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.
RCT Entities:
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-infectedpatients 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.
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
Authors: Michael P Girouard; Paul E Sax; Robert A Parker; Babafemi Taiwo; Kenneth A Freedberg; Roy M Gulick; Milton C Weinstein; A David Paltiel; Rochelle P Walensky Journal: Clin Infect Dis Date: 2015-12-09 Impact factor: 9.079