To the Editor: Diagnosis of hepatitis-C virus (HCV) infection is based primarily on detection of HCV antibodies in serum (1). Immune dysfunction associated with HIV disease could restrict the ability to detect HCV coinfection in patients with HIV disease.
Impaired ability to detect antibody to several chronic viral infections is described in HIV disease. For example, loss of antibodies to hepatitis-B surface antigen (2), HIV p24 antigen (3), δ hepatitis (4), and HCV (5) is found with HIV disease progression.
The mechanisms that underlie impaired antibody detection in HIV disease are unclear and worthy of closer investigation. Possible mechanisms include reduced antibody synthesis or increased viral antigen production. Increased antigen, by complex formation with antibody, could reduce detectable free-antibody levels. Reported findings of increased levels of p24 antigen (3), appearance of HDV antigen (4), and increased HCV levels in sera from patients with AIDS (6) suggest that increased complex formation between antigen and antibody could account for the reduced levels of circulating antibody detected.
We measured anti-HCV antibody titers in sera from intravenous drug users (IVDUs) at various stages of HIV disease. Prompted by findings of reduced anti-HCV antibody titers in HIV-infected sera, we repeated anti-HCV measurements in sera pretreated with acid buffer to determine whether reduced anti-HCV titers could be related to increased HCV antigen-antibody immune-complex formation.
Patients were divided into three groups: HIV negative (n = 39), HIV positive (n = 86), and AIDS (n = 12). There were no significant differences in age, gender, or serum transaminase levels between any of the three patient groups. Anti-HCV was measured in sera that had been stored at -20°C, using first- or second-generation enzyme immunoassay (EIA) (Abbott Diagnostics, Abbott Park, IL, U.S.A.). Antibody titer was estimated by determining the ratio of absorbance value measured in the Abbott assay to the cutoff value for the assay (Abs/COV).
Eight samples were randomly selected from each group for acid pretreatment to dissociate antigen-antibody complexes. Briefly, sera were incubated with an equal volume of 1.5 M glycine buffer, pH 2.0, for 60 min at 37°C. Acid-treated samples were neutralized by addition of 1.5 M Tris buffer, pH 9.0 (6). The antibody titer was subsequently determined within 30 min of neutralization by the Abbott EIA 2.0 kit.
The mean Abs/COV ratio in non-HIV-infected sera was significantly higher than in sera from HIV-infected patients with or without AIDS (Table 1). Abs/COV ratios were not significantly altered by acid pretreatment in sera from any of the three patient groups (Table 2).
This study indicates that anti-HCV antibody titers in serum are lower in HIV-infected IVDUs, with or without AIDS, than in non-HIV-infected IVDU controls. These findings are in line with published data (5,7,8). Loss of anti-HCV antibodies has been demonstrated in patients whose cases have been followed prospectively during HIV disease progression (5,8).
At least two possible mechanisms could account for the observed reduction in antibody titers in HIV-infected patients. First, it could be the result of defective antibody synthesis. The follicular dendritic cell network—which is the major antigen-presenting cell network for germinal center B cells and is responsible for initiating B-cell responses and memory—is gradually and progressively destroyed by HIV disease (9).
Secondly, increased HCV replication, as described in HIV infection (6), may increase antigen-antibody complex formation leading to decreased free antibody titer. However, pretreatment of our samples with acid to dissociate complexes prior to antibody detection had no significant effect on the Abs/COV ratio. Thus, the reduced HCV antibody titers measured in HIV-coinfected IVDUs are unlikely to be related to immune-complex formation.
In summary, anti-HCV titer is reduced in people with HIV infection. This reduction does not appear due to increased antibody-antigen complex and more likely reflects reduced antibody synthesis. In HIV-infected patients with suspected HCV disease, the diagnosis of chronic HCV infection may need to be confirmed by measurement of HCV RNA.
Darius Sorbi; Denis Shen; Gerard Lake-Bakaar
Department of Medicine; SUNY Health Science Center; Stony Brook, New York and Veterans Administration Medical Center; Northport, New York, U.S.A.
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