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.
OBJECTIVE
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.
Kirk
O
O
Departments of Infectious Diseases, Hvidovre Hospital, University of Copenhagen, Hvidovre, Denmark. oki@cphiv.dk
Gerstoft
J
J
Pedersen
C
C
Nielsen
H
H
Obel
N
N
Katzenstein
T L
TL
Mathiesen
L
L
Lundgren
J D
JD
D000328:Adult; D015331:Cohort Studies; D005260:Female; D015658:HIV Infections / Q000188:drug therapy*; D006801:Humans; D019469:Indinavir / Q000009:adverse effects; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D016016:Proportional Hazards Models; D011480:Protease Inhibitors / Q000009:adverse effects / Q000145:classification / Q000627:therapeutic use*; D016032:Randomized Controlled Trials as Topic; D012307:Risk Factors; D019438:Ritonavir / Q000009:adverse effects; D019258:Saquinavir / Q000009:adverse effects; D017211:Treatment Failure; D016312:Treatment Refusal; D015431:Weight Loss
D011480:Protease Inhibitors; D019469:Indinavir; D019258:Saquinavir; D019438:Ritonavir