EVIDENCE THAT BOTH HIV AND HIV-INDUCED IMMUNODEFICIENCY ENHANCE HCV REPLICATION AMONG HCV SEROCONVERTERS

The objective of this retrospective cohort study is to assess the mech anism by which human immunodeficiency virus type 1 (HIV) influences he patitis C virus (HCV) replication in injecting drug users. Virological (HCV and HIV RNA levels) and immunological (CD4(+), CD8(+) cell count s, and anti-CD3 reactivity) parameters were determined in 19 HCV seroc onverters in sequential samples over a period of 1 to 9 years. Among t hese subjects, 10 were HIV-seronegative (HIVneg), 4 were HIV-seroposit ive (HIVpos), and 5 seroconverted for HIV (HIVsc) during the observati on period. HCV RNA levels were higher in HIVpos subjects than in HIVne g subjects. In subjects seroconverting for HIV, HCV RNA levels increas ed significantly immediately after HIV seroconversion (P < 0.0001), wh ile they remained stable over time in HIVpos and HIVneg subjects. HCV RNA correlated inversely with CD4(+) cell counts in both the HIVpos po pulation (R = -0.22, P < 0.05) and the HIVneg population (R = -0.45, P < 0.0001). In addition, when subjects were stratified according to CD 4(+) cell counts a significant difference was found in HCV RNA levels between HIVpos and HIVneg subjects with CD4(+) cell counts >500 cells/ mu l (P = 0.001), but not in the population with CD4(+) cell counts <5 00 cells/mu l. In no population was a correlation found between HCV RN A levels and CD8(+) cell counts or anti-CD3 reactivity. Both HIV infec tion and CD4(+) cell counts are apparently associated with HCV RNA lev els, The direct association, independent of CD4(+) cell counts, betwee n HIV infection and HCV replication appears to be stronger than the as sociation between HIV-induced CD4(+) cell decline and HCV replication. We conclude that (i) HCV replication is in some way directly influenc ed by the presence of HIV; (ii) HCV-specific host immunity controls, i n part, HCV replication; and (iii) HCV replication increases when the immune system is impaired by HIV. (C) 1998 Academic Press.