Effect of hepatitis G virus infection on progression of HIV infection in patients with hemophilia. Multicenter Hemophilia Cohort Study

BACKGROUND: Infection with hepatitis G virus (HGV), also known as GB virus C, is prevalent but is not known to be associated with any chronic disease. Infection with HGV may affect the risk for AIDS in HIV-infected persons. OBJECTIVE: To compare AIDS-free survival in patients with and those without HGV infection during 16 years of follow-up after HIV seroconversion. DESIGN: Subanalysis of a prospective cohort study. SETTING: Comprehensive hemophilia treatment centers in the United States and Europe. PATIENTS: 131 patients with hemophilia who became HIV-positive between 1978 and 1985. MEASUREMENTS: Age, CCR5 genotype, HIV and HCV viral loads, CD4+ and CD8+ lymphocyte counts, and 12-year AIDS-free survival by HGV positivity (viremia [RNA] or anti-E2 antibodies). RESULTS: Compared with HGV-negative patients, the 60 HGV-positive patients (46%), including 22 who were positive for HGV RNA, had higher CD4+ lymphocyte counts (difference, 211 cells/mm3 [95% Cl, 88 to 333 cells/mm3]) and 12-year AIDS-free survival rates (68% compared with 40%; rate difference, 1.9 per 100 person-years [Cl, -0.3 to 4.2 per 100 person-years]), despite similar ages and HIV viral loads. In multivariate proportional hazards models, risk for AIDS was 40% lower for HGV-positive patients independent of age, HIV and HCV viral loads, CD4+ and CD8+ lymphocyte counts, and CCR5 genotype. CONCLUSIONS: Patients with past or current HGV infection have higher CD4+ lymphocyte counts and better AIDS-free survival rates. The mechanism of this association is unknown.     

GB virus C during the natural course of HIV-1 infection: viremia at diagnosis does not predict mortality

OBJECTIVE: To investigate whether GBV-C viremia at diagnosis of HIV-1 infection predicts disease outcome in patients not receiving combination antiretroviral therapy (ART), and whether longitudinal changes in GBV-C viremia are associated with disease progression. DESIGN: Prospective cohort study. METHODS: 230 patients with a serum sample available for testing obtained within 2 years of HIV-1 diagnosis were followed until either initiation of ART, death, or their last visit to our clinic (median follow-up 4.3 years). Baseline and follow-up serum samples (available from 163 patients) were tested for GBV-C RNA and antibodies against GBV-C envelope E2 protein (anti-E2; signifying resolved GBV-C viremia). RESULTS: At inclusion, 62 patients (27%) had GBV-C viremia and 69 (30%) had anti-E2. Baseline GBV-C status was not associated with all-cause mortality (P = 0.12), HIV-related mortality (P = 0.18), or development of AIDS (P = 0.84). However, GBV-C RNA was less prevalent in patients with AIDS at inclusion (P = 0.008). Eleven of 44 patients with baseline GBV-C viremia lost GBV-C RNA during follow-up without showing anti-E2 seroconversion. In comparison with anti-E2-negative patients with either persistent absence, persistent presence, or acquisition of GBV-C viremia, these subjects had significantly increased all-cause mortality (P = 0.018), HIV-related mortality (P = 0.007), and AIDS incidence (P < 0.001). CONCLUSIONS: GBV-C status at diagnosis did not predict disease outcome in this HIV cohort. GBV-C viremia was rare in patients with AIDS, and tended to disappear without occurrence of anti-E2 in patients with progressive disease. This suggests that the GBV-C status of HIV-1-infected patients could be a phenomenon secondary to HIV progression, rather than an independent prognostic factor.     

Reduced mother-to-child transmission of HIV associated with infant but not maternal GB virus C infection

BACKGROUND: Prolonged coinfection with GB virus C (GBV-C) has been associated with improved survival in human immunodeficiency virus (HIV)-infected adults. We investigated whether maternal or infant GBV-C infection was associated with mother-to-child transmission (MTCT) of HIV-1 infection. METHODS: The study population included 1364 HIV-infected pregnant women enrolled in 3 studies of MTCT of HIV in Bangkok, Thailand (the studies were conducted from 1992-1994, 1996-1997, and 1999-2004, respectively). We tested plasma collected from pregnant women at delivery for GBV-C RNA, GBV-C antibody, and GBV-C viral genotype. If GBV-C RNA was detected in the maternal samples, the 4- or 6-month infant sample was tested for GBV-C RNA. The rates of MTCT of HIV among GBV-C-infected women and infants were compared with the rates among women and infants without GBV-C infection. RESULTS: The prevalence of GBV-C RNA in maternal samples was 19%. Of 245 women who were GBV-C RNA positive, 101 (41%) transmitted GBV-C to their infants. Of 101 infants who were GBV-C RNA positive, 2 (2%) were infected with HIV, compared with 162 (13%) of 1232 infants who were GBV-C RNA negative (odds ratio [OR] adjusted for study, 0.13 [95% confidence interval {CI}, 0.03-0.54]). This association remained after adjustment for maternal HIV viral load, receipt of antiretroviral prophylaxis, CD4(+) count, and other covariates. MTCT of HIV was not associated with the presence of GBV-C RNA (adjusted OR [aOR], 0.94 [95% CI, 0.62-1.42]) or GBV-C antibody (aOR, 0.90 [95% CI, 0.54-1.50]) in maternal samples. CONCLUSIONS: Reduced MTCT of HIV was significantly associated with infant acquisition of GBV-C but not with maternal GBV-C infection. The mechanism for this association remains unknown.     

