SUMMARY: HIV/HCV coinfected people have higher levels of 2 biomarkers of endothelial (blood vessel) dysfunction compared to individuals with neither virus, researchers reported in a poster presentation at the 17th Conference on Retroviruses and Opportunistic Infections (CROI 2010) last week in San Francisco. Levels of sICAM-1 and sVCAM-1 decreased significantly, however, among patients who received interferon-based hepatitis C treatment and achieved a sustained virological response (SVR), suggesting that this may decrease their risk of cardiovascular disease.

By Liz Highleyman

Chronic hepatitis C virus (HCV) infection can progress to advanced liver disease, including cirrhosis and hepatocellular carcinoma, and this may happen more rapidly in HIV/HCV coinfected individuals. But people with chronic HIV and/or HCV infection are also at higher risk for a host of other conditions not directly caused by these viruses.

Prior studies in both HIV negative and HIV/HCV coinfected populations have shown that people treated with interferon-based therapy have reduced odds of liver disease progression and liver-related death, especially if they achieve SVR, or a "cure."

At CROI, Juan Berenguer presented data showing that sustained response to hepatitis C treatment not only reduces rates of liver-related complications and death in coinfected people, but also decreases the risk of AIDS-defining conditions, AIDS-related death, and death due to other causes.

Cardiovascular disease has become an increasingly important cause of death as people with HIV live longer. A growing body of evidence suggests that chronic viral infection can trigger ongoing immune activation and inflammation that causes problems throughout the body. Among these is atherosclerosis, or "hardening of the arteries," which can lead to blockage of blood vessels causing a heart attack or stroke.

In their CROI poster, Isabel Fernandez de Castro from Istituto de Salud Carlos III in Madrid and colleagues assessed whether endothelial (blood vessel lining) dysfunction in HIV/HCV coinfected individuals is a consequence of HIV infection, HCV infection, or both.

To do this, they measured 2 blood biomarkers of endothelial injury, soluble intercellular adhesion molecule (sICAM) and soluble vascular cell adhesion molecule (sVCAM). Both substances have been linked to atherosclerosis and increased risk of cardiovascular events.
This cross-sectional study included 183 HIV/HCV coinfected patients taking combination antiretroviral therapy (ART) and 24 healthy control participants not infected with either virus. Most (75%) were men, the average age was 39 years, and 90% had a history of injection drug use.

With regard to baseline HIV status, participants had been on ART for a median duration of about 4 years, a majority had HIV RNA < 50 copies/mL, the median current CD4 cell count was 476 cells/mm3, and the median CD4 cell nadir (lowest-ever level) was 196 cells/mm3. Looking at hepatitis C status, the estimated duration of HCV infection was 21 years, about 60% had hard-to-treat HCV genotype 1, nearly one-quarter had high HCV viral load, and about one-third had advanced liver fibrosis or cirrhosis (stage F3-F4).

A total of 32 coinfected patients (17.4%) were treated with interferon-alfa (pegylated or conventional was not stated) plus ribavirin for 48 weeks.

Results

	HIV/HCV coinfected individuals had significantly higher levels of both sICAM-1 and sVCAM-1 compared with the uninfected control group.
	Patients with HCV genotype 1, advanced fibrosis (stage F3 or higher), and moderate-to-severe histological activity (grade A2 or higher) had the highest sICAM-1 and sVCAM-1 levels.
	In a univariate (single factor) analysis, elevated sICAM-1 and sVCAM-1 levels were significantly associated with CD4 cell count, time on ART, insulin resistance, HCV genotype 1, and advanced fibrosis.
	In a multivariate analysis controlling for other factors, only HCV genotype 1 and advanced fibrosis remained significant predictors of elevated sICAM-1.
	These same 2 factors plus longer time on ART were significantly associated with elevated sVCAM-1.
	sICAM-1 and sVCAM-1 levels were also positively correlated with elevated levels of circulating liver enzyme (ALT, AST, and alkaline phosphatase).
	Looking at hepatitis C treatment response, non-responders had significantly higher sICAM-1 and sVCAM-1 levels.
	Patients who achieved SVR had significantly reduced sICAM-1.

"HIV and HCV coinfection induces alterations in plasma endothelial adhesion molecules," the investigators concluded. "Therefore, the cardiovascular risk is increased in HIV/HCV coinfected patients in an advanced stage of chronic hepatitis C infection."

Instituto de Salud Carlos III, Madrid, Spain; Hosp Univ Gregorio Marañon, Madrid, Spain.

2/23/10

Reference
I Fernández de Castro, J Berenguer, D Micheloud, and others. Hepatitis C Infection Increases Endothelial Dysfunction in HIV/HCV Co-infected Patients. 17th Conference on Retroviruses & Opportunistic Infections (CROI 2010). San Francisco. February 16-19, 2010. Abstract 667.