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

Vernazza, Pietroa; Daneel, Synøvea; Schiffer, Véroniqueb; Decosterd, Laurentc; Fierz, Walterd; Klimkait, Thomase; Hoffmann, Matthiasa; Hirschel, Bernardb; The Swiss HIV Cohort Study

doi: 10.1097/QAD.0b013e32814e6b1c
Clinical Science

Objectives: To limit exposure to anti-HIV drugs and minimize risk of long-term side effects, studies have looked at the possibility of simplified maintenance strategies. Ritonavir-boosted protease-inhibitor (PI)-monotherapies are an attractive alternative, but limited compartmental penetration of PI remains a concern.

Design: Non-comparative 24-week pilot study.

Method: Ritonavir-boosted atazanavir (ATV/r) monotherapy administered to fully suppressed patients (>3 month HIV RNA < 50 copies/ml). Plasma was obtained every 4 weeks and cerebrospinal fluid (CSF) and semen at W24.

Results: Two patients (7%) failed ATV/r monotherapy. One patient was subsequently identified as a protocol violator since he had a previous history of treatment failure under indinavir. The second patient deliberately decided to stop treatment after W20. Excluding failing patients, individual measurements of HIV RNA in patients having occasional viral ‘blips’ was found in five patients. At W24, 3/20 patients had elevated viral loads in CSF (HIV RNA > 100 copies/ml), and 2/15 in semen, despite viral suppression in plasma (< 50 copies/ml). Samples with elevated HIV RNA (> 500 copies/ml) in CSF were all wild type. The mean ATV drug concentration ratio (CSF/blood, n = 22) was 0.9%. Indicators of altered immune activation (CD8CD38 C-reactive protein) remained unchanged.

Conclusion: This study supports previous results indicating the potential use of PI-based mono-maintenance therapies. However, our results in CSF cautions against the uncontrolled use of PI-based monotherapies.

From the aDivision of Infectious Diseases, Department of Internal Medicine, Cantonal Hospital, St. Gallen, Switzerland

bDivision of Infectious Diseases, University Hospital, Geneva, Switzerland

cLaboratory of Clinical Pharmacology, University Hospital, Lausanne, Switzerland

dLogolab, Zurich, Switzerland

eInstitute of medical Microbiology, University of Basel, Switzerland.

Received 14 January, 2007

Revised 20 February, 2007

Accepted 5 March, 2007

Correspondence to P. Vernazza, DIM, Infektiologie, Kantonsspital St. Gallen, 9007 St. Gallen, Switzerland. Tel: +41 71 494 2631; fax: +41 71 494 6114; e-mail: Pietro.Vernazza@kssg.ch

© 2007 Lippincott Williams & Wilkins, Inc.