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CMV retinitis is a serious eye disease that affects 40 percent of patients with advanced AIDS and can lead to blindness.
The study reported on five patients who had taken protease inhibitors. Although the treatment was successful in fighting HIV infection as evidenced by a rise in patient CD4+ cells, the increase to approximately 200 cells per cubic millimeter from fewer than 100 did not protect them from developing CMV retinitis.
"Previously we believed that patients who had CD4+ cell counts below 50 were susceptible to CMV retinitis," said Mark Jacobson, M.D., associate professor of medicine at the UCSF AIDS Program at San Francisco General Hospital and the first author of the study. "Now we have found that patients can have counts well over 100 and still develop CMV retinitis and that it might be triggered by taking protease inhibitors."
The researchers commented in the study, which was published in the May 17 issue of Lancet, that these observations have important implications for treatment.
"If you give protease inhibitors to a patient with low CD4+ cells, you need to be vigilant. In the cases we reported, the patients developed CMV retinitis within a few weeks. Clinicians should be aware that patients with CD4+ cell counts well over 100 can be affected and that an increase in CD4+ cells following protease inhibitor treatment is not necessarily protective," Jacobson said.
The cause of the phenomenon is not yet understood, he said. However, it is possible that as the patients responded well to the protease inhibitor therapy, the effect of their strengthened immune systems was to trigger the onset of CMV retinitis. This could happen, Jacobson said, as the protease inhibitors subdued the HIV infection sufficiently for the body to increase its infection-fighting CD4+ cells which are destroyed by HIV. Those new and increased numbers of infection-fighting cells would then seek out and "attack" CMV infection in the retina of the eye creating an inflammatory response in the process thus leading to CMV retinitis.
The study was conducted in collaboration with National Institute of Allergy and Infectious Diseases AIDS Clinical Trials Group (ACTG) sites around the country and was supported by a grant from the ACTG.
Co-authors of the study are Peter R. Pavan, M.D., University of South Florida, Tampa; Fred Sattler, M.D., and Narsing Rao, M.D., University of Southern California/Los Angeles County Medical Center; Susan Owens, Frontier Sciences, Buffalo, NY; Richard Pollard, M.D., University of Texas, Galveston; Michael Zegans, M.D., UCSF fellow at the Francis I. Proctor Foundation/UCSF; and James J. O'Donnell, M.D., UCSF professor and vice-chair of ophthalmology.
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