The anti-inflammatory drug Disalcid (salsalate) reduces blood vessel inflammation, which may decrease the risk of a heart attack in people living with HIV, according to study results published in the March 12 issue of AIDS. The authors caution, however, that use of the drug may be associated with liver-related side effects, which could limit its use as an adjunctive HIV treatment.
The endothelium is the thin layer of cells that line the inner surface of blood vessels. When the endothelium becomes inflamed, blood vessels have difficulty expanding and contracting as needed, potentially leading to blood clots. Disalcid, a non-steroidal anti-inflammatory drug (NSAID) sometimes used to treat rheumatoid arthritis, has been eyed as a potential strategy to reduce the inflammation and endothelial dysfunction that can be caused by HIV.
Samir Gupta, MD, of the Indiana University School of Medicine in Indianapolis, and his colleagues enrolled 11 people living with HIV who were not taking antiretrovirals, but who had endothelial dysfunction. This was determined using flow-mediated dilation (FMD), a cardiovascular test that measures the ability of blood vessels to expand.
The average age of the patients was 38 years, and 55 percent were black. The average FMD before starting Disalcid was 2.7 percent, which is considered very low and a sign of significant inflammation.
Gupta’s team provided the patients with the maximum daily dose of Disalcid, which is 1500 mg twice daily for eight weeks, in order to increase the chance that a treatment effect would be observed. By week eight, FMD had nearly doubled on average—a statistically significant difference, meaning that the difference was too great to have occurred by chance.
During the course of the study, however, two patients had serious elevations in their liver enzymes and had to stop taking Disalcid. Two other patients had less serious elevations, but had to reduce their dose of Disalcid by half. Though Disalcid and other anti-inflammatory drugs can cause liver toxicity in people who are HIV-negative, it is quite uncommon, and Gupta’s team hadn’t expected so many HIV-positive people in the study to have this side effect.
Gupta’s team again measured FMD eight weeks after stopping treatment in the two patients who’d had the best response to Disalcid. They found that FMD levels returned to pre-treatment levels, indicating that people who need to take anti-inflammatory drugs for this purpose will likely require continuous treatment.
The team comments that, although reducing blood vessel inflammation in people living with HIV is a worthwhile goal, future studies should employ lower doses of Disalcid or agents without known liver side effects. Notably, a separate study conducted in 2007 found antiretroviral therapy on its own can reduce HIV-associated inflammation and improve endothelial function.�
