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Pravastatin and Bezafibrate Show Greater Effectiveness
in Reducing Lipid Elevations Than Switching Therapy from a Protease
Inhibitor to Nevirapine or Efavirenz
Dyslipidemia
in HIV positive individuals on protease
inhibitors remains a serious concern. Drug treatment
has involved either switching from the PI to an NNRTI and/or using
lipid-lowering agents. In the July 1, 2005 issue of AIDS,
researchers report the results of a study that evaluates simplified
protease inhibitor (PI)-sparing antiretroviral treatment versus
lipid-lowering therapy for the management of HAART-induced hyperlipidemia.
This is the first randomized, open-label, clinical trial
to compare PI-sparing simplified therapy with hypolipidemic pharmacological
treatment for the management of HAART-induced dyslipidemia.
This was a
randomized, open-label clinical trial assessing the effect on hyperlipidemia
of switching therapy from PI to non-nucleoside reverse transcriptase
inhibitor (NNRTI) nevirapine (Viramune) or efavirenz (Sustiva)
versus a hypolipidemic treatment (with pravastatin or bezafibrate)
added to current, unchanged antiretroviral combination.
All HIV-infected patients in the study on their first
HAART regimen, with stable immuno-virological features, naive to
all NNRTIs, and with mixed hyperlipidemia, were randomized to replace
PI with nevirapine (arm A) or efavirenz (arm B), or to receive pravastatin
(arm C) or bezafibrate (arm D) with unchanged HAART regimen, and
were followed-up for 12 months.
Results
·
One hundred and thirty
patients were evaluated: 29 patients were randomized to arm A, 34
to arm B, 36 to arm C, and 31 to arm D.
·
At the end of the
12-month follow-up, a reduction of 25.2, 9.4, 41.2 and 46.6% in
mean triglyceridemia
versus respective baseline values was reported in groups A, B, C
and D, respectively, with statistically significant difference between
arms A-B and C-D (P < 0.01).
·
Similar results were
reported for total and low-density lipoprotein cholesterol levels.
·
Viro-immunological
efficacy and tolerability profile were comparable in all considered
arms.
The authors conclude, “Pravastatin and bezafibrate proved
significantly more effective in the management of HAART-related
hyperlipidaemia than the switching therapy from PI to nevirapine
or efavirenz.
Discussion
Lipid-lowering therapy becomes suitable
when dietary changes, physical exercise and switching
treatment are ineffective or not applicable. Drug
therapy for dyslipidemia in HIV-infected persons receiving HAART
is problematic, because of potential drug interactions, toxicity,
intolerance, and decreased patient adherence to multiple pharmacologic
regimens.
Consequently, it is reasonable, say the
authors, to recommend the use of pravastatin (Pravacol) or low dosage
of atorvastatin (Lipitor) as first-line treatment for hypercholesterolemia
in PI-treated patients, and the use of fluvastatin (characterized
by a slightly lower efficacy), as second-line regimen.
On the other hand, note the authors, simvastatin
and lovastatin should be avoided, because they present a great risk
of pharmacological interactions with PIs.
Fibrates represent the cornerstone of drug
therapy for hypertriglyceridaemia and mixed hyperlipidaemia, according
to the authors. Treatment with gemfibrozil, bezafibrate or fenofibrate
generally results in a significant reduction in triglyceride and
cholesterol levels in HIV-infected patients receiving a PI-containing
therapy, with a more evident improvement of hypertriglyceridaemia.
Recent data demonstrate additive effect
for the statin-fibrate combination therapy: the mean reduction in
both cholesterol and triglyceride levels was significantly higher
than with statin or fibrate monotherapy.
“However,” caution the authors, “the statin-fibrate
association therapy should only be used with great caution because
of the increased risk of skeletal muscle toxicity.”
In this study, pharmacological therapy with
pravastatin or bezafibrate proved significantly more effective in
the management of diet-resistant mixed hyperlipidemia in HAART-treated
patients than the switch from PIs to non-nucleoside analogues.
Particularly, hypolipidemic agents obtained
a significantly greater reduction in both triglyceride, total and
LDL and cholesterol levels than simplification therapy with nevirapine
or efavirenz.
With regard to simplification therapy, switch
to nevirapine led to a significantly higher decrease both in plasma
triglyceride and cholesterol concentrations than substitution of
efavirenz for PI.
However, only about 50% of patients in pravastatin
and bezafibrate groups reached normal plasma lipid levels after
a 12-month follow-up, and a slight-to-moderate hyperlipidaemia persisted
in the remaining subjects.
Hypolipidemic compounds and simplification
therapy with NNRTIs showed a favorable tolerability and adherence
profile, according to the authors, and there were no appreciable
differences in the incidence of clinical and laboratory adverse
effects in all the four study groups.
In their closing statement, the authors
write, “In conclusion, simplification of a PI-based treatment with
nevirapine or efavirenz in patients with a sustained virological
response and no prior suboptimal antiretroviral therapy had a significant
probability of maintaining viral suppression, and lowering plasma
lipid levels, but pharmacological treatment with pravastatin or
bezafibrate added to current HAART had a superior hypolipidaemic
efficacy and was usually well tolerated.”
From
the Department of Clinical and Experimental Medicine, Division of
Infectious Diseases, Alma Mater Studiorum University of Bologna,
S. Orsola Hospital, Bologna, Italy.
06/20/05
Reference
L
Calza and others. Substitution of
nevirapine or efavirenz for protease inhibitor versus lipid-lowering
therapy for the management of dyslipidaemia. AIDS 19(10):
1051-1058, July 1, 2005.
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