Faculty Bibliography

Ten patients with AIDS and progressive cytomegalovirus disease were treated with ganciclovir and foscarnet concurrently. The patients had received ganciclovir and foscarnet monotherapy a median of 330 days before receiving combination therapy for a median of 80 days. Nine of the 10 patients responded to the combination. No electrolyte abnormalities were noted during combination therapy, but rates of neutropenia (relative rate, combination vs. ganciclovir, 1.99; P = .229) and thrombocytopenia (relative rate, combination vs. ganciclovir, 1.53; P = .616) were higher with combination therapy than with either drug alone. The relative rate of anemia was significantly increased with combination therapy compared with monotherapy (relative rate, combination vs. ganciclovir, 2.69; P = .025). These data suggest that combination ganciclovir and foscarnet therapy after failure of either alone appears to be as effective as standard therapy with single agents. The rate of anemia with combination therapy was significantly greater than either agent alone, but no significant difference was noted among the other parameters of toxicity studied

This compassionate-use study examined the efficacy of foscarnet in patients with AIDS and cytomegalovirus (CMV) gastrointestinal disease who had failed ganciclovir induction. Nineteen male homosexuals with AIDS and biopsy-proven CMV gastrointestinal disease who had twice failed standard ganciclovir induction (defined as progression of clinical CMV disease) were studied. Foscarnet 60 mg/kg every 8 h was administered intravenously for 14 days, then maintenance was utilized at 90 or 120 mg/kg every day with 1 L normal saline daily. Endpoints included endoscopic appearance, blinded histopathologic analysis of biopsies for CMV inclusions, and changes in symptoms by 50% from baseline. Patients were evaluated before and 2-3 wk after foscarnet. Histopathologic improvement was seen in 67%, whereas 74% improved clinically after a median duration of 7.5 days (1-12). Among the nine with esophageal disease, six patients (68%) had a clinical response and six of eight (75%) had a pathologic response. Among the 10 with colonic disease, eight patients (80%) had a clinical response and six (60%) had a pathologic response. Reversible elevations in creatinine were seen in two of 17 (12%). Three patients with esophageal disease developed strictures late in therapy requiring dilation. Median survival after foscarnet induction was 5.0 months. Foscarnet appears to induce remission of CMV gastrointestinal disease in 67% of patients when ganciclovir induction has failed. Reversible nephrotoxicity occurred in 12%. Strictures may be a late complication of CMV esophagitis

Cytomegalovirus (CMV) is a common cause of diarrhea in patients infected with the human immunodeficiency virus (HIV). Infection with this entity is typically regarded as an effect of severe immunosuppression, only seen in AIDS patients when their CD4+ count is below 100 cells/mm3, and usually below 50 cells/mm3. We report two cases of HIV seropositive patients without a history of prior opportunistic infections, both with CD4+ counts over 500 cells/mm3 (510, and 664) documented on two separate occasions. Each patient presented with diarrhea and fever. One also had cramping abdominal pain, and the other hematochezia. Examination of stool samples for enteric bacterial pathogens, ova and parasites, acid fast bacilli, fungi, and assay for Clostridium difficile toxin failed to reveal an etiology. On sigmoidoscopy, the colonic mucosa of each appeared erythematous and inflamed. Biopsies of mucosa showed characteristic CMV inclusions and inflammation, diagnostic for CMV colitis. Both patients underwent induction with ganciclovir, which resulted in clinical endoscopic improvement. Post treatment biopsies showed no evidence of CMV. These patients illustrate the remarkable variability of CMV infection in patients infected with HIV. In patients with CD4+ counts above 500 who present with diarrhea of unknown etiology, CMV must remain a consideration