Bulletin of Experimental Treatments for AIDS, No. 26 September 1995
Harvey Bartnof, MD

The first article is a Phase I/II Study that evaluated the benefits of different doses of ganciclovir. The lead author is Stephen Spector, MD, and colleagues from the University of California at San Diego. Co-authors include Stephen Follansbee, MD, and W. Lawrence Drew, MD, from UCSF. Nineteen people were chosen for primary prevention intervention, while 50 were enrolled for the prevention of recurrent disease. Five different dosing regimens were used.

Decreased CMV was found in all bodily fluids tested. The following numbers of days to progression of CMV retinitis were observed with the following dosing regimens: 1,000 mg every 8 hours, 62 days; 2,000 mg every 8 hours, 139 days; 500 mg every 3 hours, 148 days; 750 mg every 3 hours, 75 days; and 1,000 mg every 3 hours, 148 days. Participants tolerated all dosage regimens fairly well. Most toxicity occurred at daily dosages approaching 6,000 mg daily. Absorption from the stomach into the bloodstream (oral bioavailability) was relatively low at 2.6-7.3%.

The second article is a multicenter trial of people with HIV who already had stable CMV retinitis after receiving IV ganciclovir. One hundred twelve (112) participants were randomized to receive oral ganciclovir, 500 mg 6 times daily for 20 weeks. In the other randomized group, 47 received IV ganciclovir, 5 mg per kg once daily, for 20 weeks.

Progression of CMV retinitis occurred in 72% of the those who received oral ganciclovir after a mean of 51 days. Progression occurred in 76% of the IV group after a mean of 62 days. The differences were not statistically significant. Progression was measured by photographs taken of the retinae and read by ophthalmologists blinded to the types of treatments. Non-blinded physicians who knew which medication the participants were taking when evaluating the retina arrived at somewhat different conclusions. Those results favored the IV group, but their interpretations are likely to be biased. Those individuals in the oral ganciclovir group had less neutropenia (low white blood cell counts) and less sepsis (blood infection with life-threatening low blood pressure); the lower sepsis rate is due to the lack of a long-term indwelling catheter needed by the IV group. Oral ganciclovir appears to be effective for preventing CMV retinitis and for maintenance therapy (see article on CMV r! etinitis by Mark Bowers in this is sue of BETA and related articles in BETA, September 1994, pages 10-11).

Spector SA and others. Pharmacokinetic, safety, and antiviral profiles of oral ganciclovir in persons infected with human immunodeficiency virus: a phase I/II study. Journal of Infectious Diseases 171(6): 1431-1437. June 1995.

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 9:471-477. May, 1995.

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