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MGH study examines impact of infection
with both HIV and hepatitis C virus
Coinfection a growing problem, may
signal need for earlier treatment
BOSTON - December 11, 2006 - Although many individuals infected
with the hepatitis C virus (HCV) are naturally able to control levels
of the virus with their immune systems, those who also become infected
with HIV, the virus that causes AIDS, may lose that ability. In
a report in the December issue of PLOS Medicine, a group
of researchers from the Partners
AIDS Research Center at Massachusetts General Hospital (PARC-MGH)
report one of the first studies of how HIV infection impacts immune
system functions involved with HCV control. Their findings suggest
that beginning antiretroviral therapy earlier than is generally
recommended may help preserve HCV control in patients infected with
both viruses.
"The global burden on health of chronic viral infections is
immense, and HCV and HIV are chief among culprit viruses,"
says Arthur Kim, MD, of PARC-MGH, co-first author of the PLOS
Medicine report. "Due to shared routes of transmission,
infection with both viruses is common. Unfortunately, HCV behaves
as an opportunistic infection in the presence of HIV and is becoming
a leading cause of illness and death in persons with HIV."
In order to examine immune system factors associated with spontaneous
control of HCV and how that control is altered by HIV infection,
the researchers enrolled four groups of participants: 60 were infected
with both viruses, and half of those had low HCV levels upon entering
the study. The other two groups of 17 participants were infected
with HCV only, with one group successfully controlling viral levels.
Spontaneous HCV control is known to rely on the activity of CD4
helper T cells specifically targeted against the virus, and destruction
of CD4 cells by HIV underlies the immune deficiency that characterizes
AIDS. Therefore the researchers measured participants' T cell response
to HCV at the outset of the study and at two- to six-month intervals
during the study period.
The results showed that those individuals able to maintain low HCV
levels in spite of HIV coinfection had stronger virus-specific responses
for both CD4 T cells and the CD8 "killer" T cells than
did those with elevated HCV counts. Not surprisingly, participants
infected only with HCV had even more powerful antiviral T cell responses.
About a quarter of those infected with both viruses who originally
controlled HCV levels lost control during the two-and-a half-year
study period, and their increased virus levels corresponded with
an overall drop in CD4 T cells. None of the viral controllers who
were infected with HCV alone had any increase in viral levels during
the study period. Loss of protective responses and susceptibility
to recurrent HCV infection may help to explain the higher rates
of persistent HCV observed in subjects who are HIV/HCV coinfected,
compared to those with HCV alone.
In analyzing factors that might be associated with the loss of HCV
control in those infected with both viruses, the researchers made
a surprising discovery. The factor most powerfully associated with
maintaining HCV control was not the CD4 T cell count upon entering
the study but the lowest previously recorded or 'nadir' CD4 count.
That finding suggests that, for individuals infected with both viruses,
beginning antiretroviral treatment before CD4 levels drop too low
to maintain HCV responses may be desirable.
The researchers also found that, among those whose HCV levels rose,
individuals who maintained some T cell responses had lower viral
levels than did those with little or no T cell response. This suggests
that the immune system retains a level of secondary immunity against
HCV - the kind of 'memory' response against a previously encountered
pathogen seen in many infections.
"Currently a nationwide trial is recruiting people for a study
examining whether earlier treatment of HIV will improve hepatitis
C treatment outcomes," Kim says. "Part of this study will
investigate how earlier treatment may affect immune responses. It
also will be important to follow the impact of loss of HCV control
on liver disease, since this will probably have important consequences
for patients with HIV." Kim is an instructor in Medicine at
Harvard Medical School.
Bruce Walker, MD, director of the Partners AIDS Research Center
at MGH and a Howard Hughes Medical Institute (HHMI) investigator
is senior author of the PLOS Medicine report, and Julian
Schulze zur Wiesch, MD, of PARC-MGH and HHMI is co-first author.
The study's co-authors are Thomas Kuntzen, MD, Joerg Timm, Daniel
Kaufmann, MD, Jared Duncan, Andrea Jones, Benjamin Davis, MD, Rajesh
Gandhi, MD, Gregory Robbins, MD, Todd Allen, PhD, and Georg Lauer,
MD, of PARC-MGH, Raymond Chung, MD, MGH Gastroenterology; and Alysse
Wurcel, Lemuel Shattuck Hospital, Boston. The study was supported
by grants from the National Institutes of Health, the Campbell Foundation,
the American Liver Foundation, the German Academic Exchange Service,
Doris Duke Charitable Foundation and the Howard Hughes Medical Institute.
Massachusetts General Hospital, established in 1811, is the original
and largest teaching hospital of Harvard Medical School. The MGH
conducts the largest hospital-based research program in the United
States, with an annual research budget of nearly $500 million and
major research centers in AIDS, cardiovascular research, cancer,
computational and integrative biology, cutaneous biology, human
genetics, medical imaging, neurodegenerative disorders, regenerative
medicine, transplantation biology and photomedicine. MGH and Brigham
and Women's Hospital are founding members of Partners HealthCare
HealthCare System, a Boston-based integrated health care delivery
system.
Media Contact: Sue
McGreevey, MGH Public Affairs
Physician Referral Service: 1-800-388-4644
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