One of the largest studies to date to assess the safety and efficacy of
cholesterol-lowering drugs in HIV-infected people shows that statins and
fibrates produce clinically meaningful improvements in lipid profiles but that
these drugs may not be quite as effective in this group as they are in
HIV-uninfected individuals [1].

The study is published in the March 3, 2009 issue of the Annals of Internal
Medicine.

"Dyslipidemia, particularly hypertriglyceridemia, is more difficult to treat in
patients with HIV infection than in the general population," the study authors,
led by Dr Michael J Silverberg (Kaiser Permanente, Oakland, CA), write. But
Silverberg, in an interview with heartwire, emphasized that the difference in
efficacy among HIV-infected subjects was small, particularly for LDL, and may in
some cases be overcome by adjusting doses of cholesterol medications or changing
the HIV-treatment regimen.

Elevated cholesterol and associated coronary events are known side effects of
HIV medications, most notably protease inhibitors (PIs) and nucleoside reverse
transcriptase inhibitors, but may also be related to other metabolic factors or
even the virus itself. As such, whether standard lipid-lowering drugs produce
the same benefits in HIV-infected people as they do in the general population
remains unclear.

Treating Abnormal Lipids in HIV

Silverberg et al's study compared LDL and triglyceride levels among 829
HIV-infected subjects and 6941 patients without HIV over a 12-month period. They
found that HIV-infected patients started on statin therapy experienced smaller
reductions in LDL over follow-up than did noninfected subjects, although the
absolute differences were small. By contrast, reductions in triglyceride levels
were substantially greater in the non-HIV-infected group for the population as a
whole, a difference of 15%. In an interesting secondary finding, however,
Silverberg et al reported that patients whose HIV was being treated with a
non-nucleoside reverse transcriptase inhibitor (NNRTI), instead of a PI or
combination therapy, and who were taking gemfibrozil for their cholesterol
experienced reductions in triglycerides that were no different from the
reductions seen in non-HIV-infected subjects.

"We're not saying that everyone who has high triglycerides, who is HIV positive,
needs to be on NNRTIs, because treating their HIV disease really needs to take
priority," Silverberg commented. "But if it's possible to have patients on an
NNRTI, then that's a good therapeutic approach to have them on an NNRTI and
treat with the fibrate, because then they are likely to have responses to
treatment that are identical to the HIV-uninfected persons."

As the authors note in the paper, the National Cholesterol Education Program
(NCEP) Adult Treatment Panel III (ATP III) guidelines recommend treating
HIV-infected patients to target LDL and triglyceride levels but note that
first-line statins should be pravastatin and atorvastatin, since lovastatin and
simvastatin are known to have adverse drug-drug interactions with PIs. To
heartwire, Silverberg explained that this means HIV-infected patients may need
to take higher doses of pravastatin--the most commonly used statin among
HIV-infected patients in the study, he said--to achieve the same effects of more
potent statins used in the non-HIV-infected population. This, in part, explains
the higher number of rhabdomyolysis cases (three patients) in the HIV group as
opposed to the non-HIV-infected group (one patient), and a slight increase in
abnormal laboratory results in the HIV-infected subjects.

Grant support for the study was provided by GlaxoSmithKline; the authors
disclosed having no financial conflicts of interest.


Silverberg MJ, Leyden W, Hurley L, et al. Response to newly prescribed
lipid-lowering therapy in patients with and without HIV infection. Ann Intern
Med 2009; 150:301-313.