Accuracy of FIB-4 and APRI scores compared to transient elastography for liver fibrosis in patients with HIV and HBV co-infection.

BACKGROUND: Due to economic shortages and concern about occupational exposure to HIV, liver biopsy and transient elastography (TE) are rarely available in patients with HIV/HBV co-infection in China, where HIV/HBV co-infection is prevalent. METHODS: The accuracy of FIB-4 and APRI for predicting liver fibrosis was compared with TE results in a series of 460 HIV/HBV co-infected patients. RESULTS: FIB-4 and APRI scores were strongly correlated to liver stiffness measurement scores by TE, and the correlation index was 81.4-96.3. An FIB-4 index >1.5 had a positive predictive value of 95.2% to consider fibrosis with a sensitivity of 85.7%. An APRI index >0.5 had a positive predictive value of 98.2% to consider fibrosis with a sensitivity of 76.0%. A FIB-4 value <1.5 or APRI <0.5 were concordant with TE results to exclude fibrosis in 94.4% and 96.8%, respectively. A FIB-4 value >1.5 or APRI >0.5 were concordant with fibrosis diagnosed by TE in 77.6-89.4% and 70.7-80.9%, respectively. CONCLUSIONS: In areas with limited resources, FIB-4 and APRI indexes were accurate, simple and inexpensive methods for assessing liver fibrosis in patients with HIV/HBV co-infection.

Plasma proteomic analysis reveals altered protein abundances in HIV-infected patients with or without non-Hodgkin lymphoma.

The identification of circulating proteins associated with acquired immunodeficiency syndrome-related non-Hodgkin lymphoma (AIDS-NHL) may help in the development of promising biomarkers for screening, diagnosis, treatment, and prognosis. Here, we used quantitative liquid chromatography-tandem mass spectrometry (LC-MS/MS) to identify differentially expressed proteins (DEPs) in plasma collected from patients with AIDS-NHL and human immunodeficiency virus (HIV)-infected patients without NHL (HIV+ ). Proteins with a log2 (fold change) in abundance >0.26 and p < 0.05 were considered differentially abundant. In total, 84 DEPs were identified, among which 20 were further validated as potential biomarkers, with immunoglobulin and complement components being the most common proteins. Some of the proteins were further verified in a retrospective analysis of the medical records of patients in a larger cohort. These markedly altered proteins were found to mediate pathophysiological pathways that likely contribute to AIDS-NHL pathogenesis, such as the humoral immune response, complement activation, and complement and coagulation cascades. Our findings provide a new molecular understanding of AIDS-NHL pathogenesis and provide new evidence supporting the identification of these proteins as possible biomarkers in AIDS-NHL.

Cell death and pathological findings of the spleen in COVID-19 patients.

The coronavirus disease 2019(COVID-19) is recognized as systemic inflammatory response syndrome. It was demonstrated that a rapid increase of cytokines in the serum of COVID-19 patients is associated with the severity of disease. However, the mechanisms of the cytokine release are not clear. By using immunofluorescence staining we found that the number of CD11b positive immune cells including macrophages in the spleens of died COVID-19 patients, was significantly higher than that of the control patients. The incidence of apoptosis as measured by two apoptotic markers, TUNEL and cleaved caspase-3, in COVID-19 patients' spleen cells is higher than that in control patients. By double immunostaining CD11b or CD68 and SARS-CoV-2 spike protein, it was found that up to 67% of these immune cells were positive for spike protein, suggesting that viral infection might be associated with apoptosis in these cells. Besides, we also stained the autophagy-related molecules (p-Akt、p62 and BCL-2) in spleen tissues, the results showed that the number of positive cells was significantly higher in COVID-19 group. And compared with non-COVID-19 patients, autophagy may be inhibited in COVID-19 patients. Our research suggest that SARS-CoV-2 may result in a higher rate of apoptosis and a lower rate of autophagy of immune cells in the spleen of COVID-19 patients. These discoveries may increase our understanding of the pathogenesis of COVID-19.

Clinical characteristics of COVID-19 patients with HIV coinfection in Wuhan, China.

