CROI 2011: Interactions of HIV Meds with HCV drugs Telaprevir and Boceprevir

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New HCV antiviral drugs can interact with some antiretroviral drugs for HIV, but others are not affected and HIV/HCV coinfected patients can be treated successfully with minimal dose adjustments.

Direct-acting antiviral drugs that target various steps of the hepatitis C virus (HCV) lifestyle are expected to usher in a new treatment paradigm. The first such medications -- the HCV protease inhibitors boceprevir and telaprevir -- are likely to be approved this summer.

A substantial number of HIV positive people are coinfected with HCV. To date, most trials of new anti-HCV agents have looked at HCV monoinfected people, but coinfected people have a pressing need for better treatments. The first data from a trial of telaprevir in HIV/HCV coinfected patients was presented this month at the 18th Conference on Retroviruses and Opportunistic Infections (CROI 2011) in Boston.

Researchers at the conference also presented findings from studies looking at interactions between HCV and HIV drugs.

Many antiretroviral drugs are processed by the CYP450 enzyme system in the liver. As such, they can speed up or slow down processing of other agents that use the same enzymes, potentially leading to sub-therapeutic drug levels or intensified side effects.

Boceprevir

Edward O'Mara from Merck presented data on interactions between boceprevir and various drugs in healthy volunteers. The researchers looked at a set of "probe" drugs and medications likely to be co-administered to patients with hepatitis C.

Results

Based on these findings, the researchers suggested that CYP3A4 and P-glycoprotein (another drug processing pathway) "do not contribute substantially" to boceprevir metabolism or elimination. Increased midazolam levels indicate that boceprevir is a strong reversible CYP3A4 inhibitor.

The investigators concluded that no boceprevir dose adjustment is needed when co-administered with pegylated interferon or tenofovir, but the clinical implications of reduced boceprevir trough concentrations when taken with efavirenz are unclear. Boceprevir is not expected to decrease the effectiveness of oral contraceptives. Studies of boceprevir interactions with ritonavir-boosted HIV protease inhibitors are forthcoming.

Telaprevir

Rudolph van Heeswijk from Tibotec followed with data on interactions between telaprevir and antiretroviral drugs in healthy volunteers.

Lopinavir/ritonavir (Kaletra), ritonavir-boosted atazanavir (Reyataz), boosted darunavir (Prezista), and boosted fosamprenavir (Lexiva) are both substrates and inhibitors of the CYP3A enzyme, as is telaprevir, the investigators noted as background. Efavirenz is an inducer of CYP3A.

Results

Based on these findings, researchers chose 750 mg 3-times-daily telaprevir plus atazanavir/ritonavir, or telaprevir 1125 mg 3-times-daily with efavirenz as regimens to evaluate in clinical trials of HIV/HCV coinfected patients.

At a CROI press conference discussing the first data from such a trial, Joseph Eron form the University of North Carolina stated that given the data so far, he would only feel comfortable giving telaprevir in combination with atazanavir or efavirenz; lead investigator Mark Sulkowski from Johns Hopkins concurred.

Investigator affiliations:

Abstract 118: Merck & Co, Inc, Kenilworth, NJ.

Abstract 119: Tibotec BVBA, Beerse, Belgium; Vertex Pharmaceuticals Inc, Cambridge, MA.

3/22/11

This article was amended on 3/25/11 to correct an inaccuracy.

References

C Kasserra, E Hughes, M Treitel, et al. Clinical Pharmacology of BOC: Metabolism, Excretion, and Drug-Drug Interactions. 18th Conference on Retroviruses and Opportunistic Infections (CROI 2011). Boston. February 27-March 2, 2011. Abstract 118.

R van Heeswijk, A Vandevoorde, G Boogaerts, et al. Pharmacokinetic Interactions between ARV Agents and the Investigational HCV Protease Inhibitor TVR in Healthy Volunteers. 18th Conference on Retroviruses and Opportunistic Infections (CROI 2011). Boston. February 27-March 2, 2011. Abstract 119.