Efficacy and safety of tenofovir double-dose in treatment-experienced HIV-infected patients: The tenoplus study

✍ Scribed by Stephanie Dominguez; Jade Ghosn; Gilles Peytavin; Hassan Izzedine; Marc Wirden; Nadine Ktorza; Michael Miller; Camille Aubron-Olivier; Aldo Trylesinski; Vincent Calvez; Gilbert Deray; Christine Katlama

• Publisher: John Wiley and Sons
• Year: 2006
• Tongue: English
• Weight: 105 KB
• Volume: 79
• Category: Article
• ISSN: 0146-6615
• DOI: 10.1002/jmv.20769

✦ Synopsis

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 ≥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. J. Med. Virol. 79:105–110, 2007. © 2006 Wiley‐Liss, Inc.