BACKGROUND: Information about the impact of HIV coinfection on clinical characteristics of COVID-19 patients remains limited. METHODS: Maximum body temperatures, fever duration, chest CT and viral shedding, lymphocyte counts, and titer of SARS-CoV-2 antibody were compared between COVID-19 patients with and without HIV infection in Zhongnan Hospital of Wuhan University from January 20th to February 14th, 2020. RESULTS: Compared with 53 COVID-19 patients without HIV infection, the patients with SARS-CoV-2 and HIV coinfection had higher maximum body temperatures (38.7°C vs 37.6°C, P = 0.044), longer duration of fever (8.7 ± 4.5 vs 4.2 ± 2.1 days, P = 0.038), longer time to have improvement of chest CT images (22 vs 15 days from the onset of illness, P = 0.011), lower level of SARS-CoV-2 IgG (5.11 ± 32.33 vs 37.45 ± 15.48 AU/ml, P = 0.042). However, no statistically significant difference of duration of SARS-CoV-2 shedding in the two groups was found (12.3 ± 2.6 vs 13.4 ± 2.4 days, , P = 0.813). CONCLUSION: Lower level of CD4+ T lymphocyte counts caused by HIV infection itself might be one of reasons for relatively weak ability to produce SARS-CoV-2 specific antibodies. The effects of anti-HIV drugs in prevention and treatment of COVID-19 appears to be limited.

Isolation and characterization of spontaneously immortalized B-lymphocyte lines from HIV-infected patients with and without non-Hodgkin's Lymphoma.

Isolation of viable circulating tumor cells (CTC) holds the promise for improving screening, early diagnosis, and personalized treatment of lymphoma. In this study, we isolated and characterized spontaneously immortalized B-lymphocyte (SIBC) lines from HIV-infected patients with and without Non-Hodgkin's Lymphoma (AIDS-NHL). A total of 22 SIBC lines was isolated from peripheral blood mononuclear cells (PBMC) of HIV-infected patients with (n = 40) and without (n = 77) clinically detectable NHL, but not from healthy individuals (n = 34). Of these, 8 SIBC lines named HIV-SIBC were generated from HIV-infected patients without AIDS-NHL (10%, 8/77), while 14 SIBCs named AIDS-NHL-SIBC were from 13 of the AIDS-NHL patients (32.5%, 13/40). Among the 14 AIDS-NHL-SIBCs, 12 were derived from AIDS-NHL patients with poor prognoses (survival time less than 1 year). SIBCs displayed markers typical of memory B cells (CD3- CD20+ CD27+ ) with EBV infection. Moreover, AIDS-NHL-SIBCs were representative of CTC as evidenced by monoclonal Ig gene rearrangement, abnormal chromosomal karyotype, and the formation of xenograft tumors, while HIV-SIBCs generated harbored some features of tumor cells, none had the capacity of xenograft tumor formation, suggesting HIV-SIBC present the precursor of CTC. These results indicate that SIBCs is associated with poor prognosis in AIDS-NHL patients and can be isolated from HIV-infected patients with NHL and without NHL. This findings point to the need for further molecular characterization and functional studies of SIBCs, which may prove the value of SIBCs in the diagnosis, prognoses, and screening for NHL among HIV-infected patients.

Clinical outcome after lipectomy in the management of patients with human immunodeficiency virus-associated dorsocervical fat accumulation: An observational cohort study.

Lipo-accumulation of the dorsocervical fat pad ("buffalo hump") is a complication observed in people living with human immunodeficiency virus (HIV). We described the clinical outcome of people living with HIV with "buffalo hump" treated by excisional lipectomy.From April 2013 to March 2018, medical records of people living with HIV, who received care in our hospital have been evaluated. Among them, patients with dorsocervical fat accumulation treated by excisional lipectomy have been retrospectively assessed.Nine patients with "buffalo hump" among 2886 people living with HIV (3.1‰, 9/2886) were included. Eight were women with a mean age of 47.9 ±â€Š8.0 years old (range, 36-60). Most of them have been infected by blood transfusion (77%, 7/9) and the mean duration of HIV infection was 14.1 ±â€Š5.5 years (range, 6-22). The mean duration for antiretroviral therapy was 8.8 ±â€Š2.1 years (range, 6-11). The mean pre-ART CD4+ T cell count was 91.3 ±â€Š76.5 cells/µL (range, 4-233) and 477.4 ±â€Š271.8 cells/µL (range, 114-926) at the time of surgery. All 9 patients underwent excisional lipectomy of their hypertrophied dorsocervical fat pad. The mean size of the excised specimens was 14 × 11 × 6 cm. The median follow-up time was 24 months (range, 2-60), all 9 patients reported satisfaction with their results, with no recurrence has been observed.Corrective surgery used to treat localized fat accumulations in people living with HIV with "buffalo hump" showed a favorable effect and can therefore be considered when necessary. Whereas drugs such as integrase inhibitors may avoid lipo-accumulation related syndrome and should be given to people living with HIV in China.

