CROI 2012: ART Liver Toxicity is Lower with Modern Regimens, but Still a Risk for HIV/HCV Coinfected

Liver toxicity related to antiretroviral therapy (ART) has become less common in recent years thanks to development of better tolerated drugs and improved understanding of how to use them. But HIV positive people coinfected with hepatitis C remain at higher risk, researchers reported at the 19th Conference on Retroviruses and Opportunistic Infections (CROI 2012) this month in Seattle.alt

Hepatotoxicity is a known side effect of certain antiretroviral drugs. The NRTIs didanosine (ddI; Videx) and stavudine (d4T; Zerit) can cause liver steatosis and enlargement related to mitochondrial toxicity, the NNRTI nevirapine (Viramune) can cause hypersensitivity reactions that involve the liver, and protease inhibitors (especially ritonavir, or Norvir) can lead to liver injury signaled by elevated alanine aminotransferase  (ALT) enzyme levels. People with pre-existing liver disease -- including viral hepatitis -- are more prone to drug-related liver toxicity.

As HIV treatment has evolved over the past 2 decades, drugs have become more effective, easier to tolerate, and more convenient. Mark Hull from the British Columbia Centre for Excellence in HIV/AIDS in Vancouver and colleagues

Looked at the association between time of ART initiation and hepatotoxicity, and its relation to hepatitis C virus (HCV) status.

This analysis included 748 treatment-naive patients enrolled in the British Columbia Drug Treatment Program who started combination ART between 1997 and 2009. Most (91%) were men, the median age was 42 years, 24% were injection drug users, and 26% were HIV/HCV coinfected. All had normal ALT at baseline and at least 12 months of follow-up laboratory results.

The researchers divided participants into 3 groups based on when they started HIV treatment:

Hepatotoxicity was defined as ALT rising to more than 5 times the baseline level. Incidence rates of liver toxicity were determined for each time period, according to HCV status.


Based on these findings, Hall's team concluded, "Incidence of hepatotoxicity has diminished in the modern combination ART era, but remains significantly higher in those with HCV coinfection."

"Early HCV therapy may serve to decrease the risk of hepatotoxicity following combination ART initiation," they suggested.

Studies have shown that coinfected people who achieve sustained virological response to hepatitis C treatment -- generally regarded as a cure -- are less likely to experience ART-related hepatotoxicity than non-responders with persistent HCV infection.

Although the researchers recommended that coinfected patients "should be assessed for consideration of HCV therapy prior to combination ART initiation as a means of decreasing subsequent combination ART-related hepatotoxicity," many experts favor treating HIV first or simultaneously, since people with well-controlled HIV and higher CD4 cell counts respond better to hepatitis C treatment.



M Hull, W Zhang, B Yip, J Montaner, et al. Initiation of ART in the Modern Era Is Associated with Decreased Risk of Hepatotoxicity in HIV/HCV Co-infected Patients. 19th Conference on Retroviruses and Opportunistic Infections (CROI 2012). Seattle, WA. March 5-8, 2012. Abstract 778.