[Show abstract][Hide abstract] ABSTRACT: HIV infection has a significant impact on the natural progression of hepatitis B virus (HBV) related liver disease. In HIV-HBV co-infected patients, little is known about mutations in the HBV genome, which can influence severity of liver disease. The aim of this study was to characterize and to determine the frequency of known clinically significant mutations in the HBV genomes from HIV-HBV co-infected patients and from HBV mono-infected patients. To accomplish this, genomic length HBV sequencing was performed in highly-active anti-retroviral therapy (HAART)-naïve HIV-HBV co-infected patients (n=74) and in anti-HBV therapy-naïve HBV mono-infected patients (n=55). The frequency of HBV mutations differed between the co-infected and mono-infected patients when comparing patients with the same genotype. BCP mutations A1762T and G1764A were significantly more frequent in HBV genotype C mono-infection and the -1G frameshift was significantly more frequent in co-infection and was only observed in HBV genotype A co-infection. PreS2 deletions were observed more frequently in the setting of co-infection. Further work is needed to determine if these mutational patterns influence the differences in liver disease progression in HIV-HBV co-infected and HBV mono-infected patients.
[Show abstract][Hide abstract] ABSTRACT: To determine if highly active antiretroviral therapy (HAART) with combination anti-hepatitis B virus (HBV) therapy compared to HAART with HBV monotherapy leads to greater HBV DNA suppression in an HIV/HBV coinfected cohort.
A cross-sectional analysis of 122 HIV/HBV coinfected patients from Australia and the United States.
Univariate analysis and ordinal logistic regression were used to determine factors associated with an HBV DNA less than 100 IU/ml.
The majority of patients were on HAART (85%), had an HIV RNA less than 50 copies/ml, a median CD4 cell count of 438 cells/microl, and had prior or current lamivudine therapy (98%). The majority (89%) of those on HAART were on HBV-active drugs including 54% on tenofovir (TDF) with either lamivudine (LAM) or emtrictabine (FTC), 34% receiving LAM or FTC monotherapy, and 12% on TDF monotherapy. Only 4% of patients in the combination (TDF + LAM/FTC) group had HBV DNA greater than 20 000 IU/ml compared to 54% in the group on no HBV-active therapy, 31% in the LAM or FTC monotherapy group, and 30% in the TDF monotherapy group (P < 0.0001). In an ordinal logistic regression model, monotherapy with either TDF or LAM remained independently associated with higher HBV DNA.
These data suggest that there may be an advantage to using TDF in combination with LAM or FTC in HIV/HBV coinfection, particularly in the setting of previous LAM experience. Continued prospective follow-up in this study will confirm whether the advantage is sustained longer-term.
AIDS (London, England) 08/2009; 23(13):1707-15. DOI:10.1097/QAD.0b013e32832b43f2 · 6.56 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Human immunodeficiency virus (HIV)-1 infection has been associated with enhanced microbial translocation, and microbial translocation is a mechanism through which alcohol and some enteric conditions cause liver disease. We hypothesized that HIV promotes liver disease by enhancing microbial translocation.
We studied human cohorts in which hepatitis C virus (HCV) and HIV outcomes were carefully characterized.
HIV-related CD4(+) lymphocyte depletion was strongly associated with microbial translocation as indicated by elevated levels of circulating lipopolysaccharide (LPS), LPS-binding protein, soluble CD14, and fucose-binding lectin (AAL) reactive to immunoglobulin G specific for the alpha-galactose epitope and suppressed levels of endotoxin core antibodies (EndoCAb IgM) in HIV-infected subjects compared with the same persons before they had HIV infection and compared with HIV-uninfected subjects. The same measures of microbial translocation were strongly associated with HCV-related liver disease progression (cirrhosis), eg, LPS, odds ratio, 19.0 (P = .002); AAL, odds ratio, 27.8 (P < .0001); in addition, levels of LPS were elevated prior to recognition of cirrhosis.
Microbial translocation may be a fundamental mechanism through which HIV accelerates progression of chronic liver disease.
[Show abstract][Hide abstract] ABSTRACT: We report a case of a patient infected with human immunodeficiency virus type 1 (HIV-1) for 20 years who has experienced CD4(+) T cell depletion in spite of maintaining undetectable viral loads. Our data suggest that immune activation can cause CD4(+) T cell depletion even when HIV-1 replication appears to be controlled by host factors.
[Show abstract][Hide abstract] ABSTRACT: Immunoglobulin (Ig) GM and KM allotypes-genetic markers of gamma and kappa chains, respectively-are associated with the outcome of hepatitis C virus (HCV) infection, but the underlying mechanisms are not well understood. We hypothesized that GM and KM allotypes could contribute to the outcome of HCV infection by influencing the levels of IgG antibodies to the HCV glycoproteins E1E2. We serologically allotyped 100 African American individuals with persistent HCV infection for GM and KM markers and measured anti-E1E2 antibodies. Subjects with the GM 1,17 5,13 phenotype had significantly higher levels of anti-E1E2 antibodies than subjects who lacked this phenotype (p = 0.008). Likewise, subjects with the KM 1-carrying phenotypes had higher levels of anti-E1E2 antibodies than subjects who lacked these phenotypes (p = 0.041). Median titers were fourfold higher in persons expressing both GM 1,17 5,13 and KM 1-carrying phenotypes compared with those who lacked these phenotypes (p = 0.011). Interactive effects of these GM-KM phenotypes were previously found to be highly significantly associated with spontaneous HCV clearance. Results presented here show that Ig allotypes contribute to the interindividual differences in humoral immunity to the HCV epitopes, a finding that may provide a mechanistic explanation for their involvement in the outcome of HCV infection.
Human Immunology 04/2008; 69(3):158-64. DOI:10.1016/j.humimm.2008.01.019 · 2.28 Impact Factor