Faculty Bibliography

OBJECTIVE: To provide recommendations for the treatment of acquired immunodeficiency syndrome-related cytomegalovirus (CMV) end-organ diseases, including retinitis, colitis, pneumonitis, and neurologic diseases. PARTICIPANTS: A 17-member panel of physicians with expertise in clinical and virological research and inpatient care in the field of CMV diseases. EVIDENCE: Available clinical and virological study results. Recommendations are rated according to the quality and strength of available evidence. Recommendations were limited to the treatment of CMV diseases; prophylaxis recommendations are not included. PROCESS: The panel was convened in February 1997 and met regularly through November 1997. Subgroups of the panel summarized and presented available information on specific topics to the full panel; recommendations and ratings were determined by group consensus. CONCLUSIONS: Although the epidemiological features of CMV diseases are changing in the setting of potent, combination antiretroviral therapy, continued attention must be paid to CMV diseases in patients infected with the human immunodeficiency virus to prevent irreversible endorgan dysfunction. The initial and maintenance treatment of CMV retinitis must be individualized based on the characteristics of the lesions, including location and extent, specific patient factors, and characteristics of available therapies among others. Management of relapse or refractory retinitis must be likewise individualized. Ophthalmologic screening for patients at high risk for retinitis or who have a prior diagnosis of extraretinal disease is recommended. Recommendations for gastrointestinal, pulmonary, and neurologic manifestations are included

A decision-analytical simulation model was constructed to perform a pharmacoeconomic analysis of the following 3 treatment strategies for previously untreated cytomegalovirus (CMV) retinitis in patients with AIDS: (i) intravenous foscarnet (IVF) for induction and maintenance therapy; (ii) intravenous ganciclovir (IVG) for induction and maintenance therapy; and (iii) intravenous ganciclovir for induction therapy, followed by oral ganciclovir for maintenance therapy (IVG-ORG). Patients who experienced significant adverse effects during, or who failed, initial therapy were switched once to one of the other 2 treatments. The model was used to estimate the direct medical cost (from the perspective of a public payer), survival, and survival adjusted for disutility because of lost vision, for each strategy in the first year following treatment initiation. The expected first-year costs of treatment initiated with IVF, IVG and IVG-ORG were $US47,918, $US38,817 and $US32,036 (1994 values), respectively, while expected first-year survival was 41 weeks, 35 weeks and 35 weeks, respectively. The incremental cost per incremental year of survival using IVF was $US78,000 versus IVG and $US138,000 versus IVG-ORG before adjustment for lost vision, and $US93,000 versus IVG and $US166,000 versus IVG-ORG after adjustment for lost vision. About 23% of the cost of the IVG treatment strategy was attributable to treatment-related adverse events, compared with 14% of the cost of IVF and 16% of the cost of IVG-ORG. Because of the high failure rate with IVG-ORG, initial treatment with IVG-ORG frequently led to switching to another treatment. Only 27% of the costs associated with the IVG-ORG treatment strategy were in fact attributable to the cost of induction and maintenance therapy prior to a switch to alternative treatment. In this analysis, initial treatment with IVG-ORG was the least costly approach for treating CMV retinitis in patients with AIDS. Initial treatment with IVF resulted in slightly longer survival adjusted for vision-related quality of life. New treatments for AIDS may reduce the survival benefit of initial treatment with IVF

