IAS: Atazanavir safe and effective in HCV-coinfected patients with cirrhosis

The protease inhibitor, atazanavir (Reyataz) is safe and effective in HIV-positive patients with liver cirrhosis, according to a retrospective Spanish study presented as a poster to the recent International AIDS Society Conference on HIV Pathogenesis, Treatment and Prevention in Sydney.

The investigators, from the Hospital Ramon y Cajal in Madrid, found that patients with cirrhosis who received atazanavir had both an immunological and virological response to the drug, but did not experience any clinically significant liver-related side-effects.

Large numbers of HIV-positive patients are coinfected with either hepatitis B virus and/or hepatitis C virus, and liver-related causes of death, often caused by hepatitis coinfections, are an increasingly important cause of mortality amongst HIV-infected individuals.

There are, however, limited data about the safety and effectiveness of antiretroviral drugs in patients with advanced liver disease. This is because studies into the safety and efficacy of drugs normally exclude patients with cirrhosis.

Although patients coinfected with hepatitis C virus who received atazanavir in clinical trials showed no evidence of significant liver-related toxicity, there are no data about the safety of the drug in patients with advanced liver disease. Atazanavir therapy is associated with a yellowing of the skin in some patients as the drug can increase levels of bilirubin. Although this is not medically dangerous, some patients find it distressing and stigmatising.

Accordingly, investigators in Madrid undertook a single-site study to assess the immunological and virological efficacy of atazanavir with or without ritonavir boosting in patients with compensated or decompensated cirrhosis. They all examined ALT and bilirubin levels to see if the drug in its boosted or unboosted forms was associated with any significant liver-related side-effects.

The study involved patients who received treatment between June 2003 and April 2007. Follow-up data for one year were analysed. A total of 34 individuals were included in the study. All were coinfected with hepatitis C virus, seven had decompensated cirrhosis and 27 had compensated cirrhosis.

The majority of patients were male, injecting drug users, and had extensive prior experience of antiretroviral therapy. Mean CD4 cell count before the initiation of atazanavir therapy was 214 cells/mm³ amongst patients with decompensated cirrhosis and 325 cells/mm³ with compensated cirrhosis. Approximately 40% of patients had an undetectable viral load.

Ritonavir-boosted atazanavir was taken by 71% of patients with decompensated cirrhosis and by 78% of those with compensated cirrhosis. Anti-hepatitis C treatment was taken at the same time as atazanavir-containing HIV therapy by 14% of those with decompensated cirrhosis and 59% of those with compensated cirrhosis.

At baseline, 71% of those with decompensated cirrhosis had significantly elevated ALTs (above 40 IU/ml), as did 90% of those with compensated cirrhosis. Total bilirubin above 1.2mg/dl was present at baseline in 57% of those with decompensated cirrhosis and 59% of those with compensated cirrhosis.

After a year of treatment with boosted or unboosted atazanavir the number of patients with decompensated cirrhosis with a viral load below 50 copies/ml increased to 80%, and all patients with compensated cirrhosis achieving this outcome (p = 0.006). Median CD4 cell count increased to a median of 450 cells/mm³ amongst patients with decompensated cirrhosis and to a median of 220 cells/mm³ amongst those with compensated cirrhosis. These increases were statistically significant (p = 0.04).

There were no significant changes in either ALT levels or bilirubin amongst patients with decompensated cirrhosis. Amongst patients with compensated cirrhosis, ALT levels did not change significantly, but mean bilirubin increased from a baseline of 1.7mg/dl to a mean of 2.4mg/ml, a statistically significant change (p = 0.035).

“In this retrospective cohort of patients with either compensated or decompensated liver cirrhosis, atazanavir boosted or unboosted has been safe and well tolerated”, comment the investigators, who add, “the efficacy of atazanavir in cirrhotic patients is high, even in this highly pre-treated group of patients.”