Incidence of adverse reactions in HIV patients treated with protease inhibitors: a cohort study. Coordinamento Italiano Studio Allergia e Infezione da HIV (CISAI) Group.
OBJECTIVE
To assess the probability that protease inhibitor (PI) therapy might be discontinued because of adverse events (AE) and to evaluate the incidence rate of adverse reactions during PI treatment.


METHODS
A prospective cohort, multicenter study on HIV-positive patients starting treatment with at least one PI.


METHODS
Ten departments of infectious diseases in Northern Italy.


METHODS
A total of 1207 patients who started PI therapy in September 1997 and were consecutively observed up to April 1999.


METHODS
Adverse reactions following initiation of PI therapy, and time to therapy discontinuation due to AE.


RESULTS
During the study period, 35.9% patients presented adverse reactions of any grade, whereas 9.7% presented at least one serious AE. After 12 months of treatment, the percentage of patients who had interrupted treatment was 36% of ritonavir-treated patients, 14.2% of those treated with indinavir, 13.6% of ritonavir-saquinavir hard gel capsules (HGC)-treated patients, and 8.5% and 2.1%, respectively, for those treated with nelfinavir and saquinavir HGC. Women and patients with hepatitis experienced a significantly greater number of adverse events compared with other categories. Gastrointestinal events were more frequently observed in patients treated with either ritonavir alone or in combination with saquinavir HGC, as well as in patients receiving nelfinavir, although in this group serious events were rare. Here again, neurologic, metabolic, and hepatic toxicity occurred more frequently in ritonavir and ritonavir-saquinavir HGC treated patients. Allergic reactions were more often observed in patients receiving nelfinavir. Indinavir-treated patients presented the highest incidence of renal toxicity.


CONCLUSIONS
Ritonavir is the drug associated with the largest number of reactions, which appear during the first few months of treatment. Saquinavir HGC and nelfinavir are the best tolerated drugs in a clinical setting.
Bonfanti
P
P
First Department of Infectious Diseases, L. Sacco Hospital, Milan, Italy. paolo.bonfanti@tin.it
Valsecchi
L
L
Parazzini
F
F
Carradori
S
S
Pusterla
L
L
Fortuna
P
P
Timillero
L
L
Alessi
F
F
Ghiselli
G
G
Gabbuti
A
A
Di Cintio
E
E
Martinelli
C
C
Faggion
I
I
Landonio
S
S
Quirino
T
T
D000328:Adult; D016907:Adverse Drug Reaction Reporting Systems / Q000706:statistics & numerical data; D015331:Cohort Studies; D016001:Confidence Intervals; D016903:Drug Monitoring / Q000706:statistics & numerical data; D005260:Female; D005500:Follow-Up Studies; D017320:HIV Protease Inhibitors / Q000009:adverse effects* / Q000627:therapeutic use; D006679:HIV Seropositivity / Q000188:drug therapy* / Q000453:epidemiology; D006801:Humans; D015994:Incidence; D019469:Indinavir / Q000009:adverse effects / Q000627:therapeutic use; D007558:Italy / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D019888:Nelfinavir / Q000009:adverse effects / Q000627:therapeutic use; D011446:Prospective Studies; D012307:Risk Factors; D019438:Ritonavir / Q000009:adverse effects / Q000627:therapeutic use; D019258:Saquinavir / Q000009:adverse effects / Q000627:therapeutic use
D017320:HIV Protease Inhibitors; D019469:Indinavir; D019888:Nelfinavir; D019258:Saquinavir; D019438:Ritonavir