Dose Modification Not Needed in Coadministration of an HIV, HCV Tx

SAN DIEGO, CA—Coadministration of tenofovir alafenamide-based single tablet regimens for HIV with ledipasvir/sofosbuvir does not require dosage alteration, results from a medication drug association study displayed at IDWeek 2015 has appeared.

Around 33% of HIV patients have a co-contamination with hepatitis C infection (HCV). Attending utilization of antivirals to treat HCV (eg, ledipasvir) with antiretrovirals for HIV (eg, tenofovir alafenamide) may strife with medication drug communications, as ledipasvir is a P-glycoprotein (P-gp) inhibitor and tenofovir alafenamide is a P-gp substrate.

Joseph Custodio, PhD, and associates from Gilead Sciences, Inc., Foster City, CA, led studies to assess medication drug connections between tenofovir alafenamide-based regimens rilpivirine/emtricitabine/tenofovir alafenamide (R/F/TAF) or elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide (E/C/F/TAF) and the altered measurement blend of ledipasvir/sofosbuvir (LDV/SOF), a hostile to HCV operators.

Study 1 (n=42) and Study 2 (n=30) were multi-measurements, randomized, hybrid studies assessed solid volunteers that got R/F/TAF 25mg/200mg/24mg (Study 1) or E/C/F/TAF 150mg/150mg/200mg/10mg (Study 2), alone or in blend with LDV/SOF day by day with sustenance for 11 (Study 1) or 10 (Study 2) days.

Dr. Custodio and group investigated plasma convergences of rilpivirine, elvitegravir, cobicistat, emtricitabine, tenofovir alafenamide and its metabolite (TFV), ledipasvir, sofosbuvir and its metabolite (GS-331007). Pharmacokinetic parameters were figured through non-compartmental examination. Geometric minimum squares mean proportion (blend versus alone) and 90% certainty interims for the analytes' AUC, Cmax, Ctau were figured by straight blended impact displaying and contrasted with absence of change limits.

Crosswise over both studies, medications were for the most part all around endured. The GLSM and 90% certainty interims for all analytes were contained inside of the prespecified limits aside from TFV when RPV/FTC/TAF was coadministered with LDV/SOF. Another special case was seen with cobicistat when E/C/F/TAF was coadministered with LDV/SOF; and with LDV/SOF when coadministered with E/C/TAF.

In spite of the fact that the TFV presentation was expanded after coadministration of R/F/TAF + LDV/SOF, the mean TFV AUCtau was around 5 times lower than TFV versus TDF. It stayed inside of the scope of TFV where it didn't prompt renal unfriendly occasions or bone misfortune (E/C/F/TAF). "There was no relationship between higher cobicistat presentation and occurrence of unfriendly occasions and renal capacity parameters," included Dr. Custodio. The higher exposures of LDV and SOF were still in the presentation wellbeing reach, supporting the decision that R/F/TAF or E/C/TAF may be coadministered with LDV/SOF without modifying the measurement.