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Susceptibility to TMC114 (Darunavir) in the UK and Drug Interactions

Excerpted from: Glasgow Meeting: Part 5
8th International Congress on Drug Therapy in HIV Infection
November 12-16, 2006, Glasgow

Mark Mascolini

Susceptibility to--and drug interactions with--darunavir
Mutations conferring resistance to darunavir (TMC114) proved relatively sparse in a UK cohort of 885 PI-experienced people, reported Clive Loveday of the ICVC Charitable Trust, Buckinghamshire [6]. Those findings suggest this new PI will help a fair portion of PI-experienced people in Britain, where darunavir stands likely to be licensed in 2007.

Loveday searched for protease mutations correlating with resistance in the three POWER trials, dividing them into high-impact mutations (V32I, L33F, I47V, I54L, and L89V) and low-impact mutations (V11I, I50V, I54M, G73S, L76V, and I84V) based on whether they arose in 10% or more virologic failures. Most viral samples (60%) came from people currently taking a failing PI regimen, 21% from people taking a non-PI regimen, and 19% from people taking no antiretrovirals; 44% of samples came from people with HIV-1 subtypes other than B.

Only 14% of the cohort--126 people--had one or more darunavir-related mutations, including 83% currently taking a failing PI, 11% off treatment, and 6% taking a non-PI regimen. Of the 126 people with darunavir mutations, 15 (12%) had two such mutations and 13 (10%) had three or more such mutations. Only 2 people had five darunavir-related mutations, including four high-impact mutations. No one in the cohort had the L89V high-impact mutation.

David Back from the University of Liverpool offered a detailed review of drug interaction studies involving darunavir [7], which has already been posted on the NATAP site (click on link at reference 7).

Tibotec researchers found that darunavir cuts concentrations of the antidepressants sertraline and paroxetine and advised clinical monitoring and--if necessary--dose adjustment when these drugs are prescribed with darunavir (click on link at reference 8). The same researchers also recommended clinical monitoring for people on methadone maintenance therapy when starting darunavir, although they found no need for up-front dose adjustments (click on link at reference 9).

References
6. Loveday C, MacRae E. Susceptibility of a protease inhibitor treatment-experienced UK clinical cohort to TMC114. 8th International Congress on Drug Therapy in HIV Infection. November 12-16, 2006. Glasgow. Abstract PL2.2.
7. Back D. Use of TMC114 in combination with other drugs: guidance from pharmacokinetic studies. 8th International Congress on Drug Therapy in HIV Infection. November 12-16, 2006. Glasgow. Abstract PL5.2 (http://www.natap.org/2006/Glasgow/Glasgow_24.htm).


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