TreatmentUpdate 69, Volume 8, No 5; July 1996
Sean Hosein

CMV causes the sight-threatening eye infection CMV retinitis in some people with AIDS, often those with less than 50 CD4+ cells. CMV also attacks the brain, intestines (called CMV colitis) and lungs. Although the anti-CMV drugs foscarnet and ganciclovir are effective, short-term treatment, patients must have a tube installed in their veins as these drugs have to be taken frequently, in some cases daily. This places them at an increased risk for bacterial infections and also reduces quality of life. Researchers have made a form of ganciclovir that can be taken by mouth as capsules and these may be more convenient. To delay and/or prevent the appearance of CMV disease (retinitis, colitis) doctors have tested oral ganciclovir in people with AIDS who were at risk of developing CMV disease.

Study details

All subjects (8 female, 717 male) had less than 100 CD4+ cells, the average being about 27 cells. Roughly 54% of subjects had had a life-threatening infection before entering the study and 94% had used anti-HIV drugs. All subjects had CMV infection but none had signs/symptoms when they entered the study. Researchers randomly assigned 486 subjects to receive ganciclovir 1 gram three times daily, and 239 others to receive fake drug (placebo). At least half the subjects remained in the study for 1 year.

Results

Over a period of 12 months the researchers found that:

* 26% of subjects on placebo

* 14% of subjects on ganciclovir

developed CMV disease - largely retinitis and a few cases of CMV colitis. Looking at retinitis alone the researchers found that:

* 24% of subjects on placebo

* 12% of subjects on ganciclovir

developed CMV retinitis after 1 year. Thus, oral ganciclovir reduced the development of CMV retinitis by 50%. This result was statistically significant, that is; not likely due to chance alone.

Other infections

Use of anti-HIV drugs and the anti-herpes drug acyclovir did not appear to affect the protection provided by ganciclovir. Subjects who received ganciclovir were less likely to develop signs/symptoms of other herpes virus infections.

Survival

By the 12th month, 26% of subjects receiving placebo and 21% receiving ganciclovir had died. This difference was not statistically significant.

Toxicity

About 16% of subjects on placebo and 19% on ganciclovir stopped taking their drugs because of side effects. Interestingly, 74% of subjects on placebo reported symptoms such as

* diarrhea

* nausea

* vomiting

* loss of appetite.

Seventy-seven percent of subjects receiving ganciclovir reported similar symptoms. Subjects given ganciclovir were more likely to have less than normal levels of a type of white blood cell called neutrophils than subjects on placebo, a difference that was statistically significant. Doctors were more likely to prescribe bone marrow stimulants (G-CSF) for subjects receiving ganciclovir than those on placebo.

Based on these results, people with AIDS with less than 100 CD4+ cells, particularly those with less than 50 CD4+ cells and who had CMV infection were able to delay the appearance of symptoms of CMV disease by using oral ganciclovir. In this study, samples of blood and urine were analysed for CMV. Those samples in which the virus was detected indicated CMV infection. So the critical decision for doctors is to identify which of their patients are at high risk of CMV disease (CMV isolated from fluid samples) and thus those who might benefit from oral ganciclovir.

REFERENCES:

1. Spector SA, McKinley GF, Lalezari JP, et al. Oral ganciclovir for the prevention of cytomegalovirus disease in persons with AIDS. New England Journal of Medicine 1996;334(23):1491-1497.

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Copyright © 1996 - TreatmentUpdate. Reproduced with permission. Reproduction of this article (other than one copy for personal reference) must be cleared through the Editor, The Canadian AIDS Treatment Information Exchange, 555 Richmond St. West, Suite 505, Box 1104, Toronto, ON, M5V 3B1 • Phone: 416-203-7122 • Toll Free: 1-800-263-1638 • Fax: 416-203-8284  http://www.catie.ca