Wasting decreases immune function, and is associated with decreased quality of life and increased mortality in patients with AIDS. Many modalities have been used in the treatment of this problem, but few promote positive nitrogen balance and increase body cell mass. We studied 21 patients with AIDS-related weight loss, defined as loss of greater than 5% usual body weight, or a baseline of less than 100% ideal body weight (IBW). Patients were treated with oxandrolone, 10 mg orally, twice daily. All subjects were men who acquired HIV through unprotected homosexual sex, with the exception of one woman who acquired the disease through unprotected heterosexual contact. The mean age of patients was 38 years, and mean CD4 count was 55. All patients were evaluated with bioelectrical impedance analysis (BIA). BIA mean values for weight, body cell mass (BCM), fat, intracellular water (ICW) and extracellular water (ECW) were calculated for patients at baseline, and then for those patients who took the medication for 30 days, 60 days, 90 days, and 120 days, respectively. Mean changes from baseline in weight, BCM, fat and ICW were significant (p is less than 0.05) at all points in time (except at 120 days, due to the small sample size at this time). At 30 days, weight increased by a mean of 6.5 pounds, BCM increased by a mean of 3.4 pounds, fat increased by a mean of 1.6 pounds, and ICW increased by a mean of 1.4 liters. At 60 days, weight increased by a mean of 12.9 pounds, BCM increased by a mean of 6.9 pounds, fat increased by a mean of 3.0 pounds, and ICW increased by a mean of 2.9 liters. At 90 days, weight increased by a mean of 11.3 pounds, BCM increased by a mean of 4.2 pounds, fat increased by a mean of 5.2 pounds, and ICW increased by a mean of 1.8 liters. At 120 days, weight increased by a mean of 16.0 pounds, BCM increased by a mean of 6.6 pounds, fat increased by a mean of 6.8 pounds, and ICW increased by a mean of 2.7 liters. Change in ECW was significant (p is less than 0.05) only at 90 days. At that time, ECW was decreased by a mean of 1.1 liters from baseline. Of note, values for mean body composition, including % ideal body weight, % BCM, and % fat were also recorded at baseline, and at 30-day intervals thereafter, and were noted to rise steadily throughout the study period. Percent IBW increased from 92.2% at baseline to 101.3% at 90 days and to 106.7% at 120 days. Treatment with oxandrolone resulted in a significant (p is less than 0.05) increase in weight gain, and importantly, in BCM at 90 days. A significant (p is less than 0.05) increase in ICW and a significant (p is less than 0.05) decrease in ECW were also found to occur at 90 days. Final analysis for the 120-day follow-up has not been completed at this time. Thus, the common nutritional abnormalities that occur in AIDS-related weight loss and wasting were reversed

Ten patients with AIDS and cytomegalovirus (CMV) gastrointestinal infection were included in an open-label study to evaluate the safety, efficacy, and pharmacokinetics of 90 mg of intravenous foscarnet/kg of body weight twice daily accompanied by (pre)hydration of 500 to 750 ml. Efficacy was documented endoscopically, while safety was evaluated clinically by patient reports and physical and laboratory observation. The pharmacokinetics of foscarnet was evaluated after the first dose and following approximately 20 days of therapy. Nine patients (90%) responded histopathologically, nine (90%) responded endoscopically, and nine (90%) responded symptomatically to foscarnet therapy. Adverse events resulted in discontinuance of medication in the case of one patient. The mean maximal concentration was 621 microM following the first dose and 687 microM at steady state (P = 0.11). The apparent elimination rate constant and elimination half-life were not different between dose 1 and steady state. There were no significant changes in foscarnet excretion or renal clearance between dose 1 and steady state. The steady-state volume of distribution was 23.4 liters following the first dose and 19.0 liters at steady state (P < 0.002). Twice-daily foscarnet appeared to be safe and efficacious in the treatment of CMV gastrointestinal disease in this study, resulting in endoscopic or histologic improvement in 9 of the 10 (90%) patients. Minor changes in clearance and volume of distribution noted at steady state compared to single-dose administration are readily explained by study design, known information about foscarnet pharmacokinetics, and changes in body weight and creatinine clearance in the patients

Liver involvement with opportunistic infections and neoplasms is a well-recognized component of AIDS, affecting most patients. The cause of hepatic disease in these patients may be divided into hepatitis, granulomatous disease, mass lesions, vascular lesions, hepatotoxic drugs, and nonspecific findings. With a rational approach, most patients with AIDS and liver disease can be diagnosed and treated in a cost-effective manner with low morbidity