Establishment and characterization of HBV-associated B lymphocytes with an immortalization potential.

Emerging evidences indicate that hepatitis B virus (HBV) infection is associated with non-Hodgkin lymphoma (NHL), but the mechanisms of HBV-induction lymphomagenesis remain unclear. In this report, retrospective analysis of the prevalence of hepatitis B surface antigen (HBsAg) among NHL cases demonstrated significantly higher HBsAg carrier rate among B-cell NHL cases than controls (other cancers except primary liver cancer) (adjusted odds ratio, 1.56; 95% confidence interval, 1.13-2.16). Furthermore, cells with an immortalization potential existed in the peripheral blood of 4 patients with chronic HBV infection. Characterization of these cells showed their immunophenotypes similar to that of the majority of HBsAg-positive B-cell NHL patients. Immunoglobulin (Ig) gene rearrangements confirmed the clonal Ig gene rearrangements. Cytogenetic analysis revealed abnormal karyotypes of these cells with an immortalization potential. Compared with cells with an immortalization potential that we previously found in B-cell NHL patients by the same way, these cells showed many similar features. In conclusion, cells with an immortalization potential existed in the part of patients with chronic HBV infection before lymphoma development and showed some malignant features. They may be the cellular basis of HBV-associated lymphomagenesis.

Polymorphisms of the NS3 Proteins of Hepatitis C Virus Genotype 1b Are Associated with Liver Cirrhosis.

Polymorphisms of the hepatitis C virus (HCV) core protein and NS3 have been described to be associated with liver cirrhosis (LC) and/or hepatocellular carcinoma in patients with chronic hepatitis C genotype 1b (HCV 1b). Here, we determine whether there is an association between LC and polymorphisms of viral core protein and NS3 in patients in Hubei province, China. A total of 42 patients with chronic HCV 1b (21 patients with LC and 21 with chronic hepatitis [CH]) were enrolled, amino acid sequence of the core protein and N-terminus of NS3 were obtained by direct sequencing and compared with the prototype strain HCV-J. No significant difference of amino acid polymorphisms was observed between isolates from LC and CH patients in the core protein. However, in the N-terminus of NS3, amino acid polymorphisms at positions A1072T (Ala 1072 chronic Thr 1072 cirrhosis), I1074V (Ile 1074 chronic Val 1074 cirrhosis), and T1098N/I (Thr 1098 chronic Asn or Ile 1098 cirrhosis) correlated significantly with LC. These findings indicate that the polymorphisms of HCV at these sites may be the risk factors for the development of LC in patients with chronic HCV 1b.

Hepatitis B Virus Stimulated Fibronectin Facilitates Viral Maintenance and Replication through Two Distinct Mechanisms.

Fibronectin (FN) is a high molecular weight extracellular matrix protein that functions in cell adhesion, growth, migration, and embryonic development. However, little is known about the role of FN during viral infection. In the present study, we found significantly higher levels of FN in sera, and liver tissues from hepatitis B virus (HBV) patients relative to healthy individuals. HBV expression enhanced FN mRNA and protein levels in the hepatic cell lines Huh7 and HepG2. HBV infection of susceptible HepG2-sodium taurocholate co-transporting polypeptide cells also increased FN expression. We also found that transcriptional factor specificity protein 1 was involved in the induction of FN by HBV. Knockdown of FN expression significantly inhibited HBV DNA replication and protein synthesis through activating endogenous IFN-α production. In addition, FN interacted with the transforming growth factor ß-activated protein kinase 1 (TAK1) and TAK1-binding protein complex and attenuated interferon signaling by inhibiting TAK1 phosphorylation. Furthermore, the nuclear translocation of NF-κB/p65 was found to be inhibited by FN. We also observed that FN promoted HBV enhancers to support HBV expression. These results suggest novel functions of endogenous FN involved in immune evasion and maintenance of HBV replication.

A Clinical Study of Acquired Immunodeficiency Syndrome Associated Penicillium Marneffei Infection from a Non-Endemic Area in China.

