The role of compartment penetration in PI-Monotherapy: the Atazanavir-Ritonavir Monomaintenance (ATARITMO) Trial

• DOI: 10.1097/qad.0b013e32814e6b1c
• Publication Date: 2007-06-01T08:04:13Z
• Authors: Pietro Vernazza; Synøve Daneel; Véronique Schiffer; Laurent Decosterd; Walter Fierz; Thomas Klimkait; Matthias Hoffmann; Bernard Hirschel
• Keywords: Ritonavir; Indinavir; Atazanavir; Saquinavir; Lopinavir; Protease inhibitor (pharmacology); Nelfinavir

Objectives: To limit exposure to anti-HIV drugs and minimize risk of long-term side effects, studies have looked at the possibility simplified maintenance strategies. Ritonavir-boosted protease-inhibitor (PI)-monotherapies are an attractive alternative, but limited compartmental penetration PI remains a concern. Design: Non-comparative 24-week pilot study. Method: atazanavir (ATV/r) monotherapy administered fully suppressed patients (>3 month HIV RNA < 50 copies/ml). Plasma was obtained every 4 weeks cerebrospinal fluid (CSF) semen W24. Results: Two (7%) failed ATV/r monotherapy. One patient subsequently identified as protocol violator since he had previous history treatment failure under indinavir. The second deliberately decided stop after W20. Excluding failing patients, individual measurements in having occasional viral 'blips' found five patients. At W24, 3/20 elevated loads CSF (HIV > 100 copies/ml), 2/15 semen, despite suppression plasma (< Samples with (> 500 copies/ml) were all wild type. mean ATV drug concentration ratio (CSF/blood, n = 22) 0.9%. Indicators altered immune activation (CD8CD38 C-reactive protein) remained unchanged. Conclusion: This study supports results indicating potential use PI-based mono-maintenance therapies. However, our cautions against uncontrolled monotherapies.