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


METHODS
Non-comparative 24-week pilot study.


METHODS
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.


CONCLUSIONS
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.
Vernazza
Pietro
P
Division of Infectious Diseases, Department of Internal Medicine, Cantonal Hospital St. Gallen, 9007 St. Gallen, Switzerland. Pietro.Vernazza@kssg.ch
Daneel
Synøve
S
Schiffer
Véronique
V
Decosterd
Laurent
L
Fierz
Walter
W
Klimkait
Thomas
T
Hoffmann
Matthias
M
Hirschel
Bernard
B
D000328:Adult; D000069446:Atazanavir Sulfate; D002097:C-Reactive Protein / Q000032:analysis; D018791:CD4 Lymphocyte Count; D016827:CD8 Antigens / Q000032:analysis; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005260:Female; D006678:HIV / Q000276:immunology; D015658:HIV Infections / Q000134:cerebrospinal fluid / Q000188:drug therapy* / Q000378:metabolism; D017320:HIV Protease Inhibitors / Q000008:administration & dosage* / Q000032:analysis; D006801:Humans; D008297:Male; D009842:Oligopeptides / Q000008:administration & dosage* / Q000032:analysis; D010865:Pilot Projects; D011725:Pyridines / Q000008:administration & dosage* / Q000032:analysis; D012367:RNA, Viral / Q000032:analysis; D019438:Ritonavir / Q000008:administration & dosage*; D012661:Semen / Q000821:virology; D016896:Treatment Outcome; D019562:Viral Load
D016827:CD8 Antigens; D017320:HIV Protease Inhibitors; D009842:Oligopeptides; D011725:Pyridines; D012367:RNA, Viral; D000069446:Atazanavir Sulfate; D002097:C-Reactive Protein; D019438:Ritonavir