The number of drugs needed to maintain lifelong HIV RNA suppression is currently debated. We aimed to compare the effects of ART simplification strategies on the risk of virological failure in CoRIS.
We selected ART-naive patients initiating triple ART from 2004 to 2017 in CoRIS who achieved undetectable viral load in the first 48 weeks of ART and either remained in triple therapy during their entire follow-up or were subsequently simplified to dual or monotherapy. The outcome was virological failure, defined as at least two consecutive viral loads >50 copies/ml. The type of regimen (triple, dual or mono) and time on regimen were analyzed as time-varying covariates. We calculated cause-specific cumulative incidence curves and used multivariate Cox proportional hazards models adjusted for potential confounders to estimate hazard ratios (HR). The proportional hazards assumption was checked graphically and by tests based on Schoenfeld residuals. HR were calculated for <24 and ≥24 months of ART to meet the proportional hazards assumptions.
From 14458 patients, 8416 met the inclusion criteria; 7665 remained in triple therapy, 424 switched to dual therapy and 327 to monotherapy. At baseline, subjects who remained in triple therapy were more likely to be men, younger, HCV negative, HBs antigen positive, showed higher pre-ART CD4 counts and initiated ART more recently than those who switched to dual or monotherapy (all P<0.05). The median time from enrolment to censoring date was 4.9, 6.9 and 8.4 years in the triple, dual and monotherapy groups, respectively (P<0.001). In the dual and monotherapy groups, the median time of regimen maintenance was 1 and 1.3 years, and 15% and 34% switched to triple therapy during follow-up, respectively. After adjustment for potential confounders, ART simplification was associated with greater risk of virological failure after 24 months from simplification (P=0.003), which was driven by higher risk in the monotherapy group.
Conclusions: In this large cohort representative of a real-life setting, we found that the durability of the simplified ART regimens was limited and, compared to triple therapy, monotherapy was associated with greater risk of virological failure in the monotherapy group, with no significant differences between dual and triple therapy. While additional information on long-term outcomes is needed, our results are consistent with the data reported in clinical trials.