High-dose statin therapy suppresses immune activation in
antiretroviral-naïve HIV-positive patients, according to the results of a small
clinical trial published in March 15th edition of The Journal of Infectious Diseases.
However, there was no evidence that treatment with statins
lowered viral load.
Nevertheless, the investigators were encouraged by their
finding that statin therapy “may influence the chronic immune activation
observed in HIV-infected patients” and call for longer, larger studies “to investigate
any clinical benefit of this drug for HIV-infected patients.”
But the author of an accompanying editorial cast doubt on
the clinical significance of the study’s findings, and notes that the significance of changes in
markers of immune activation in response to treatment is unknown.
Statins are best known as lipid-lowering drugs. However,
laboratory studies suggest that they may also have an anti-HIV effect and may lower
levels of immune activation.
Studies looking at the effect of statin therapy on viral
load have had conflicting results.
To gain a better understanding of the anti-HIV effects of
statins, US investigators designed a randomised, double-blind, placebo
controlled, cross-over study. It involved a total of 22 HIV-positive patients.
None were currently taking antiretroviral therapy and all had a CD4 cell count
above 350 cells/mm3.
They were randomised into arms. The first was treated with a
once-daily 80 mg dose of atorvastatin, the other with a placebo. After eight
weeks, treatment was stopped and was followed by a “washout” phase, after which
the patients switched their treatment assignments and the study entered a
second eight-week phase.
The investigators monitored the impact of statin therapy on
viral load. Tests were also performed to assess the impact of the drug on
markers of cellular immune activation: expression of CD38 and HLA-DR on CD4 and
CD8 cells. Liver and kidney function were regularly monitored to assess the
safety of treatment.
During the statin phase of therapy, viral load fell by a
median of 0.03 log10 copies/ml, compared to a fall of 0.08 log10
copies/ml during the placebo phase. These differences were not significant, and
the investigators comment: “we did not observe an overall effect on HIV-1 RNA
However, statin therapy did have an effect on markers of
cellular immune activation.
Expression of HLA-DR on CD4 cells and CD8 cells was
significantly lower during treatment with atorvastatin than during the placebo
phase (p = 0.02 and p = 0.0060 respectively. In addition, statin therapy lead
to a reduction in expression of both CD38 and HLA-DR on CD8 cells (p = 0.03).
The investigators noted that the patients who had the
greatest reductions in immune activation when taking statins also had the
biggest falls in their viral load.
Total cholesterol and LDL cholesterol were also
significantly reduced during the statin phase of the study (both p < 0.001).
However, there was no relationship between levels of cholesterol and markers of
Treatment was safe, and none of the patients had moderate or
severe changes in their liver function. Three patients had altered kidney
function, but this was possibly connected to their patterns of exercise.
“Although atorvastatin had no overall effect on HIV-1 RNA
levels in our study, its used resulted in significant reductions in the
proportion of activated CD8+ T lymphocytes,” write the
They stress that their study was not “designed to
demonstrate clinical benefits” and they call for larger studies with longer
follow-up periods to investigate any benefits from therapy with this drug.
Nevertheless they conclude: “The availability of generic
formulations and the results of recent studies revealing a benefit to statin
use in the primary prevention of cardiovascular disease, a common complication
in HIV-infected patients, make the continued study of statins as
disease-modifying agents in HIV-infected individuals particularly attractive.”
Andrew Carr, the author of the accompanying editorial, believes that the
results of this study mean that statins should be evaluated over a longer
period in a trial involving patients who are taking successful HIV therapy, but
who continue to have immune activation.
However, he cautions that “a very large study would probably
be required to determine whether the potentially positive effects of statin
therapy on inflammatory biomarkers will translate into less HIV disease
progression and fewer cases of inflammatory non-AIDS-related illnesses, such as
cardiovascular disease and end-stage liver disease.”