Effect of tenofovir on abacavir phosphorylation
20 April 2009. Related: Conference reports, PK and drug interactions, CROI 16 (Retrovirus) 2009.
hiv-druginteractions.org
Intracellular concentrations of the active phosphorylated metabolites of abavavir (carbovir triphosphate) and tenofovir (tenofovir disphosphate) were determined in HIV-positive, treatment-naive subjects following administration of abacavir (600 mg once daily) and tenofovir (300 mg once daily) alone and in combination.
The addition of tenofovir had no effect on carbovir triphosphate AUC (1694 vs 1895 fmol.h/106 cells, alone vs combination), but there was a trend towards an increase in tenofovir diphosphate AUC on addition of abacavir, though this was not statistically significant (1209 vs 2700 fmol.h/106cells, alone vs combination, p=0.08).
Interestingly, viral decay during tenofovir plus abacavir dual therapy was 0.04 log10/day faster than during tenofovir monotherapy.
Comment
This interesting study still doesnt help shed light on why triple-nuke combinations including abacavir and tenofovir disastrously underperformed clinically.
Reference:
Goicoechea M et al. Viral dynamics and pharmacokinetics in vivo of tenofovir disoproxil fumarate and abacavir: evidence of a non-additive antiviral effect. 16th CROI, Montreal, 2009. Abstract 703.
http://www.retroconference.org/2009/Abstracts/33853.htm