title: Efficacy and safety of tenofovir double-dose in treatment-experienced HIV-infected patients: the TENOPLUS study.
abstract: Drug resistance is an increasing problem in the treatment of HIV infection. Tenofovir has been shown to inhibit HIV replication even with thymidine-associated resistance mutations (TAMs) if they are limited to two or less. Double-dose of tenofovir disoproxil fumarate (TDF) (600 mg QD) was used to determine weather the drug could be virologically effective in patients harbouring HIV-strains resistant to nucleoside analogues (NRTI). A pilot, open, non-comparative add-on study, where patients failing a current antiretroviral regimen, with at least two TAMs, and naive for tenofovir, were given tenofovir 600 mg once-daily for 4 weeks, in addition to their current failing antiretroviral regimen. The primary end-point was the percentage of patients with plasma viral load (VL) reduction of at least 0.8 log(10) between baseline and week 4 (W4). Ten patients were enrolled. At baseline, the median viral load was 3.66 log(10) copies/ml (range 3.13-4.03) and the median CD4 cell count was 407/mm(3) (range 136-1102). The percentage of patients with reduction the viral load > or =0.8 log(10) was 40% at W4. After 4 weeks of treatment with tenofovir 600 mg, the median decrease in the viral load was -0.61 log(10) (range -0.05; -0.88) and the median gain of CD4 was +109/mm(3). Despite a twofold increase tenofovir plasma concentrations, no serious drug-related adverse event were recorded except for one patient experiencing an de Fanconi syndrome at week 2. This add-on pilot study supports the concept of double dose tenofovir to virologically overcome the decreased sensitivity of NRTI-resistant viruses. However, the safety of this regimen needs to be considered carefully.
authors.affiliation: Département des Maladies Infectieuses et Tropicales/INSERM U720, CHU Pitié-Salpétrière, Paris, France. stephanie.dominguez@psl.ap-hop-paris.fr
authors.forename: Stephanie
authors.initials: S
authors.lastname: Dominguez
authors.forename: Jade
authors.initials: J
authors.lastname: Ghosn
authors.forename: Gilles
authors.initials: G
authors.lastname: Peytavin
authors.forename: Hassan
authors.initials: H
authors.lastname: Izzedine
authors.forename: Marc
authors.initials: M
authors.lastname: Wirden
authors.forename: Nadine
authors.initials: N
authors.lastname: Ktorza
authors.forename: Michael
authors.initials: M
authors.lastname: Miller
authors.forename: Camille
authors.initials: C
authors.lastname: Aubron-Olivier
authors.forename: Aldo
authors.initials: A
authors.lastname: Trylesinski
authors.forename: Vincent
authors.initials: V
authors.lastname: Calvez
authors.forename: Gilbert
authors.initials: G
authors.lastname: Deray
authors.forename: Christine
authors.initials: C
authors.lastname: Katlama
mesh_terms: D000225:Adenine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000627:therapeutic use; D000328:Adult; D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use; D018791:CD4 Lymphocyte Count; D024882:Drug Resistance, Viral; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology; D015497:HIV-1 / Q000187:drug effects* / Q000235:genetics / Q000502:physiology; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D063065:Organophosphonates / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use; D010865:Pilot Projects; D012367:RNA, Viral / Q000097:blood; D018894:Reverse Transcriptase Inhibitors / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use; D000068698:Tenofovir; D019562:Viral Load
chemical_list: D019380:Anti-HIV Agents; D063065:Organophosphonates; D012367:RNA, Viral; D018894:Reverse Transcriptase Inhibitors; D000068698:Tenofovir; D000225:Adenine