May 8, 2012

HCV Independently Raises Risk of Premature Death in AIDS Patients

From Reuters Health Information

By Megan Brooks

NEW YORK (Reuters Health) May 04 - Despite competing risks, chronic hepatitis C virus (HCV) infection is independently associated with a 50% increase in mortality among patients with a diagnosis of AIDS, new research suggests.

"Effective HCV treatment may benefit HIV/HCV co-infected patients with AIDS," according to a report online April 24 in Clinical Infectious Diseases by Dr. Andrea D. Branch at Mount Sinai School of Medicine in New York City and colleagues.

In the United States and Europe, about 30% of HIV-positive patients are also infected with HCV. A recent meta-analysis showed that the overall mortality risk ratio for HIV/HCV co-infected patients is increased by about 35%.

Yet, it's not clear, say the researchers, whether these results apply to patients with CDC-defined AIDS in the era of combination antiretroviral therapy, "because their mortality rate continues to be approximately five times higher than that of HIV-positive patients without a diagnosis of AIDS. Competing risk factors might eclipse the mortality risk of HCV infection in current patients with AIDS, just as they did in the early years of the epidemic."

Dr. Branch and colleagues tracked 2,025 patients with AIDS enrolled in the Longitudinal Studies of the Ocular Complications of AIDS (LSOCA) and followed prospectively for a median of over six years. LOSCA is one of only a few cohort studies limited to persons diagnosed with AIDS, but without further exclusion criteria. It focuses exclusively on the era following introduction of combination antiretroviral therapy.

An analysis of plasma banked at enrollment from all 2,025 patients revealed that 428 (21%) had evidence of past or current HCV infection. Nearly four-fifths (337, or 79%) were HCV RNA positive, indicating chronic HCV infection, and 91 (21%) had HCV antibodies but no HCV RNA, indicating past infection. The remaining 1,597 had no HCV markers.

Overall, 558 study subjects died during follow up. After adjusting for demographic factors and known risk factors for death, the relative risk of dying during follow-up was 1.5 (p=0.001) in patients with chronic HCV infection. In contrast, mortality was not increased in patients with past (cleared) infection (RR, 0.9; p=0.82). In patients with chronic HCV infection, 20.4% of deaths were liver-related vs 3.8% in patients without HCV infection.

Dr. Melanie Ott, senior investigator at the Gladstone Institutes in San Francisco, California, who was not involved in the study, told Reuters Health that a 1.5-fold increase in mortality is "not earth-shattering in AIDS patients with chronic HCV coinfection."

Nor is it surprising, she said, that the mortality due to liver-related diseases is increased in these patients. "It is actually surprising that 'only' approximately 20% of death in these patients is liver-related given the fact that HIV coinfection worsens the outcome of HCV infection."

Dr. Ott also said the finding that liver-related but not overall mortality is also elevated in HIV patients who cleared HCV suggests that "transient contact with HCV could prime the liver for fatal liver damage on the background of HIV infection."

Dr. Branch and colleagues add, "The negative impact of liver disease on survival emphasizes the need for patients with AIDS to be aware of their HCV status so that they can fully participate in their health care and risk reduction."

They also found that 100 (30%) of 337 subjects with chronic HCV infection said that they had never been given a diagnosis of this disease.

"Heightened HCV awareness" may increase the proportion of patients seeking treatment and achieving sustained virological response (SVR), Dr. Branch and colleagues say.

They point out that while current anti-HCV treatments produce a sustained viral response (SVR) in only 25% to 50% of HIV/HCV co-infected patients, "SVR rates are expected to rise soon as (direct) acting antiviral drugs for HCV enter the clinic."

Even so, "optimizing treatment and managing drug-drug interactions will be significant challenges in the years ahead," the authors conclude.

The study was supported by grants from the National Institutes of Health Eye Institute to the Mount Sinai School of Medicine; the Johns Hopkins University Bloomberg School of Public Health and the University of Wisconsin; and by grants from the National Institute of Drug Addiction and the National Institute of Digestive Diseases and Kidney Disease to the Mount Sinai School of Medicine. One author has relevant financial disclosures, all listed with the original article.


Clin Infect Dis 2012.


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