OBJECTIVE: To investigate the clinical characteristics, diagnosis, treatment and prognosis of penicilliosis among the patients with acquired immunodeficiency syndrome (AIDS) in non-endemic areas of China, and then to discuss its incubation period and the diagnostic performance of serum galactomannan test for penicilliosis. METHODS: Medical records and travel histories of penicilliosis patients in Zhongnan hospital from January 2006 to December 2013, and the interval from when the patients left the endemic area to the onset of the disease was analyzed. Serum galactomannan levels of penicilliosis patients and AIDS patients with fever were measured by the Platelia Aspergillus Enzyme Immunoassay Kit. RESULTS: A total of 47 AIDS-associated penicilliosis were confirmed by fungal culture, which accounted for 4.8% of 981 AIDS-related admissions. The sensitivity and specificity of serum galactomannan test for penicilliosis were 95.8% (23/24) and 90.9% (30/33), respectively, (cutoff index = 1.0). Two independent predictors for early mortality (death within 12 weeks) of the patients (21.3%, 10/47) were a delayed diagnosis and no treatment with antifungal therapy. Among 14 patients who became ill after leaving endemic areas, ten patients presented with the onset symptoms within 12 months (from 11 days to 360 days). We found a patient living with asymptomatic P. marneffei fungemia who had not received any antifungal therapy until 18 months' follow up. CONCLUSIONS: The co-infection of P. marneffei and HIV was not uncommon in the non-endemic areas of penicilliosis in China. There exists a latent form of infection for P. marneffei. The incubation period of penicilliosis may be quite different from one patient to another. In AIDS patients, the serum galactomannan test has utility for the diagnosis of penicilliosis. When patients with penicilliosis/AIDS were diagnosed early and treated with standardized antifungal therapy and combined antiretroviral therapy, their prognosis improved.

Heroin use promotes HCV infection and dysregulates HCV-related circulating microRNAs.

Hepatitis C virus (HCV) infection is common among injection drug users (IDUs). There is accumulating evidence that circulating microRNAs (miRNAs) are associated with HCV infection and disease progression. The present study was undertaken to determine the in vivo impact of heroin use on HCV infection and HCV-related circulating miRNA expression. Using the blood specimens from four groups of the study subjects (HCV-infected individuals, heroin users with/without HCV infection, and healthy volunteers), we found that HCV-infected heroin users had significantly higher viral load than HCV-infected non-heroin users (p = 0.0004). Measurement of HCV-related circulating miRNAs in plasma showed that miRs-122, 141, 29a, 29b, and 29c were significantly increased in the heroin users with HCV infection, whereas miR-351, an HCV inhibitory miRNA, was significantly decreased in heroin users as compared to control subjects. Further investigation identified a negative correlation between the plasma levels of miR-29 family members and severity of HCV infection based on aspartate aminotransferase to platelet ratio index (APRI). In addition, heroin use and/or HCV infection also dysregulated a panel of plasma miRNAs. Taken together, these data for the first time revealed in vivo evidence that heroin use and/or HCV infection alter circulating miRNAs, which provides a novel mechanism for the impaired innate anti-HCV immunity among IDUs.

[Analysis of cervical HPV infection in HIV positive Chinese women].

OBJECTIVE: To investigate prevalence HPV infections in cervix among HIV-infected Chinese women. METHODS: From September 2009 to May 2011, 293 women with positive HIV underwent cervical cancer screening as study group matched with 200 women with negative HIV as control group. Questionnaires including demographic information and HIV associated information were collected, Pap smear and 23 subtype of HPV were performed in those women. The women with positive HPV were followed up per 6 months, and the period of following up were more than 12 months. Binary logistic analysis was used for high risk factors of HPV persistent infection. RESULTS: Prevalent HPV infection was 44.4% (130/293) in study group and 20.0% (40/200) in control group, respectively, which reached statistical difference (P < 0.05). The most common genotype of HPV was HPV 16, which prevalence was 13.7% (40/293) in study group and 7.0% (14/200) in control group. The other HPV subtype prevalence was HPV-58, HPV-52, HPV-43 and HPV-18, which was 9.2% (27/293), 8.2% (24/293), 8.2% (24/293), 6.8% (20/293) in study group and 3.0% (6/200), 2.5% (5/200), 1.5% (3/200), 2.5% (5/200) in control group. At time point of 12 months following up, the persistent prevalence of HPV was 47.5% (48/101) in study group and 21.1% (8/38) in control group, which reached statistical difference (P < 0.05). Multiple HPV infections (OR = 6.4, 95%CI: 1.6 - 25.6), abnormal cytology (OR = 18.1, 95%CI: 4.5 - 76.9) and lower CD(4) T cell count (compared with CD(4) > 3.5 × 10(8)/L, if 2.0 × 10(8) ≤ CD(4) ≤ 3.5 × 10(8), OR = 8.1, 95%CI: 1.3 - 56.3; if CD(4) < 2.0 × 10(8)/L, OR = 9.1, 95%CI: 1.8 - 46.9) were independently associated with HPV persistence among HIV-positive subjects. CONCLUSIONS: Prevalence and persistence of HPV infections were more common among HIV-positive Chinese women than those in HIV-negative Chinese women. Improving immune function, decreasing multiple HPV infections, treating abnormal cervical cytology could decrease prevalence of HPV infection.

