HIV Physicians Are Cautiously Optimistic About Boceprevir, Telaprevir For HIV-HCV Co-Infected Patients

Courtney McQueen from The AIDS Beacon, interviews Dr. Kenneth Mayer from Brown University's HIV program and Dr. Bruce Bacon ce Bacon,co-director of the Liver Center at St. Louis University Medical School on the use of Telaprevir and Boceprevir in co-infected patient. It appears both are cautiously hopeful about the use of either drugs in the co-infected setting, but need to fully understand the ramifications of the final data set, that should arrive in June 2012 for telaprevir and November 2012 for boceprevir. The largest cause for caution are the known drug interactions with many of the currently marketed antiretrovirals


HIV Physicians Are Cautiously Optimistic About Boceprevir, Telaprevir For HIV-HCV Co-Infected Patients
By Courtney McQueen
Published: May 6, 2011 6:02 pm

Last week an advisory panel to the U.S. Food and Drug Administration recommended that boceprevir and telaprevir be approved for the treatment of hepatitis C. For people with HIV and hepatitis C co-infection, the new drugs are an exciting development; however, a number of studies still need to be completed before the drugs are considered for people with HIV.

“It has the potential to revolutionize care, but I think it’s just the beginning of the journey,” said Dr. Kenneth Mayer, a professor of medicine at Brown University, director of the Brown University AIDS Program, and medical research director at Fenway Community Health. Dr. Mayer was not involved with development of either of the drugs.

Dr. Mayer, who has been seeing HIV and AIDS patients since the beginning of the epidemic, thought the early results for both drugs are promising. However, he also thought a lot more research needs to be done before clinicians can feel comfortable prescribing the drugs to people with HIV.

“The vast majority of the studies so far are in mono-infected individuals [people with hepatitis C only], so I think there’s a bunch of questions that have to be answered before we’re sure of how to use these drugs best for people with HIV,” he said.

If the Food and Drug Administration (FDA) approves the drugs, they could be available to patients as soon as late May. Although the FDA is not required to follow the recommendations of its advisory committees, it usually does.

For People With HIV, Boceprevir And Telaprevir Clinical Trials Are Still In Early Stages

The approval recommendations from last week are based on Phase 3 clinical trials in people infected only with hepatitis C virus (HCV). The trials showed that adding boceprevir or telaprevir to standard HCV treatment raised cure rates from about 40 to 45 percent to about 65 to 80 percent.

Standard HCV treatment consists of 48 weeks of ribavirin (Rebetol, Copegus) plus Pegasys (pegylated interferon alfa-2a) or PegIntron (pegylated interferon alfa-2b). Typically, standard HCV treatment is less effective in people who are also infected with HIV (see related AIDS Beacon news).

For people with HIV, the benefits of the new drugs are not clear yet. Both drugs are currently in Phase 2 clinical trials for people who are co-infected with HIV and HCV, with estimated trial completion dates of June 2012 for telaprevir and November 2012 for boceprevir.

Dr. Bruce Bacon, a professor of internal medicine and co-director of the Liver Center at St. Louis University Medical School, was involved in clinical trials for both drugs and expressed optimism about their success in co-infected patients.

“Definitely the cure rates, or sustained virologic response, for co-infected patients will be significantly improved with either boceprevir or telaprevir. How much they will be improved, I don’t know yet,” he said.

Preliminary results for telaprevir were presented in March at the Conference on Retroviruses and Opportunistic Infections (see related AIDS Beacon news). Results at that time were promising; 70 percent of HIV-HCV patients receiving telaprevir in addition to standard therapy of ribavirin and Pegasys had undetectable HCV levels after four weeks, compared to 5 percent of patients receiving the placebo plus standard therapy.

Among the participants who received telaprevir for 12 weeks, 68 percent had undetectable HCV levels, compared to 14 percent of participants receiving ribavirin plus Pegasys alone. However, not all participants had reached 12 weeks of treatment by the time of the analysis.

Additionally, overall hepatitis C cure rates were not yet available. Clinicians consider a patient to be cured of hepatitis C if the virus remains undetectable for 24 weeks after stopping treatment (called a sustained virologic response).

Dr. Bacon stated that the telaprevir results should be taken with caution. “That’s pretty early data. I think it’s probably a little too early to know the significance of [the telaprevir results],” he said.

Results for boceprevir in people who are HIV-HCV co-infected are not yet available.

