The Safety and Effectiveness of Ganciclovir in the Prevention of Cytomegalovirus (CMV) of the Eyes and Disease of the Stomach and Intestines in Patients With HIV

A Randomized, Comparative, Placebo-Controlled Trial of the Safety and Efficacy of Oral Ganciclovir for Prophylaxis of Cytomegalovirus (CMV) Retinal and Gastrointestinal Mucosal Disease in HIV-Infected Individuals With Severe Immunosuppression

To evaluate the safety and efficacy of oral ganciclovir for prophylaxis against cytomegalovirus (CMV) retinal and gastrointestinal mucosal disease in HIV-infected patients with severe immunosuppression.

The most recent treatments against CMV disease have been ganciclovir and foscarnet. Until recently, both drugs required intravenous administration. An oral form of ganciclovir, if shown to be effective therapy against CMV, would be a more suitable method of administration for prophylaxis.

The most recent treatments against CMV disease have been ganciclovir and foscarnet. Until recently, both drugs required intravenous administration. An oral form of ganciclovir, if shown to be effective therapy against CMV, would be a more suitable method of administration for prophylaxis.

Patients are randomized in a 2:1 ratio to receive either oral ganciclovir or placebo for a minimum of 12 months. PER AMENDMENT 9/19/94: Patients who have not reached a study endpoint may choose to continue blinded prophylaxis or discontinue blinded prophylaxis and begin open-label ganciclovir. PER AMENDMENT 5/2/95: After the common closing date (6/3/95) patients who have not met a CMV end point or experienced a serious toxicity that required permanent discontinuation of active oral ganciclovir will be eligible to receive open-label oral ganciclovir through an open-label extension phase of study 023 until 8/31/95.

Inclusion Criteria

Concurrent Medication:

Allowed:

• Antiretroviral therapy.
• Anti-PCP prophylaxis.
• Maintenance or prophylaxis therapy for other opportunistic infections besides CMV.

Patients must have:

• Working diagnosis of HIV infection.
• CD4 count <= 100 cells/mm3.
• Positive CMV serology (IgG) or CMV culture, in the absence of active disease, documented at any time prior to study entry.
• Reasonably good health.
• Life expectancy of at least 6 months.

Exclusion Criteria

Co-existing Condition:

Patients with the following symptoms or conditions are excluded:

• Acute life-threatening illness.
• Active lymphoma.
• Hypersensitivity to acyclovir.
• Lack of willingness or ability, in the opinion of the clinician, to comply with protocol requirements.

Concurrent Medication:

Excluded:

• Vidarabine.
• Amantadine hydrochloride (Symmetrel).
• CMV hyperimmune globulin/intravenous immune globulin.
• Cytarabine.
• Fiacitabine (FIAC) or fialuridine (FIAU).
• Foscarnet.
• Intravenous ganciclovir.
• HPMPC.
• Idoxuridine.
• Intravenous acyclovir.
• Oral acyclovir at > 1 g/day.
• Other drugs with potential anti-CMV activity.

Prior Medication:

Excluded within 60 days prior to study entry:

• Foscarnet.

Excluded within 2 weeks prior to study entry:

• Vidarabine.
• Amantadine hydrochloride (Symmetrel).
• CMV hyperimmune globulin/intravenous immune globulin.
• Cytarabine.
• Fiacitabine (FIAC) or fialuridine (FIAU).
• Ganciclovir.
• HPMPC.
• Idoxuridine.
• Intravenous acyclovir.
• Oral acyclovir at > 1 g/day.
• Other drugs with potential anti-CMV activity.