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HIV/HCV Coinfected Veterans Have Elevated Risk of Chronic Kidney Disease

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.

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.


Overall, 12% of the 23,155 HIV positive veterans studied had CKD.
A significantly higher proportion of HIV/HCV coinfected participants had CKD compared with HIV monoinfected patients (14% vs 11%; P < 0.001).
37% of study participants died during follow-up.
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).
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).
HCV coinfection was independently associated with increased mortality (IRR 1.23).
Adjusted mortality rates were consistently higher for HIV/HCV coinfected patients across all eGFR levels (P < 0.001).
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.


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.























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