*This study has been registered as a randomized trial at http://www.clinicaltrials.gov under identifier NCT 00234923.
Long-term (96-week) follow-up of antiretroviral-naïve HIV-infected patients treated with first-line lopinavir/ritonavir monotherapy in the MONARK trial*
Article first published online: 13 AUG 2009
© 2009 British HIV Association
Volume 11, Issue 2, pages 137–142, February 2010
How to Cite
Ghosn, J., Flandre, P., Cohen-Codar, I., Girard, P.-M., Chaix, M.-L., Raffi, F., Dellamonica, P., NgoVan, P., Norton, M., Delfraissy, J.-F., for the MONARK and Study Group (2010), Long-term (96-week) follow-up of antiretroviral-naïve HIV-infected patients treated with first-line lopinavir/ritonavir monotherapy in the MONARK trial. HIV Medicine, 11: 137–142. doi: 10.1111/j.1468-1293.2009.00752.x
- Issue published online: 4 JAN 2010
- Article first published online: 13 AUG 2009
- Accepted 11 June 2009
- antiretroviral monotherapy;
- clinical study;
- HIV infection;
- HIV protease inhibitors;
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.
A total of 136 antiretroviral-naïve patients, with a CD4 cell count above 100 cells/μL 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).
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.
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.