For people with HIV-HCV co-infection, the lack of definitive results means that some patients may need to decide whether to take the drugs when they become available, or wait until the clinical trials are complete and physicians have more information on the drugs’ efficacy and safety in people with HIV.

“If a person is not in acute need of treatment, it may be prudent to wait, to know how to best manage [treatment],” said Dr. Mayer.

“The initial guidelines will not recommend these drugs for co-infected people until there is more data, so there would also be a question of whether third party payers or insurers would reimburse for the cost of the medications, and I’m sure that the cost of the medications would be considerable,” he added.

Dr. Bacon stated that he was likely to start prescribing the drugs without waiting for all of the clinical trial results. “I have a large number of co-infected patients who are waiting for treatment, and I’m probably not going to wait until the results of all the studies are done. But I do need to make sure that I find out about the drug-drug interaction issues,” he said.

More Data Needed On Drug Interactions, Safety In People With HIV

Both Dr. Mayer and Dr. Bacon agreed that one of the main concerns for people with HIV will be the safety of the drugs and whether they interact with HIV medications.

“I’m hoping that there will be a very robust program of research for dually infected individuals, so we can get a better sense of the expanded safety profile of these drugs,” said Dr. Mayer.

Both boceprevir and telaprevir have associated side effects, such as anemia and rash (see related AIDS Beacon news). The Phase 2 trials in co-infected people should demonstrate whether these side effects are more common or more severe in people with HIV.

In addition, the clinical trials that are underway for both drugs will monitor how they interact with common HIV antiretrovirals. For example, researchers will test whether the hepatitis C drugs affect the concentrations of antiretrovirals in the bloodstream – either decreasing them, which would make them less effective against HIV, or increasing them, which could cause greater side effects.

They will also test whether the antiretrovirals, in turn, affect the hepatitis C drugs and their efficacy. If drug interactions are found, dosages of either the hepatitis C drugs or certain antiretrovirals may need to be adjusted for people with HIV.

For telaprevir, there are some preliminary indications that there might be interactions with certain antiretrovirals, namely protease inhibitors boosted with Norvir (ritonavir). It is not clear yet whether these will require dosage adjustments of either telaprevir or the protease inhibitors in patients taking these drugs.

No information is available yet on drug interactions for boceprevir.

People With HIV Should Get Tested – And Retested – For Hepatitis C

With the two new drugs potentially available in the near future, both physicians urged people with HIV to get tested for HCV so they can start treatment if necessary.

“This underscores the importance of everybody who’s HIV infected to know their hepatitis C status. If somebody has engaged in any behaviors that might put them at risk for acquiring hepatitis C, they should be retested,” said Dr. Mayer.

“Even if somebody is not going to start these medications tomorrow, we are getting into the mode where, fairly soon, we’ll be able to start treating hepatitis C earlier,” he added.

Hepatitis C is spread in much the same way as HIV – unprotected sexual intercourse, sharing of needles, and other exposures to infected bodily fluids.

Dr. Bacon said patients who are co-infected should not avoid treatment.

“If they do know that they’re co-infected, they should know that there’s something that will be better than what there used to be. They ought to see a specialist who is knowledgeable about [the new drugs], and they ought to be treated,” said Dr. Bacon.

“I think it’s a new era for hepatitis C patients, and it will be a new era for co-infected patients as well,” he added.

Next Steps For Hepatitis C Treatment

Researchers have already begun to discuss the next phases of hepatitis C treatment. Both Dr. Mayer and Dr. Bacon were optimistic about the future for people with hepatitis C and HIV-HCV co-infection.

“Hopefully in the next few years we’ll be in the position to have a lot of different choices, much in the same way that we have for HIV,” said Dr. Mayer.

Dr. Bacon agreed. “Most people feel that there will be new regimens that are going to be used, and both telaprevir and boceprevir, as first generation protease inhibitors, will be replaced by second and third generation drugs and different regimens. Hopefully interferon-free regimens,” he said.

Interferon (Pegasys or PegIntron), which is part of the current standard treatment regimen for hepatitis C, is difficult to take (it must be injected, usually once a week) and is associated with many side effects.

“I think we’re within a couple of years of having large studies with non-interferon based treatment that will be successful,” said Dr. Bacon.

Original article: http://www.aidsbeacon.com/news/2011/05/06/hiv-aids-physicians-are-cautiously-optimistic-about-boceprevir-telaprevir-for-hiv-hcv-co-infected-patients/