Coinfection

Experts Issue Provisional Guidance on New Hepatitis C Drugs for HIV/HCV Coinfected Patients

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HIV and hepatitis C virus (HCV) experts have issued preliminary recommendations for the use of the new HCV protease inhibitors boceprevir (Victrelis) and telaprevir (Incivek) for HIV/HCV coinfected patients. Though not yet FDA-approved for this group, studies to date show that the drugs improve the likelihood of a cure for coinfected as well as HCV monoinfected people.

[Editors' note (2/27/12): the preliminary recommendations have been temporarily withdrawn and removed from the Clinical Infectious Disease advance publication web section due to new data that may influence the guidance] 

Approval of the first direct-acting antiviral agents (DAAs) for HCV have ushered in a new era of treatment, but they are not yet approved for some of the most difficult-to-treat patients, including HIV positive people. HIV/HCV coinfected individuals tend to experience more rapid liver diseases progression than those with HCV alone, and they do not respond as well to interferon-based hepatitis C treatment.

A group of prominent HIV and hepatitis C researchers developed guidance for the state of Maryland, to inform coverage by its AIDS Drug Assistance Program (ADAP); the recommendations were published in the December 14, 2011, advance online edition of Clinical Infectious Diseases.

The U.S. Food and Drug Administration (FDA) approved the 2 HCV protease inhibitors for hepatitis C monoinfected people this past May. Clinical trials of the drugs in HIV/HCV coinfected patients are underway.

Interim data reported last year show that coinfected people have higher virological response rates when they add boceprevir or telaprevir to pegylated interferon plus ribavirin, and adverse events were similar to those seen in people with HCV alone. Though not yet approved for this population, clinicians may prescribe drugs "off-label" as they deem appropriate.

Recommendations

  • Pegylated interferon/ribavirin alone remains the standard of care for coinfected people with easier-to-treat HCV genotypes 2 or 3, or with genotype 4.
  • Boceprevir or telaprevir for coinfected HCV genotype 1 patients should only be used in combination pegylated interferon/ribavirin, as monotherapy can lead to drug resistance.
  • Though people with significant liver fibrosis have lower rates of response to hepatitis C therapy of any kind, they stand to benefit more from successful treatment.
  • Coinfected people considering use of boceprevir or telaprevir should have well-controlled HIV -- either with a CD4 T-cell count > 500 cells/mm3 and HIV viral load < 20,000 copies/mL if not yet on antiretroviral therapy (ART), or with undetectable HIV RNA (< 50 copies/mL) if on ART.
  • Boceprevir or telaprevir should not be given to coinfected patients unless interactions with antiretroviral agents and other necessary drugs can be ruled out or safely managed.
  • Coinfected patients taking boceprevir should either not be on ART or using a regimen containing raltegravir or a ritonavir-boosted HIV protease inhibitor -- preferably atazanavir (Reyataz) -- plus tenofovir/emtricitabine; boceprevir should not be used with NNRTIs.
  • Coinfected patients taking telaprevir should either not be on ART or receiving a regimen containing raltegravir (Isentress), boosted atazanavir, or efavirenz (Sustiva) plus tenofovir/emtricitabine (Truvada); telaprevir dose should be increased to 1125 mg if taken with efavirenz.
  • Boceprevir or telaprevir should be discontinued if HIV viral load increases by 1 log or more.
  • All hepatitis C treatment should be discontinued if HCV viral load remains above 100 IU/mL at weeks 4 and 12, or is still detectable at week 24.

The authors of the recommendations stressed that decisions about the use of boceprevir or telaprevir should be made on a patient-by-patient basis, as "the benefits of including these medications will outweigh the risks for some individuals."

In conclusion, they recommended that HIV/HCV coinfected people should be included at earlier stages of drug development "so that practical guidance can be based more on data and less on expert opinion.”

Investigator affiliations: Department of Medicine, Johns Hopkins School of Medicine, Baltimore, MD; Department of Medicine, University of California San Francisco School of Medicine, San Francisco, CA; Department of Medicine, University of Cincinnati School of Medicine, Cincinnati, OH.

1/17/12

Reference

DL Thomas, JG Bartlett, MG Peters, et al. Provisional Guidance on the Use of Hepatitis C Virus Protease Inhibitors for Treatment of Hepatitis C in HIV-Infected Persons. Clinical Infectious Diseases. December 14, 2011 (Epub ahead of print).