Epidemiologic risk profile of human papillomavirus infections in human immunodeficiency virus-positive Chinese women.

The aim of this study was to evaluate the prevalence and risk factors of human papillomavirus (HPV) infection among human immunodeficiency virus (HIV)-positive women in China. To this end, we enrolled 200 HIV-positive and 182 HIV-negative women in this cross-sectional cohort study. The following sampling methods were used: (i) structured interview, (ii) CD4 cell counts, and (iii) cervical specimens. HPV genotype (total 23 types) was analyzed using polymerase chain reaction assay. Logistic regression analysis was used to identify independent causative factors for HPV infection. The prevalence of HPV infection was 3-fold higher in the HIV-positive women than in the HIV-negative women. The overall prevalences of HPV infection, high risk (HR)-HPV infection, and multiple HPV infections in the HIV-positive women were 36.5%, 33.5%, and 13.0%, respectively, and the corresponding values in HIV-negative women were 12.1%, 10.4%, and 6.0%, respectively (P < 0.05). The types of HR-HPVs were similar in the HIV-positive and HIV-negative women (HPV-16, -52, -58, and -18), and the prevalences of infections by these viruses were 1.5- to 3-fold higher in the HIV-positive group than in the HIV-negative group. HR-HPV infection among the HIV-positive women was associated with three factors: low CD4 count (OR for 200 ≤ CD4 ≤ 350 and CD4 < 200/µL were 2.11 and 3.13, respectively), HIV infection through sexual contact (OR, 7.90; 95% CI, 2.38-14.60), and having HIV-positive sexual partners (OR, 2.02; 95% CI, 1.03-3.95). We found that the prevalence of HPV infection among the HIV-positive Chinese women was higher than that among the HIV-negative women; moreover, among the HIV-positive women, factors associated with HIV infection were risk factors for HR-HPV infection.

Interference of replication between hepatitis B and C viruses in patients infected with HIV.

The clinical and cellular interactions between hepatitis B virus (HBV) and hepatitis C virus (HCV) were investigated in patients co-infected with the human immunodeficiency virus (HIV). One hundred ninety-nine patients followed for 6 years were evaluated to compare the level of HBV DNA and HCV RNA in patients co-infected with HIV and HBV, and patients co-infected with HIV, HBV, and HCV. A full-length HBV genome and HCV JFH1 RNA were co-transfected into HuH-7.5.1 cells in vitro to examine the impact of co-infection and dependence on the HBV PreC mutant for replication interference. Before 2',3'-dideoxy-3'-thiacytidine (3TC)-based antiretroviral therapy (ART) was initiated, HBV DNA was found in 56/123 (45.4%) patients co-infected with HIV and HBV, and in 19/76 (25.0%) patients co-infected with HIV, HBV, and HCV. After 3TC-based ART was initiated, detectable HBV DNA decreased to 7/76 (9.2%) in patients co-infected with HIV, HBV, and HCV, but HCV RNA increased from 43/76 (56.6%) to 60/76 (78.9%) (P = 0.003). In vitro HBV and HCV co-infection led to decreased replication of both viruses. The primary factors that influenced the decreased replication were the order of the HBV and HCV infection and the HBV PreC mutation.

Cancer in cohort of HIV-infected population: prevalence and clinical characteristics.

