Can Statins Reduce Inflammation in People with HIV?

Statin medications such as atorvastatin (Lipitor), usually used to lower blood cholesterol, may also reduce immune activation in HIV positive people, according to a small study described in the March 15, 2011, Journal of Infectious Diseases. Reducing immune activation and inflammation may decrease the risk of chronic non-AIDS conditions such as cardiovascular disease, but a much larger study will be required to demonstrate clinical benefits.

There is now substantial evidence that excessive immune activation and chronic low-level inflammation triggered by persistent virus may help explain the higher risk of cardiovascular disease, neurocognitive dysfunction, and other non-AIDS conditions seen in people with HIV, even while CD4+ T-cell counts remain high. Large studies including SMART and FRAM have found that elevated levels of inflammation biomarkers are associated with increased risk of death, progression to AIDS, and non-AIDS conditions.

In the present study, Anuradha Ganesan from the National Naval Medical Center and colleagues conducted a randomized trial to investigate the effects of atorvastatin on viral load and cellular markers of immune activation among HIV positive people who were not on antiretroviral therapy (ART).

Statins -- also known as HMG-CoA reductase inhibitors -- were developed and approved for reducing LDL "bad" cholesterol in the blood, but more recent research has shown that they also reduce inflammation throughout the body. A few studies have suggested that statins may suppress HIV replication and lower viral load, but data are conflicting.

Ganesan's group analyzed 24 participants who were randomly assigned to receive either 80 mg atorvastatin or placebo each day for 8 weeks. Then, after a 4-6 week "washout" period, they switched to the other treatment assignment.

All participants were men, 63% were white, and they were relatively young, with a median age of 30 years. They had CD4+ cell counts above 350 cells/mm3 and none were on ART. Their LDL cholesterol levels were below the usual threshold for using statins (< 130 mg/dL). All but 2 patients completed the study.

The researchers measured HIV RNA levels as well as immune activation, indicated by expression of CD38 and HLA-DR surface markers on CD4+ and CD8+ T-cells. They did not, however, measure inflammation biomarkers such as C-reactive protein.

Results

Based on these findings, the investigators concluded, "Short-term use of atorvastatin was associated with modest but statistically significant reductions in the proportion of activated T lymphocytes."

While this study was not large enough and not designed to demonstrate a clinical benefit, the authors said that understanding the mechanisms by which statins influence immune activation markers may suggest new approaches for managing inflammation and its detrimental effects in people with HIV. They noted, however, that it will be important to also study the effects of statins in people on ART with undetectable viral load.

In an accompanying editorial, Andrew Carr from St. Vincent's Hospital in Sydney speculated that other statins besides atorvastatin are unlikely to suppress HIV.

He recommended that this class of drugs should be further assessed in larger and longer trials to evaluate their effects on HIV-related inflammation, but acknowledged that "[a] very large study would probably be required to determine whether the potentially positive effects of statin therapy on inflammatory markers 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."

Investigator affiliations: National Naval Medical Center, Division of Infectious Diseases and Infectious Disease Clinical Research Program, Uniformed Services University, Bethesda, MD; Naval Medical Center San Diego, Division of Infectious Diseases, CA; AIDS Monitoring Laboratory, Clinical Services Program, Science Applications International Corporation-Frederick, Inc, National Cancer Institute, Frederick, MD; Biostatistics Research Branch, Clinical Research Section, National Institute of Allergy and Infectious Diseases, Bethesda, MD; Department of Medicine, Drexel University College of Medicine, Philadelphia, PA; Merck Research Laboratories, North Wales, PA; Pharmaceutical Product Development, Incorporated, Wilmington, DE; HIV Drug Resistance Program, National Cancer Institute, National Institutes of Health, Frederick, MD.

2/25/11

References

A Ganesan, and others. High dose atorvastatin decreases cellular markers of immune activation without affecting HIV-1 RNA levels: results of a double-blind randomized placebo controlled clinical trial. Journal of Infectious Diseases 203(6): 756-764 (free full text). March 15, 2011.

A Carr. Statins as anti-inflammatory therapy in HIV disease? (Editorial). Journal of Infectious Diseases 203(6): 751-752 (free full text). March 15, 2011. March 15, 2011.