All other authors have no conflict of interest to declare. “
“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 selleck inhibitor (n=53). We focus here on patients in the lopinavir/ritonavir monotherapy arm followed to week 96. The intent-to-treat Selleck CX 5461 (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 new 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. Concerns about the long-term toxicity and cost of, and adherence to, highly active antiretroviral therapy (HAART), which typically combines two nucleoside reverse transcriptase inhibitors (NRTIs) plus either one ritonavir-boosted protease inhibitor (PI) or one nonnucleoside reverse transcriptase inhibitor (NNRTI) , have prompted the search for other options for the management of HIV infection [2,3]. Strategies of treatment simplification have thus been explored, especially single-drug therapy, with the aim of improving patient quality of life and adherence to treatment while maintaining viral suppression . Ritonavir-boosted PIs are appealing candidates for such single-drug therapy because of their high antiviral potency and high genetic barrier to the development of resistance [5–7]. Ritonavir-boosted lopinavir (LPV/r) has been suggested to show efficacy as maintenance monotherapy after virological suppression [8–11] or as a first-line regimen [12,13].