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Randomized controlled study demonstrating failure of LPV/r monotherapy in HIV: the role of compartment and CD4-nadir

Gutmann, Christinea; Cusini, Alexiab; Günthard, Huldrych Fb; Fux, Christophc; Hirschel, Bernardd; Decosterd, Laurent-Arthure; Cavassini, Matthiase; Yerly, Sabinef; Vernazza, Pietro La; the Swiss HIV Cohort Study (SHCS)

doi: 10.1097/QAD.0b013e32833db9a1
Clinical Science

Background: Long-term side-effects and cost of HIV treatment motivate the development of simplified maintenance. Monotherapy with ritonavir-boosted lopinavir (LPV/r-MT) is the most widely studied strategy. However, efficacy of LPV/r-MT in compartments remains to be shown.

Methods: Randomized controlled open-label trial comparing LPV/r-MT with continued treatment for 48 weeks in treated patients with fully suppressed viral load. The primary endpoint was treatment failure in the central nervous system [cerebrospinal fluid (CSF)] and/or genital tract. Treatment failure in blood was defined as two consecutive HIV RNA levels more than 400 copies/ml.

Results: The trial was prematurely stopped when six patients on monotherapy (none in continued treatment-arm) demonstrated a viral failure in blood. At study termination, 60 patients were included, 29 randomized to monotherapy and 13 additional patients switched from continued treatment to monotherapy after 48 weeks. All failures occurred in patients with a nadir CD4 cell count below 200/μl and within the first 24 weeks of monotherapy. Among failing patients, all five patients with a lumbar puncture had an elevated HIV RNA load in CSF and four of six had neurological symptoms. Viral load was fully resuppressed in all failing patients after resumption of the original combination therapy. No drug resistant virus was found. The only predictor of failure was low nadir CD4 cell count (P < 0.02).

Conclusion: Maintenance of HIV therapy with LPV/r alone should not be recommended as a standard strategy; particularly not in patients with a CD4 cell count nadir less than 200/μl. Further studies are warranted to elucidate the role of the central nervous system compartment in monotherapy-failure.

aCantonal Hospital St. Gallen, Switzerland

bUniversity Hospital and University of Zurich, Switzerland

cBern University Hospital and University of Bern, Switzerland

dUniversity Hospital Geneva, Switzerland

eUniversity Hospital Lausanne, Switzerland

fLaboratory of Virology, Geneva's University Hospitals and University of Geneva Medical School, Geneva, Switzerland.

Received 26 April, 2010

Revised 24 June, 2010

Accepted 29 June, 2010

Correspondence to Pietro Vernazza, MD, Division Infectious Diseases, Cantonal Hospital St. Gallen, CH-9007 St. Gallen, Switzerland. Tel: +41 71 494 2631; fax: +41 71 494 6114; e-mail: pietro.vernazza@kssg.ch

© 2010 Lippincott Williams & Wilkins, Inc.