Predictors of long‐term HIV RNA suppression on darunavir/ritonavir monotherapy in the MONET trial

Background In previous studies of protease inhibitor (PI) monotherapy, patients with higher nadir CD4 counts, baseline HIV RNA<1 copy/mL and high adherence to treatment have been most likely to show sustained HIV RNA suppression<50 copies/mL. Methods In the MONET trial, 256 patients with HIV RNA <50 copies/mL at screening switched to DRV/r 800/100 mg once daily, either as monotherapy (n=127) or with 2 NRTIs (n=129). HIV RNA results were classified as either<5 (no detection), 5–49 (virus detected under quantification limit) or >50 copies/mL. Treatment failure was defined as two consecutive HIV RNA levels >50 copies/mL (TLOVR) by Week 144, or discontinuation of study drugs. Additional analyses were conducted (i) excluding discontinuations for adverse events or other reasons (ii) including patients who intensified with NRTIs. Multivariate logistic regression was used to identify factors predictive of treatment failure by Week 144. Results By Week 144, the percentage of patients with HIV RNA <50 copies/mL (ITT, TLOVR, Switch=Failure) was 69% versus 75% in the DRV/r monotherapy and triple therapy arms respectively. In the Switch Included analysis, HIV RNA <50 copies/mL was 84.0% versus 83.5% in the DRV/r monotherapy and triple therapy arms respectively. In the multivariate analysis for the TLOVR endpoint, positive HCV serology correlated with treatment failure (odds ratio [OR]=2.44, 95% CI 1.20–5.00). In the analysis including only virological endpoints, both positive HCV serology (OR=2.77, 95% CI 1.18‐6.67) and baseline HIV RNA >5 copies/mL (OR=2.71, 95% CI 1.21‐6.08) predicted treatment failure. In the Switch Included analysis, only HIV RNA >5 copies/mL was predictive of treatment failure (OR=2.78, 95% CI 1.28–6.01). Nadir CD4 count and prior PI use were not predictive of treatment failure in any analysis. In the ITT TLOVR analysis, the response rates in the DRV/r monotherapy arm at Week 144 were 79% (66/84) for HCV‐ve patients with baseline HIV RNA <5 copies/mL, 63% (12/19) for HCV‐ve patients with baseline HIV RNA >5 copies/mL, 47% (9/19) for HCV+ve patients with baseline HIV RNA<5 copies/mL and 20% (1/5) for HCV+ve patients with baseline HIV RNA>5 copies/mL. Conclusions In the MONET trial, patients without HCV co‐infection (based on serology), and with baseline HIV RNA <5 copies/mL by the Roche Amplicor assay (i.e. no virus detected) were most likely to show sustained HIV RNA suppression<50 copies/mL on DRV/r monotherapy.