Reuters Health Information (2010-06-23): Ribavirin causing mitochondrial toxicity in patients with HIV/HCV is a good sign: study
Ribavirin causing mitochondrial toxicity in patients with HIV/HCV is a good sign: study
Last Updated: 2010-06-23 17:19:42 -0400 (Reuters Health)
NEW YORK (Reuters Health) - In HIV patients being treated with ribavirin for hepatitis C, mitochondrial toxicity might actually be a good sign. It's associated with higher rates of sustained virologic response, say researchers from Austria.
"Mitochondrial toxicity is not necessarily a bad thing to happen during antiviral therapy for hepatitis C since it was not detrimental to our patients in any way," said senior author Dr. Markus Peck-Radosavljevic from Medical University of Vienna in e-mail to Reuters Health. Instead, he said, it could be a marker of adequate exposure to ribavirin.
In 48 patients infected with both viruses, Dr. Peck-Radosavljevic and colleagues studied the incidence of mitochondrial toxicity and hemolytic anemia during concomitant therapy with HAART and pegylated-interferon alpha (PEG-IFN) plus ribavirin. They also studied another 16 coinfected patients who were not receiving HAART.
During anti-HCV therapy with PEG-IFN plus ribavirin, patients with and without HAART had higher venous lactate levels (a marker of mitochondrial toxicity), although the increases were greater in patients with concomitant HAART, the authors report in a study published online May 20th in The Journal of Infectious Diseases.
By week 4, there was a significant correlation of higher doses of ribavirin and greater increases in venous lactate levels, but this association disappeared after week 24, when there was a dosage reduction of ribavirin for patients with HCV genotypes 1 and 4.
Fourteen patients developed asymptomatic hyperlactatemia. Lactate acidosis developed in only 1 patient who was treated with HAART and high-dose ribavirin. Nine patients who received high-dose ribavirin had severe weight loss.
Rates of hepatic steatosis tended to decrease among patients who received HAART and low-dose ribavirin (from 67% at baseline to 40% after treatment) and to increase in patients who received HAART and high-dose ribavirin (from 36% to 56%).
Patients who developed mitochondrial toxicity during treatment with PEG-IFN plus ribavirin had significantly higher ribavirin response rates at week 4 (51%) compared to patients without mitochondrial toxicity (21%; p = 0.015). Also, sustained virologic responses were more common in patients who had mitochondrial toxicity events than in those who didn't (73% vs 44%; p = 0.031).
"This has the potential to become an interesting tool for tailoring ribavirin dosages," the investigators say. Mitochondrial toxicity might eventually be used to titrate the dose of ribavirin prospectively.
"Adjusting the ribavirin-dose according to plasma levels has already been shown to be an effective means of getting optimal response, but this is technically demanding and not widely available," Dr. Peck-Radosavljevic said. "Instead, ribavirin dose could be titrated according to lactate levels, which are much easier to obtain."
As for treatment, he advises: "Do not be afraid of treating HIV-HCV coinfected patients under HAART with full-dose PEG-IFN/ribavirin just like you would treat any HCV-monoinfected patient."
The study was supported by Roche, which markets ribavirin. Dr. Peck-Radosavljevic and 2 of the other 8 authors reported having received research support, speaker fees, and/or travel grants from Roche.
J Infect Dis 2010;202:156-160.