Could anti-cholesterol statins also be low-cost antiretrovirals?

Spanish researchers have discovered that statins – drugs used to reduce levels of cholesterol in both HIV-infected and -uninfected individuals – prevent HIV infection in the test-tube and in mice and, in a small proof-of-concept study, reduced viral loads and increased CD4 counts in six chronically HIV-positive individuals not on HAART. The study was published in the August 16^th issue of the Journal of Experimental Medicine, and suggests that further research should be done to establish whether statins could be a potentially low-cost addition to the anti-HIV armamentarium.

Statins reduce cholesterol levels by targeting an enzyme known as HMG-CoA. This not only blocks the body’s production of cholesterol but, the researchers suggest, after various studies in the test-tube and in mice infected with human PBMCs (peripheral blood mononuclear cells), also affects another enzyme, Rho guanosine triphosphatase. By interfering with this enzyme, statins block production of an intracellular protein called Rho. Rho is needed by HIV in order to enter cells, and the investigators’ experiments suggest that statins, in this case lovastatin, act on a cellular level in two ways; as an HIV entry inhibitor by preventing HIV from opening the cell membrane, and by preventing the virus from leaving already infected cells.

In order to ascertain whether the test-tube and animal models could work in vivo, the researchers enrolled five men and one woman in a preliminary proof-of-concept study. All six were not on HAART, had a minimum CD4 count of 465 cells/mm³ and had a stable viral load ranging from 16,800 copies/ml to 84,000 copies/ml. The participants were aged between 23 and 53, and three were also co-infected with hepatitis C virus and were also on methadone treatment. The participants were chronically infected with HIV, having been diagnosed with HIV infection between 1996 and 2000, although the date was not determined in one 24 year-old man.

After one month of treatment with 40mg lovastatin once daily, a decrease in viral load and increase in CD4 counts was seen in all six participants. However, only one participant had a greater than one log reduction in viral load, from 84,000 copies/ml to 3,590 copies/ml. The other five had between a 0.2 and 0.9 log viral load reduction. The researchers do not include analysis indicating the statistical significance of their CD4 and viral load measurements, which, in this small study, may have been due to chance. However, viral load measured three months after stopping treatment with lovastatin did show a rebound to pre-treatment levels in most of the participants, and in all cases viral load was higher three months after treatment than on treatment.

Additionally, absolute CD4 counts rose after one month on lovastatin, and fell to baseline levels, or below, in five of the six individuals, although the difference was only obvious in the two individuals with the greatest viral load changes (from 798 cells/mm³ at baseline to 940 cells/mm³ after one month of lovastatin, to 690 cells/mm³ in one individual whose viral load ranged from 16,800 copies/ml to 2330 copies/ml to 16,100 copies/ml during the same period; and from 760 cells/mm³ at baseline to 1010 cells/mm³ after one month lovastatin to 501 cells/mm³ in another individual whose viral load ranged from 84,000 copies/ml to 3590 copies/ml to 26,400 copies/ml).

The authors conclude that having found evidence that statins prevent HIV infection in cultured cells and in animal models, and preliminary evidence that HIV infection reduces viral load and increases CD4 cell counts in chronically infected individuals, “we suggest that these compounds have direct antiretroviral effects and might be appropriate drugs for more accessible treatment of the AIDS pandemic.”