Salvage therapy with atazanavir/ritonavir combined to tenofovir in HIV-infected patients with multiple treatment failures: randomized ANRS 107 trial.
BACKGROUND
Ritonavir (RTV)-boosted atazanavir (ATV) and tenofovir disoproxil fumarate (TDF-DF) are promising in highly experienced patients because of their pharmacokinetic profile, activity, safety and resistance properties.


METHODS
A 26-week study of the safety and efficacy of RTV-boosted ATV plus TDF-DF was conducted in 53 HIV-infected patients who were failing their current highly active antiretroviral therapy (HAART) regimen. Patients with history of failure to at least two protease inhibitors (PIs) and one non-nucleoside reverse transcriptase inhibitor (NNRTI) were randomized to either continue their current regimen (group 1) or replace the PI by ATV (300 mg once daily) boosted by RTV (100 mg; group 2) for 2 weeks. Then, all patients received the same combination of ATV, RTV and TDF-DF (300 mg) plus optimized NRTIs regimen.


RESULTS
At baseline, median CD4+ T-cell count was 206/mm3, median viral load (VL) 5.0 log10/ml and median numbers of NRTI, NNRTI and PI resistance mutations were 7, 1 and 8, respectively. At week 2, median VL remained unchanged from baseline in group 2 as compared with group 1 (-0.1 vs -0.1 log10/ml). At week 26, a mild decrease in median VL from baseline of 0.2 log10/ml was observed, with 16 (31%) and 9 (17%) patients exhibiting a decrease in viral load of at least 0.5 and 1.0 log10/ml, respectively. Baseline phenotypic and genotypic resistance to ATV were the most predictive independent factors of virological response. The regimen was well tolerated.


CONCLUSIONS
In these very advanced patients failing highly HAART, the combination of boosted ATV plus TDF-DF yielded low antiretroviral activity.
Piketty
Christophe
C
Department of Immunology, Hôpital Georges Pompidou, Assistance Publique-Hôpitaux de Paris, Paris, France. christophe.piketty@egp.aphp.fr
Gérard
Laurence
L
Chazallon
Corine
C
Marcelin
Anne-Geneviève
AG
Clavel
François
F
Taburet
Anne-Marie
AM
Calvez
Vincent
V
Madelaine-Chambrin
Isabelle
I
Molina
Jean-Michel
JM
Aboulker
Jean-Pierre
JP
Girard
Pierre-Marie
PM
D000225:Adenine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000328:Adult; D019380:Anti-HIV Agents / Q000009:adverse effects / Q000627:therapeutic use; D000069446:Atazanavir Sulfate; D024882:Drug Resistance, Viral; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology; D015497:HIV-1 / Q000187:drug effects / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009842:Oligopeptides / Q000009:adverse effects / Q000627:therapeutic use*; D063065:Organophosphonates / Q000009:adverse effects / Q000627:therapeutic use*; D011725:Pyridines / Q000009:adverse effects / Q000627:therapeutic use*; D019438:Ritonavir / Q000009:adverse effects / Q000627:therapeutic use*; D016879:Salvage Therapy; D000068698:Tenofovir; D017211:Treatment Failure
D019380:Anti-HIV Agents; D009842:Oligopeptides; D063065:Organophosphonates; D011725:Pyridines; D000069446:Atazanavir Sulfate; D000068698:Tenofovir; D000225:Adenine; D019438:Ritonavir