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Do Statins Reduce Risk of Death for People with HIV?

HIV positive people on suppressive antiretroviral therapy (ART) were significantly less likely to die if they were also taking a statin drug to manage blood lipids, researchers reported in the July 12, 2011, online edition of the open access journal PLoS ONE. The researchers suggested that statins' ability to reduce inflammation may have a survival benefit for people with HIV.

A growing body of evidence links chronic immune activation and persistent inflammation due to HIV infection with non-AIDS conditions such as cardiovascular disease and neurocognitive impairment. Studies indicate that these conditions develop more often and sooner in people with HIV, even if they maintain undetectable viral load on ART.

Antiretroviral treatment reduces inflammation, but not to the level of HIV negative people. Researchers are studying various other approaches for lessening inflammation among people with HIV, including some drugs primarily used for other indications. For example, HMG-coenzyme A reductase inhibitors -- better known as statins -- are known to inhibit several pro-inflammatory processes and dampen immune activation.

Richard Moore and colleagues from Johns Hopkins School of Medicine evaluated whether statins might have a beneficial effect on HIV disease progression and outcomes including mortality.

The analysis included 1538 HIV positive participants in the Johns Hopkins HIV Clinical Cohort who started a new combination ART regimen between January 1998 and December 2009 and achieved virological suppression within 6 months.

About two-thirds were men, 72% were black, 23% were white, and the median age was 43 years; about one-third had a history of injection drug use. The median baseline CD4 count was 225 cells/mm³, 30% took medications for high blood pressure, and 35% had hepatitis C coinfection.

Within this population 238 people (15.5%) were also taking statins: 69% atorvastatin (Lipitor), 24% pravastatin (Pravachol), and 7% rosuvastatin (Crestor). Statin users were older, more likely to be white, had higher baseline CD4 counts, and started ART earlier than non-users. Importantly, this observational study looked at patients who happened to be taking statins for any indication; it did not randomly assign participants to use or not use statins.

Participants were followed until death or until their viral load rose above 500 copies/mL, with a median follow-up period of about 1.5 years.

Results

• There were a total of 85 deaths during follow-up, 7 among statin users and 78 among non-users.
• In a multivariate analysis, statin use was associated with a decrease in the risk of death after adjusting for factors including demographics, CD4 count, HIV viral load, cholesterol level, type of ART, and viral hepatitis coinfection.
• Other factors significantly associated with increased risk of death were older age, low baseline hemoglobin level, injection drug use, and prior AIDS-defining illness.
• The relative hazard of death was 0.33 for the statin user group, indicating a 67% reduction in risk, which was highly statistically significant (P = 0.009).
• The most common causes of death were malignancies, non-AIDS-defining infections, liver failure, and cardiovascular disease.

Based on these findings, the study authors concluded, "Statin use was associated with significantly lower hazard of dying in these HIV-infected patients who were being effectively treated with HAART as determined by virologic suppression."

"[W]e found that patients who maintained virologic suppression on effective HAART appeared to derive additional survival benefit from the use of a statin," they elaborated in their discussion.

"It is notable that a lower baseline hemoglobin was also strongly associated with survival in these patients," the researchers wrote. "'Anemia of chronic disease' is an anemia of chronic inflammation, regulated by the peptide hormone hepcidin, whose expression is increased during inflammation, infection, and iron overload."

"Anemia has been shown to be associated with survival in HIV-infected persons," they continued. "The strong association between anemia and survival in our patients whose viral loads were suppressed suggests an independent association between ongoing inflammation and mortality."

"Arguably, anemia is a reasonable measure of chronic inflammation when more specific inflammatory biomarkers...are not routinely measured in clinical practice," they suggested, adding that since inflammatory biomarkers and cellular markers of immune activation were almost never measured as part of clinical care for this cohort, they were unable to look at associations between these other biomarkers, statin use, and mortality.

The researchers recommended that if these results are confirmed in further observational studies, a randomized clinical trial of statin use in people with HIV would be warranted.

Investigator affiliations: Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD.

8/9/11

Reference

RD Moore, JG Bartlett, and JE Gallant. Association between Use of HMG CoA Reductase Inhibitors and Mortality in HIV-Infected Patients. PLoS ONE 6(7):e21843 (open access). July 12, 2011.