Cholesterol-lowering statin drugs showed a trend toward
lowering the risk of non-AIDS events and death among people with HIV in a large
US cohort, researchers
reported last week at the 19th Conference on Retroviruses and Opportunistic
Infections in Seattle.
observational studies have shown that people with HIV are at higher risk than
the general population for non-AIDS conditions including cardiovascular disease
and cancer. While the underlying cause is not yet fully understood, persistent
HIV infection itself, resulting in inflammation, antiretroviral drug side-effects
and traditional risk factors such as smoking may all contribute.
are exploring a variety of approaches that may help reduce this risk including
medications and lifestyle modifications.
Turner Overton from the University of Alabama at Birmingham
presented findings from a study of statin use and its association with major
clinical events and non-accidental death among participants in the ACTG Longitudinal Linked Randomized Trials (ALLRT) cohort.
This was an observational study looking at what type of treatment patients
happened to receive; they were not randomly assigned to receive or not receive
Statins are generally used to lower elevated low-density
lipoprotein (LDL) or 'bad' cholesterol, but they also have anti-inflammatory
effects and large studies of HIV-negative people have shown that they reduce
the risk of cardiovascular events such as heart attacks and strokes even among
people without elevated cholesterol.
Overton's study included 3601 participants who had started
combination antiretroviral therapy (ART) in an ACTG study and remained in
long-term follow-up. Participants were not taking statins at baseline. About
80% were men, about half were white, 30% were black and the median age was 39
years. The median current CD4 cell count was about 350 cells/mm3,
but the median nadir (lowest-ever) level was 180 cells/mm3.
Looking at baseline cardiovascular risk factors, just under
40% were current smokers, the median systolic blood pressure was 120 (normal),
73% had normal LDL (<130 mg/dL) and only 10% had a Framingham score
indicating high cardiovascular risk.
The researchers looked at how many participants started
statins during the study and time to development of non-AIDS-defining end-organ
disease or non-accidental death. Over the course of follow-up (15,135
person-years), 481 participants (13%) started taking statins and 616 events of
interest occurred. These included 144 new cases of diabetes, 124 severe
bacterial infections, 115 cases of kidney disease, 81 non-AIDS cancers, 42
cardiovascular events, 17 cases of thrombosis (blood clots) or pulmonary
embolism, 9 cases of liver disease, 8 non-traumatic fractures and 76
In an unadjusted analysis more people taking statins
experienced events than those not on statins (4.4 vs 4.0 per 100 person-years),
but this reflected in part the greater risk and poorer health of people who
needed to start these medications.
After controlling for baseline factors, the adjusted hazard
ratio (HR) was 0.81, reflecting 19% reduction in the risk of non-AIDS events or
non-accidental death, but the difference did not reach statistical
significance. When early events were excluded (those occurring soon after
starting statins, before they had much time to work) the risk fell by 12%. The
beneficial effect was greatest for older patients and those with low nadir CD4
Separating out event types, the adjusted risk of
cardiovascular events was 11% lower among statin recipients (HR 0.89) while
non-cardiovascular events decreased by 15% (HR 0.85), both also
non-significant. The only significant decline was in cancer rates, which fell
by 57% among statin recipients (HR 0.43). Looking at non-accidental death
alone, the reduction was 18% (HR 0.82).
The researchers concluded that, "Statin therapy
was associated with a non-significant reduction in time to first non-AIDS
events or death."
"Although not statistically significant, they added,
"the observed effect increased with age and was influenced by nadir CD4
Responding to a question about the reduction in cancer risk,
Overton suggested that perhaps statins might have an influence on immune
surveillance of malignancies.