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Switching
to Atazanavir (Reyataz) Improves Metabolic Disorders in Antiretroviral-experienced
Patients with Severe Hyperlipidemia
Hyperlipidemia is a common and significant problem among treatment-experienced
patients with HIV disease that can lead to severe cardiovascular
effects. The aim of this German study was to describe
the efficacy and change in lipid profile in patients with severe
hyperlipidemia
after switching to an atazanavir
(Reyataz)-containing HAART regimen.
This was an open
label, 24-week, prospective observational cohort study including
33 HIV-infected, antiretroviral-experienced patients with hyperlipidemia.
Changes in lipid
profiles were evaluated by analyses of triglycerides,
total
cholesterol, high- and low-density lipoprotein (HDL
and LDL) cholesterol, and efficacy by HIV RNA and CD4 cell changes,
both from baseline to week 24.
Results
·
A
rapid and significant decrease of 46% (P = 0.002) in triglyceride
levels was shown.
·
Similarly,
a sustained improvement of 18% was observed in total cholesterol
levels during the first 24 weeks after switching to atazanavir (P
= 0.001).
·
After
24 weeks of treatment there was a significant decrease of 22% in
non-HDL cholesterol (P = 0.003).
·
HDL
and LDL cholesterol profiles did not change significantly nor did
the viral load or CD4 cell count.
The authors conclude,
“Switching to atazanavir results in a significant improvement in
HIV therapy-induced hyperlipidemia.
“A switch to atazanavir
is proposed as a valuable option to improve atherogenic lipid profiles
while maintaining virologic control.”
Discussion
This
study demonstrates the beneficial effects on hyperlipidemia after
switching to an atazanavir-containing regimen in pretreated HIV-infected
patients. Patients receiving atazanavir therapy showed a significant
decrease in triglyceride and total cholesterol levels. Most of these
changes occurred in as little as 4 weeks after switching the regimen.
Reduction
of triglycerides was more pronounced than reduction of total cholesterol
and remained stable during the total study period of 24 weeks. Such
improvement may have an influence in reducing the risk of cardiovascular
effects, the need for lipid-lowering agents, and the associated
risks of drug-drug interactions. In addition, reduction in high
triglyceride levels may lead to a significant decrease in the risk
for developing acute pancreatitis.
Finally,
hypertriglyceridemia and increased free fatty acids have been proposed
to significantly contribute to insulin
resistance in HIV-associated lipodystrophy
together with the direct drug-mediated mechanisms. The study authors
speculate that a beneficial intervention on these factors could
potentially also improve fat redistribution, peripheral and hepatic
insulin resistance, and hepatic steatosis.
Although only
incompletely assessed in this study, many HIV-infected patients
receiving PI therapy develop signs and symptoms of the metabolic
syndrome including hypertriglyceridemia,
hypercholesterinemia, low HDL cholesterol, insulin resistance, and
central
obesity. The clinical features of the metabolic syndrome
in HIV-seronegative patients are associated with increased risk
of cardiovascular disease,
including greater risk of CHD for a given level of LDL cholesterol,
and premature death. Several studies indicate the positive association
between the metabolic syndrome and cardiac morbidity.
In
this study the investigators observed a 21.7% decrease in non-HDL
cholesterol after 24 weeks of treatment with atazanavir. Thus, switching
to atazanavir successfully ameliorates secondary targets for lipid
therapy in patients with normal LDL cholesterol and moderate to
high hypertriglyceridemia--a condition present in a significant
proportion of the study cohort. Future studies should analyze the
impact of a switch to atazanavir on the proportion of patients that
achieve their individual lipid goals.
The
researchers were are able to show that switching patients with hyperlipidemia
to an ART containing atazanavir leads to a significant reduction
in total cholesterol, non-HDL cholesterol, and triglyceride levels
and is therefore a treatment option in patients with a high-risk
lipid profile for cardiovascular events.
Virologic and Immunologic Outcome and Treatment Failure
At
baseline only 16 (48.5%) of all 33 participants had HIV-1 RNA levels
<50 copies/mL. Overall, 19 of 33 study subjects (57.6%) showed
HIV-1 RNA levels <50 copies/mL after 24 weeks of treatment and
9 of 16 (56.3%) after 48 weeks. Mean HIV RNA and CD4 cell count
changes from baseline to 24 or 48 weeks were not statistically significant.
Two patients (6.1%) experienced virologic
failure under atazanavir therapy defined as increase
in HIV RNA levels above the level of quantification (50 copies/mL)
from baseline and 10 patients (30.3%) remained having detectable
viral replication. All patients with detectable viral replication
had been heavily pretreated prior to starting the study.
In addition to
the favorable lipid changes, therapy with atazanavir appears to
be safe, effective, and well tolerated. It remains to be addressed
to what extent the changes in the lipid profile correlate with a
decrease in cardiovascular events.
05/23/05
Reference
U
Mobius and others. Switching to Atazanavir Improves Metabolic Disorders in Antiretroviral-Experienced
Patients with Severe Hyperlipidemia. Journal of Acquired Immune Deficiency
Syndromes 39(2):174-180, June 1, 2005.
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