Carriage of GB virus C/hepatitis G virus RNA is associated with a slower immunologic, virologic, and clinical progression of human immunodeficiency virus disease in coinfected persons

The prevalence of GB virus C (GBV-C) infection is high in human immunodeficiency virus (HIV)-infected persons. However, the long-term consequences of coinfection are unknown. HIV-positive persons with a well-defined duration of infection were screened on the basis of their GBV-C/hepatitis G virus (HGV) RNA status and studied. GBV-C/HGV viremia was observed in 23, who carried the virus over a mean of 7.7 years. All parameters (survival, CDC stage B/C, HIV RNA load, CD4 T cell count) showed significant differences in terms of the cumulative progression rate between persons positive and negative for GBV-C/HGV RNA. When GBV-C/HGV RNA-positive and -unexposed subjects were matched by age, sex, baseline HIV RNA load, and baseline CD4 T cell count, HIV disease progression appeared worse in GBV-C/HGV RNA-negative subjects. The carriage of GBV-C/HGV RNA is associated with a slower progression of HIV disease in coinfected persons.     

Short Communication: Evaluation of GB Virus C/Hepatitis G Viral Load Among HIV Type 1-Coinfected Patients in São Paulo, Brazil

Abstract Recent studies suggest that GB virus C/hepatitis G virus (GBV-C/HGV) infection in HIV-positive individuals is associated with a slower progression to AIDS, leading to a lower HIV viral load and higher counts of CD4(+) T cells, although many studies have failed to demonstrate these beneficial effects. We developed a Real-Time PCR (TaqMan RT qPCR) to quantify the viral load of GBV-C/HGV in 102 HIV-1-infected patients, who were also evaluated for the presence of anti-E2. The prevalence of GBV-C/HGV infection was 21% among infected patients and the mean plasma viral load was 3.62±0.64 log(10) copies/ml. Despite the high prevalence, there was no statistical difference when we compared the mean viral load (p≤0.46) and the average count of CD4(+) (p≤0.29) and CD8(+) (p≤0.64) among patients infected by GBV-C/HGV and HIV and patients infected only by HIV. This fact can be explained by the number of patients included in the study. Nevertheless, compared to other studies, we observed a discrete number of patients with undetectable HIV load and lower median viral load in the group presenting GBV-C/HGV RNA. Our study suggests that there may be an impact on HIV viral load in GBV-C/HGV-coinfected patients. However, further studies are needed to elucidate the molecular and cellular mechanisms involved in this viral interaction, previously reported in other studies, with the aim of contributing to the development of new targets for drugs against HIV.     

No association between GB virus-C viremia and virological or immunological failure after starting initial antiretroviral therapy

INTRODUCTION: Co-infection with GBV-C ('Hepatitis G' virus) appears to be associated with slower disease progression in HIV-infected, untreated individuals. We wished to determine whether detection of GBV-C RNA was associated with differential response to HIV therapy in a population-based cohort of 461 individuals initiating antiretroviral therapy between June 1996 and August 1998, in British Columbia, Canada. METHODS: The presence of GBV-C RNA in plasma was identified by nested RT-PCR, using detection of HIV RNA as a positive control. Time to virological success [achieving HIV plasma viral load (pVL) < or = 500 copies/ml], virological failure (subsequent confirmed pVL > 500 copies/ml) and immunological failure (confirmed CD4 cell count below baseline) were assessed by Kaplan-Meier methods and Cox proportional hazard regression. RESULTS: Of the 441 individuals for whom results were available, 90 (20.4%) had detectable plasma GBV-C RNA. GBV-C RNA was significantly associated with a lower HIV pVL at baseline (P = 0.004). In univariate and multivariate Cox models, GBV-C RNA positive and negative individuals did not differ with respect to time to virological success [risk ratio (RR), 0.98; 95% confidence interval (CI), 0.75-1.27], time to virological failure (RR, 1.10; 95% CI, 0.74-1.65), or time to immunological failure (RR, 1.09; 95% CI, 0.73-1.63). There was no correlation between detection of GBV-C RNA and mutations in the human chemokine receptors CCR5 and CX CR1, or HIV viral tropism as predicted by the HIV envelope sequence (P > 0.1). CONCLUSION: GBV-C viremia is relatively common in individuals seeking treatment for HIV infection; however, it does not appear to have any effect on initial antiretroviral therapy response.     