OBJECTIVE: To determine the incidence and survival time of acquired immunodeficiency syndrome-related malignancies among HIV-infected population. METHODS: A clinical database search, chart review and verification with health records were undertaken for all AIDS-defining cancers diagnosed in Zhongnan Hospital Wuhan University, Hubei Province, China. Kaplan-Meier method was used to evaluate survival time in HIV-infected patients with cancer. RESULTS: A total of 3,554 patients with 11,072 person-years of HIV follow-up care were reviewed from January 2004 to December 2008. Sixty-three cancer cases were identified. The median ages of HIV-positive cancer cases were 42.4 ± 8.8 years, CD4 count were 220.9 ± 142.3/µl. The common cancers were non-Hodgkin's lymphoma (NHL, 28.6%), cervical cancer (22.2%), liver cancer (17.5%). Statistically significantly elevated SIRs were observed in NHL (SIR in all = 34.5, 95% CI 11.7-89.9, SIR in males = 45.3, 95% CI 24.7-138.9, females = 12.2, 95% CI 3.9-38.2), invasive cervical cancer (SIR = 68.1, 95% CI 19.2-84.5), liver cancer (SIR = 6.0, 95% CI 2.6-12.2), nasopharyngeal cancer (SIR = 6.2, 95% CI 1.5-44.9), bladder cancer (SIR = 4.9, 95% CI 0.9-22.9), esophageal cancer (SIR = 3.1, 95% CI 0.7-14.3), and stomach cancer (SIR = 2.6, 95% CI 0.6-11.6). All cancers combined showed a statistically significantly elevated SIR of 4.1 (95% CI 2.5-4.6), SIR for all cancers was much higher in female (SIR = 4.8, 95% CI 3.2-7.3) than in male (SIR = 3.1, 95% CI 2.1-4.3). Among HIV-positive patients with cancer, the median survival time was 14.5 ± 3.8 months in NHL group, 28.9 ± 3.6 months in cervix group, 5.1 ± 1.1 months in liver group, and 26.7 ± 6.7 months in other groups. The median survival time in HIV-infected group (23.1 ± 3.5 months) was shorter than that in non-HIV-infected group (43.0 ± 5.1 months), (P < 0.05). CONCLUSIONS: NHL, cervical cancers and liver cancer are common cancers among HIV-infected individuals in Hubei, China. Most malignant diseases that arise in the setting of HIV infection tend to occur at a more advanced stage with shorter survival time.

The comparison of human immunodeficiency virus type 1 transmission between couples through blood or sex in central China.

To examine whether there are any differences in the rates of HIV-spousal transmission between those who have acquired the virus through blood or through sex in central China. A total of 650 HIV-infected individuals were enrolled, 420 of them were either former commercial plasma donors or recipients of blood (blood transmission group [BTG]), and 230 had acquired HIV infection through sex (sex transmission group [STG]). The spousal transmission rate of HIV was 2% per year (94/420, 11.2 years) in BTG and 8.9% per year (115/230, 5.6 years) in STG. There was a significantly higher transmission rate of HIV through male-to-female (11.7% per year, 84/128, 5.6 years) than through female-to-male (5.4% per year, 31/102, 5.6 years, P<0.05) in STG, but there was no significant gender based differences in BTG. In BTG, all HIV-1 tested were subtype B', while in STG, HIV-1 tested were predominantly subtypes CRF01_AE or CRF07_BC. Our results show that the HIV-spousal transmission rate was higher in STG than in BTG, and that there was a higher rate through male-to-female than female-to-male in STG.

Impact of human immunodeficiency virus infection on the course of hepatitis C virus infection: a meta-analysis.

AIM: To analyze the influence of human immunodeficiency virus (HIV) infection on the course of hepatitis C virus (HCV) infection. METHODS: We performed a meta-analysis to quantify the effect of HIV co-infection on progressive liver disease in patients with HCV infection. Published studies in the English or Chinese-language medical literature involving cohorts of HIV-negative and -positive patients coinfected with HCV were obtained by searching the PUBMED, EMBASE and CBM. Data were extracted independently from relevant studies by 2 investigators and used in a fixed-effect meta analysis to determine the difference in the course of HCV infection in the 2 groups. RESULTS: Twenty-nine trails involving 16750 patients were identified including the outcome of histological fibrosis or cirrhosis or de-compensated liver disease or hepatocellular carcinoma or death. These studies yielded a combined adjusted odds ratio (OR) of 3.40 [95% confidence interval (CI) = 2.45 and 4.73]. Of note, studies that examined histological fibrosis/cirrhosis, decompensated liver disease, hepatocellular carcinoma or death had a pooled OR of 1.47 (95% CI = 1.27 and 1.70), 5.45 (95% CI = 2.54 and 11.71), 0.76 (95% CI = 0.50 and 1.14), and 3.60 (95% CI = 3.12 and 4.15), respectively. CONCLUSION: Without highly active antiretroviral therapies (HAART), HIV accelerates HCV disease progression, including death, histological fibrosis/cirrhosis and decompensated liver disease. However, the rate of hepatocellular carcinoma is similar in persons who had HCV infection and were positive for HIV or negative for HIV.

