Drug interactions in patients infected with human immunodeficiency virus.

Patients with AIDS who are receiving optimal medical care, including combination therapy with antiretroviral agents and more effective prophylaxis and therapy for opportunistic infections and neoplasms, are surviving longer. However, the potential for drug interactions in these patients is increased because many of the currently used antibiotics and antiviral agents have profound effects on the hepatic cytochrome P-450 enzyme system, on renal tubular function, and on bone marrow function. In this AIDS Commentary, Dr. Piscitelli and colleagues have succinctly reviewed the current state of our knowledge regarding the potential for additive or synergistic drug interactions that can result in enhanced toxicity or, alternatively, augmented therapeutic benefit. Information on these interactions will become more important as more intensive and effective therapy becomes available for persons with far-advanced infection due to human immunodeficiency virus type 1.

Immune-based therapies for treatment of HIV infection.

OBJECTIVE: To review the in vitro, animal, and clinical data on immune-based therapies for treatment of HIV infection. DATA SOURCES: An extensive MEDLINE search was performed for interleukins, interferons, immunotoxins, tumor necrosis factor (TNF)-directed agents, vaccines, and gene therapy. STUDY SELECTION: In vitro experiments with immune-based agents in cell lines infected with HIV were included. In addition, all human studies and case reports that used these agents in patients infected with HIV were selected. Additional literature included abstracts from international meetings on HIV and AIDS. DATA EXTRACTION: Data regarding activity, efficacy, and toxicity were extracted from in vitro and in vivo studies. When conflicting data were observed, both viewpoints were stated to give an unbiased analysis. Because HIV research involves multiple social, ethical, and scientific issues, perspectives on these problems were addressed, where appropriate. DATA SYNTHESIS: Current antiretroviral therapy is limited to short-term responses and has minimal effect on overall survival. Because the human immune response to HIV infection is effective at keeping the virus suppressed for a number of years, a focus of HIV research has been to examine immune-based therapies for treatment of HIV infection that attempt to augment enhance, or boost the patient's immune system. Interleukins, interferons, immunotoxins, TNF-directed therapies, vaccines, and gene therapy have been studied in patients infected with HIV. Properties shared among these therapeutic modalities include adverse effect profiles, response rates dependent on baseline immunocompetence, the potential to activate viral replication, the need for supportive care, and sensitive laboratory tests required for monitoring. CONCLUSIONS: Immune-based agents represent a new approach to the treatment of HIV infection. Whereas antiretrovirals only inhibit viral replication, these agents are designed to enhance the immune system of the patient. Future attempts to manage HIV infection may combine standard nucleoside analogs with immune-based therapies.

Compatibility and activity of aldesleukin (recombinant interleukin-2) in presence of selected drugs during simulated Y-site administration: evaluation of three methods.

The compatibility and biological activity of aldesleukin (a form of recombinant interleukin-2) in the presence of selected i.v. drugs during simulated Y-site administration was studied. Five milliliters of aldesleukin 33,800 IU/mL in 5% dextrose injection was mixed in glass test tubes with 5 mL of each of 19 i.v. drugs prepared at concentrations used in routine clinical practice. The compatibility of the combinations was assessed by visual examination and spectrophotometry at 0, 0.5, 1, and 2 hours after preparation, and bioassays were conducted to determine the activity of aldesleukin in the combinations. Lorazepam was the only drug visually incompatible with aldesleukin. All the secondary drugs were spectrophotometrically compatible with aldesleukin. However, the bioassays showed that the following drugs reduced the activity of aldesleukin: ganciclovir sodium, lorazepam, pentamidine isethionate, prochlorperazine edisylate, and promethazine hydrochloride. Thus, aldesleukin became less biologically active when combined with four drugs for which visual examination suggested compatibility and when combined with five drugs for which spectrophotometry indicated compatibility. Aldesleukin 33,800 IU/mL in 5% dextrose injection lost significant biological activity in the presence of prochlorperazine edisylate, promethazine hydrochloride, lorazepam, ganciclovir sodium, and pentamidine isethionate during simulated Y-site administration. Visual assessment and spectrophotometry may not be valid methods for assessing possible changes in the biological activity of aldesleukin when combined with other agents.

The AIDS research agenda at the National Institutes of Health.

The foundation, goals, and components of the research strategy developed by the National Institutes of Health to combat AIDS and HIV infection are discussed. The AIDS research agenda, based on systems originally designed to coordinate cancer research, involves a national effort to study various aspects of the disease, disseminate information, and rapidly develop and test drugs and vaccines to treat and prevent AIDS and HIV disease. AIDS research makes up approximately 10% of the total NIH budget of $7.6 billion, and the largest portion of that allocation goes to improving current treatments and developing new agents. Drug discovery efforts are supported by the National Institute of Allergy and Infectious Diseases (NIAID) through the Division of Intramural Research, in which biomedical and clinical research is conducted, and the Division of AIDS, which coordinates extramural research in university-based centers and community programs. By providing educational materials and sponsoring conferences, NIAID also helps to disseminate the results of the research it coordinates. Pharmacists support AIDS research through their involvement with study drug products and their role in protocol development, regulatory affairs, product development, and accumulation and distribution of drug information. Research initiatives sponsored by the federal government combine resources of investigators from government, academia, and the pharmaceutical and biotechnological industries to meet the challenges posed by the AIDS epidemic.