Sustained CD4+ T cell response after virologic failure of protease inhibitor-based regimens in patients with human immunodeficiency virus infection

The relationship between plasma human immunodeficiency virus (HIV) RNA levels and peripheral CD4+ T cell counts was examined in 380 HIV-infected adults receiving long-term protease inhibitor therapy. Patients experiencing virologic failure (persistent HIV RNA >500 copies RNA/mL) generally had CD4+ T cell counts that remained greater than pretherapy baseline levels, at least through 96 weeks of follow-up. The CD4+ T cell response was directly and independently related to degree of viral suppression below the pretreatment baseline. For any given HIV RNA level measured 12 weeks after virologic failure, subsequent CD4+ T cell decline was slower in patients receiving a protease inhibitor-based regimen than in a historical control group of untreated patients. These observations suggest that transient or partial declines in plasma HIV RNA levels can have sustained effects on CD4+ T cell levels.     

HIV entry inhibition by the envelope 2 glycoprotein of GB virus C

Epidemiological studies have revealed an association between GB virus C (GBV-C) long-term viraemia and ameliorated HIV disease progression. We have provided evidence that a single protein of GBV-C, the glycoprotein E2, interferes with early HIV replication steps of both X4- and R5-tropic HIV strains. Preincubation with anti-E2 antibody specifically abrogates the inhibitory effect. Results were confirmed by the in-vitro expression of GBV-C E1/E2 encoding RNA.     

GB virus C genotype 1 is rarely transmitted vertically but acquired during infancy in West Africa

Paired Ghanaian plasma and cord blood from pregnant women, alongside plasma samples from children aged 1 day to 70 months, were tested for GBV-C, HIV-1 RNA loads and anti-E2. Frequency of GBV-C vertical transmission in West Africa is significantly lower than in Europe, the USA or East Asia where genotype 2 or 3 is prevalent. While horizontal transmission appears predominant in West Africa, the lower viral load of African genotype 1 might explain limited vertical transmission.     

Relationship of CD4+ T cell counts and HIV type 1 viral loads in untreated, infected adolescents. Adolescent Medicine HIV/AIDS Research Network

The REACH Project (Reaching for Excellence in Adolescent Care and Health) of the Adolescent Medicine HIV/AIDS Research Network was designed as a study of an adolescent cohort composed of HIV-1-infected and -uninfected subjects. The goal of the analysis presented was to examine the relationship of CD4+ T cell counts and HIV-1 plasma viral loads in adolescents. The CD4+ T cell counts of 84 HIV+ subjects who were 13 to 19 years of age were measured at the clinical sites, using ACTG standardized techniques. HIV-1 viral loads in frozen plasma were determined by the NASBA/NucliSens assay at a central laboratory. Past and current treatment with antiretroviral drugs was determined by medical record abstraction and interview data. The slope of the line generated by regressing log10 HIV-1 RNA (copies/ml) versus CD4+ T cell counts of REACH subjects who are antiretroviral drug naive was negative and significantly different than zero. A negative association has also been reported for antiretroviral drug-naive, adult males in the Pittsburgh Men's Study, a component of MACS (Pitt-MACS) (Mellors J, et al.: Science 1996;272:1167). These data show that in adolescents, as in adults, HIV-1 RNA concentrations are correlated with corresponding absolute CD4+ T cell count. The slopes of the lines generated with data from each cohort were different (p = 0.003). In addition to age, there are sex and racial differences in the makeup of the two cohorts. Any or all of these differences may affect the slopes of the lines.     

HIV和HCV重迭感染者病毒载量间及与T淋巴细胞计数的相关性研究

目的探讨艾滋病病毒(HIV)和丙型肝炎病毒(HCV)重迭感染者两病毒载量间及其与T淋巴细胞计数的相关性。方法采用流式细胞技术和荧光定量PCR技术，对15例HIV和FICV重迭感染者进行了CD3^ 、CD4^ 、CD8^ 淋巴细胞计数和病毒核酸载量测定，并选用多种数学模型进行相关性分析。结果单因素相关回归分析显示：HIV病毒载量与CD3^ 和CD4^ 细胞计数分别呈现良好的负相关关系(r=-0．6013，P=0．0177；r=-0．8828，P=0．0000)，HCV病毒载量与CD3^ 和CD4^ 细胞计数分别呈现良好的正相关关系(r=0．5931，P=0．0198；r=0．8627，P=0．0000)，HIV和HCV病毒载量间存在统计学负相关关系(r=-0．8954，P=0．0000)。多因素线性相关回归分析表明：CD3^ 和CD4^ 细胞计数及HCV病毒载量与HIV病毒载量间均呈现良好的统计学负相关关系(r=-0．6051，P=0．0169；r=-0．8828，P=0．0000；r=-0．8954，P=0．0000)。逐步回归分析显示：CD4^ 细胞计数和CD4^ ／CD8^ 比值及HCV病毒载量与HIV病毒载量间分别存在统计学负相关关系。结论HIV／HCV重迭感染时．两病毒间表现出竞争性抑制或干扰现象．导致CD4^ 细胞计数多样化改变并呈现出下降趋势。