The following article is reprinted from Medscape.com's HIV/AIDS section.
http://www.medscape.com/Medscape/HIV/journal/2001/v07.n06/ca-mha1112.01/ca-mha1112.01.html
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Moyle GJ, Lloyd M, Reynolds B, Baldwin C, Mandalia S, Gazzard
BG
AIDS. 2001;15:1503-1508
Protease inhibitor (PI)-containing HAART regimens
have been associated with hypercholesterolemia and other metabolic disturbances.
Cholesterol elevations are characterized by increases in low-density lipoprotein
(LDL) and very-low-density lipoprotein (VLDL), while high-density lipoprotein
(HDL) remains low despite suppression of viremia. This atherogenic profile has
led to the suggestion that individuals receiving PI-based HAART may be at
elevated risk of vascular events.
The control of hypercholesterolemia in HAART
recipients is complicated by potentially harmful interactions between HMG-CoA
reductase inhibitors (statins) and protease inhibitors due to a common pathway
for metabolism via cytochrome p450 CYP3A. Dietary advice alone has not been
studied as an intervention for PI-associated hypercholesterolemia.
This study was designed to test the efficacy and safety of pravastatin in patients with PI-associated hypercholesterolemia, and to test whether pravastatin was more effective than dietary adjustment alone in controlling cholesterol elevations. Pravastatin is not metabolized by the cytochrome p450 CYP3A pathway and does not bind extensively to plasma proteins. Levels of the drug have been demonstrated to be reduced when combined with ritonavir and saquinavir.
A total of 31 male patients on stable PI-containing regimens with total
cholesterol levels > 240 mg/dL (> 6.5 mmol/L) were randomized to receive
either dietary advice alone or dietary advice plus pravastatin (20 mg once daily
for 14 days, increased to 40 mg once daily thereafter). The study was
open-label.
Dietary intake was assessed at baseline using a 3-day food diary, and an
ideal body weight was recommended for each patient after assessment of intake,
together with exercise and smoking cessation. Mean total cholesterol was 7.4
mmol/L (286 mg/dL) and 7.5 mmol/L (290 mg/dL) in the dietary-advice-alone and
pravastatin groups at baseline.
During the 24-week study, 4 patients withdrew from the dietary-advice-alone
arm of the study, and 1 from the pravastatin arm. There were no discontinuations
due to adverse events. After 24 weeks, total cholesterol had fallen
significantly from baseline in the pravastatin arm (1.2 mmol/L [46 mg/dL], or
17.3%, P < .05) but not in the dietary-advice-only group (0.3
mmol/L, 4%). HDL cholesterol levels increased by 0.6 mmol/L (2.3 mg/dL) in both
groups. At the end of 24 weeks, triglyceride levels had not fallen significantly
in either group, although a 12% decline was noted at week 12 in the pravastatin
group. Patients with the highest baseline cholesterol levels were most likely to
have cholesterol levels above the recommended range at week 24 in the
pravastatin group, suggesting either that a higher pravastatin dose should be
tested in this group, or that other agents such as fibrates should be tested in
combination with pravastatin.
Dietary advice had little effect on intake in the pravastatin group; while
saturated fat intake fell by 38% in the dietary-advice group, it increased by 2%
in the pravastatin group; and while sugar intake was halved in the
dietary-advice group, it fell by only 8% in the pravastatin group.
It is important to note that this study was powered to compare the change
from baseline in each arm, not to compare the cholesterol values at specific
time points across the arms, although the differences between the groups
approached significance over time.
These results indicate that pravastatin may provide an
LDL-cholesterol-lowering benefit in HIV-infected persons receiving PI-based
therapies comparable to that seen in non-HIV-infected populations. It is
interesting to note that the ongoing AIDS Clinical Trials Group study 5087,
which compares fenofibrate and pravastatin in the treatment of HIV-infected
patients with elevated LDL and elevated triglycerides, was modified after an
interim analysis revealed that monotherapy with either agent did not achieve the
rigorous goals for LDL, HDL, and triglyceride levels. This suggests that
aggressive therapy of dyslipidemia may require other, more potent agents or
combination therapy.
Related Article:
-- Safety
and Efficacy of HMG-CoA Reductase Inhibitors for Treatment of Hyperlipidemia in
Patients With HIV Infection
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