HIV-positive patients co-infected
with HCV up to 80% more likely to die even with HIV treatment
Michael Carter,
Wednesday, August 17, 2005
Infection with
hepatitis C virus increases the risk of death in HIV-positive
individuals by between 30% - 80%, even after factors such as the use and
success of anti-HIV treatment are controlled for, according to a US
study published in the August 15th edition of the Journal
of Acquired Immune Deficiency Syndromes. The investigators, from the
US’s largest provider of HIV care, the Department of Veterans’ Affairs,
question whether currently available treatment for hepatitis C, which
has a lower response rate in HIV-positive individuals, would
significantly reduce this level of excess mortality and suggest instead
that efforts should be made to treat the high levels of mental illness
and drug and alcohol abuse present in their coinfected patients, factors
which they believe “contribute directly and indirectly to poor outcome
in HIV and HCV coinfection.”
It is estimated that as many as 300,000 HIV-positive individuals (15% -
30% of all HIV cases) are coinfected with hepatitis C virus. Since
effective anti-HIV therapy became available, liver disease caused by
hepatitis C has emerged as a major cause of illness and death in
HIV-positive patients.
Investigators wished to determine the impact of hepatitis C infection on
mortality in HIV-positive patients receiving antiretroviral therapy.
Their analysis controlled for potential confounding factors including
virologic and immunologic response to anti-HIV treatment.
The study included a total of 12,216 individuals who were treated with
their first potent anti-HIV treatment regimen at the Department of
Veterans’ Affairs between early 1997 and 2003. To be included in the
study individuals also had to have been tested for hepatitis C and to
have CD4 and viral load tests conducted prior to starting HIV therapy.
A total of 4,668 patients (38%) were coinfected with hepatitis C virus.
Coinfected individuals were older than patients who tested negative for
hepatitis C and were also more likely to be black or Hispanic, have a
history of psychiatric illness (71% versus 60%, p < 0.001), abuse drugs
(62% versus 20%, p <0.001), and have alcohol problems (63% versus 30%, p
< 0.001). Prior to starting potent anti-HIV therapy, hepatitis C
coinfected patients had higher viral loads than patients who were only
infected with HIV (median 26,000 copies/ml versus 19,000 copies/ml, p <
0.001), but baseline CD4 cell counts were comparable between the two
groups of patients (median 257 cell/mm3 versus 248 cells/mm3).
Hepatitis C-infected and hepatitis C-negative individuals had a similar
virologic response to HAART with approximately 80% of both groups of
patients achieving an undetectable viral load at least once. Nor was
there any difference in the proportion of patients who maintained good
control of HIV replication (37% hepatitis C-infected, versus 39%
hepatitis C-negative). CD4 cell gain was, however, lower amongst the
patients infected with hepatitis C (median peak gain 199 cells/mm3
versus 239 cells/mm3 for hepatitis C-uninfected patients, p <
0.001).
A total of 2087 deaths occurred during follow-up. There were
proportionately more deaths amongst hepatitis C virus-infected patients
than individuals who were not infected with hepatitis C (22% versus 14%,
p < 0.001). The unadjusted risk of death was 6.4 per 100 patient years
for coinfected patients and 4 per 100 patient years for patients who
only had HIV. This difference was highly statistically significant (p <
0.001).
The investigators repeated their analysis, limiting their analysis to
patients with controlled HIV replication on at least one occasion and
still found that coinfected patients had a significantly higher risk of
death (hazard ratio, 1.77, p < 0.001). The result was similar when
analysis was restricted to individuals with well-controlled viral load -
coinfected patients having a hazard ratio of death of 1.69, p < 0.001).
The investigators then controlled for CD4 cell response to anti-HIV
therapy and still found a significantly increased hazard ratio of death
for coinfected patients (1.34, p < 0.001).
“Hepatitis C virus infection increases the risk of death in HIV patients
who received HAART, controlling for numerous demographic and clinical
factors, including exposure to HAART and response to HAART”, write the
investigators. They add, “depending on the factors for which we
controlled, we found that the risk of death among HAART-treated HIV
patients was between 30% and 80% higher for those who were also infected
with HCV.”
The investigators suggest that their study “raises the pressing question
of whether HCV treatment can ameliorate the observed increase in the
risk of death.” They note that the study was largely completed before
pegylated interferon and ribavirin became the standard of treatment for
hepatitis C virus. However, they emphasise that the response to
hepatitis C therapy is poorer in patients who are coinfected with HIV.
They therefore suggest that until better hepatitis C treatment becomes
available efforts to treat the high rates of mental illness, and drug
and alcohol abuse seen in their cohort may help lower mortality.
Reference
Backus LI et al. Effects of hepatitis C virus coinfection on survival
in veterans with HIV treated with highly active antiretroviral therapy.
J Acquir Immune Defic Syndr 39: 613 – 619, 2005.
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