Colorado Chapter of the National Hemophilia Foundation

In February 2012, Merck informed physicians in the U.S. of the results of a pharmacokinetic study assessing interactions between Victrelis™, the company’s protease inhibitor (PI) drug boceprevir for the treatment of the hepatitis C virus (HCV), and certain HIV antiretroviral (ARV) drugs.

In May of 2011, two PIs were approved by the U.S. Food and Drug Administration for use in HCV genotype 1 patients: Victrelis and Vertex Pharmaceutical’s telaprevir (Incivek™). These drugs help augment the standard HCV combination therapy of interferon and ribavirin.

According to a Merck press release, administration of Victrelis with the ARV ritonavir (Norvir®) in combination with atazanavir (Reyataz®) or darunavir (Prezista®), or with lopinavir/ritonavir (Kaletra®) resulted in reduced concentrations of both classes of drugs in the blood. Merck stated that these drug interactions may be “clinically significant” for patients infected with both chronic HCV and HIV, decreasing the effectiveness of the medicines when administered together. Merck has shared these data with regulatory authorities in the countries where Victrelis is approved or under review. It is now up to these agencies to review the data and consider changes in labeling.

In December 2011, a group of Maryland physicians published provisional treatment guidelines for the use of PIs in patients co-infected with HIV and HCV in the journal Clinical Infectious Diseases. Although the new PIs were not approved for use in co-infected patients, interim data showed that these patients had a higher virological response when a PI was added to peginterferon/ribavirin and that adverse events were no different than patients with HCV alone. Physicians are interested in the possible off-label use of these drugs in co-infected patients because: their liver disease progression is more accelerated; pegylated interferon/ribavirin is less effective for them; and liver transplantation is neither highly successful nor widely available to them.

“Though Victrelis™ is not indicated for the treatment of chronic HCV in those who are also infected with HIV, we recognize that some physicians have prescribed or may be considering prescribing Victrelis™ for patients taking ritonavir-boosted HIV protease inhibitors. We felt it was important to share these data as part of our commitment to patient safety and transparency,” said Robin Isaacs, vice president, Clinical Research, Infectious Diseases, Merck Research Laboratories. “What is most critical to remember is that all patients taking medicines for chronic HCV or HIV, or both, should not discontinue their medication regimens without first consulting with their physicians.”

Source: Merck press release dated February 8, 2012

According to a recent study from the University of California at San Francisco (UCSF), tenofovir, one of the more effective and commonly prescribed antiretroviral therapies for HIV/AIDS, is associated with significant and progressive risk of kidney damage and chronic kidney disease. The lead investigator of the study was Rebecca Scherzer, PhD, a researcher and statistician at the San Francisco VA Medical Center (SFVAMC) and UCSF.

Scherzer and her colleagues analyzed the electronic health records of 10,841 HIV-infected veterans who began treatment with antiretroviral therapies between 1997 and 2007. The mean age of the subjects was 46; 98% were men. The researchers found that this use of tenofovir (Viread®) was associated with a higher risk of kidney disease, even in individuals who had no pre-existing risk factors for it. Tenofovir, which comes in pill form, can be taken alone or in combination with other HIV antiretroviral drugs. It is a first-line therapy for patients with HIV, favored for its potency, easy dosing and ability to control viral load.

Investigators found that each year of treatment with tenofovir was associated with a 34% rise in risk for proteinuria, protein in the urine (a key indicator of kidney damage); an 11% risk of a rapid decline in kidney function; and a 33% increased risk of developing chronic kidney disease. These results were independent of other factors, including age and whether the veteran had high blood pressure, diabetes or hepatitis C. After they stopped taking tenofovir, patients remained at elevated risk for kidney complications for six months to one year.

The authors reported that these damaging side effects may be irreversible, prompting them to stress the importance of closely observing patients on an ongoing basis. “The best strategy right now is to work with your health care provider to continually monitor for kidney damage,” said coauthor Michael G. Shlipak, MD, MPH, chief of general internal medicine at SFVAMC, and professor of medicine and epidemiology and biostatistics at UCSF. “Early detection is the best way to determine when the risks of tenofovir begin to outweigh the benefits.”

The researchers acknowledge that one of the limitations of the study was a short treatment period and follow-up after patients stopped taking tenofovir. Further research is needed to corroborate their findings.

The study, “Association of Tenofovir Exposure with Kidney Disease Risk in HIV Infection,” was published online by the journal AIDS on February 4, 2012.

Source: UCSF news release dated February 10, 2012