Background: Guidelines for the use of antiretroviral agents for HIV-1 infection recommend combining at least three agents. The toxicity, cost, and complexity of such regimens warrant the search for other options.
Methods: MONARK is a prospective, open-label, randomized, 96-week trial comparing the safety and efficacy of lopinavir/ritonavir monotherapy with a standard lopinavir/ritonavir plus zidovudine and lamivudine regimen as an initial treatment regimen in HIV-infected patients with HIV-RNA levels less than 100 000 copies/ml. The primary endpoint was the proportion of patients with HIV-1-RNA levels below 400 copies/ml at week 24 and below 50 copies/ml at week 48.
Results: Eight-three and 53 patients were randomly assigned and exposed in the monotherapy and triple-drug groups, respectively. At week 48, by an intent-to-treat analysis, 53 of 83 patients (64%) in the monotherapy group and 40 of 53 patients (75%) in the triple-drug group achieved the primary endpoint (P = 0.19). The on-treatment analysis indicates that 80 and 95% of patients reached the primary endpoint in the monotherapy and triple-drug groups, respectively (P = 0.02). In the monotherapy arm, protease inhibitor-associated resistance mutations were seen in three of the 21 patients qualifying for genotypic resistance testing, with a modest impact on lopinavir susceptibility. None of the serious reported adverse events were considered to be related to study treatment.
Conclusion: Our results suggest that lopinavir/ritonavir monotherapy demonstrates lower rates of virological suppression when compared with lopinavir/ritonavir triple therapy and therefore should not be considered as a preferred treatment option for widespread use in antiretroviral-naive patients.
From the aAP-HP, Department of Internal Medicine and Infectious Diseases, Bicetre University Hospital, Le Kremlin-Bicêtre, France
bINSERM U 720, Pierre and Marie Curie University, Paris, France
cAP-HP, Virology Department, Necker University Hospital, Paris, France
dDepartment of Infectious Diseases, Warsaw, Poland
eAP-HP, Department of Infectious Diseases, Saint-Antoine University Hospital, Paris, France
fAbbott Laboratories, Rungis, France
gAP-HP, Laboratory of Clinical Pharmacology, Bicetre University Hospital, Le Kremlin-Bicêtre, France.
Received 17 July, 2007
Revised 21 September, 2007
Accepted 9 October, 2007
Correspondence to Jean-François Delfraissy, Service de Médecine Interne et Maladies Infectieuses, Centre Hospitalier Universitaire de Bicêtre, 78 Rue du Général Leclerc, 94275 Le Kremlin-Bicêtre Cedex, France. Tel: +33 1 45 21 28 91; fax: +33 1 45 21 27 41; e-mail: email@example.com