10th Conference on Retroviruses and Opportunistic Infections


Boston, MA USA - February 10 -14, 2003

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Pharmacokinetic Parameters of Atazanavir/Ritonavir when Combined to Tenofovir in HIV Infected Patients with Multiple Treatment Failures: A Sub-study of Puzzle2-ANRS 107 Trial.

Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 537
A. M. Taburet1 , C. Piketty2, L. Gérard3, I. Vincent1, C. Chazallon3, F. Clavel4, V. Calvez5, J. P. Aboulker3, P.M Girard6
1Hosp Bicêtre, Paris, France; 2Hosp G Pompidou, Paris, France; 3INSERM, Villejuif, France; 4Hosp Bichat, Paris, France; 5Hosp Pitié Salpétrière, Paris, France; and 6Hosp St Antoine, Paris, France

BACKGROUND: Combinations of new drugs could prove effective in patients (pts) who have failed multiple lines of antiretroviral therapy, provided that interactions do not alter exposure to the drugs. Tenofovir (TDF) and a Ritonavir (RTV) enhanced Atazanavir (ATV) regimen were combined as salvage therapy. The pharmacokinetic (pk) part of this study is described.

METHODS: A prospective, open-label, multicentre trial in pts with plasma HIV RNA> 10,000 copies/ml after failure of regimen lines containing at least 2 PIs and 1 NNRTI. For the first 2 weeks (wks), pts were randomized to unchanged PI and NRTIs (group 1) or to a combination of ATV (300 mg once a day), RTV (100 mg once a day), and unchanged NRTIs (group 2). From wks 2-26, all pts received ATV/RTV, TDF 300 mg (once a day) and recycled NRTIs. Fifty-three (53) pts were randomized in the study. Samples for ATV and RTV pk were drawn at wk 2 and wk 6 in 11 patients fromgroup 2.

RESULTS: Ten (10) male pts (mean 45 years) completed the pk study. At baseline, median CD4+ was 117/mm3 and median HIV RNA was 5.1 log10 copies/ml. Median number of antiretrovirals taken prior to randomization was 11. ATV and RTV pk parameters (geometric means at wk 2 and wk 6 and their ratio (standard 90% CI), median and range of Tmax) were as follows:

  ATV RTV
  wk 2 wk 6 wk 6/wk 2 wk 2 wk 6 wk 6/wk 2
Cmax (ng/ml) 4,422 3190 0.72 (0.50–1.05) 886 642 0.72 (0.43–1.21)
Tmax (h) 3 (2–5) 5 (1–5) – 3 (2–8) 3 (0-5) –
AUC24 (ng.h/ml) 46,073 34,459 0.75 (0.58–0.97) 7,011 5217 0.75 (0.44–1.24)
Cmin (ng/ml) 636 491 0.77 (0.54–1.10) 43 39 0.91 (0.73–1.13)
C24 (ng/ml) 696 513 0.74 (0.53–1.02) 50 44 0.88 (0.69–1.13)

CONCLUSIONS: At wk 2, ATV pk parameters when combined with RTV are in agreement with data obtained in healthy volunteers. After TDF introduction, both ATV and RTV parameters seemed to be reduced. These preliminary findings suggest that decrease in ATV concentrations at wk 6 could result from lowered RTV concentrations, even though the differences on most parameters did not reach statistical significance. The impact of TDF on ATV pk when given alone is unknown. Mechanism of this interaction, likely to occur at the absorption level, needs further investigation.

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Copyright © 2003 - Foundation for Retrovirology and Human Health. Reproduction of this abstract (other than one copy for personal reference) must be cleared through the Foundation for Retrovirology and Human Health. Licensed (AIDSLINE) from National Library of Medicine.