Activation Contributes to HIV Disease Progression in HIV/HCV
HIV/HCV coinfected women with detectable hepatitis
C virus (HCV) in their blood had a higher percentage
of activated CD8 T-cells, as well as a significantly
higher risk of progression to AIDS, according to a
study described in the March
15, 2010 Journal of Infectious Diseases.
Increased immune activation may help explain more
the rapid HIV disease progression seen in some studies
of coinfected patients.
Considerable research has shown that HIV/HCV
coinfected individuals tend to experience more rapid liver
disease progression than HIV negative people with hepatitis
C alone. The effect of HCV on HIV disease progression is
less clear, however, as studies have produced conflicting results.
growing body of evidence indicates that increased CD4 and CD8
T-cell immune activation is a risk factor both for HIV disease
progression and for non-AIDS conditions such as cardiovascular
disease. Additive immune activation due to 2 co-existing infections
may further increase the risk.
Kovacs from the University of Southern California Keck School
of Medicine and colleagues analyzed the risk of new onset clinical
AIDS and AIDS-related deaths among 1307 HIV positive women with
and without hepatitis C.
study included 813 HIV positive/HCV negative women, 87 HIV/HCV
coinfected women with undetectable HCV viremia (blood viral
load), and 407 HIV/HCV coinfected women with detectable HCV.
researchers assessed percentages of activated CD4 and CD8 T-cells,
as determined by expression of CD38 and HLA-DR markers, in blood
samples from 592 study participants with available data, and
looked at the association between immune activation and disease
progression over a median duration of 5.2 years.
Most of the 592 participants with immune activation data were
African-American or Hispanic, the mean age was about 37 years,
about half had a history of injection drug use (though <
20% were active users during follow-up), the average CD4 cell
count was 439 cells/mm3, and the average CD8 cell count was
964 cells/mm3. Among the HCV positive women, most (80%) had
HCV genotype 1, and only 19 received interferon treatment (without
among the 1307 women without AIDS at baseline, 495 progressed
to AIDS, including 162 who died of AIDS-related causes during
10 years of follow-up.
coinfected women with detectable HCV had a significantly
higher percentage of activated CD8 T-cells than HIV positive
women without HCV (P < 0.001).
women also had a significantly higher incidence of AIDS-related
illness or death compared with HCV negative women (P <
women with HCV viremia were more likely to develop bacterial
pneumonia, wasting syndrome, and encephalopathy (brain disease).
risk of progression to AIDS-defining conditions or AIDS-related
death was nearly 3 times higher among coinfected women with
the highest third of CD38+/HLA-DR+ CD8 cells (> 43%)
compared to those with the lowest third (< 26%) (hazard
ratio 2.94; P < 0.001).
magnitude of difference was not observed between HIV positive/HCV
negative women with the highest and lowest CD8 cell activation
levels (hazard ratio 1.87; P = 0.16).
contrast, CD4 T-cell activation predicted progression to
AIDS or AIDS-related death similarly in both HIV/HCV coinfected
women and those with HIV alone.
percentages of CD38-/HLA-DR+ and CD38-/HLA-DR- CD8 cells
and CD38-/HLA-DR- CD4 cells -- that is, T-cells lacking
the CD38 marker -- were associated with a 50%-70% lower
risk of AIDS for both coinfected women with HCV viremia
and HCV negative women.
viremia was associated with progression to AIDS independent
of CD4 count, HIV viral load, use of antiretroviral therapy
(ART), and injection drug use.
viral load was associated with CD4 and CD8 T-cell activation
independent of HIV viral load.
coinfected women had nearly twice the risk of developing
AIDS as HCV negative women even if they never had a CD4
cell count < 200 cells/mm3.
Based on these findings, the investigators stated, "HCV
positive viremic women with HIV coinfection who have high levels
of T-cell activation may have increased risk of AIDS."
"These data suggest that the increased risk of HIV disease
progression among HCV coinfected women with high levels of CD8
activation may be due to immune dysfunction," they elaborated
in their discussion. "Our finding of increased incidence
of AIDS-defining conditions in relation to high levels of immune
activation suggests that there is impaired T-cell function in
HCV positive viremic women that may potentially put them at
higher risk of HIV disease progression compared with HCV negative
In conclusion, the authors wrote, "our study demonstrates
that HIV coinfected HCV positive viremic women are at increased
risk for AIDS-defining conditions compared with HCV negative
women, possibly because of high levels of activation of T-cells,
especially CD8 T-cells, which indicates increased immune dysregulation
in this population of women. Lower levels of activation of both
CD8 and CD4 T-cells and activation of CD8 T-cells expressing
only HLA-DR is protective against AIDS."
treatment of HIV and HCV infection may be beneficial" for
coinfected individuals, they suggested.
Child, and Adolescent Center for Infectious Diseases & Virology
and Department of Preventive Medicine, University of Southern
California Keck School of Medicine, Los Angeles, CA; Department
of Medicine, University of California, San Francisco, CA; San
Francisco Veterans Affairs Medical Center, San Francisco, CA;
Department of Immunology and Microbiology, Rush University Medical
Center, Chicago, IL; Division of Infectious Diseases, Georgetown
University, Washington, DC; Department of Medicine, State University
of New York Downstate College of Medicine, Brooklyn, NY; Department
of Epidemiology and Population Health, Albert Einstein College
of Medicine, Bronx, NY.
Kovacs, R Karim, WJ Mack, and others. Activation of CD8 T Cells
Predicts Progression of HIV Infection in Women Coinfected with
Hepatitis C Virus. Journal of Infectious Diseases 201(6):
March 15, 2010.