Hydroxyurea does not enhance the anti-HIV activity of low-dose tenofovir disoproxil fumarate

Tenofovir disoproxil fumarate (DF) is an adenosine analogue with significan t activity against HIV-1. Hydroxyurea decreases the intracellular concentra tions or deoxyadenosine triphosphate, the active metabolite of adenosine. W e therefore tested the hypothesis that hydroxyurea could enhance the anti-H IV activity of low-dose tenofovir in vivo. Eight patients received tenofovi r DF, 75 mg, plus hydroxyurea, 500 mg bid, for 28 days. Changes in plasma H IV RNA levels were compared with a previously studied cohort of patients tr eated with tenofovir DF, 75 mg once daily (n = 8), or tenofovir placebo (n = 12). The median change in HIV RNA levels after 28 days of continuous trea tment was -0.01 log(10) copies/ml for tenofovir placebo, -0.33 log(10) copi es/ml for tenofovir 75 mg once daily, and -0.22 log(10) copies RNA/ml for t enofovir plus hydroxyurea. The difference between placebo and tenofovir-tre ated groups was significant (p < .05); however, the difference between the tenofovir and tenofovir plus hydroxyurea groups was not significant (p = .9 0). We conclude that hydroxyurea does not significantly enhance the antivir al activity of low-dose tenofovir.