TreatmentUpdate61; Volume 7, No. 7 - July 1995
Sean Hosein

One of the complications that can occur in people with AIDS is the sight-threatening infection CMV retinitis. This problem usually happens when the CD4+ cell count falls below 50 cells. Although intravenous drugs such as foscarnet and ganciclovir can block the spread of infection, they do not destroy the virus, therefore patients must keep taking anti-CMV drugs for the rest of their lives. Further details on treatment of CMV retinitis appear in TreatmentUpdate56 and 60.

Due to the frequent infusion of medications needed to treat CMV, a small tube must be inserted into some patients to prevent their veins from collapsing. These tubes can become infected, and these infections can be life-threatening. As a result, more people would like the convenience and safety of taking ganciclovir orally.

We now report results from a European/Australian study comparing intravenous ganciclovir to oral ganciclovir as maintenance therapy against CMV.

* STUDY DETAILS

All subjects (149 men and 10 women) were adults with an average CD4+ cell count of 20 cells. Subjects had already been treated for retinitis with intravenous ganciclovir for between 2 and 3 weeks, and their retinitis was stable. Researchers then randomly assigned subjects to receive oral ganciclovir (112 subjects) or intravenous ganciclovir (47 subjects) as maintenance to keep the infection in check. Intravenous ganciclovir was given 5mg/kg/day for 1 hour and oral ganciclovir 500 mg 6 times daily with a "snack or meal." Technicians took photographs of the retina and sent them to a doctor not involved with this study. This investigator analysed the photographs and made decisions (was retinitis getting worse or better?) that were relayed to the study doctors. In this way, researchers hoped to reduce bias in the study. The trial lasted for 20 weeks.

* RESULTS

According to the photographs, CMV retinitis became worse in these subjects later in the study:

+ 72% on oral ganciclovir + 76% on intravenous ganciclovir

On average, subjects developed worsening retinitis in

+ 51 days (oral) + 62 days (intravenous)

This difference of 11 days between the 2 groups was not statistically significant. For subjects who had never used anti-CMV drugs before entering this study, the development of worsening retinitis took:

+ 54 days (oral) + 64 days (iv)

This difference was not statistically significant. Among those subjects who had used ganciclovir before this study, similar events took place in:

+ 37 days (oral) + 38 days (iv)

This difference was not statistically significant. At least half of the subjects used anti-HIV agents while in this study, and although further eye damage seemed to take longer to appear in subjects taking these drugs, researchers discounted this by noting that the number of subjects was small (for those calculations) and that dividing them into sub-groups would not provide meaningful results. This is because as groups get smaller, statistically significant events occur by chance. In any case in two larger important studies where subjects also took anti-HIV drugs and anti-CMV drugs, the anti-HIV drugs did not have any significant effect on the length of time for retinitis to spread.

Roughly 11% to 12% of subjects developed retinitis in both eyes after between 122 and 125 days.

- Infections

Only 3 subjects developed a new herpes virus infection in other parts of their body, 2 on oral and 1 on intravenous ganciclovir.

- Toxicity

There were no statistically significant differences in the side effects reported; anemia, diarrhea, lower-than-normal levels of certain white blood cells (neutrophils) and platelets. Three subjects on iv ganciclovir developed blood infections because of the tubes inserted into them for delivering the ganciclovir. Eleven subjects on oral ganciclovir reported rashes on their skin.

The researchers summarized their results by stating that oral ganciclovir "was well tolerated and...offers the patient and physician an alternative to iv [ganciclovir] in the maintenance of CMV retinitis."

REFERENCES:

1. The oral ganciclovir European and Australian cooperative study group. Intravenous versus oral ganciclovir: European/Australian comparative study of efficacy and safety in the prevention of cytomegalovirus retinitis recurrence in patients with AIDS. AIDS 1995;9(5):471-477.

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Copyright © 1995 - 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