Screening for CD8 cytotoxic T lymphocytes specific for Gag of human immunodeficiency virus type 1 subtype B' Henan isolate from China and identification of novel epitopes restricted by the HLA-A2 and HLA-A11 alleles.

The human immunodeficiency virus type 1 (HIV-1) epidemic in China is increasing rapidly at an irrepressible rate. It is caused by HIV-1 subtype B' in central China. After the full-length genome sequencing of the Henan isolate was performed, the definition of optimal cytotoxic T-lymphocyte (CTL) epitopes across the Henan isolate genome has become crucial for vaccine design. In this study, by using ELISPOT assays with synthetic peptides corresponding to the sequence of the Henan isolate, the identification and analysis of Gag-specific CTL responses among 28 treated and 26 untreated infected paid blood donors (PBDs) from the Henan and Hubei provinces of China are presented. These studies focused on CTL responses restricted by the human leukocyte antigen (HLA)-A2 and -A11 molecules, two of the most prominent HLA-A alleles in the Chinese population. The results suggested that, in the subgroup analysis, the magnitude of response in the infected treated subgroup [median, 93 spot-forming cells (SFCs) per 10(6) peripheral blood mononuclear cells (PBMCs)] was significantly lower than that in the chronically infected untreated subgroup (median, 221 SFCs per 10(6) PBMCs), and HLA-A2-restricted treated PBDs had a response of a much higher frequency and magnitude than that of HLA-A11-restricted treated PBDs. Moreover, some novel peptides restricted by the HLA-A2 and -A11 molecules were identified.

[A survey of children with HIV/AIDS in highly epidemic villages of AIDS].

OBJECTIVE: To estimate prevalence of HIV/AIDS among children and the transmission routes in a highly endemic villages of AIDS. METHODS: Totally 208 high-risk women of child bearing age and 159 of their children aged 0 - 14 years were investigated. Their medical histories of blood donation or transfusion were collected, blood samples were taken and sera were separated for HIV test. Enzyme-linked immunosorbent assay (ELISA) and Western blot assay were performed for HIV antibody. The Nested-polymerase chain reaction (PCR) assay amplifying gag gene p17 was performed on samples of children aged less than 18 months. RESULTS: Thirty-seven HIV infected cases were found among 159 children aged 0 - 14 years of whom 33 were infected by mother-to-child transmission (89.2%, 33/37), 3 by blood transfusion (8.1%, 3/37) and one by iatrogenic route (2.7%, 1/37). Sixty seven mothers who were seropositive for HIV and their 86 children who were born after 1992 were investigated, 33 cases of them were infected with HIV. The rate of vertical transmission was 38.4% (33/86). The HIV vertical transmission rate among mothers with AIDS (68.8%, 22/32) was significantly greater than that among mothers with asymptomatic HIV infection (20.4%, 11/54, P < 0.05). The number of children infected with HIV through vertical transmission increased from 1993 to 2001. Among 37 children infected with HIV, 12 cases developed AIDS and 4 of them died, of whom 2 cases died from tuberculosis. The morbidity of AIDS was 27.3% (9/33). Ninety three point nine percent (31/33) of infected mothers didn't know their HIV seropositive status before pregnancy and delivery. Of 8 pregnant women infected with HIV, one had aggravation of AIDS, 2 miscarried, 2 terminated their pregnancy and 3 continued their pregnancy. CONCLUSION: Mother-to-child transmission of HIV was the major route of HIV/AIDS transmission to the children. The main reason leading to HIV infection in children was the lack of prenatal HIV counseling and testing for the high-risk women of childbearing age and lake of interventions. The countermeasures must be taken to control the further transmission of AIDS in order to protect the health of women and children in the highly endemic areas of AIDS.