Analysis of drug resistance during HIV RNA viraemia in the MONET trial of darunavir/ritonavir monotherapy

作者：Pulido Federico^*; Arribas Jose R; Hill Andrew; Van Delft Yvon; Moecklinghoff Christione

来源：Antiviral Therapy, 2011, 16(1): 59-65.

DOI：10.3851/IMP1710

Background: When patients have HIV RNA suppressed to < 50 copies/ml on current treatment, switching to darunavir (DRV)/ritonavir (DRV/r) monotherapy could prevent the development of resistance to other drug classes.
Methods: In the MONET trial, 256 patients with HIV RNA < 50 copies/ml on current highly active antiretroviral therapy (57% with protease inhibitors [Pis] and 43% with non-nucleoside reverse transcriptase inhibitors) and no history of virological failure were randomized to DRV/r 800/100 mg once daily, either as monotherapy (monotherapy arm) or with two nucleoside reverse transcriptase inhibitors (NRTIs; triple therapy arm). All samples with HIV RNA >= 50 copies/ml were genotyped, and a virtual phenotype was calculated (Virco Type HIV-1 assays; Vireo BVBA, Mechelen, Belgium).
Results: A total of 63 patients had HIV RNA result >= 50 copies/ml, of whom 38 were successfully gcnotyped. Most HIV RNA increases were transient and in the range of 50-200 copies/ml. Overall, 36 of the 38 (95%) successfully genotyped patients showed no International AIDS Society-USA major PI mutations, DRV mutations or NRTI mutations. Two patients showed some evidence of PI resistance during transient HIV RNA elevations: one patient in the monotherapy arm had a single DRV mutation (L33F) when HIV RNA was 63 copies/ml (the virus was phenotypically sensitive to DRV [fold change 0.8]) and one PI pretreated patient taking tenofovir disoproxil fumarate/emtricitabine/DRV/r had re-emergence of preexisting NRTI (M184V) and PI (V82I and L90M) mutations after a short treatment interruption (this virus remained phenotypically sensitive to DRV/r). Both patients showed sustained HIV RNA suppression to week 48 remaining with the same treatment.
Conclusions: Emergence of drug resistance after changing a suppressive triple antiretroviral therapy to DRV/r with or without nucleoside analogues is uncommon.

• 出版日期2011