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NLM AIDSLINE

Delavirdine (DLV) in combination with zidovudine (ZDV) causes sustained antiviral and immunological effects in HIV-1 infected individuals




 

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



 




Information in this article was accurate in November 30, 1996. The state of the art may have changed since the publication date. This material is designed to support, not replace, the relationship that exists between you and your doctor. Always discuss treatment options with a doctor who specializes in treating HIV.