Boceprevir and Antiretroviral Pharmacokinetic Interactions in HIV/HCV Co-infected Persons: AIDS Clinical Trials Group Study A5309s.

TitleBoceprevir and Antiretroviral Pharmacokinetic Interactions in HIV/HCV Co-infected Persons: AIDS Clinical Trials Group Study A5309s.
Publication TypeJournal Article
Year of Publication2017
AuthorsKiser JJ, Lu D, Rosenkranz SL, Morse GD, DiFrancesco R, Sherman KE, Butt AA
Corporate AuthorsACTG A5309s study team
JournalDrugs R D
Volume17
Issue4
Pagination557-567
Date Published2017 Dec
ISSN1179-6901
Abstract

OBJECTIVE: The objective of this study was to determine the magnitude of drug interactions between the hepatitis C virus (HCV) protease inhibitor boceprevir (BOC) and antiretroviral (ARV) agents in persons with HIV/HCV co-infection.

METHODS: Participants taking two nucleos(t)ide analogs with either efavirenz, raltegravir, or ritonavir-boosted atazanavir, darunavir, or lopinavir underwent intensive pharmacokinetic (PK) sampling for ARV 2 weeks before (week 2) and 2 weeks after initiating BOC (week 6) and for BOC at week 6. Geometric mean ratios (GMRs) and 90% confidence intervals (CIs) were used to compare ARV PK at weeks 2 and 6 and BOC PK at week 6 to historical data (HD) in healthy volunteers and HCV mono-infected patients.

RESULTS: ARV PK was available for 55 participants. BOC reduced atazanavir and darunavir exposures by 30 and 42%, respectively. BOC increased raltegravir maximum concentration (C) by 71%. BOC did not alter efavirenz PK. BOC PK was available for 53 participants. BOC exposures were similar in these HIV/HCV co-infected participants compared with HD in healthy volunteers, but BOC minimum concentrations (C) were lower with all ARV agents (by 34-73%) compared with HD in HCV mono-infected patients.

CONCLUSIONS: Effects of BOC on ARV PK in these HIV/HCV co-infected individuals were similar to prior studies in healthy volunteers. However, some differences in the effects of ARV on BOC PK were observed, indicating the magnitude of interactions may differ in HCV-infected individuals versus healthy volunteers. Findings highlight the need to conduct interaction studies with HCV therapies in the population likely to receive the combination.

DOI10.1007/s40268-017-0205-9
Alternate JournalDrugs R D
PubMed ID28875397
PubMed Central IDPMC5694418
Grant ListUM1 AI069494 / AI / NIAID NIH HHS / United States
UM1 AI069503 / AI / NIAID NIH HHS / United States
UM1 AI069501 / AI / NIAID NIH HHS / United States
UL1 TR000445 / TR / NCATS NIH HHS / United States
UL1 TR000005 / TR / NCATS NIH HHS / United States
UL1 RR024153 / RR / NCRR NIH HHS / United States
UM1 AI069432 / AI / NIAID NIH HHS / United States
UM1 AI069471 / AI / NIAID NIH HHS / United States
U01 AI069439 / AI / NIAID NIH HHS / United States
UL1 RR024156 / RR / NCRR NIH HHS / United States
UL1 TR000042 / TR / NCATS NIH HHS / United States
UM1 AI069439 / AI / NIAID NIH HHS / United States
UM1AI106701 / / University of Buffalo Pharmacology Specialty Laboratory / United States
UM1 AI069412 / AI / NIAID NIH HHS / United States
UM1 AI069470 / AI / NIAID NIH HHS / United States
U01 AI069501 / AI / NIAID NIH HHS / United States
UM1AI068636 / / National Institute of Allergy and Infectious Diseases / United States
UM1 AI069481 / AI / NIAID NIH HHS / United States
UL1 TR000439 / TR / NCATS NIH HHS / United States
UL1 TR001082 / TR / NCATS NIH HHS / United States
UL1 TR000040 / TR / NCATS NIH HHS / United States
UM1 AI069511 / AI / NIAID NIH HHS / United States
U01 AI069494 / AI / NIAID NIH HHS / United States
UM1AI68634 / / Statistical and Data Management Center / United States
U01 AI069471 / AI / NIAID NIH HHS / United States
K23DK082621 / / National Institute of Diabetes and Digestive and Kidney Diseases / United States