GBV‐C viremia and clinical events in advanced HIV infection

Abstract

GB Virus C (GBV-C) is a non-pathogenic flavivirus, commonly found in HIV infected patients. Studies suggest a survival benefit of GBV-C viremia in HIV infection. Impact of GBV-C viremia was evaluated on clinical outcome in multidrug-resistant HIV. The OPTIMA study enrolled advanced multidrug-resistant HIV patients with a CD4 count ≤300 cells/mm(3). This study included a subset of OPTIMA patients. Primary endpoints included AIDS events or death. GBV-C status was assessed at baseline and last time point on study by real-time PCR. Cox proportional hazards models were used to determine if CD4 count (</>100/mm(3)), treatment assignment, presence or disappearance of GBV-C viremia, GBV-C viral load level and Hepatitis C virus antibody status were associated with outcome. Of 288 patients (98% male, baseline mean age 48 years, HIV viral load 4.67 log10/ml, and CD4 127 cells/mm(3)), 62 (21.5%) had detectable GBV-C viremia. The mortality rate for GBV-C infected subjects was lower, 19/62 (30.7%) versus 87/226 (38.5%), and time to death shorter (HR 0.67, 95% CI 0.41-1.11), but the results were not significantly different. The time to development of AIDS events was not different (HR 0.90, 95% CI 0.52-1.53). Among covariates, only CD4 count (HR 0.28, CI 0.19-0.42) had a significant survival effect. A trend in decreased mortality was seen in GBV-C+ patients with CD4 <100/mm(3) in multivariate analyses. GBV-C co-infection in multidrug-resistant HIV infected patients was associated with a trend in improved survival but not decreased AIDS events. Analysis was limited by cohort size.

Human pegivirus isolates characterized by deep sequencing from hepatitis C virus‐RNA and human immunodeficiency virus‐RNA–positive blood donations, France

“…[1][2][3] Recent taxonomic evolutions and proposals related to these single-stranded RNA viruses allow the current description of 11 species within the genus Pegivirus (Pegivirus A-K), the human and nonhuman primate pegivirus isolates being assigned to species Pegivirus C. 4 Despite a nonnegligible blood prevalence in healthy persons, that is 1% to 5% in developed countries and up to 20% in developing countries, and higher values in immunocompromised patients, both natural history and potential implication of pegiviruses in host's health are largely unknown despite their identification more than 20 years ago. [5][6][7][8][9][10][11][12][13][14] Of note, however, human immunodeficiency (HIV)-HPgV association studies were extensively explored, due to a possible beneficial effect in HIV infection motivating investigations about HIV-HPgV interactions at the molecular level. [15][16][17][18][19][20][21][22] Mechanisms of viral persistence and host-immune modulation remain also poorly characterized.…”

Use of Flaviviral genetic fragments as a potential prevention strategy for HIV-1 Silencing

“…GBV-A, B and C, DV, YFV and WNV) from the NCBI and human miRNAs from miRBase. The hypothesis is that upon infection with any of the six members of the Flaviviridae the intracellular immune defenses will be activated and upregulate numerous miRNAs, some amongst them showing homology to HIV-1 RNA and hence being able to block its replication at various stages of the life cycle [3,24]. …”

“…Hosts miRNA provides intracellular immune defense when the body is faced with challenges from transgenes, viruses, transposons, and aberrant mRNAs [16][17][18]24]. MiRNA molecules trigger gene silencing in eukaryotic cells [24,28,29].…”

“…MiRNA molecules trigger gene silencing in eukaryotic cells [24,28,29]. More than 3,000 different human miRNAs (hsa-miRs) have been identified thus far, and it is generally agreed that cellular gene regulation is significantly impacted by cellular miRNAs [16,28].…”

“…Given genetic mutational capacity, these particular mobile elements consistently threaten host genomic integrity. RE mutagenic ability may be silenced by sophisticated molecular mechanisms [18,24,27,30]. This apparently occurs via a process of strategic RE expression involving genetic entities that have become incorporated during past evolutionary periods [18].…”