Treatment with protease inhibitors associated with peripheral insulin resistance and impaired oral glucose tolerance in HIV-1-infected patients.
BACKGROUND
The use of protease inhibitors in the treatment of HIV-1 infection is associated with the new onset of diabetes mellitus, hyperlipidaemia and lipodystrophy. It is unclear whether these findings are coincidental or whether they reflect a causative effect of protease inhibitors.


OBJECTIVE
To evaluate the effect of treatment with protease inhibitors on insulin sensitivity, oral glucose tolerance and serum lipids in HIV-infected patients in order to determine whether treatment with protease inhibitors can cause peripheral insulin resistance.


METHODS
Cross-sectional controlled study in HIV-infected patients treated with protease inhibitors to assess insulin sensitivity, oral glucose tolerance and changes in serum lipids.


METHODS
Sixty-seven patients treated with protease inhibitors, 13 therapy-naive patients and 18 HIV-negative control subjects were tested for insulin sensitivity (intravenous insulin tolerance test). In a subgroup of 24 treated patients, oral glucose tolerance was determined. Serum lipids prior to and under treatment with protease inhibitors were compared.


RESULTS
Patients on protease inhibitors had a significantly decreased insulin sensitivity when compared with therapy-naive patients (median, 75 and 156 micromol/l/min, respectively; P < 0.001). All treated patients with impaired (n=4) or diabetic (n=9) oral glucose tolerance, and four out of 11 patients with normal glucose tolerance showed peripheral insulin resistance; all therapy-naive patients had normal insulin sensitivity. Treatment with protease inhibitors led to a significant increase in total triglycerides and cholesterol in the 67 treated patients (median increase, 113 and 37 mg/ml, respectively).


CONCLUSIONS
Treatment with protease inhibitors is associated with peripheral insulin resistance, leading to impaired or diabetic oral glucose tolerance in some of the patients, and with hyperlipidaemia. Overall, there is a large variation in the severity and clinical presentation of protease inhibitor-associated metabolic side-effects.
Walli
R
R
Infektionsambulanz, Medizinische Poliklinik, Ludwig-Maximilians Universität München, Germany.
Herfort
O
O
Michl
G M
GM
Demant
T
T
Jäger
H
H
Dieterle
C
C
Bogner
J R
JR
Landgraf
R
R
Goebel
F D
FD
D000328:Adult; D019380:Anti-HIV Agents / Q000009:adverse effects*; D002784:Cholesterol / Q000097:blood; D005260:Female; D005951:Glucose Tolerance Test; D015658:HIV Infections / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology; D017320:HIV Protease Inhibitors / Q000009:adverse effects*; D015497:HIV-1; D006801:Humans; D007333:Insulin Resistance; D008297:Male; D008875:Middle Aged; D014280:Triglycerides / Q000097:blood
D019380:Anti-HIV Agents; D017320:HIV Protease Inhibitors; D014280:Triglycerides; D002784:Cholesterol