We found a match
Your institution may have rights to this item. Sign in to continue.
- Title
Efficacy and safety of adefovir dipivoxil with antiretroviral therapy: a randomized controlled trial.
- Authors
Kahn, James; Lagakos, Stephen; Wulfsohn, Michael; Cherng, Deborah; Miller, Michael; Cherrington, Julie; Hardy, David; Beall, Gildon; Cooper, Richard; Murphy, Robert; Basgoz, Nesli; Ng, Edmund; Deeks, Steven; Winslow, Dean; Toole, John J.; Coakley, Dion; Kahn, J; Lagakos, S; Wulfsohn, M; Cherng, D
- Abstract
<bold>Context: </bold>Adefovir dipivoxil is a nucleotide analog that has demonstrated effective antiretroviral activity against human immunodeficiency virus (HIV) with once-daily administration.<bold>Objective: </bold>To determine if adefovir confers antiretroviral or immunologic benefit when added to stable antiretroviral therapy.<bold>Design: </bold>Multicenter, 24-week, randomized, double-blind, placebo-controlled study. Enrollment was conducted from June 3, 1996, through May 6, 1997.<bold>Setting: </bold>Thirty-three US HIV treatment centers.<bold>Participants: </bold>Of 1171 patients screened, 442 patients infected with HIV receiving stable antiretroviral therapy for at least 8 weeks with plasma HIV RNA greater than 2500 copies/mL and CD4+ cell count above 0.20 x 10(9)/L were randomized.<bold>Intervention: </bold>Patients were randomized to receive either a single 120-mg/d dose of adefovir dipivoxil (n = 219) or an indistinguishable placebo (n = 223). All patients received L-carnitine, 500 mg/d. Open-label adefovir was offered after 24 weeks and was continued until the end of the study.<bold>Main Outcome Measures: </bold>Changes in HIV RNA from baseline, based on area under the curve and CD4+ cell levels, adverse events, and effect of baseline genotypic resistance on response to adefovir.<bold>Results: </bold>Patients assigned to adefovir demonstrated a 0.4-log10 decline from baseline in HIV RNA compared with no change in the placebo group (P<.001), which continued through 48 weeks. CD4+ cell counts did not change. During the initial 24 weeks, elevated hepatic enzyme levels (P<.001), gastrointestinal tract complaints (P<.001), and weight loss (P<.001) were associated with use of adefovir. Between 24 weeks and 48 weeks elevations in serum creatinine occurred in 60% of patients, usually returning to baseline after discontinuation of adefovir. Patients with lamivudine or lamivudine and zidovudine resistance mutations demonstrated anti-HIV effects with adefovir (P< or =.01 vs placebo group).<bold>Conclusions: </bold>This study suggests that once-daily adefovir therapy reduces HIV RNA and is active against isolates resistant to lamivudine or lamivudine and zidovudine. Nephrotoxicity occurred when treatment extended beyond 24 weeks but was reversible.
- Subjects
AIDS treatment; IMMUNODEFICIENCY; CLINICAL trials; IMMUNOLOGIC diseases; THERAPEUTICS; REVERSE transcriptase inhibitors; AZIDOTHYMIDINE; COMBINATION drug therapy; COMPARATIVE studies; DRUG resistance in microorganisms; HIV; HIV infections; RESEARCH methodology; MEDICAL cooperation; ORGANOPHOSPHORUS compounds; PURINES; RESEARCH; RNA; VIRAL load; EVALUATION research; RANDOMIZED controlled trials; BLIND experiment; LAMIVUDINE; ANTI-HIV agents; CD4 lymphocyte count; GENOTYPES; PHARMACODYNAMICS
- Publication
JAMA: Journal of the American Medical Association, 1999, Vol 282, Issue 24, p2305
- ISSN
0098-7484
- Publication type
journal article
- DOI
10.1001/jama.282.24.2305