The boceprevir label will be updated to reflect these drug interactions. Another HCV PI, telaprevir (Incivek, Vertex Pharmaceuticals Inc.), already carries warnings about drug interactions with HIV PIs.
“There has been considerable concern about the off-label use of these drugs and how they are used in patients with retroviral infections,” said Andrew Talal, MD, MPH, associate professor of medicine and associate medical director, Center for the Study of Hepatitis C, Weill Cornell Medical College, New York City. “I am pleased by the release of these data.”

Data presented on March 6 at the 19th Conference on Retroviruses and Opportunistic Infections (CROI) from researchers at Merck (Hulskotte E et al, paper 771LB) support the FDA action.

 Investigators evaluated drug interactions between boceprevir and ritonavir-boosted HIV PIs in 39 healthy adults. Blood samples were analyzed for pharmacokinetic characteristics of HIV PIs, ritonavir and boceprevir. The researchers found that boceprevir in combination with ritonavir-boosted atazanavir, darunavir and lopinavir resulted in reduced steady-state exposures of the HIV medications. Darunavir and lopinavir, but not atazanavir, lowered boceprevir exposure.

However, another study, presented on the same day at CROI (Sulkowski M et al, oral abstract Q-175), came to a different conclusion. This study evaluated the efficacy of boceprevir in patients co-infected with HIV and HCV genotype 1 who were previously untreated for HCV. Patients were treated with HIV PIs and also received boceprevir in combination with peginterferon alfa-2b/ribavirin (B/PR; n=64) or peginterferon alfa-2b/ribavirin (PR; n=34) alone. In an interim analysis, sustained virologic response at week 12 was achieved in 61% of patients in the B/PR group compared with 27% of patients in the PR group. The rates of HIV breakthrough (defined as HIV RNA >50 copies/mL at two consecutive visits) were 4.7% (three of 64) for patients who received boceprevir and 11.8% (four of 34) for those who did not.

“Although this study included a small number of patients, it did not demonstrate an increased rate of HIV breakthrough in patients receiving boceprevir plus HIV protease inhibitors compared with subjects receiving protease inhibitors alone,” said Kristen Marks, MD, assistant professor of medicine, Division of Infectious Diseases, Weill Cornell Medical College, New York City, and investigator, Cornell Clinical Trials, who was not involved in the study. “However, further study is needed to determine if HCV and HIV protease inhibitors can be safely used together.”

Dr. Talal said he would hold off initiating combination therapy with boceprevir and ritonavir-boosted HIV PIs in a patient with HCV–HIV co-infection who had not already been started on such therapy. As for patients who have already been started on the combination, the FDA alert recommends they should be closely monitored for HCV treatment response and potential HCV and HIV virologic rebound.

Dr. Marks said that she would make decisions about whether to continue treatment with boceprevir and a ritonavir-boosted HIV PI on a case-by-case basis.
“For example, if a patient has been on combination therapy for half a year and is doing well with respect to both HIV and HCV, I would leave them on it,” she said.