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HIV-HCV Coinfection
Hepatitis C
Hepatitis B
HIV-HBV Coinfection
HIV-HCV Coinfection
SMART Study Shows Antiretroviral Treatment Interruption Is Particularly Risky for Patients with HIV-HBV or HIV-HCV Coinfection

Liver disease related to coinfection with hepatitis B or hepatitis C virus (HBV or HCV) is an increasingly important cause of illness and death among people with HIV.

A growing body of evidence indicates that CD4-guided interruption of antiretroviral therapy (ART) is potentially hazardous, and this may be especially true for HIV-HBV and HIV-HCV coinfected patients, according to an analysis from the SMART study published in the December 1, 2008 issue of Clinical Infectious Diseases.

As previously reported, SMART included more than 5000 mostly treatment-experienced participants with a baseline CD4 cell count above 350 cells/mm3. They were randomly assigned to either start and remain on continuous ART ("viral suppression" arm) or to interrupt therapy while their CD4 count was above 350 cells/mm3 and resume when it fell to 250 cells/mm3 ("drug conservation" arm).

The study was halted in January 2006 after it became apparent that participants in the treatment interruption arm not only had a higher rate of AIDS-related opportunistic disease or death due to any cause, but also were more likely to develop serious cardiovascular, liver, and kidney disease.

In the present retrospective analysis, the investigators assessed whether the subgroup of SMART participants with viral hepatitis coinfection were at increased risk for these endpoints.

Patients were classified as HIV-HBV coinfected if they had positive hepatitis B surface antigen for more than 6 months, and HIV-HCV coinfected if they tested HCV antibody positive. Among the total 5472 participants enrolled between January 2002 and January 2006, 930 patients (17%) were HBV and/or HCV coinfected.


The relative risk of death due to causes other than opportunistic disease in participants randomized to the treatment interruption versus the continuous therapy arm was comparable regardless of hepatitis status (hazard ratio [HR] 1.9 for coinfected and HIV monoinfected participants, respectively).

Opportunistic disease or death occurred at a rate of 3.9 events per 100 person-years in the hepatitis coinfected group, compared with 2.0 per 100 person-years in the HIV monoinfected group.

This excess risk was due to a higher rate of non-opportunistic disease deaths among the coinfected participants (HR 3.6).

The risk of opportunistic disease, however, was comparable in hepatitis coinfected and HIV monoinfected groups (HR 1.1).

The 3 leading causes of non-opportunistic disease death in HIV-HBV and HIV-HCV coinfected participants were unknown cause, substance abuse, and non-AIDS-defining cancers (there were also several suicides).

Based on these findings, the researchers concluded, "Interruption of antiretroviral therapy is particularly unsafe in persons with hepatitis virus coinfection."

"Although HCV- and/or HBV-coinfected participants constituted 17% of participants in the SMART study, almost one-half of all non-opportunistic disease deaths occurred in this population," they continued.

Finally, they noted, "Viral hepatitis was an unlikely cause of this excess risk."

Liver cancer (hepatocellular carcinoma) -- a known complication of chronic hepatitis B or C -- is not classified as an AIDS-defining malignancy, but like the 3 AIDS-defining cancers (Kaposi's sarcoma, non-Hodgkin lymphoma, and cervical cancer), it is associated with an infectious organism that may gain an advantage when immune function is suppressed. Several studies have indicated that ART reduces liver disease progression, but some antiretroviral drugs have the potential to cause liver toxicity.

In SMART, however, liver disease was not a predominant cause of the excess deaths in the coinfected group. Since HIV, HBV, and HCV can all be spread via injection drug equipment, injection drugs users -- a group with a higher risk of death due to various causes -- were overrepresented in the coinfected group. The coinfected patients were also, on average, older and more likely to be heavy alcohol users.

Temple University School of Medicine, Philadelphia, PA; School of Public Health, University of Minnesota, Minneapolis, MN; Montreal Chest Institute, McGill University Health Centre, Montreal, Quebec, Canada; Copenhagen HIV Programme, University of Copenhagen and Centre for Viral Diseases/KMA, Rigshospitalet, Copenhagen, Denmark; Institute of Infectious and Tropical Diseases, University of Brescia, Brescia, Italy; Medizinische Universitätsklinik, Bonn, Germany; Royal Free and University College Medical School, London, UK; Service of Infectious Diseases, Hospital Carlos III, Madrid, Spain; Hospital Universitari Germans Trias i Pujol, Badalona, Catalonia, Spain; National Centre in HIV Epidemiology and Clinical Research, University of New South Wales, Sydney, Australia.


E Tedaldi, L Peters, J Neuhaus, and others. Opportunistic Disease and Mortality in Patients Coinfected with Hepatitis B or C Virus in the Strategic Management of Antiretroviral Therapy (SMART) Study. Clinical Infectious Diseases 47(11): 1468-1475. December 1, 2008. (Abstract).

































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