Literature DB >> 19682100

Long-term (96-week) follow-up of antiretroviral-naïve HIV-infected patients treated with first-line lopinavir/ritonavir monotherapy in the MONARK trial.

Jade Ghosn1, P Flandre, I Cohen-Codar, P-M Girard, M-L Chaix, F Raffi, P Dellamonica, P Ngovan, M Norton, J-F Delfraissy.   

Abstract

BACKGROUND: The toxicities, cost and complexity of triple combinations warrant the search for other treatment options, such as boosted protease inhibitor (PI) monotherapy. MONotherapy AntiRetroviral Kaletra (MONARK) is the first randomized trial comparing lopinavir/ritonavir monotherapy to triple combination therapy with zidovudine/lamivudine and lopinavir/ritonavir in antiretroviral-naïve patients.
METHODS: A total of 136 antiretroviral-naïve patients, with a CD4 cell count above 100 cells/microL and a plasma HIV RNA below 100,000 HIV-1 RNA copies/mL, were randomized and dosed with either lopinavir/ritonavir monotherapy (n = 83) or lopinavir/ritonavir + zidovudine/lamivudine (n = 53). We focus here on patients in the lopinavir/ritonavir monotherapy arm followed to week 96. The intent-to-treat (ITT) analysis initially involved all patients randomized to lopinavir/ritonavir monotherapy (n = 83), and then focused on patients who had an HIV RNA < 50 copies/mL at week 48 (n = 56).
RESULTS: At week 96, 39 of 83 patients (47%) had HIV RNA < 50 copies/mL, five of 83 had HIV RNA between 50 and 400 copies/mL, and three of 83 had HIV RNA > 400 copies/mL. Focusing on the 56 patients with an HIV RNA < 50 copies/mL at week 48, 38 of 56 patients (68%) had a sustained HIV RNA < 50 copies/mL to week 96. To week 96, a total of 28 patients (34%) had discontinued the study treatment. In addition, the allocated treatment was changed for seven patients. PI-associated resistance mutations were evident in five of 83 patients in the monotherapy arm from baseline to week 96.
CONCLUSION: By ITT analysis, 39 of the 83 patients initially randomized to lopinavir/ritonavir monotherapy had HIV RNA < 50 copies/mL at week 96. The occurrence in some patients of low-level viraemia (50-500 copies/mL) may increase the risk of drug resistance. First-line lopinavir/ritonavir monotherapy cannot be systematically recommended.

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Year:  2009        PMID: 19682100     DOI: 10.1111/j.1468-1293.2009.00752.x

Source DB:  PubMed          Journal:  HIV Med        ISSN: 1464-2662            Impact factor:   3.180


  16 in total

Review 1.  Protease inhibitor monotherapy: what is its role?

Authors:  Miriam Estébanez; Jose R Arribas
Journal:  Curr HIV/AIDS Rep       Date:  2012-06       Impact factor: 5.071

2.  HIV-1 protease mutations and protease inhibitor cross-resistance.

Authors:  Soo-Yon Rhee; Jonathan Taylor; W Jeffrey Fessel; David Kaufman; William Towner; Paolo Troia; Peter Ruane; James Hellinger; Vivian Shirvani; Andrew Zolopa; Robert W Shafer
Journal:  Antimicrob Agents Chemother       Date:  2010-07-26       Impact factor: 5.191

3.  Lopinavir/ritonavir monotherapy after virologic failure of first-line antiretroviral therapy in resource-limited settings.

Authors:  John A Bartlett; Heather J Ribaudo; Carole L Wallis; Evgenia Aga; David A Katzenstein; Wendy S Stevens; Michael R Norton; Karin L Klingman; Mina C Hosseinipour; John A Crump; Khuanchai Supparatpinyo; Sharlaa Badal-Faesen; Beatrice A Kallungal; Nagalingeswaran Kumarasamy
Journal:  AIDS       Date:  2012-07-17       Impact factor: 4.177

Review 4.  Lopinavir/Ritonavir: a review of its use in the management of HIV-1 infection.

Authors:  Jamie D Croxtall; Caroline M Perry
Journal:  Drugs       Date:  2010-10-01       Impact factor: 9.546

5.  Potential for simplification of HIV treatment with boosted protease inhibitor monotherapy.

Authors:  Elena Reina; Ramón San Miguel; Natalia Larrea; Patricia Garcia; Victor Napal
Journal:  Int J Clin Pharm       Date:  2012-09-25

6.  Polymorphism in Gag gene cleavage sites of HIV-1 non-B subtype and virological outcome of a first-line lopinavir/ritonavir single drug regimen.

Authors:  Jade Ghosn; Constance Delaugerre; Philippe Flandre; Julie Galimand; Isabelle Cohen-Codar; François Raffi; Jean-François Delfraissy; Christine Rouzioux; Marie-Laure Chaix
Journal:  PLoS One       Date:  2011-09-20       Impact factor: 3.240

Review 7.  CD4saurus Rex &HIVelociraptor vs. development of clinically useful immunological markers: a Jurassic tale of frozen evolution.

Authors:  Andrea De Maria; Andrea Cossarizza
Journal:  J Transl Med       Date:  2011-06-16       Impact factor: 5.531

8.  Novel strategies in the use of lopinavir/ritonavir for the treatment of HIV infection in children.

Authors:  Beatriz Larru Martinez; F Andrew I Riordan
Journal:  HIV AIDS (Auckl)       Date:  2010-03-29

9.  Lopinavir/ritonavir versus darunavir plus ritonavir for HIV infection: a cost-effectiveness analysis for the United States.

Authors:  Kit N Simpson; Pamela P Pei; Jörgen Möller; Robert W Baran; Birgitta Dietz; William Woodward; Kristen Migliaccio-Walle; J Jaime Caro
Journal:  Pharmacoeconomics       Date:  2013-05       Impact factor: 4.558

10.  Phenotypic characterization of virological failure following lopinavir/ritonavir monotherapy using full-length Gag-protease genes.

Authors:  Katherine A Sutherland; Jean L Mbisa; Jade Ghosn; Marie-Laure Chaix; Isabelle Cohen-Codar; Stephane Hue; Jean-Francois Delfraissy; Constance Delaugerre; Ravindra K Gupta
Journal:  J Antimicrob Chemother       Date:  2014-08-04       Impact factor: 5.790

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