treatment].

OBJECTIVE: To observe the dynamic changes of peripheral blood T lymphocytes and monocytes, which serve as HIV-1 viral reservoirs, in Chinese HIV-infected patients receiving highly-active antiretroviral treatment (HAART) for 48 weeks and its clinical significance. METHODS: A total of 35 chronic HIV-1 infected adults initial received HAART. The peripheral blood T lymphocyte subsets counts were determined by flux cytometry at week 0, 24 and 48. Magnetic activated cell sorting was used to extract cellular DNA from monocytes and T lymphocytes purified from peripheral blood mononuclear cells. Real-time fluorescent quantitative PCR was used to detect the serum HIV RNA and HIV DNA of monocytes and T lymphocytes. SPSS 18.0 software was used to analyze the collected data. RESULTS: At week 0, 24, and 48 after initiation of HAART, HIV RNA levels of peripheral blood were (4.12 ± 1.41), ≤ 1.69, and ≤ 1.69 lg copies/ml, respectively; CD(4)(+) T cells were (196 ± 101), (321.90 ± 112) and (392 ± 127) cells/µl, respectively; HIV DNA level in T lymphocytes were (4.03 ± 0.53), (2.74 ± 1.16) and (2.45 ± 0.41) lg copies/10(6) cells respectively; while in monocytes, HIV DNA levels were (2.51 ± 0.68), (2.16 ± 0.34)and (2.03 ± 0.25)lg copies/10(6) cells. Statistical analysis revealed that HIV RNA level was negatively correlated with the CD(4)(+) T cell count through the whole trail, while positively correlated with the HIV DNA level in blood T lymphocytes and monocytes. HIV DNA level in T lymphocytes decreased more slowly than HIV DNA in monocytes. Moreover, peripheral blood CD(4)(+) T cell count was negatively associated with the HIV DNA capacity from T lymphocytes. CONCLUSIONS: Both T lymphocyte and monocyte may serve as viral reservoirs, and T lymphocyte might play a more important role as HIV reservoirs. The blood HIV RNA is correlated positively with the cellular HIV DNA, whereas, CD(4)(+) T cell count is correlated negatively with HIV DNA from lymphocytes, which suggests that HIV DNA levels in T lymphocyte might be one of indicators of AIDS progress during HAART.

[Clinical characteristics of highly active antiretroviral therapy-associated immune reconstruction inflammation in acquired immunodeficiency syndrome].

OBJECTIVE: To summarize the morbidity, mortality, clinical manifestations and risk factors for IRIS (immune reconstruction inflammatory syndrome) during HAART (highly active antiretroviral therapy) in China. METHODS: From October 2007 to September 2009, a prospective cohort of 238 AIDS (acquired immunodeficiency syndrome) patients on HAART from Hunan and Jianxi provinces was recruited for a follow-up of 24 weeks. And 47 and 191 patients were assigned into the IRIS and non-IRIS groups respectively. The data of general information, clinical manifestations and treatment of two groups were collected and compared. Blood samples were collected in both groups at pre-and post-HAART 12 weeks, 24 weeks for HIV viral load and CD4(+) cell count examinations. A statistical analysis was performed. RESULTS: A total of 47 (19.7%) IRIS cases was analyzed. The median onset of IRIS was 28 (9 - 36) days. And 29 (61.7%) cases of tuberculosis IRIS were found. There was no significant difference in age, gender, route of transmission and antiretroviral regimens between the IRIS and non-IRIS groups. At baseline, Weeks 12 and 24, both groups showed a significant decline of viral load. And there was no significant difference between them. Both groups showed a significant increase of CD4(+) cell count. But there was no significant difference between two groups. However, the baseline CD4(+) cell count was markedly lower in the IRIS group than that in the non-IRIS group. In 85.1% (40/47) of cases, the CD4(+) cell count was < 100 × 10(6)/L in the IRIS group at the baseline of HAART. CONCLUSION: IRIS mostly occurs during 3 months of HAART initiation. The age, gender, route of transmission and antiretroviral treatment regimens of patients on HAART are not risk factors for the development of IRIS. The HIV RNA viral load decreases in both IRIS and non-IRIS groups without any significant difference. The patients with a CD4(+) cell count < 100/µl are more vulnerable to develop IRIS.

Evaluation of a 6-year highly active antiretroviral therapy in Chinese HIV-1-infected patients.

