Low body weight and type of protease inhibitor predict discontinuation and treatment‐limiting adverse drug reactions among HIV‐infected patients starting a protease inhibitor regimen: consistent results from a randomized trial and an observational cohort

Abstract

Departments of Infectious Diseases, 1 Hvidovre Hospital, University of Copenhagen, Hvidovre, 2 Rigshospitalet, University of Copenhagen, Copenhagen, 3 Odense University Hospital, Odense, 4 Aalborg Hospital, Aalborg and 5 Marselisborg University Hospital, Aarhus, Denmark Objectives To assess predictors for discontinuation and treatment‐limiting adverse drug reactions (TLADR) among patients starting their first protease inhibitor (PI). Methods Data on patients starting a PI regimen (indinavir, ritonavir, ritonavir/saquinavir and saquinavir hard gel) in a randomized trial (RAS, n = 318) and an observational cohort (OBC, n = 505) were used to document reasons for discontinuation and TLADR. Risk factors for discontinuation of the initial PI/developing TLADR were assessed in Cox models. Results A total of 43 (RAS) and 48% (OBC) discontinued the initial PI therapy within less than 2 years. In both populations TLADR were the most common reason for discontinuation. The incidence of TLADR in RAS was: 8.5 (indinavir), 66.0 (ritonavir), 15.6 (saquinavir hard gel) per 100 person‐years of follow‐up ( P < 0.001). Body weight and type of PI initiated were independent risk factors for treatment discontinuation and TLADR in both groups. In OBC, the risk of developing TLADR increased by 12% per 5 kg lower body weight when starting the PI regimen [the relative hazard (RH) was 1.12 (95% confidence interval: 1.05–1.19) per 5 kg lighter], and starting ritonavir was associated with a three‐ to sixfold higher risk of TLADR relative to other PI regimens. Very similar results were documented in RAS [RH for body weight was 1.18 (1.07–1.29)]. Conclusions Nearly half of the patients stopped treatment with the initial PI, most commonly as a result of adverse drug reactions. Low body weight and initiation of ritonavir relative to other PIs were associated with an increased risk of TLADRs. Very consistent results were found in a randomized trial and an observational cohort.