‘Continue CMV Prophylaxis for 2 to 3 Months After Starting HAART’

SAN FRANCISCO—“The onset of highly active antiretroviral treatment (HAART) has dramatically changed the epidemiology of cytomegalovirus (CMV) retinitis, leading to a 90% to 95% reduction in incidence among patients with AIDS,” W. Lawrence Drew, MD, PhD, of the University of California, San Francisco, said at a conference on globally emerging viral infections.

Manifestations of CMV

Human cytomegalovirus (CMV) as an opportunistic infection has two major manifestations, retinitis and pneumonia. The incidence of CMV retinitis is high in AIDS patients with low CD4 counts, while CMV pneumonia occurs more often in immunosuppressed transplant recipients.

Dr. W. Lawrence Drew explained that “the higher prevalence of CMV retinitis in AIDS patients may stem from HIV damage to the retina, as evidenced by cotton wool spots, vascular injury that may be the forerunner allowing CMV to further damage the retina.” CMV pneumonia , on the other hand, is thought to be an immunologically mediated host response, not entirely due to invasion by the virus, which would account for its higher incidence in transplant recipients than in AIDS patients.

With respect to epidemiology, he said, “CMV has remarkable parallels with Kaposi’s sarcoma herpesvirus (KSHV). Both viruses usually require another condition—either AIDS or immunosuppression—to cause disease.”

This improvement has come about because CMV retinitis is rare among patients with CD4 cell counts above 100 cells/mm³ or even 50 cells/mm³, he said, and one effect of HAART is a rapid increase in CD4 count.

However, “CMV retinitis has not been completely eliminated in these patients,” Dr. Drew said, “because if they start treatment with very low CD4 counts, although these counts rise briskly, they don’t get immediate restoration of full immune function.” CMV viral load after 1 to 2 months of HAART remains elevated; at 2.5 to 4.5 months, it drops 1 log; and at 13 weeks, some patients still have elevated levels.

Thus, there is a 2 to 3 month lag after HAART begins during which prophylaxis of CMV or close ophthalmologic monitoring must continue, until full immunologic restoration. Three drugs are FDA approved for CMV treatment: ganciclovir (Cytovene), foscarnet (Foscavir), and cidofovir (Vistide). (Only ganciclovir has FDA approval for prophylaxis.)

Although initially effective, these drugs eventually permit relapses due to limitations in drug delivery and the development of resistant CMV strains.

New assays for CMV are now commercially available, Dr. Drew said, including CMV DNA hybrid capture. Individuals with very high CMV DNA values have a 70% likelihood of getting CMV retinitis within a year and should be considered for prophylaxis.

“Right now we don’t have to think about prophylaxis in any serious way in patients responding well to HAART,” Dr. Drew said, “but in those failing HAART, either because of toxicity or actual virologic failure coupled with immunologic failure, you may again want to think about prophylaxis or certainly close monitoring by an ophthalmologist.” In patients with low CD4 counts, a rising CMV DNA value over time will predict CMV retinitis.