Lopinavir/Ritonavir as Single-Drug Therapy for Maintenance of HIV-1 Viral Suppression: 48-Week Results of a Randomized, Controlled, Open-Label, Proof-of-Concept Pilot Clinical Trial (OK Study)

Arribas, José R MD*; Pulido, Federico MD†; Delgado, Rafael MD‡; Lorenzo, Alicia MD*; Miralles, Pilar MD§; Arranz, Alberto MD∥; González-García, Juan J MD*; Cepeda, Concepción MD†; Hervás, Rafael MD†; Paño, José R MD*; Gaya, Francisco MD¶; Carcas, Antonio MD#; Montes, María L MD*; Costa, José R MD†; Peña, José M MD*

JAIDS Journal of Acquired Immune Deficiency Syndromes:
Clinical Science
Abstract

Objective: This study evaluated maintenance with lopinavir/ritonavir monotherapy vs. continuing lopinavir/ritonavir and 2 nucleosides in HIV-infected patients with suppressed HIV replication.

Design: Randomized, controlled, open-label, multicenter, pilot clinical trial.

Methods: Adult patients were eligible if they had no history of virologic failure while receiving a protease inhibitor, were receiving 2 nucleosides + lopinavir/ritonavir (400/100 mg b.i.d.) for >1 month and had maintained serum HIV RNA <50 copies/mL for >6 months prior to enrollment.

Results: Forty-two patients were randomly assigned 1:1 to continue or stop the nucleosides. At baseline there were no significant differences between groups in median CD4 cells/μL (baseline or nadir), pre-HAART (highly active antiretroviral therapy) HIV log10 viremia, or time with HIV RNA <50 copies/mL prior to enrollment. After 48 weeks of follow-up, percentage of patients remaining at <50 HIV RNA copies/mL (intention to treat, M = F) was 81% for the monotherapy group (95% CI: 64% to 98%) vs. 95% for the triple-therapy group (95% CI: 86% to 100%); P = 0.34. Patients in whom monotherapy failed had significantly worse adherence than patients who remained virally suppressed on monotherapy. Monotherapy failures did not show primary resistance mutations in the protease gene and were successfully reinduced with prerandomization nucleosides. Mean change in CD4 cells/μL: +70 (monotherapy) and +8 (triple) (P = 0.27). Mean serum fasting lipids remained stable in both groups. No serious adverse events were observed.

Conclusion: Most of the patients maintained with lopinavir/ritonavir monotherapy remain with undetectable viral load after 48 weeks. Failures of lopinavir/ritonavir monotherapy were not associated with the development of primary resistance mutations in the protease gene and could be successfully reinduced adding back prior nucleosides.

Author Information

From the *Internal Medicine Service, ¶Investigation Unit, and #Pharmacology Service, Hospital La Paz, Autónoma University School of Medicine; †HIV Unit and ‡Laboratory of Molecular Microbiology, Hospital 12 de Octubre, Complutense University School of Medicine; §Infectious Diseases Service, Hospital Gregorio Marañón, Complutense University School of Medicine; and ∥Internal Medicine Service, Hospital Príncipe de Asturias, Alcalá University School of Medicine, Madrid, Spain.

Received for publication April 4, 2005; accepted July 21, 2005.

Supported with an unrestricted grant from Abbott Laboratories. The funding source had no role in the study design, data collection, analysis and interpretation of the data, preparation of the manuscript, or the decision to submit the manuscript for publication.

J. R. Arribas and F. Pulido contributed equally to this study.

Reprints: Jose R. Arribas, Hospital La Paz, Consulta de Medicina Interna II, Paseo de la Castellana, n° 261, 28046 Madrid, España (e-mail: josearribas@telefonica.net).

© 2005 Lippincott Williams & Wilkins, Inc.