OBJECTIVE: To evaluate the long-term efficacy and tolerability of nevirapine (NVP)-based regimens in the treatment of human immunodeficiency virus (HIV)-infected Chinese patients in routine clinical practice. METHODS: From October 2002 to May 2004, 57 HIV-1-infected patients commenced antiretroviral therapy (ART), and were followed up to December 2008. These antiretroviral-naïve patients, who originally received two nucleoside reverse transcriptase inhibitors and NVP, had HIV RNA levels, T lymphocyte subsets and safety parameters assessed over 6 years. RESULTS: Of the 57 patients, 34 patients participated in the long-term follow-up. After 5-6 years, >60% of the patients had HIV RNA levels <50 copies/microl, and the median increase in CD4 cell counts from baseline was 329 cells/microl. gamma-Glutamyl transferase increased in 17 patients (29.8%); serum cholesterol and triglyceride levels were elevated in 15 patients (26.3%), and 25.0% (6/24) of the patients developed lipodystrophy (mainly females). Grade 3/4 adverse events occurred in 3 cases. CONCLUSION: ART with NVP-based regimens suppressed HIV viremia and produced continued CD4 cell increases in a majority of subjects for 6 years. Safety and tolerance were good with no unexpected long-term toxicity. Though based on a small group, this study demonstrates durable effects of ART in Chinese patients.

[Effects of different mutated sites in vpr gene of HIV on apoptosis of host cells: experiment with HeLa cells].

OBJECTIVE: To investigate the effects of different mutated sites in the vpr gene of HIV on the apoptosis of host cells, and the possible mechanism thereof. METHODS: Fourteen HIV-1 vpr fragments were obtained from HIV-infected persons. Eukaryotic expression vector pcDNA3.1 (+) plasmid was extracted, the PCR purified product was double-cut by HindIII and BamH, and the cut products were ligated to vectors, thus establishing the JM109 competent cells. Sequencing was used to confirm the reconstruction of pcDNA-vpr eukaryotic expression vectors that were then transfected into HeLa cells. Blank vectors were transfected as control group. Cells were harvested after 24 hours and underwent Hoechst 33258 staining and observed under fluorescence microscope. Annexin-FITC-PI staining and flow cytometry were used to observe the percentage of apoptosis. The caspase-3 activity was detected by enzyme labeling instrument. RESULTS: The apoptotic rates shown by Hoechst and annexin--FITC-PI staining methods, and caspase-3 activity levels of the HeLa cells transfected with the gene fragments with mutated sites 70, 85, 86, and 94 cells were all lower than the cells transfected with the gene fragments without these mutated sites. The apoptosis causing ability levels of the No 1-7 recombinant plasmids (all of the Vpr AE subtype) were all lower than those of the No 8-14 plasmids (of Vpr B, AB, C, and C/BC subtypes). CONCLUSION: The apoptosis causing ability of the HIV with the vpr sequence with mutated sites 70, 85, 86, 94 is significantly lower than those without these sites. AE subtype induces lower apoptotic behavior in the hoist cells, and decreased activation of the caspase-3 pathway may be one of the mechanisms.

Identifying factors affecting the pharmacokinetics of voriconazole in patients with liver dysfunction: A population pharmacokinetic approach.

Voriconazole is a broad-spectrum antifungal agent commonly used to treat invasive fungal infections. Voriconazole has significant intraindividual and interindividual pharmacokinetics variability in different patient populations. Pharmacokinetic data of voriconazole in patients with liver dysfunction were limited. The aims of this study were to evaluate the population pharmacokinetics of voriconazole in patients with liver dysfunction and to identify the factors that affect voriconazole pharmacokinetics. A total of 166 samples taken from 57 patients with liver dysfunction were included in the study. A one-compartment pharmacokinetic model with first-order absorption and elimination was used to describe the data. Voriconazole clearance (CL) was 0.58 L/h, the volume of distribution (Vd ) was 134 L, and oral bioavailability (F) was 80.8%. This study showed that platelet count was significantly associated with voriconazole pharmacokinetic parameters. CYP2C19 polymorphisms had no effect on voriconazole pharmacokinetic parameters. Voriconazole CL was significantly decreased in patients with liver dysfunction. This study provides useful pharmacokinetics information for patients with liver dysfunction while highlighting the value of therapeutic drug monitoring in adjusting doses.

Cryptococcosis manifesting as isolated biliary infection: Case report and brief review of literature.

BACKGROUND: Biliary cryptococci infection is rare, which is frequently diagnosed by exploratory laparotomy, preoperative diagnosis is difficult. CASE PRESENTATION: A 14-year-old girl presented with intermittent jaundice for 6 years. She had no pruritus, anorexia, nausea or vomiting, fever, abdominal pain, or clay stools. Laboratory tests showed obstructive jaundice, eosinophilia, and increased IgE levels. The patient was ultimately diagnosed as Cryptococcal infection by bone marrow culture. The patient responded to antifungal therapy. CONCLUSION: Unnecessary surgical intervention was avoided by an early and accurate diagnosis. Cryptococcosis infection of bile duct should be highly suspected, when the children with obstructive jaundice have eosinophilia and increased IgE levels.

