Background:  The recruitment of HIV-infected T cells and/or the accumulation of HIV within non-parenchimal cells of the liver could represent the source of additional viral antigens that may favor the immunologically mediated events, responsible for the fast progression of liver disease observed in HIV/hepatitis C virus (HCV) patients. The aim of this study was to determine HIV DNA intrahepatic content and to relate these findings to immunological and pathological correlates of liver disease.

Methods:  We randomly selected 56 HIV/HCV chronically infected patients, with similar age and risk factors, among those who underwent liver biopsy for diagnostic purposes. The patients were divided into 2 groups based on levels of HIV viremia:  31 HIV/HCV-co-infected patients had undetectable HIV viremia (group 1) and 25 HIV/HCV-co-infected patients had HIV viremia >25,000 copies/mL (group 2). All patients in group 1 were treated with HAART, whereas 15 patients in group 2 were in structured treatment interruptions before liver biopsy, 5 patients in HAART failure, and 6 naïve to HAART. Total intrahepatic HIV DNA was determined by using a quantitative real time polymerase chain reaction (RT-PCR). The present study was performed according to the Helsinki declaration.

Results:  The 2 groups of patients had comparable time of HIV/HCV co-infection (group 1, 14.1±0.9 years vs 12.6±1.3 years in group 2, p = ns), HCV genotypes were similarly distributed and there was no difference in HCV RNA viremia (group 1, 1099 + 180 x10³ copies/mL vs 1577±374 x10³ in group 2, p = ns). Intrahepatic HIV DNA was detected in 20 out of 31 group 1 patients and in 23 out of 25 group 2 patients. The mean intrahepatic content of HIV DNA was 40.4±12.5 copies/µg DNA and 120±37 copies/µg DNA in groups 1 and 2 respectively (p <0.001). The prevalence of moderate to severe grading of hepatic histology was 58% in group 1 and 76% in HIV viremic subjects (p <0.05), with higher median alanine aminotransferase (ALT) levels in group 2 patients (group1 vs 2 = 94±15 IU/L vs 125±16).

Conclusions:  These data suggest that in HIV/HCV-co-infected patients uncontrolled HIV viremia is associated with the accumulation of HIV-infected cells within non-parenchimal cells of the liver. The accumulation of intrahepatic HIV DNA represents the source of additional viral antigens that may favor the immunologically mediated events, responsible for the fast progression of liver disease in HCV co-infected patients.