Improved treatment coming for HIV/ HCV co-infection

DDW Daily News

Improved treatment coming for HIV/ HCV co-infection

May 22, 2012

Interim results from Phase 2b trials of direct-acting antiviral therapy in patients co-infected with HIV and HCV are showing promising results. So promising, in fact, that it may be time to alter treatment.

“We have tantalizing data from two trials,” said John Vierling, MD, FACP, professor of medicine and surgery at the Baylor College of Medicine, Houston, TX. “I would encourage enrollment in Phase 3 trials that are now open rather than individual, off-label use of these agents.”

Dr. Vierling was the lead speaker for a Monday afternoon symposium on Liver Disease in Patients with HIV Infection sponsored by the AASLD.

HCV has emerged as a significant clinical problem among patients infected with HIV, Dr. Vierling noted. About a third of HIV patients in the U.S. are coinfected with HCV.

“The success of HIV therapy in reducing viral loads and extending life has led to the recognition that liver disease is a significant comorbidity with HIV,” he said. “HCV infection, in particular, is associated with increased morbidity and mortality from liver disease in patients with HIV.”

The primary goal in treating these co-infected individuals is to prevent progression to cirrhosis. In patients who already show signs of cirrhosis, the goal is to prevent progression to liver cancer or the need for liver transplantation.

Boceprevir and telaprevir have been approved for the treatment of HCV genotype 1, which is responsible for about 75 percent of HCV infection in the U.S. and about 90 percent of HCV infection among African Americans. Trials for HIV/HCV co-infection are less advanced.

Boceprevir

An interim analysis of boceprevir plus peginterferon/ribavirin (PR) versus PR alone was reported in April. Early trials suggested that the combination is more effective than PR alone, but questions remain about the safety and efficacy of the combination.

The interim analysis assessed treatment results after 12 weeks, Dr. Vierling said. The trial was relatively small — 64 patients randomized to boceprevir/PR and 34 to PR alone. Patients in both arms were in early middle age, he said, predominantly male and white. There was a very low incidence of cirrhosis — just 3 percent in the PR arm and 6 percent in the boceprevir/PR arm.

All of the patients enrolled in the trial received at least one treatment. In the PR arm, 18 patients (53 percent) discontinued and 12 patients (35 percent) completed treatment. The other four patients crossed over to the boceprevir/PR arm after a futility analysis. In the boceprevir/PR arm, 24 patients (38 percent) discontinued and 40 (63 percent) completed treatment.

At four, eight, 12, and 24 weeks, the sustained viral response was higher in the boceprevir/PR arm. The sustained viral response rate at 12 weeks, the intended interim endpoint, was 60.7 percent in the boceprevir/ PR arm and 26.5 percent in the PR arm.

There were also three HIV breakthroughs in the boceprevir/PR arm, all of them at week 24 or later in the trial. Pharmacokinetic data show drug-drug interactions between boceprevir and multiple antiretroviral agents. It may be appropriate to adjust antiretroviral dosing to account for the interactions, Dr. Vierling said.

There were no major differences in safety profiles between the two arms, with no deaths in either arm and adverse events in 100 percent of patients in the PR arm compared to 98 percent in the boceprevir/PR arm. There were some differences in side effects but no surprises, Dr. Vierling said.

“These adverse events are not unique to the co-infected population,” he said. “They are very similar to the adverse events we see in the moninfected population.”

Telaprevir

Telaprevir plus PR showed similarly positive results compared to PR alone. Dr Vierling reviewed interim findings from the Phase 2 Study 110 trial first released in March 2012.

The Study 110 trial included patients who were on antiretroviral therapy (ART) and patients who were not on ART. Of the patients on ART, 74 percent on telaprevir showed sustained viral response at 12 compared to 45 percent of patients on PR alone. The results were similar in patients not on ART — 71 percent in the telaprevir arm showed sustained viral response compared to 33 percent for PR only. Three of the telaprevir patients showed HVC breakthrough, but there were no HIV viral load rebounds in either group.

“The rates of efficacy are quite encouraging for both of these trials, as are safety and tolerability,” Dr. Vierling said.