M. Beld et al., EVIDENCE THAT BOTH HIV AND HIV-INDUCED IMMUNODEFICIENCY ENHANCE HCV REPLICATION AMONG HCV SEROCONVERTERS, Virology, 244(2), 1998, pp. 504-512
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.