Very low rate of liver problems seen with Kaletra

Treatment with Kaletra (lopinavir/ritonavir) does not involve a high rate of major liver side-effects, according to an Italian study published in the September 2^nd edition of AIDS. The investigators found that, even though over 40% of the patients enrolled in their study were coinfected with hepatitis B or C virus, the incidence of a grade III or IV liver abnormality was less than one per 100 person years of follow-up.

Since effective antiretroviral therapy became available, liver-related illness has emerged as a major cause of illness and death amongst HIV-positive individuals. This is because of the high rate of viral hepatitis coinfection amongst HIV-positive patients and the hepatotoxicity which some drugs in each of the three main classes of antiretrovirals can cause.

Studies suggest that between 2 - 11% of patients taking Kaletra will develop severe hepatotoxicity. Italian investigators used data obtained from an online reporting system for severe side-effects caused by antiretrovirals (the SCOLTA project) to determine the incidence of severe (grade III and IV) liver-related side-effects in 755 patients treated with Kaletra.

A total of 44% of patients were coinfected with hepatitis B or C virus and the mean period of observation was 17 months. The total incidence of severe adverse events was 11 per 100 patient years of follow-up. There was a lower incidence of severe side-effects amongst treatment-naive patients (7 per 100 person years) compared to treatment- experienced patients (12 per 100 person years). The most common side-effects were metabolic-related events (5 per 100 person years).

The investigators then examined liver-related side effects. They observed that “hepatic toxicity was not frequent”, with an overall incidence of 0.59 per 100 person years. There was a marginally higher incidence in treatment-naive patients (0.54 per 100 person years) compared to treatment-experienced individuals (0.48 per 100 person years).

One treatment-naive and four treatment-experienced patients experienced severe liver-related events. Four of these patients were coinfected with hepatitis C virus. Two cases developed shortly after treatment was initiated, the other three after a year of therapy. In all five cases treatment had to be stopped.

“This study comprises the biggest series to date of patients treated with Kaletra and followed prospectively outside clinical trials...this HIV-positive population had a high prevalence of coinfection with hepatitis viruses”, comment the investigators. They suggest that the retrospective design of other studies could explain the apparently higher rate of hepatotoxicity they found.