Stereotactic biopsy of cerebral lesions in AIDS.

Stereotactic brain biopsy was used to establish diagnoses of conditions in patients with AIDS. Two hundred fifty stereotactic biopsies and one open resection were performed for 243 patients. Pathologically abnormal tissue was obtained in 246 (98%) of the procedures, and 16 patients (6%) had >1 diagnosis. Diagnoses included lymphoma in 82 (33%), progressive multifocal leukoencephalopathy in 73 (30%), and tumors not ordinarily associated with AIDS in 7 (3%). In one-third of the cases, the tissue diagnosis differed from the predicted diagnosis. Four of the first 32 patients (12%) developed intracranial bleeding hours after surgery, which was fatal in 3 (9%). Subsequently, all patients were treated with a coagulopathy protocol that included preoperative and postoperative administration of coagulation factors, and there were no further instances of delayed bleeding in the 218 subsequent patients. Among those later patients, there were 7 complications (3%), leading to 4 deaths (2%), a complication rate that compares favorably with that among patients without AIDS.

Improving patient adherence with antiretroviral therapy: evaluation of once-daily administration of didanosine.

One important goal of antiretroviral therapy should be simplification of treatment regimens whenever possible, in order to enhance adherence and potentially improve treatment outcome. While the nucleoside didanosine (ddI) has generally been dosed twice daily in clinical trials, the long intracellular half-life (>12 h) of its active metabolite, dideoxyadenosine triphosphate, should permit once-daily administration of this antiretroviral agent. The STADI trial evaluated this possibility by administering once-daily ddI and twice-daily stavudine (d4T) to antiretroviral-naive patients with human immunodeficiency virus type 1 (HIV-1) infection. This combination was well tolerated and at the end of 24 weeks of therapy, viral load was reduced by -1.48 log copies/ml and HIV-1 RNA was below the lower limit of quantification (500 copies/ml) in 62% of patients. Twenty-four weeks of treatment with d4T plus once-daily ddI increased average CD4 cell counts by 139/ml. The effectiveness of once-daily administration of ddI will be evaluated further in a new multinational clinical trial, AI454-148, in which it will be combined with d4T and the protease inhibitor, nelfinavir. The primary endpoint of this trial will be durable reduction of plasma HIV-1 RNA below 400 copies/ml. Such a change in the treatment regimen for this nucleoside has the potential to improve patient adherence and, thus, treatment outcome.

Surgical therapy for 101 patients with acquired immunodeficiency syndrome and symptomatic cholecystitis.

BACKGROUND: Hepatobiliary disease in patients with acquired immunodeficiency syndrome (AIDS) has been well documented. Cytomegalovirus and Cryptosporidium are the pathogens most frequently associated. Previous reports of cholecystectomies and AIDS have had conflicting results on morbidity and mortality. METHOD: Retrospective review of 101 patients with AIDS and symptomatic cholecystitis who underwent cholecystectomy from December 1989 to May 1995. RESULTS: All patients had symptoms characteristic of gallbladder disease, the most common being abdominal pain and fever. Thickening of the gallbladder was the most common diagnostic finding. Fifty-six patients underwent open cholecystectomy and 45 laparoscopic cholecystectomy. Pathologic examination revealed an abnormal gallbladder in all cases and gallstones in 29%. A specific pathogen or malignancy was identified as the etiologic agent in 44% of patients. Perioperative morbidity was similar (<5%) in both surgical groups. Perioperative mortality was 4% among all the patients treated. CONCLUSIONS: Both open and laparoscopic cholecystectomy improved the quality of life of these patients and should be considered as the treatment for persistent hepatobiliary symptoms in patients with AIDS.

Oral atovaquone compared with intravenous pentamidine for Pneumocystis carinii pneumonia in patients with AIDS. Atovaquone Study Group.

OBJECTIVE: To test the hypothesis that the therapeutic success rate of oral atovaquone is not worse than that of intravenous pentamidine in the primary treatment of mild and moderate Pneumocystis carinii pneumonia in patients with the acquired immunodeficiency syndrome and to detect differences in the toxicity rates of the two treatments. DESIGN: Patients were randomly assigned to receive 21 days of open-label therapy with either atovaquone, 750 mg orally with meals three times daily, or intravenous pentamidine, 3 to 4 mg per kg body weight once daily. SETTING: Multicenter study including university and community treatment facilities. PATIENTS: Patients with human immunodeficiency virus infection and clinical presentations consistent with mild or moderate P. carinii pneumonia were eligible. For efficacy and safety analyses, patients with histologically confirmed P. carinii pneumonia were emphasized. MEASUREMENTS: Patients were monitored by clinical and laboratory evaluations for therapeutic efficacy and adverse events during the acute treatment phase and for 8 weeks after therapy was discontinued. RESULTS: As initial therapy for a histologically confirmed episode of P. carinii pneumonia, 56 patients received atovaquone and 53 received pentamidine. More patients were successfully treated with atovaquone (57%) than with pentamidine (40%), a difference of 17% (95% CI, -3% to 38%; P = 0.085), but more patients failed to respond to atovaquone (29%) than to pentamidine (17%), a difference of 12% (CI, -6% to 29%; P = 0.18). Discontinuation of original therapy because of treatment-limiting adverse events was more frequent in the pentamidine group (36%) than in the atovaquone group (4%) (difference, -32%; CI, -48% to -17%; P < 0.001). Nine patients in each treatment group died during the study. CONCLUSIONS: Oral atovaquone and intravenous pentamidine have similar rates for successful treatment of mild and moderate P. carinii pneumonia, but atovaquone has significantly fewer treatment-limiting adverse events.

Candida osteomyelitis. Report of five cases and review of the literature.

Candida species have emerged as important pathogens in human infection. Although a variety of deep-seated candidal infections have been reported, Candida osteomyelitis has rarely been described. Five patients with Candida osteomyelitis are presented, and the 32 adult cases previously reported are reviewed. Candida osteomyelitis is noted as a simultaneous occurrence or late manifestation of hematogenously disseminated candidiasis. Osteomyelitis may not be prevented by a course of amphotericin B adequate to control the acute episode of disseminated candidiasis, particularly in immunosuppressed patients. Less commonly, Candida osteomyelitis presents as a postoperative wound infection. Like bacterial osteomyelitis, the most common presenting symptom is local pain. The insidious progression of infection, the nonspecificity of laboratory data, and the failure to recognize Candida as a potential pathogen may lead to diagnostic delay. Diagnosis can be made by either open biopsy or closed needle aspiration. Successful therapeutic regimens have employed combinations of antifungal therapy (most often amphotericin B) with surgical debridement when indicated. It is anticipated that osteomyelitis will become a more commonly recognized manifestation of hematogenously disseminated candidiasis.