By Liz Highleyman

Due to overlapping risk factors, many people are coinfected with some combination of HIV, hepatitis C virus (HCV), and hepatitis B virus (HBV). Treating patients with more than one virus involves additional complications, including the potential for drug interactions.

In a poster presented at the 48th International Conference on Antimicrobial Agents and Chemotherapy (ICAAC 2008), taking place this week in Washington, DC, researchers from Tibotec described a study looking at interactions between the company's experimental HCV protease inhibitor telaprevir (VX-950) and the widely prescribed anti-HIV drug tenofovir (Viread, also in the Truvada and Atripla combination pills), which was also recently approved as a treatment for chronic hepatitis B.

This randomized, open-label study assessed pharmacokinetic (PK) interactions between telaprevir -- a substrate and inhibitor of the CYP3A4 liver enzyme and P-glycoprotein -- and tenofovir in 18 healthy volunteers without HIV or HCV. During 3 separate 7-day treatment periods, participants received 300 mg tenofovir alone once-daily, 750 mg telaprevir alone every 8 hours, and both drugs combined; all treatments were taken with food.

Complete PK profiles were determined on day 7 of each period and analyzed using non-compartmental methods.

Results

• Co-administration of tenofovir did not influence the pharmacokinetics of telaprevir.

• However, exposure to tenofovir increased by about 30% when combined with telaprevir.

• All treatments were generally well tolerated.

• Adverse events were mild to moderate (grade 1 or 2).

• 2 participants discontinued the study:

• 1 withdrew consent;

• 1 due to an adverse event (hand fracture) unrelated to study drugs.

Based on these findings, the investigators concluded, "[Tenofovir] did not influence the PK of [telaprevir]. Exposure to tenofovir, however, was increased by about 30% during combination with [telaprevir]."

"Similar changes have been observed during combination of [tenofovir] with antiretroviral drugs," they added. "Results from ongoing interaction studies with [telaprevir] and other antiretroviral drugs are required before clinical evaluation of [telaprevir]-containing HCV/HIV therapeutic regimens can be initiated."

Tibotec, Mechelen, Belgium.

10/28/08

Reference
R Van Heeswijk, V Gysen, G Boogaerts, and others. The Pharmacokinetic (PK) Interaction Between Tenofovir Disoproxil Fumarate (TDF) and the Investigational HCV Protease Inhibitor Telaprevir (TVR). 48th International Conference on Antimicrobial Agents and Chemotherapy (ICAAC 2008). Washington, DC. October 25-28, 2008. Abstract A-966.