Caution is recommended when using this combination due to the wide confidence intervals
Pharmacokinetics of asunaprevir, daclatasvir and raltegravir in HCV/HIV co infected patients, with or without cirrhosis, and previously null responders to pegylated interferon + ribavirin (ANRS HC30 - QUADRIH study).
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Study Design
The pharmacokinetics (PK) of asunaprevir (ASV), daclatasvir (DCV) and raltegravir (RAL) in combination with peg-interferon and ribavirin (peg-RBV) were evaluated in a PK sub-study among HIV/HCV coinfected patients enrolled in the ANRS HC30 study. The first 20 patients (previous null responders to peg-RBV) were all on RAL-based antiretroviral therapy (RAL 400mg bid) combined with tenofovir and either emtricitabine or abacavir, or emtricitabine + enfuvirtide. Eleven subjects had HCV genotype was 1a and 9 subjects had HCV genotype 4.
Participants were treated with peg-RBV for 4 weeks, then ASV and DCV were added for 24 additional weeks. ASV was dosed as 100mg bid and DCV as 60mg QD. Blood samples for PK analysis were drawn during a dosing interval at day 0 before, and 8 weeks after peg-RBV initiation.
Study Results
The PK data for RAL were only reported for 7 subjects, all of who had liver cirrhosis. RAL PK data for the non-cirrhotic participants will be presented later.
Using Least Squares Mean (LSM) ratios and corresponding 90% confidence intervals (90% CI), the Cmax, Cmin and AUC for RAL when coadministered with ASV + DCV and peg-RBV were 0.92 (0.48-1.76), 0.91 (0.30-2.75) and 0.77 (0.41-1.44), respectively.
The investigators reported that the ASV and DCV exposure in this HIV/HCV population was in the same range as in mono-infected patients.
All 20 participants had plasma HIV-RNA less than 50 copies/ml at week 8.
The LSM ratios for RAL only represent the magnitude of PK change in patients with liver cirrhosis, and cannot be extrapolated to other populations.
Caution is warranted when using this combination due to the very wide confidence intervals reported.
Study Conclusions
**The manufacter reports that they do not expect an interaction between raltegravir and daclatasvir, and that no dosage adjustment is required for either agent. However, this interaction has not been formally studied.
**Since ASV and DCV are also being studied in combination with BMS-791325 in the HIV/HCV population, it is prudent to consider the drug interaction profile of BMS-791325 too, which was not included in this study.
References
Taburet A, Piroth L, Paniez H. Pharmacokinetics of asunaprevir, daclatasvir and raltegravir in hcv/hiv co infected patients, with or without cirrhosis, and previously null responders to pegylated interferon + ribavirin (anrs hc30 -. Hepatology. 2014; S1: 1156A.
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