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Delavirdine (DLV) in combination with zidovudine (ZDV) causes sustained antiviral and immunological effects in HIV-1 infected individuals
Freimuth WW; Wathen LK; Cox SR; Chuang-Stein CJ; Greenwald CA; Daemzer
November 30, 1996
3rd Conf Retro and Opportun Infect. 1996 Jan 28-Feb 1;:162. Unique

Delavirdine mesylate, a potent non-nucleoside reverse transcriptase inhibitor, has been shown in vitro to be highly effective in blocking HIV-1 viral replication in strains that were either highly resistant or sensitive to ZDV. To evaluate the synergy between DLV and ZDV, HIV-1 infected individuals with CD4 counts 200-500 were enrolled into a blinded protocol in which patients were stratified into four treatment arms (ZDV + placebo, ZDV + DLV 200 mg TID, ZDV + DLV 300 mg TID, and ZDV + DLV 400mg TID). About 60% of patients were naive and 40% ZDV-experienced. Approximately 200 patients per group with an average CD4 = 320-330 have been randomized with about 19% female, 31% non-caucasian and 10% intravenous drug user representation in the trial. Interim analysis of the first 800 patients enrolled in this ongoing trial showed that Delavirdine treatment (300 or 400 mg TID) caused a prolonged increase in CD4 count of about 20 cells above baseline for more than one year. After 40-60 weeks, patients in the ZDV + DLV (300 or 400 mg TID) groups had between 35 to 70 cell higher CD4 count than ZDV monotherapy patients. After four weeks of therapy, delavirdine treated patients experienced about a 1 log decrease in plasma viral burden which was twice the drop in viral burden seen in the ZDV monotherapy group. Combination therapy with 300 and 400 mg TID DLV + ZDV, on average maintained a 0.5 log or greater diminution in viral load for at least 60 weeks. DNA PCR on patient lymphocytes and ICD p24 corroborate the enhanced antiviral response seen with ZDV + DLV combination therapy. Dose-response and concentration-response relationships were seen for all surrogate markers. The combination of ZDV + DLV demonstrated an excellent safety profile and a sustained antiviral effect.

Antiviral Agents/ADMINISTRATION & DOSAGE/*THERAPEUTIC USE CD4 Lymphocyte Count DNA, Viral/BLOOD Drug Therapy, Combination Female HIV Core Protein p24/BLOOD HIV Infections/*DRUG THERAPY/IMMUNOLOGY HIV-1/DRUG EFFECTS/GENETICS/PHYSIOLOGY Human Indoles/ADMINISTRATION & DOSAGE/PHARMACOLOGY/*THERAPEUTIC USE Male Piperazines/ADMINISTRATION & DOSAGE/PHARMACOLOGY/*THERAPEUTIC USE Polymerase Chain Reaction Reverse Transcriptase Inhibitors/ADMINISTRATION & DOSAGE/ PHARMACOLOGY/*THERAPEUTIC USE Virus Replication/DRUG EFFECTS Zidovudine/ADMINISTRATION & DOSAGE/*THERAPEUTIC USE ABSTRACT

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