Treatment with statins reduces mortality risk for patients taking effective HIV therapy

Treatment with statins significantly reduces the risk of death for patients taking virologically suppressive antiretroviral therapy, US investigators report in the online journal PLoS One. The investigators believe that statins were beneficial because of their anti-inflammatory effects.

The observational study included patients who received their HIV care at Johns Hopkins University, Baltimore, between 1998 and 2009.

Statin therapy reduced the risk of death by 67%.

“We found that statin use was associated with a significantly deceased hazard of dying,” comment the investigators.

It is now well established that HIV infection causes chronic inflammation and immune activation. These are reduced by antiretroviral therapy but still persist at higher levels than those seen in the general population.

Long-term inflammation and immune activation have been associated with an increased risk of cancer, cardiovascular disease, liver disease, and renal failure. These now are important causes of illness and death in patients with HIV.

Therapy with statins has established anti-inflammatory properties and it is also known to dampen immune activation.

Because HIV-positive patients have an increased risk of inflammation-related illnesses, a team of investigators lead by Dr Richard D. Moore conducted an observational study to see if treatment with statins reduced the risk of death.

Recruitment was restricted to 1538 patients who achieved an undetectable viral load within six months of starting antiretroviral therapy. Most  of the patients were men, 72% were black, and 34% had a history of injecting drug use.

A total of 238 individuals (16%) received statins. Most (69%) were taking atorvastatin, with 24% receiving pravastatin and 7% rosuvastatin.

Patients who were treated with statins were older, and they were also more likely to be men and to have been infected with HIV through sex with another man.

The majority of statin users (51%) were already taking the drug when they started antiretroviral therapy, and the median duration of statin treatment was 745 days.

There were 85 deaths, seven of which were in statin users.

Statistical analysis that controlled for both HIV-related and non-HIV-related prognostic factors showed that statin therapy reduced the risk of death by a highly significant 67% (relative hazard, 0.33, 95% CI, 0.14-0.76, p = 0.009).

“We found that patients who maintained virologic suppression on effective HAART [highly active antiretroviral therapy] appeared to derive an additional benefit from the use of statins,” write the authors.

Another factor associated with an increased risk of death was a low haemoglobin level (p = 0.0003).

“Anemia is a reasonable measure of chronic inflammation when more specific inflammatory biomarkers are not routinely measured in clinical practice,” note the investigators.

They add, “anemia has been shown to be associated with survival in HIV-infected persons. The strong association between amemia and survival in our patients whose viral loads were suppressed suggests an independent association between ongoing inflammation and mortality.”

Inflammation related diseases were important causes of death in the cohort, with cancers, non-HIV-related infections and liver failure especially prominent.

The small number of deaths meant that the investigators were unable to say if therapy with any particular statin was especially beneficial. Nor do the authors regard their findings as definitive, cautioning: “It is certainly possible that statins were used selectively in patients with a better survival prognosis and that there are unmeasured confounders that would explain the association we found.”

Nevertheless, they conclude that statin therapy reduced the risk of death for patients who were taking HIV therapy and had an undetectable viral load. They therefore call for further research, writing : “if additional observational data support this finding, a randomized clinical trial would be warranted to confirm this association.”