Atazanavir safe and effective for HIV/HCV patients with cirrhosis

Atazanavir (Reyataz) is a safe and effective option for HIV-positive patients who are co-infected with hepatitis C virus (HCV) and who have liver cirrhosis, investigators report in an online advance publication in the journal AIDS.

“Our study demonstrated the safety and adequate tolerance of atazanavir-based regimens in HCV-HIV-1 coinfected patients, even when used in the worst clinical situations”, comment the investigators, adding “there were no episodes of hepatoxicity, and virological and immunological efficacy was adequate.”

Many patients with HIV are co-infected with hepatitis C, and liver disease is an important cause of illness and death in these patients.

The protease inhibitor atazanavir has been shown to be effective when taken as part of antiretroviral therapy in both treatment-naive and treatment-experienced individuals. The usual dose of the drug is 300mg boosted by 100mg of ritonavir (Norvir) once daily. However, the drug can cause bilirubin levels to increase, and in some patients this leads to the development of non-dangerous jaundice.

There is little information about the safety and efficacy of atazanavir when used as a component of antiretroviral therapy for co-infected patients with advanced liver disease.

Investigators in Madrid therefore performed a retrospective study involving 34 co-infected patients with cirrhosis. The patients were followed for a year and the impact of atazanavir treatment on their liver function, viral load and CD4 cell count was monitored.

Most of the patients (80%) were male, and their mean age was 43.

A quarter of patients had a Child-Pugh class B or C score – which is associated with a poorer prognosis – and 21% of patients had decompensated cirrhosis.

All but one of the patients were treatment experienced and median baseline CD4 cell count was 238 cells/mm³. On entry to the study, 41% of individuals had an undetectable viral load.

Three-quarters of patients were treated with atazanavir boosted by ritonavir. The investigators suggest that nearly a quarter of patients were treated with unboosted atazanavir because their doctors feared intolerance of ritonavir.

The patients were monitored at three-monthly intervals for one year. The median duration of atazanavir therapy was 437 days and a total of 551 person-months of treatment were available for analysis.

Therapy was well tolerated, and only six individuals stopped taking atazanavir. Two patients with advanced cirrhosis died because of gastrointestinal bleeding.

Bilirubin increased by a mean of 0.72 mg/dl. The investigators described this increase as “surprisingly mild” and only 9% of patients developed jaundice. However, higher mean increases were recorded in individuals with Child-Pugh class B or C (mean 1.03 mg/dl). No new cases of hepatic decompensation were observed during the study.

The median MELD (Model for End-stage Liver Disease) stage increased from 10.6 to 11.9 at month twelve, which was significant (p = 0.02). However, the investigators note, “no patient changed the pretreatment situation (transplant allocation) after atazanavir introduction.”

After a year of therapy with atazanavir 79% of patients had an undetectable viral load and 80% had a CD4 cell count above 200 cells/mm³.

These outcomes lead the investigators to write “the usual dose of atazanavir seems to be adequate with good tolerance and efficacy.”

They conclude, “our study emphasizes the safety of atazanavir-based regimens in HCV-HIV-1 co-infected patients with cirrohsis…boosted or unboosted atazanavir could be considered a safe option in patients with cirrhosis in the clinical setting.”