Treatment Interruption Spurs Fibrosis in HIV/HCV Coinfected People

SUMMARY
Stopping antiretroviral therapy led to liver fibrosis progression in HIV/HCV coinfected people, an effect that was not fully attributable to increased HIV viral load or reduced CD4 cell count.

By Liz Highleyman

Liver damage due to chronic hepatitis C virus (HCV) infection tends to progress more rapidly in HIV/HCV coinfected people compared to those with hepatitis C alone.

The SMART trial and other studies have shown that antiretroviral therapy (ART) interruption can increase the risk of non-AIDS conditions including heart, kidney, and liver disease, which researchers have linked to increased immune activation and inflammation related to resurgent HIV replication.

As described in the April 24, 2011, issue of AIDS, Julia Thorpe and fellow investigators with the Canadian Coinfection Cohort Study (CTN222) examined the effects of ART interruption on liver fibrosis progression in HIV/HCV coinfected adults.

This prospective analysis included 541 coinfected patients enrolled between 2003 and 2009. ART interruption was defined as cessation of all antiretroviral drugs for at least 14 days. Fibrosis was assessed every 6 months, and participants were followed for a median of just over 1 year.

The researchers estimated liver fibrosis using the APRI (aspartate aminotransferase-to-platelet ratio index) method, a calculation based on blood biomarkers. This method is considered less reliable than the "gold standard" of liver biopsy, and possibly also less so than the non-invasive transient elastometry (FibroScan) technique. Participants had absent or minimal fibrosis at baseline. The primary endpoint was an APRI score of at least 1.5, reflecting significant fibrosis; a score of 2.0 or greater indicates fibrosis.

Results

	53 participants (10%) interrupted ART during follow-up (including 2 people who did so twice), with a median interruption duration of 180 days.
	The same number (though not always the same 53 individuals) developed significant fibrosis during a total 760 person-years of follow-up.
	After accounting for potential confounding factors including age, sex, CD4 cell count, HIV viral load, and baseline APRI score, ART interruption had a hazard ratio of 2.52, or about a 2.5-fold increased risk of fibrosis progression.
	ART interruption also more than doubled the risk of clinical liver disease (hazard ratio 2.12), though this did not reach statistical significance likely due to small numbers.

Based on these findings, the study authors concluded, "ART interruption was associated with an increased risk of fibrosis progression in HIV/HCV coinfection that was only partially accounted for by HIV viral load and CD4 T-cell counts."

"Our findings suggest that liver disease progression observed in ART-treated coinfected patients is partly due to the consequences of treatment interruptions," they added.

"Studies to determine factors associated with antiretroviral treatment interruption in coinfected patients would be beneficial to assist clinicians in reducing treatment discontinuations, as would studies aimed at understanding the underlying mechanisms driving fibrosis in this setting," they elaborated in their discussion.

These findings support prior research indicating that early and continuous antiretroviral treatment can slow or alleviate liver damage related to chronic viral hepatitis in people with HIV.

Investigator affiliations: Department of Medicine, Divisions of Infectious Diseases/Immunodeficiency, Royal Victoria Hospital, Canada; Department of Epidemiology & Biostatistics, McGill University, Montreal, Quebec, Canada.

4/26/11

Reference
Thorpe, Juliaa; S Saeed, E Moodie, and MB Klein (for the Canadian Co-infection Cohort Study; CTN222). Antiretroviral treatment interruption leads to progression of liver fibrosis in HIV-hepatitis C virus co-infection. AIDS 25(7):967-975 (abstract). April 24, 2011.