In
the first study, researchers investigated the influence of HCV coinfection on
CD4 cell recovery among patients with maximum HIV suppression (at least 2 viral
loads below 50 copies/mL) after starting HAART (a combination of at least 3 drugs)
in the large EuroSIDA cohort.
A total of 3892 HIV patients were included,
representing 34,178 pairs of HIV viral load measurements of < 50 copies/mL
and 10,422 person-years of follow up. About three-quarters were men, the median
age was 41 years, the baseline CD4 cell count was 429 cells/mm3, and the CD4 count
at the time of HAART initiation was 214 cells/mm3. In this group, 809 patients
(21%) were HCV coinfected, of whom 621 (77%) had detectable HCV RNA.
Results
•
The unadjusted annual median change in CD4 count was 42 cells/mm3 among HIV-HCV
coinfected patients and 41 cells/mm3 among HIV monoinfected patients.
•
After adjusting for potential confounding factors, there was no significant difference
in annual CD4 cell change according to:
•
Adjusting further for hepatitis C treatment and HCV viral load did not change
these findings.
"In
this prospective EuroSIDA cohort study we have shown compelling evidence that
HCV coinfection does not impair the CD4 recovery in HIV-1 infected patients who
are maximally HIV suppressed (viral load < 50 copies/mL) compared to HIV-monoinfected
patients," the investigators concluded.
Similarly,
they added, "no difference in CD4 [cell] increase was found when comparing
HCV seropositive vs seronegative patients or when comparing distinct HCV genotypes,
although the power of this latter analysis is limited due to the small number
of viral load pairs for genotype 2 and 4."
They
suggested, however, that hepatitis C treatment may nonetheless be beneficial for
coinfected patients, stating, "Although we have shown that hepatitis C coinfection
did not impair the CD4 response to combination antiretroviral therapy, still HCV
eradication will lower the risk of hepatotoxicity induced by antiretroviral drugs
and progression of liver disease."
CD4
Cell Apoptosis
In
a related study, German researchers looked at apoptosis - often referred to as
programmed cell death or cell "suicide" - of CD4 T-cells.
As
background, they noted that coinfection has been suggested to be associated with
accelerated development of AIDS and enhanced mortality in HIV positive patients.
Apoptosis may play a major role in CD4 cell demise, though it remains unclear
whether HCV coinfection has any effect on CD4 cell apoptosis.
The investigators
studied 50 HIV monoinfected, 10 HCV monoinfected, and 39 HIV-HCV coinfected patients,
plus 12 healthy control subjects with neither virus. With regard to treatment,
25 HIV monoinfected and 14 coinfected patients were antiretroviral-naive or off
treatment for at least a year; 25 in each group were on suppressive HAART with
HIV viral load below 50 copies/mL. None of the patients with HCV had received
interferon-based therapy for at least a year.
Results
•
As expected, antiretroviral-naive HIV positive patients displayed significantly
higher rates of CD4 cell apoptosis (4%) compared with healthy control subjects
(1%) or HCV monoinfected individuals (1%).
•
The apoptosis rate was significantly increased in HIV-HCV coinfected treatment-naive
patients (6 %) compared with both HIV monoinfected patients and uninfected control
subjects.
•
Effective HAART was associated with a reduction of CD4 cell apoptosis, 2% in both
HIV monoinfected and HIV-HCV coinfected patients.
•
However, apoptosis rates still remained elevated relative to healthy uninfected
subjects.
"Our
results demonstrate increased rates of apoptosis in HIV monoinfection, which are
even higher in HCV-HIV coinfection," the researchers concluded. "These
findings imply enhanced apoptosis to be involved in loss of CD4 T-cells during
HIV infection and suggest that increased apoptosis could be relevant regarding
accelerated progression of HIV in hepatitis C coinfected patients.
Do
HIV-HCV Coinfected Patients Have Impaired CD4 Cell Recovery after Starting HAART?
Results
