Nevirapine, zidovudine, and didanosine compared with zidovudine and didanosine in patients with HIV-1 infection a randomized, double-blind, placebo-controlled trial

Richard T. D'Aquila, Michael D. Hughes, Victoria A. Johnson, Margaret A. Fischl, Jean Pierre Sommadossi, Song Heng Liou, Joseph Timpone, Maureen Myers, Nesli Basgoz, Manette Niu, Martin S. Hirsch, Michael Saag, Jill Weingarten, John Gnann, Diane Havlir, Chris Fegan, Stephen Spector, Douglas Richman, Mark Jacobson, Kathy DybeckPatrick Joseph, Kathleen Clanon, Stacey McKenzie, Pam Daniel, Dale Dayton, Jill Leonard, Robert Schooley, Daniel Kuritzkes, Graham Ray, Beverly Putnam, Dushyantha Jayaweera, Janie Patrone-Reese, Thomas Tanner, Jo Moebus, Nancy Reed, Renee St Jacque, Keith Henry, Susan Swindells, Joe Eron, David Ragan, James Horton, Timothy Lane, Ian Frank, Anne Norris, Roger Pomerantz, Stephen Hauptman, Jan Geiseler, John Leedom, Frances Canchola, Connie Olson, Lawrence Deyton, Carla Pettinelli

Research output: Contribution to journalArticlepeer-review

281 Scopus citations


Objective: To study the addition of a third human immunodeficiency virus type 1 (HIV-1) reverse transcriptase inhibitor, nevirapine, to the combination of zidovudine and didanosine. Design: A 48-week, randomized, double-blind, placebocontrolled trial at 16 AIDS (acquired immunodeficiency syndrome) Clinical Trials Units. Patients: 398 adults who had HIV-1 infection, had 350 or fewer CD4+ T lymphocytes/mm3, and had had more than 6 months of previous nucleoside therapy. Intervention: of Either nevirapine or placebo (200 mg/d for 2 weeks, then 400 mg/d thereafter) and 2) open-label zidovudine (600 mg/d) and didanosine (400 mg/d for patients weighing ≥60 kg). Measurements: CD4+ T lymphocyte counts, time to first HIV-1 disease progression event or death, adverse events, and nevirapine levels in plasma samples taken at random were measured in all patients. Plasma levels of HIV-1 RNA; HIV-1 infectivity titer in peripheral blood mononuclear cells; serum p24 antigen levels; and plasma levels of zidovudine and didanosine were measured in patients enrolled at half the study sites. Results: After 48 weeks of study treatment, the patients assigned to the triple-combination regimen (nevirapine, zidovudine, and didanosine) had an 18% higher mean absolute CD4 cell count (95% Cl, 7% to 29%; P = 0.001), a 0.32 log10, lower mean infectious HIV-1 titer in peripheral blood mononuclear cells (Cl, 0.05 to 0.59 log10 infectious units per million cells; P = 0.023), and a 0.25 log10 lower mean plasma HIV-1 RNA level (Cl, 0.03 to 0.48 log10 RNA copies/ml; P = 0.028) than did patients assigned to the double-combination regimen (zidovudine and didanosine). Severe rashes were more common among patients assigned to receive the triple combination (9% compared with 2%; P = 0.002). Risk for disease progression did not differ between the two groups (relative hazard of the triple-combination group, 1.24 [Cl, 0.75 to 2.06]; P > 0.2), although the study had only moderate power to detect a major difference. Conclusions: Adding nevirapine to zidovudine and didanosine improved the long-term immunologic and virologic effects of therapy and was associated with severe rash among the patients studied, who had had extensive previous therapy. These results support 1) the continuing development of combinations of more than two antiretroviral drugs to increase and prolong HIV-1 suppression and 2) the potential utility of nevirapine in combination regimens.

Original languageEnglish (US)
Pages (from-to)1019-1030
Number of pages12
JournalAnnals of internal medicine
Issue number12
StatePublished - 1996
Externally publishedYes

ASJC Scopus subject areas

  • Internal Medicine


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