An intensive effort was directed toward studying the preventive and therapeutic aspects of human immunodeficiency virus (HIV) infection and the acquired immunodeficiency syndrome (AIDS). Immunization of healthy volunteers to the gp160 envelope protein of HIV-1 was capable of inducing group specific T lymphocytes directed towards the envelope and titers of neutralizing antibodies as high as 1:8. Phase I trials of AZDU and rCD4-lgG failed to demonstrate efficacy in HIV infection. Low-dose GM-CSF reversed the neutropenia caused by interferon-alpha (IFN-alpha) plus zidovudine (ZDV) without impairing the antiretroviral activity of the combination. A randomized trial comparing therapy with ZDV versus IFN-alpha versus the combination in 180 patients with early HIV-1 infection completed accrual and will be undergoing interim analysis. A controlled trial of foscarnet demonstrated significant benefit in patients with AIDS-related cytomegalovirus retinitis. Phase I/II trials were continued of ZDV + IFN-Alpha, ZDV + IL-2, IFN-Alpha + IL-2. and DDI + IFN-Alpha. BW566C80 was shown to be effective for mild to moderate episodes of pneumocystis carinii pneumonia (PCP) as well as for salvage therapy of central nervous system (CNS) Toxoplasmosis. A multi-center phase II/III study of BW566C80 versus trimethoprim- sulfamethoxazole for treatment of PCP, and a phase 1 study of BW566C80 for treatment of cryptosporidial/microsporidial diarrhea, were also begun. Phase 1 studies of L-697,639 and L-697,661 established the safety and oral bioavailability of both agents. A randomized, double-blinded, phase II study of L-697,661 versus ZDV was initiated using surrogate markers as efficacy parameters. Phase 1 studies of N-acetyl cysteine and CD4-Pseudomonas Exotoxin (sCD4-PE-40) in HIV-infected patients were initiated. A phase 1 analysis of clarithromycin established the oral bioavailability of this agent and a study of its efficacy in MAl-infected patients was initiated. A study of azithromycin as salvage therapy in CNS Toxoplasmosis was also begun. Immunotherapy protocols involving active immunization of HIV-1 infected individuals with HIV-1 gp160 or p24 were continued, and passive immunotherapy utilizing peripheral blood lymphocytes and bone marrow from gp160 primed donors was also instituted.
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