HIV/HCV
Coinfected Veterans Have Elevated Risk of Chronic Kidney Disease
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SUMMARY:
HIV positive people coinfected with hepatitis C virus
(HCV) are more likely to have chronic kidney disease
than individuals with HIV alone, and kidney disease
is linked to significantly greater risk of death,
according to a study of U.S. veterans described in
the February
2010 Journal of Acquired Immune Deficiency Syndromes.
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By
Liz Highleyman
People
with HIV have been shown to
have higher rates of kidney disease, including HIV-associated
nephropathy, which disproportionately affects black patients.
Use of certain antiretroviral
drugs, including tenofovir
(Viread, also in the Truvada
and Atripla combination
pills), may also play a role. Hepatitis
C is associated with kidney disease too, but its occurrence
among HIV/HCV coinfected
people has not been extensively studied.
Michael Fischer and colleagues with the Veterans Aging Cohort
Study (VACS) Project Team designed a study to examine the effect
of HCV on the prevalence of chronic kidney disease (CKD) among
HIV positive veterans and to evaluate independent associations
between HCV, CKD, and mortality.

The
investigators studied a subset of 23,155 HIV positive participants
in a national cohort of patients receiving care through the
Veterans Healthcare Administration from 1998 through 2004. Most
were men and the median CD4 cell count was 336 cells/mm3. A
large proportion -- 40% -- were coinfected with HCV, and coinfected
participants had a lower median CD4 count, higher median HIV
viral load, and were less likely to have received combination
antiretroviral therapy (ART) at baseline.
Participants
were followed for a median duration of 7.6 years. CKD was defined
as an estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73
m(2), estimated from baseline serum creatinine using the Modification
of Diet in Renal Disease (MDRD) equation. At baseline, 12% of
patients had eGFR < 60; participants with reduced eGFR were
on average older, more often African-American, had more advanced
HIV disease, were less likely to be on ART, and had a higher
rate of comorbidities.
Results
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Overall,
12% of the 23,155 HIV positive veterans studied had CKD.
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A
significantly higher proportion of HIV/HCV coinfected participants
had CKD compared with HIV monoinfected patients (14% vs
11%; P < 0.001). |
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37%
of study participants died during follow-up. |
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A
graduated increase in adjusted mortality rates was seen
with lower eGFR levels, ranging from 39% for those with
normal kidney function to 60% for those with eGFR < 15
(P < 0.001). |
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In
multivariate analysis, reduced eGFR was associated with
significantly increased mortality compared with eGFR >60
(incidence rate ratio [IRR] 1.61 for eGFR 30-59 and IRR
2.75 for eGFR 15-29). |
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HCV
coinfection was independently associated with increased
mortality (IRR 1.23). |
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Adjusted
mortality rates were consistently higher for HIV/HCV coinfected
patients across all eGFR levels (P < 0.001). |
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The
difference in adjusted mortality rates between HIV/HCV coinfected
and HIV monoinfected patients became smaller after adjusting
for eGFR. |
"CKD is prevalent in HIV-infected veterans and associated
with substantially higher mortality," the study authors
wrote. "Compared with their monoinfected counterparts,
veterans coinfected with HCV have significantly higher rates
of CKD and mortality."
The
rate of CKD in this study was higher than those observed in
some past studies, which the investigators attributed to a larger
proportion of African-American participants, high prevalence
of other traditional CKD risk factors, more advanced HIV disease,
and relatively low levels of ART use, which has been shown to
improve the course of HIV-associated nephropathy.
"We
demonstrated consistently higher adjusted mortality rates among
HCV-coinfected veterans at all levels of eGFR, and it seems
that only approximately 25% of this excess mortality in HCV-coinfected
veterans can be attributed to the higher prevalence of CKD,"
they noted in their discussion. "Moreover, HCV coinfection
independently increased the likelihood of death by nearly 25%,
after adjustment for other important HIV- and HCV-related factors."
A
limitation of this study was that it used a single creatinine
value to estimate GFR and did not look at changes over time
or include data on proteinuria (protein in the urine), another
indicator of kidney dysfunction.
"The
results of the current study demonstrate that CKD affects more
than 1 in 8 HIV-infected veterans and is associated with significantly
higher mortality," the investigators concluded. "Veterans
coinfected with HCV incur even higher rates of CKD and mortality
than those with only HIV infection. Efforts should be targeted
toward optimizing medical care for mono- and coinfected veterans,
including HAART therapy, HCV antiviral therapy, and treatment
of comorbid medical conditions."
Jesse
Brown VA Medical Center, University of Illinois Medical Center,
Chicago, IL; Center for the Management of Complex Chronic Care,
Hines VA Hospital, Hines, IL; Mount Sinai School of Medicine,
New York, NY; West Haven VA Medical Center, New Haven, CT; VA
Medical Center, George Washington University Medical Center,
Washington, DC; James J. Peters VA Medical Center; Atlanta VA,
Emory University School of Medicine, Atlanta, GA; Michael E.
DeBakey VA Medical Center, Baylor College of Medicine, Houston,
TX; Schools of Medicine and Public Health, Yale University,
New Haven, CT.
2/9/10
Reference
M Fischer, C Wyatt, K Gordon, and others (VACS Project Team).
Hepatitis C and the Risk of Kidney Disease and Mortality in
Veterans With HIV. Journal of Acquired Immune Deficiency Syndromes
53(2): 222-226 (Abstract).
February 2010.