Evaluation of human immunodeficiency virus type 1-infected Chinese patients treated with highly active antiretroviral therapy for two years.

The purpose of this study was to evaluate the long-term efficacy and safety of nevirapine in combination with didanosine and stavudine in the treatment of human immunodeficiency virus (HIV)1-infected Chinese patients in routine clinical practice. The study, from April 2003 to May 2005, with follow-up through 24 mo, was conducted at the Department of Infectious Diseases, Second Xiangya Hospital, Central-South University in Changsha, Hunan Province, China. Twenty-seven HIV1-infected patients received didanosine, stavudine, and nevirapine. Information from case notes regarding age, sex, side effects, viral load, naive and memory T cells, and CD4(+) and CD8(+) T cell count at baseline, 3, 6, 12, 18, and 24 mo was collected and analyzed. Virologic suppression, defined as an HIV RNA concentration of less than 50 copies/mL at months 3, 6, 12, 18, and 24, was considered the main outcome measure. Of 27 patients, 17 were men with a mean age 33.5 yr. The mean baseline viral load was 5.15 log copies/mL and the mean CD4(+) cell count was 185 cells/dL. Of 27 patients, 3 patients discontinued study medication; treatment was changed, because of side effects, from didanosine (ddI), stavudine (d4T), and nevirapine (NVP) to zidovudine, lamivudine, and NVP for 24 patients who had completed 24 mo of treatment with ddI, d4T, and NVP; and viral load suppression was attained in 17 patients (70.8%) at 12 mo, in 14 patients (58.3%) at 18 mo, and in 13 patients (56.6%) at 24 mo. The CD4 T cell count increased by 114 cells/microL (mean, 299 cells/microL) after 12 mo of treatment and by 132 cells/microL (mean, 317 cells/microL) after 24 mo of treatment. Naive T cells and memory cells also increased in number, but at a slower rate. Activated (CD38(+)) CD8(+) T cells were elevated at baseline (67.7%) and declined by month 24 (49.7%), but did not reach normal levels. We conclude that a regimen of NVP with ddI and d4T provided durable suppression of plasma viral load in HIV-infected patients, with significant improvement in the CD4 cell count, and can be well tolerated by patients with HIV-1 infection.

The Role of IL-27 and its Receptor in the Pathogenesis of HIV/AIDS and Anti-viral Immune Response.

BACKGROUND: Cytokines have been widely demonstrated to involve in the pathogenesis of AIDS and the mechanisms of antiretroviral therapy. Interleukin 27 (IL-27) is a new member of the IL-12 cytokine family and has been shown to interfere HIV-1 virus replication with controversial findings. This study is to investigate the dynamic changes in plasma IL-27 level and cell surface IL-27 receptor expression in HIV/AIDS patients who underwent HAART. METHODS: Whole blood was collected from 34 HIV-positive/AIDS patients 0, 6, and 12 months after initiation of HAART and 27 healthy subjects. Plasma IL-27, IFN-γ, and IL-4 were measured by enzyme-linked immunosorbent assay, while peripheral blood CD3+CD4+ T cells count and the gp130 expressed CD3+CD4+cell were measured by flow cytometry. RESULTS: The plasma IL-27 concentration, IFN-γ concentration, and percentage of positive gp130 CD4 cells were significantly decreased in previously treatment-naive HIV/AIDS patients compared to healthy controls, but gradually increased 6 and 12 months after initiation of HAART. Conversely, IL-4 levels were significantly increased in treatment-naive HIV/AIDS patients compared to healthy controls, but gradually decreased 6 and 12 months after HAART. The concentrations of plasma IL-27 were positively correlated with the percentage of gp130 positive CD4 cells (r=0.438, p=0.016). Both plasma IL-27 concentration and gp130 positive cell percentage were positively associated with peripheral blood CD3+CD4+ T cell count (P<0.05 or P<0.01), but negatively associated with plasma HIV viral load (P<0.05 or P<0.01). CONCLUSION: IL-27 signaling (IL-27 and its receptor) may be involved in the pathogenesis of HIV infection and immune reconstitution in HIV/AIDS patients who underwent HAART. IL-27 may exert effects through regulating Th1 / Th2 ratio.

Improvement of phenylethanoid glycosides biosynthesis in Cistanche deserticola cell suspension cultures by chitosan elicitor.

