HAMBURG, GERMANY -- Simultaneously giving AIDS patients the antiviral ganciclovir via pill as well as in a tiny pellet implanted in the eye delays or prevents complications of cytomegalovirus (CMV), one of the most common opportunistic infections associated with AIDS, reports Emory University's Daniel F. Martin, M.D., during his presentation Oct. 11 of a late-breaking abstract at the Sixth European Conference on Clinical Aspects and Treatment of HIV Infection. Dr. Martin also presented this data Sept. 29 in Toronto at a session of the Interscience Conference on Antimicrobial Agents and Chemotherapy.
Dr. Martin and his colleagues from Roche Ganciclovir Study Group and elsewhere randomly assigned 377 AIDS patients diagnosed with CMV retinitis in one eye to receive one of the following three treatments: 1) ganciclovir eye implant plus ganciclovir pill, 2) eye implant plus placebo pill or 3) intravenous ganciclovir.
"Patients who received the combination therapy had by far the best outcomes," says Dr. Martin, principal investigator of the trial and assistant professor of Ophthalmology at the Emory University School of Medicine. He concludes the abstract by saying, "Oral ganciclovir 4.5 grams daily, used in conjunction with an intravitreal ganciclovir implant, delays the onset of new CMV disease and time to progression of CMV retinitis and reduces the incidence of Kaposi's sarcoma."
In addition, subjects in the combined therapy group had fewer hospitalizations and spent less time in the hospital when they were admitted. The incidence of new AIDS-associated conditions was also reduced among those subjects receiving combined therapy.
Median survival time among the groups, though not statistically significant, was 568 days for the combination group, 388 for the implant-alone group and 426 for the intravenous group.
"Improvement in the quality of patients' lives with the combined therapy is substantial," Dr. Martin says. "We've shown that combining eye implants with capsules offers a positive alternative to the undesirable intravenous administration of ganciclovir that eventually requires hours-long, daily infusions and the insertion of a permanent indwelling catheter in the chest."
After six months of treatment, 22.4 percent of subjects on combined treatment developed CMV retinitis in the unaffected eye or developed new extraocular CMV complications, compared with 37.8 percent of subjects on implant-alone or 17.9 percent on intravenous therapy. The researchers calculated that adding the pill to the implant treatment reduced the overall risk of developing new systemic CMV complications by 40 percent.
Systemic administration of ganciclovir either by pill or intravenous catheter significantly reduced the development of Kaposi's sarcoma, a cancer common among AIDS patients that is not, however, considered a complication of CMV. Only 1.5 percent of subjects receiving the antiviral intravenously and 2.7 percent receiving it by pill and implant developed the cancer compared to 11.3 percent of patients who received the implant alone.
Study authors include the following: Dr. Martin; Baruch D. Kuppermann MD, Ph.D. of University of California, Irvine; Rick Wolitz of Kaiser Permanente, San Francisco; Alan Palestine of Georgetown University; and Charles Robinson of Roche Global Development, Palo Alto, Calif.
The study was funded by Roche Global Development.
Treating CMV in Persons with AIDS
B A C K G R O U N D
Cytomegalovirus (CMV) retinitis is the most common opportunistic infection of the eye in patients with AIDS and is the most common complication of CMV disease. Without treatment, CMV damages the light-catching retina on the back wall of the eye -- and can thus lead to blindness.
Prior to the advent of highly active antiretroviral therapy (HAART), up to 45 percent of persons with AIDS were affected. The incidence is now reduced but still remains a significant problem.
1994 -- Daniel F. Martin, M.D., assistant professor of Ophthalmology, Emory University School of Medicine, published the first randomized, controlled trial that evaluated the ganciclovir eye implant. Results suggested the implant was highly effective for delaying CMV retinitis in patients with AIDS, but patients remained at risk for development of CMV disease outside of the involved eye. (Arch Ophthalmol 1994 Dec;112:1531-9)
1996 -- Chiron Vision receives U.S. marketing clearance by Food & Drug Administration for Vitrasert Implant for treating CMV retinitis in AIDS patients. The implant is co-marketed by Chiron Vision and Hoffmann-La Roche.
1997 -- The Ganciclovir Implant Study Group reported in the July 10 New England Journal of Medicine a comparison of ganciclovir administered via eye implant and intravenously. Dr. Martin was second author of that paper. (N Engl J Med 1997 July;337 :83-90)
Cytovene, the trade name for ganciclovir marketed by Hoffmann-LaRoche, inhibits replication of CMV, and thus closes the progression of complications associated with CMV disease. Cytovene-I.V. is indicated for the treatment of CMV retinitis in immunocompromised patients, including those with AIDS, and for preventing CMV in transplant recipients at risk for CMV. Cytovene capsules are indicated only for preventing CMV in solid organ transplant recipients and in persons with advanced HIV infection at risk for CMV. Cytovene capsules are also available as an alternative to the intravenous form for maintenance treatment of CMV retinitis in certain immunocompromised patients, including AIDS patients.