Ongoing hepatitis C replication inhibits
improvements in the CD4 cell counts of HIV-positive patients taking
antiretroviral therapy, Canadian investigators report in the July
31st edition of AIDS.
Researchers monitored changes in the CD4
cell counts of HIV-positive patients who had antibodies to hepatitis C virus.
Falls in CD4 cell counts before HIV treatment was started, and increases in
such counts after the initiation of antiretroviral therapy were compared
between individuals who had spontaneously cleared hepatitis C, and those who
had chronic infection with the virus.
Ongoing hepatitis C replication was
associated with slightly higher CD4 cell count loss prior to starting HIV
treatment. There was also clear evidence that individuals with chronic hepatitis
C had blunted CD4 cell responses to antiretroviral therapy.
“Spontaneous clearance of HCV [hepatitis C
virus] is independently associated with a better rate of CD4 cell recovery once
ART [antiretroviral therapy] is introduced”, comment the investigators, who
stress that their “findings were robust.”
Investigators from the Canadian Coinfection
Cohort Study performed their research because there is uncertainty about the
impact of hepatitis C co-infection on HIV disease progression. Moreover, they
were concerned that earlier research exploring this question may have been
limited because antibody status was used to define hepatitis C infection. A
significant proportion of patients infected with hepatitis C spontaneously
clear the infection, leading the researchers to postulate that the results of
some studies could have been confounded because some individuals in the
hepatitis C arm were in fact free from the infection.
Their study population included 271
patients. All were infected with HIV, and all had antibodies to hepatitis C.
However, they divided the patients into two
groups. The first involved 236 with chronic hepatitis C infection (and
therefore ongoing replication of the virus), the other, those who had
spontaneously cleared the infection.
Changes in the CD4 cell counts of these two
groups were then compared before and after the initiation of antiretroviral
A total of 95 patients, 25 of whom had
spontaneously cleared hepatitis C, were naïve to HIV treatment on recruitment
to the study.
CD4 cell counts fell by a non-significant
average of 44 cells/mm3 per year amongst the patients
who had cleared hepatitis C, and by an average of 84
cells/mm3 each year in those with ongoing replication of
the virus. However, after adjustment for follow-up time the association between
chronic hepatitis C infection and greater loss of CD4 cells was not significant.
Information on CD4 cell count increases
after the initiation of antiretroviral therapy was available for 226
individuals. Once again, 25 patients had spontaneously cleared their hepatitis
C infection. The median duration of follow-up was 18 months for those with
chronic hepatitis C and 15 months for those who had cleared the infection.
Average annual CD4 cell count increases
were seven-fold higher for patients who had cleared hepatitis C infection than
for those with ongoing hepatitis C replication (4 vs. 24
cells/mm3 p < 0.001).
The association between spontaneous
clearance of hepatitis C virus and more robust increases in CD4 cell count
during HIV therapy remained significant after the investigators adjusted their
results to take into account potentially confounding factors.
Moreover, the researchers also founded that
the blunted CD4 cell response seen in the patients with chronic hepatitis C did
not improve over time.
Limiting analysis to patients who started
HIV treatment for the first time after entry to the study cohort did not affect
However, when the researchers restricted
their analysis to patients who maintained an undetectable HIV viral load
throughout follow-up, the impact of chronic hepatitis C virus infection on CD4
cell count recovery was attenuated. CD4 cell counts still increased more slowly
in those with ongoing replication of hepatitis C, but the interaction between
chronic infection and CD4 cell gain ceased to be statistically significant.
“We found that CD4 cell progression is
negatively affected by the presence of ongoing HCV replication in coinfected
individuals taking ART”, write the investigators. They add, “elucidating the
mechanisms by which this difference occurs and investigating the impact of HCV treatment
on CD4 cell progression should be prioritised.”
study’s authors conclude, “when successful, HCV treatment might have an
important role not only in improving HCV related outcomes, but for HIV-related
prognosis as well”.