48-Week Analysis of Lopinavir/Ritonavir Monotherapy Compared to LPV/r + Zidovudine/Lamivudine

US government-sanctioned guidelines for the use of antiretrovirals for HIV-1 infection recommend combining 3 anti-HIV agents for the treatment of HIV. However, toxicities, cost, and the complexity of these regimens warrant the search for other options.

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.

Sub-optimal virological response occurred in 9 (11%) for LPV/r 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.

The authors conclude, "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."

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

08/18/06

Reference
J-F Delfraissy, P Flandre, C Delaugerre, and others. 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. 16th International AIDS Conference. August 13-18, 2006. Toronto, Canada. Abstract THLB0202.