Pharmacokinetics of oral ganciclovir alone and in combination with zidovudine, didanosine, and probenecid in HIV-infected subjects.

The aim of this study was to determine whether oral ganciclovir interacted pharmacokinetically with zidovudine (AZT), didanosine (ddI), or probenecid. A multicenter, open-label, randomized, crossover pharmacokinetic study with four phases was undertaken at an outpatient private research center and at university research clinics. Twenty-six HIV-infected adults (23 men, 3 women) with cytomegalovirus (CMV) seropositivity and CD4+ T-lymphocyte count > or =100 cells/microl were studied. Patients had to be stable on antiretroviral therapy for at least 4 weeks. Patients with a history of opportunistic infection or gastrointestinal symptoms were excluded. Measurements included serial blood and urine samples during the dosing intervals at steady state. The steady-state pharmacokinetics of ganciclovir were determined after the participants had stabilized and were tolerating AZT or ddI therapy. When a 1000-mg dose of oral ganciclovir was taken every 8 hours, there was a significant mean increase in Cmax and dosing interval area under the serum concentration time curve over a dosing interval (AUC) for the two antiretroviral drugs: for AZT, 61.6% and 19.5%, respectively; for ddI when administered sequentially (2 hours before ganciclovir), 116.0% and 114.6%; and for ddI administered simultaneously with ganciclovir, 107.9% and 107.1%, respectively. There was no significant change in renal clearance for either antiretroviral drug, suggesting that the interaction did not occur through a renal mechanism. There was no significant change in mean ganciclovir Cmax and AUC(0-8) when coadministered with AZT. Mean increases in Cmax and AUC(0-8) of oral ganciclovir averaged 40.1% and 52.5%, respectively, when coadministered with probenecid, but decreased by 22.1% and 22.7%, respectively, when oral ganciclovir was administered 2 hours after ddI. There was no change in the mean ganciclovir Cmax or AUC(0-8) when administered simultaneously with ddI. The mean renal clearance of oral ganciclovir was not affected by AZT or ddI coadministration intake, but there was a mean decrease of 19% when coadministered with probenecid. We conclude the increased serum concentration and reduced renal clearance of ganciclovir suggests competition with probenecid for secretion at the renal tubule. The mechanism of the interaction of oral ganciclovir with either AZT or ddI remains to be determined. The magnitude of the effect of oral ganciclovir on ddI pharmacokinetics may result in an increase in ddI concentration-related toxicities. Similarly, the small but significant decrease in ganciclovir concentration with sequential combination ddl therapy may impair the efficacy of oral ganciclovir. For HIV-infected patients receiving ganciclovir and ddI, clinicians should recommend administering the two drugs simultaneously, and patients should be monitored closely for ddI-associated toxicities.

Nutritional health: prevention and treatment of HIV-associated malnutrition. A case manager's guide.

AIDS: Nutritional health in HIV-infected patients is critical because it optimizes existing immune system function, can help reduce the incidence of complications of HIV disease, reduces the overall cost of medical care, helps achieve maximum benefit from drug therapies, and improves the patient's quality of life. The following areas of nutrition relative to HIV disease are discussed: nutrition and the immune system; malnutrition and cost of medical care; the immune system; nutritional status and immune function; the effects of HIV disease on nutritional status; and the nutritional management of HIV disease. It is advised that, in order to be most cost-effective and have the greatest benefits, nutritional intervention should begin at the time of HIV disease diagnosis and continue throughout the disease process. Nutritional therapeutic options include nutrition education and counseling, oral supplements and, when necessary, appetite stimulants, anabolic agents and enteral or parenteral nutrition.^ieng

Care model benefits HIV patients, hospitals.

In the battle against acquired immune deficiency syndrome (AIDS), focusing treatment on early intervention of its underlying condition, human immunodeficiency virus (HIV) infection, may help reduce the disability associated with AIDS. A comprehensive care hospital unit featuring physicians with expertise in HIV treatment, clinical research activities, and home health services may offer the most effective care for HIV patients. The preventive nature of comprehensive care also can reduce costs through decreased hospitalization, integrated hospital revenue centers, patients' minimized lost work time, and reduction of medical disability.