Abstract

MONARK Trial (MONotherapy AntiRetroviral Kaletra): 48-Week Analysis of Lopinavir/Ritonavir (LPV/r) Monotherapy compared to LPV/r + Zidovudine/Lamivudine (AZT/3TC) in Antiretroviral-Naïve Patients

J.-F. Delfraissy¹, P. Flandre², C. Delaugerre³, A. Horban⁴, P.-M. Girard⁵, C. Rouzioux⁶, M. Norton⁷, I. Cohen-Codar⁸, P. NgoVan⁸, J.-P. Chauvin⁹

¹Le Kremlin Bicêtre Hospital, Department of Internal Medecine, Univ 11, Paris, France, ²Pierre and Marie Curie Univ, Inserm Unit 720, Paris, France, ³Necker Virology EA 3620, Univ 5, Paris, France, ⁴AIDS Diagnosis and Therapy Center, Hospital of Infectious Diseases, Warsaw, Poland, ⁵Saint-Antoine Hospital, Infectious Diseases, Paris, France, ⁶Necker Virology EA 3620, Univ Paris, France, ⁷Abbott Park, Chicago, United States, ⁸Abbott France, Rungis, France, ⁹Abbott GPRD, Rungis, France

Background: Guidelines for the use of antiretrovirals for HIV-1 infection recommend combining 3 agents. However, toxicities, cost, complexity of such regimens warrant the search for other options.

Methods: MONARK is a pilot, prospective, open-label, randomized, 96-week trial comparing the safety and efficacy of LPV/r monotherapy to a standard LPV/r+AZT/3TC regimen. Antiretroviral naïve subjects without baseline resistance to study drugs, viral load (VL) 100,000 copies/mL, CD4 100 cells/mm3, were randomized to either LPV/r or LPV/r+AZT/3TC. The primary endpoint was VL <400 copies/mL at W24 and <50 copies/mL at W48. Sub-optimal virologic response was defined as (i) <1 log VL decrease by W4 (ii) VL >400 c/mL by W24 (iii) VL rebound after VL<400 c/mL, confirmed in a second specimen.

Results: 136 subjects were randomized (83 LPV/r; 53 LPV/r+AZT/3TC). Baseline characteristics were similar: VL (median 4.5 log LPV/r; 4.3 log LPV/r+AZT/3TC), CD4 (median 235 LPV/r; 224 LPV/r+AZT/3TC). Discontinuations through W48 were 19% for LPV/r arm and 30% for LPV/r+AZT/3TC arm. † p= 0.03, ‡p=0.02
Sub-optimal virological response occurred in 9 (11%) for LPVr and 7 (13%) for LPV/r+AZT/3TC. At W48, median CD4 increase from baseline was 152 for LPV/r, 159 for LPV/r+AZT/3TC. Through Wk 48, 2/83 (2%) subjects on LPV/r monotherapy developed resistance mutations (both in protease), versus 1/53 (2%) on LPV/r+AZT/3TC (M184V). Similar tolerance was observed.

Conclusions: Initiating antiretroviral therapy with LPV/r monotherapy demonstrated a sustained virological efficacy. However LPV/r monotherapy was associated with more episodes of viremia compared with 3-drug therapy.

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