ABSTRACT
Capravirine is a nonnucleoside reverse-transcriptase inhibitor (NNRTI) with a unique resistance profile. Although single mutations allow resistance to established NNRTIs, human immunodeficiency virus (HIV)-1 must undergo multiple mutations to achieve resistance to capravirine. In the present phase 1 study, capravirine was administered orally for up to 28 days to 55 HIV-1-infected individuals with CD4+ T lymphocyte counts of 50-500 cells/microL. The most frequent adverse events were diarrhea (5%) and nausea (4%), with no drug-related rashes observed. The day 15 median (mean) HIV-1 load decreased by 1.34 (1.45) log(10) copies/mL in the patients receiving 25 mg/kg/day. Capravirine demonstrated potent antiviral activity, even in antiretroviral-experienced patients.
Subject(s)
Anti-HIV Agents/therapeutic use , HIV Infections/drug therapy , HIV-1 , Reverse Transcriptase Inhibitors/therapeutic use , Administration, Oral , Anti-HIV Agents/adverse effects , Anti-HIV Agents/pharmacokinetics , CD4 Lymphocyte Count , Diarrhea/chemically induced , Female , Humans , Imidazoles , Male , Nausea/chemically induced , Reverse Transcriptase Inhibitors/adverse effects , Reverse Transcriptase Inhibitors/pharmacokinetics , Sulfur Compounds , Viral LoadABSTRACT
BACKGROUND: hNM01 is a humanized monoclonal antibody that binds to the V(3) region of the HIV-1 envelope protein gp120. This binding leads to the activation of complement and the disruption of the viral envelope. OBJECTIVES AND STUDY DESIGN: The aim of this study was to investigate the clinical responses of the individuals when treated with the humanized antibody NMO1. In this phase I study, four HIV-1 infected patients with CD4 counts between 50 and 500 cells/mul received a total of four doses of hNM01 in an intrapatient dose escalation fashion: day 1-0.2 mg/kg, day 15-1 mg/kg, day 29-5 mg/kg, and day 43-5mg/kg. Patients were required to have virus that reacted to hNM01 by a virion capture assay and to have a viral load > or =15,000 copies/mL. RESULTS AND CONCLUSION: The antibody was well-tolerated; no significant adverse events were observed even at the highest dose tolerated. None of the patient developed either human anti-hNM01 (anti-idiotype) or human anti-rat antibodies. The mean elimination half-life was 153 h (6.4 days). During hNMO1 therapy effects were observed on CD4 cell counts and plasma viral loads and further dose finding trials are necessary to better determine the therapeutic activity of hNM01 in HIV-infected individuals.
