title: Hydroxyurea does not enhance the anti-HIV activity of low-dose tenofovir disoproxil fumarate.
abstract: Tenofovir disoproxil fumarate (DF) is an adenosine analogue with significant activity against HIV-1. Hydroxyurea decreases the intracellular concentrations of deoxyadenosine triphosphate, the active metabolite of adenosine. We therefore tested the hypothesis that hydroxyurea could enhance the anti-HIV activity of low-dose tenofovir in vivo. Eight patients received tenofovir DF, 75 mg, plus hydroxyurea, 500 mg bid, for 28 days. Changes in plasma HIV RNA levels were compared with a previously studied cohort of patients treated 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 treatment was -0.01 log(10) copies/ml for tenofovir placebo, -0.33 log(10) copies/ml for tenofovir 75 mg once daily, and -0.22 log(10) copies RNA/ml for tenofovir plus hydroxyurea. The difference between placebo and tenofovir-treated groups was significant ( p <.05); however, the difference between the tenofovir and tenofovir plus hydroxyurea groups was not significant ( p =.90). We conclude that hydroxyurea does not significantly enhance the antiviral activity of low-dose tenofovir.
authors.affiliation: San Francisco General Hospital AIDS Program, University of California, San Francisco, California 94110, USA. sdeeks@php.ucsf.edu
authors.forename: S G
authors.initials: SG
authors.lastname: Deeks
authors.forename: P
authors.initials: P
authors.lastname: Barditch-Crovo
authors.forename: A
authors.initials: A
authors.lastname: Collier
authors.forename: A
authors.initials: A
authors.lastname: Smith
authors.forename: M
authors.initials: M
authors.lastname: Miller
authors.forename: I
authors.initials: I
authors.lastname: McGowan
authors.forename: D F
authors.initials: DF
authors.lastname: Coakley
mesh_terms: D000225:Adenine / Q000031:analogs & derivatives / Q000627:therapeutic use*; D000328:Adult; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D015331:Cohort Studies; D004359:Drug Therapy, Combination; D015658:HIV Infections / Q000188:drug therapy*; D015497:HIV-1; D006801:Humans; D006918:Hydroxyurea / Q000494:pharmacology* / Q000627:therapeutic use; D008297:Male; D063065:Organophosphonates; D009943:Organophosphorus Compounds / Q000627:therapeutic use*; D000068698:Tenofovir
chemical_list: D019380:Anti-HIV Agents; D063065:Organophosphonates; D009943:Organophosphorus Compounds; D000068698:Tenofovir; D000225:Adenine; D006918:Hydroxyurea