Meta-analysis Shows Hepatitis C Virus Coinfection Does Not Lead to HIV Disease Progression

		SUMMARY: Coinfection with hepatitis C virus (HCV) is associated with higher mortality among HIV positive individuals in the highly active antiretroviral therapy (HAART) era, but this is not due to an increased risk of progression to AIDS-defining events, according to a meta-analysis described in the November 15, 2009 issue of Clinical Infectious Diseases.

By Liz Highleyman

Numerous studies have shown that HIV infection is linked to faster HCV-related liver disease progression, but the effect of HCV on HIV disease progression and mortality is less clear.

To explore this issue, Ting-Yi Chen and colleagues performed a meta-analysis to estimate the effect of HCV coinfection on HIV disease progression and overall mortality in the pre-HAART and HAART eras.

The investigators searched the PubMed and EMBASE databases for studies reporting disease progression or mortality among HIV/HCV coinfected patients published through April 2008; further studies were identified from cited references. Cross-sectional studies, trials without HCV negative control subjects, and studies involving children or liver transplant recipients were excluded.

The meta-analysis included 37 studies -- 10 from the pre-HAART era (i.e., before 1996) and 20 from the HAART era -- with more than 100,000 total participants (about 14,600 pre-HAART and about 87,000 HAART era).

Results

	In the pre-HAART era, the risk ratio for overall mortality among HIV/HCV coinfected patients compared with HIV monoinfected individuals was 0.68, indicating a modestly lower risk of death.
	In the HAART era, the risk ratio for AIDS-defining events was 1.12, or 12% higher, for coinfected compared with HIV monoinfected patients --not a significant difference.
	The HAART era risk ratio for overall mortality was 1.35, indicating a 35% higher risk for coinfected individuals.
	Looking at the combined outcomes of AIDS diagnosis or death, coinfected individuals had a risk ratio of 1.49, or a 49% increased risk.
	The risk of death increased with longer duration of HIV/HCV coinfection.

"HCV coinfection did not increase mortality among patients with HIV infection before the introduction of HAART," the study authors concluded. "In contrast, in the HAART era, HCV coinfection, compared with HIV infection alone, increases the risk of mortality, but not the risk of AIDS-defining events."

In their discussion, they suggested that while HIV positive patients in the pre-HAART era typically did not survive long enough to develop advanced HCV-related liver damage, liver disease is likely the major contributor to mortality among coinfected individuals since HAART has become widely available. Numerous studies in the U.S. and Europe have shown that liver disease is now a leading cause of death for HIV positive people, especially coinfected patients.

"Future studies should determine whether successful treatment of HCV infection could reduce this excess risk of mortality in coinfected patients," the researchers recommended.

Wayne State University, Detroit Medical Center, Detroit, MI; Departments of Nutrition and Epidemiology, Harvard School of Public Health, Boston, MA; Division of Infectious Diseases, Massachusetts General Hospital, Boston, MA.

11/17/09

Reference
T-Y Chen, EL Ding, GR Seage, and others. Meta-Analysis: Increased Mortality Associated with Hepatitis C in HIV-Infected Persons Is Unrelated to HIV Disease Progression. Clinical Infectious Diseases 49(10): 1605-1615. November 15, 2009.