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HCV PI Boceprevir Lowers Levels of Three Key HIV PIs
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19th Conference on Retroviruses and Opportunistic Infections, March 5-8, 2012, Seattle
Mark Mascolini
Boceprevir, the recently licensed HCV protease inhibitor (PI), lowered concentrations of three ritonavir-boosted HIV PIs--atazanavir, darunavir, and lopinavir--in a pharmacokinetic study that enrolled 39 healthy volunteers [1].
The FDA advises that "healthcare professionals who have started patients infected with both chronic HCV and HIV on Victrelis [boceprevir] and antiretroviral therapy containing a ritonavir-boosted protease inhibitor should closely monitor patients for HCV treatment response and for potential HCV and HIV virologic rebound" [2].
In a letter to healthcare professionals, the manufacturer cautioned that "these drug interactions may be clinically significant for patients infected with both chronic HCV and HIV by potentially reducing the effectiveness of these medicines when coadministered [3]." The statement stressed that "Merck does not recommend the coadministration of Victrelis [boceprevir] and ritonavir-boosted HIV protease inhibitors."
Boceprevir and telaprevir, another HCV PI, won FDA approval in 2011 for use with pegylated interferon and ribavirin in adults with genotype 1 chronic HCV and compensated liver disease. Neither boceprevir nor telaprevir is licensed for use in people coinfected with HCV and HIV.
In work reported separately by NATAP, a placebo-controlled trial of boceprevir plus pegylated interferon and ribavirin for 100 people coinfected with genotype 1 HCV and HIV logged undetectable HCV RNA levels in 39 of 61 people (64%) randomized to boceprevir and 10 of 34 (29%) randomized to placebo at week 48 [4]. All study participants had an HIV load below 50 copies when the trial began.
The pharmacokinetic study involved 39 healthy volunteers between 19 and 55 years old [1]. No one had HIV infection, and none tested positive for hepatitis B surface antigen or HCV antibodies. Everyone took boceprevir at the standard dose of 800 mg three times daily on study days 1 to 6 then took no drugs for 4 days. On days 10 to 31 study participants took 300/100 mg of atazanavir/ritonavir once daily, 400/100 mg of lopinavir/ritonavir twice daily, or 600/100 mg of darunavir/ritonavir twice daily. On days 25 through 31, they also took the standard dose of boceprevir.
Taking boceprevir with an HIV PI lowered trough concentrations by an average 49% for atazanavir, 43% for lopinavir, and 59% for darunavir. Average area under the concentration-time curve (AUC) fell 35% for atazanavir, 34% for lopinavir, and 44% for darunavir. Respective average drops in peak concentrations were 25% for atazanavir, 30% for lopinavir, and 36% for darunavir.
Taking atazanavir with boceprevir did not alter boceprevir AUC. But lopinavir cut boceprevir AUC 45%, and darunavir lowered boceprevir AUC 32%.
The FDA also issued online guidance about these findings for patients and patient advocates [5]. The agency cautioned that HIV-positive people taking boceprevir with an HIV PI should not stop taking any of their drugs without first talking to their clinician.
In a separate study involving 24 healthy volunteers, boceprevir did not affect levels of the integrase inhibitor raltegravir [6].
References
1. Hulskotte E, Feng HP, Xuan F, et al. Pharmacokinetic interaction between the HCV protease inhibitor boceprevir and ritonavir-boosted HIV-1 protease inhibitors atazanavir, lopinavir, and darunavir. 19th Conference on Retroviruses and Opportunistic Infections. March 5-8, 2012. Seattle. Abstract 771LB.
2. US Food and Drug Administration. FDA drug safety communication: important drug interactions between Victrelis (boceprevir) and ritonavir-boosted human immunodeficiency virus (HIV) protease inhibitor drugs. February 8, 2012. http://www.fda.gov/Drugs/DrugSafety/ucm291119.htm.
3. Reddy SSK. Merck & Co, Inc. Important drug warning. February 6, 2012. http://www.merck.com/newsroom/pdf/FINAL_DHCP_2_6_2012.pdf.
4. Sulkowski M, Pol S, Cooper C, et al. Boceprevir + pegylated interferon + ribavirin for the treatment of HCV/HIV-co-infected patients: end of treatment (week 48) interim results. 19th Conference on Retroviruses and Opportunistic Infections. March 5-8, 2012. Seattle. Abstract 47.
5. US Food and Drug Administration. Victrelis (boceprevir) and ritonavir-boosted HIV protease inhibitor drugs--drug interactions. For patients and patient advocates. http://www.fda.gov/ForConsumers/ByAudience/ForPatientAdvocates/ucm291389.htm.
6. de Kanter C, Blonk M, Colbers A, Fillekes Q, Schouwenberg B, Burger D. The influence of the HCV protease inhibitor boceprevir on the pharmacokinetics of the HIV integrase inhibitor raltegravir. 19th Conference on Retroviruses and Opportunistic Infections. March 5-8, 2012. Seattle. Abstract 772LB.
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