Effects of ritonavir-boosted darunavir vs. ritonavir-boosted atazanavir on lipid and glucose parameters in HIV-negative, healthy volunteers.
BACKGROUND
Darunavir (TMC114) is a new HIV protease inhibitor (PI).


METHODS
This Phase I, randomized, open-label trial compared the effects of darunavir plus low-dose ritonavir (RTV) (darunavir/RTV) with those of atazanavir/RTV on lipid and glucose parameters.


METHODS
Forty-nine HIV-negative, healthy male volunteers received RTV 100 mg once a day (qd) for 7 days, followed by either darunavir/RTV 800/100 mg qd (n=25) or atazanavir/RTV 300/100 mg qd (n=24) for 21 days. Mean changes in fasting lipid and glucose parameters at day 28 were calculated using post-RTV alone (day 7) and baseline (day -1) values as references. Short-term safety, tolerability and RTV pharmacokinetic parameters were evaluated.


RESULTS
After 7 days of RTV treatment, the mean triglyceride concentration increased by approximately 30 mg/dL in both groups, changes in other lipid and glucose parameters were relatively small. Mean concentrations of lipids and glucose over the treatment period were mostly similar between the treatment groups. Mean changes from day 7 to day 28 for the darunavir/RTV and atazanavir/RTV groups, respectively, were -3.6 and -0.5 mg/dL for high-density lipoprotein cholesterol; 5.0 and 5.3 mg/dL for low-density lipoprotein cholesterol; 4.9 and 1.2 mg/dL for total cholesterol; 6.4 and 14.0 mg/dL for triglycerides; -1.7 and -2.4 mg/dL for glucose; and -1.4 and 0.3 mg/dL for insulin. No grade 3 or 4 lipid or glucose laboratory abnormalities were reported. Treatment-emergent hyperbilirubinaemia was reported for all volunteers (including five grade 4 cases) during atazanavir/RTV treatment.


CONCLUSIONS
Co-administration of darunavir or atazanavir with low-dose RTV resulted in minor and similar changes in lipid and glucose parameters in HIV-negative healthy volunteers.
Tomaka
F
F
Tibotec Inc., Yardley, PA, USA. ftomaka@tibus.jnj.com
Lefebvre
E
E
Sekar
V
V
Van Baelen
B
B
Vangeneugden
T
T
Vandevoorde
A
A
Diego Miralles
G
G
D000293:Adolescent; D000328:Adult; D000069446:Atazanavir Sulfate; D001786:Blood Glucose / Q000187:drug effects* / Q000378:metabolism; D000069454:Darunavir; D004347:Drug Interactions; D016903:Drug Monitoring; D004359:Drug Therapy, Combination; D005215:Fasting; D017320:HIV Protease Inhibitors / Q000008:administration & dosage / Q000009:adverse effects* / Q000493:pharmacokinetics; D018023:HIV Seronegativity; D006801:Humans; D007328:Insulin / Q000097:blood; D050356:Lipid Metabolism / Q000187:drug effects*; D008074:Lipoproteins / Q000097:blood; D008297:Male; D008875:Middle Aged; D009842:Oligopeptides / Q000008:administration & dosage / Q000009:adverse effects* / Q000493:pharmacokinetics; D011725:Pyridines / Q000008:administration & dosage / Q000009:adverse effects* / Q000493:pharmacokinetics; D019438:Ritonavir / Q000008:administration & dosage / Q000009:adverse effects* / Q000493:pharmacokinetics; D013449:Sulfonamides / Q000008:administration & dosage / Q000009:adverse effects* / Q000493:pharmacokinetics; D014280:Triglycerides / Q000097:blood; D055815:Young Adult
D001786:Blood Glucose; D017320:HIV Protease Inhibitors; D007328:Insulin; D008074:Lipoproteins; D009842:Oligopeptides; D011725:Pyridines; D013449:Sulfonamides; D014280:Triglycerides; D000069446:Atazanavir Sulfate; D019438:Ritonavir; D000069454:Darunavir