Effect of chitosan elicitor on growth and phenylethanoid glycosides (PeGs) accumulation in Cistanche deserticola cell suspension cultures was investigated. PeGs accumulation was dramatically improved by addition of selected chitosan at optimal elicitation conditions. Furthermore, a strategy of repeated addition of the chitosan elicitor for enhancing PeGs accumulation was developed. The chitosan elicitor of 10 mg l(-1)-medium repeatedly added on days 15 and 17 improved PeGs accumulation further, and the final PeGs production in the treated cell cultures of C. deserticola reached 364.6 mg l(-1), which was 3.4-fold higher than that of the control without elicitation. The increase of PeGs accumulation in C. deserticola cell suspension cultures was related to the increase of phenylalanine ammonium lyase activity stimulated by the chitosan elicitor.

Microwave-assisted extraction of solanesol from tobacco leaves.

Solanesol is the starting material for many high-value biochemicals, including co-enzyme Q10 and Vitamin K analogues. In the present study, a microwave-assisted extraction (MAE) technique has been developed for the fast extraction of solanesol from tobacco leaves. Compared to heat-reflux extraction, MAE reduced extraction time and obtained higher percentage extracted of solanesol. The effect of microwave on cell destruction of plant material was observed by scanning electron microscopy (SEM). The microwave-assisted extraction efficiency was further improved by adding NaOH into the extraction solvent, and the maximum percentage extracted of solanesol reached 0.91% (weight solanesol/weight tobacco) in 40 min at an optimum NaOH concentration of 0.05 M. The developed MAE integrated with saponification process provided an efficient method for solanesol recovery from tobacco leaf materials, and it also alleviated emulsification in the following separation and purification procedure as well.

Rapid determination of solanesol in tobacco by high-performance liquid chromatography with evaporative light scattering detection following microwave-assisted extraction.

Solanesol is the starting material for many high-value biochemicals, including coenzyme Q(10) and Vitamin-K analogues. The aim of the current study was to develop a reliable and fast analytical procedure for the determination of solanesol in tobacco using high-performance liquid chromatography (HPLC) with evaporative light scattering detection (ELSD) coupled with microwave-assisted extraction (MAE) as an efficient sample preparation technique. The HPLC conditions were Agilent C18 column using acetonitrile-isopropanol (60:40, v/v) as mobile phase at a flow rate of 1 ml/min. ELSD conditions were optimized at nebulizer-gas flow rate of 1.5 l/min and drift tube temperature of 65 degrees C. The method was validated to achieve the satisfactory precision and recovery, and the calibration range was 0.1-1.5 mg/ml. The developed analytical procedure was successfully applied to determine solanesol content in tobacco samples from different growing regions in China.

The preliminary efficacy of interferon-alpha and ribavirin combination treatment of chronic hepatitis C in HIV-infected patients.

BACKGROUND: It is internationally accepted that in drug-naïve individuals with hepatitis C virus (HCV) and human immunodeficiency virus (HIV) co-infection, chronic hepatitis C should be treated first if the CD4 cell count does not require the initiation of anti-retroviral therapy. Present paper evaluated the clinical effect and side-effect of interferon-alpha (IFN-alpha) and ribavirin (RBV) combination therapy for Chinese patients with HCV-HIV co-infection, and compared with them for HIV infection alone. METHODS: Ten patients with HCV-HIV and 17 patients with HCV received 5 million unit IFNalpha-2b every other day intramuscularly, and 300 mg RBV triple daily by oral. Dynamic observations were made for HCV RNA and HIV RNA loads, CD4+ and CD8+ T lymphocyte counts, liver function and blood cell measurement, and the medicine side-effects. RESULTS: After 12-week and 24-week treatments of IFN-alpha and RBV combination therapy, mean HCV RNA levels reduced 1.14 logs and 1.56 logs from the baseline at week 0 in HCV-HIV co-infection, and reduced 1.48 logs and 1.75 logs in HCV infection, respectively. The HIV RNA levels decreased 1.22 logs and 1.32 logs from the base line; however, there were no obvious different changes at T lymphocyte counts of HCV-HIV and HCV patients through 24-week treatments. Whole 27 patients showed satisfactory biochemical response to therapy. There were some mild or mediate influence-like symptoms, intestinal uncomfortable and depressed blood cell counts in early stage of the treatments. No neuropsychiatric and auto-immune disorders were found. CONCLUSIONS: IFN-alpha and RBV combination therapy had similar anti-HCV effects during 24-week treatment for HCV-HIV and HCV infected Chinese patients, and some anti-HIV effect. There were no obvious different biochemical responses and side-effects between two groups above.

[Interferon-alpha and ribavirin combination therapy for co-infection of hepatitis C virus and human immunodeficiency virus].

OBJECTIVE: To evaluate the clinical effect and side-effect of interferon-alpha (IFN-a) and ribavirin (RBV) combination therapy for Chinese patients with co-infection of hepatitis C virus (HCV) and human immunodeficiency virus (HIV), and to compare them with only HIV infection patients. METHODS: 10 patients with HCV-HIV and 17 patients with only HCV infection received 5 million units of IFNalpha-2b every other day intramuscularly, and 300 mg RBV orally three times a day. Dynamic observations were done for HCV RNA and HIV RNA loads, CD4+ and CD8+ T lymphocyte counts, liver function and blood cell measures, and the side-effects of the medicines. RESULTS: After 12 weeks and 24 weeks of IFNalpha and RBV combination therapy, mean HCV RNA levels reduced 1.14 log (t = 3.843, P < 0.01) and 2.08 log (t =6.564, P < 0.01) from the baseline at week 0 in the HCV-HIV co-infection group, and reduced 1.48 log (t = 6.438, P less than 0.01) and 2.33 log (t = 7.343, P < 0.01) in the HCV infection group. Meanwhile, the HIV RNA levels decreased 1.22 log (t = 3.662, P < 0.01) and 1.73 log (t = 6.119, P < 0.01) from the base line. However, there were no obvious different changes among T lymphocyte counts of HCV-HIV and HCV patients at week 0, week 12 and week 24. All 27 patients showed satisfactory biochemical response to therapy. There were some mild or moderate influenza-like symptoms, intestinal discomfort and decreased blood cell counts in the early stages of the treatments. No neuropsychic and auto-immune disorders were found. CONCLUSIONS: IFNalpha-2b and RBV combination therapy showed similar anti-HCV effects during the 24 week treatment for HCV-HIV and HCV infected patients, and some anti-HIV effect was also observed. No obvious different biochemical responses and side-effects were found between the above two groups.

Interleukin-21 plays an important role in CD8 T-cell activation and poor outcome in HIV infection.

To present the relationship between high CD8+ T-cell activation and poor outcome in HIV-1 pathogenesis. We hypothesized that the decrease of interleukin-21 (IL-21) levels would lead to alterations in survival of elevated immune activation with disease progress. Fifty-eight HIV-1-seropositive subjects and 21 uninfected healthy control volunteers were recruited in this study. The serum IL-21 concentrations and the levels of expression of CD38, HLA-DR, and IL-21 receptor in CD8 T cells were detected by flow cytometry. The percentages of both CD38 and HLA-DR cells in CD8 T cells were significantly inversely related to the serum IL-21 levels. IL-21 plays an important role in the mechanism of elevated CD8+ T cell immune activation leading to poor outcome in HIV-1 pathogenesis, which will be helpful for the development of current and future anti-HIV strategies.

Prospective observation for seven-year's highly active antiretroviral therapy in Chinese HIV-1 infected patients.

To prospectively observe the efficacy, tolerability, immune reconstitution and toxicity of long-term highly active antiretroviral therapy (HAART) in Chinese patients infected HIV. 437 cases originally received two nucleoside reverse transcriptase inhibitors (NRTIs) and one non-nucleoside reverse transcriptase inhibitor (NNRTI) during a mean period of 4.3 years (3.1-7.3). Patients were followed up by HIV RNA levels, T lymphocyte subsets, blood routine test, and biochemical parameters. If active opportunistic infections, apparent side effects or virological failure appeared, appropriate treatment would be taken immediately. 30 patients (6.86%) died, most in the first 6 months of HAART. The proportion of subjects with HIV-1 RNA <500 copies/ml was 90.8%, 63.5%, 69.4%, 70.0% and 72.2% at 1, 4, 5, 6 and 7 year. The CD4+ T cell count was 115, 246, 301, 334, 363, 356,386 and 373 cells/ul at 0, 1, 2, 3, 4, 5, 6 and 7 year. 67.9% showed various drug-related side effects, most including gastrointestinal side-effects, nervous disorder, myelotoxicity and abnormal liver function, rashes, serum cholesterol elevation, mostly appearing in the first 12 months. Grade 3 and Grade 4 adverse events occurred in 41 cases. This is the first to report results from the prospectively 7-year follow-up of Chinese patients infected HIV taking HAART. It demonstrates that two NRTIs and one NNRTI regimens may persistently suppress HIV viremia and continuously induce CD4 cell increase, with good safety and tolerance. The majority took first-line regimens effectively. 19.2% changed to other first-line drug due to drug-related side effects, 10.2% switched to second-line regimens due to viral resistance. Some discontinued or got virological failure because of poor compliance.