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JAMA. 1999 Dec 22-29;282(24):2305-12.

Efficacy and safety of adefovir dipivoxil with antiretroviral therapy: a randomized controlled trial.

Author information

1
Positive Health Program University of California San Francisco, San Francisco General Hospital, 94110, USA. jkahn@php.ucsf.edu

Abstract

CONTEXT:

Adefovir dipivoxil is a nucleotide analog that has demonstrated effective antiretroviral activity against human immunodeficiency virus (HIV) with once-daily administration.

OBJECTIVE:

To determine if adefovir confers antiretroviral or immunologic benefit when added to stable antiretroviral therapy.

DESIGN:

Multicenter, 24-week, randomized, double-blind, placebo-controlled study. Enrollment was conducted from June 3, 1996, through May 6, 1997.

SETTING:

Thirty-three US HIV treatment centers.

PARTICIPANTS:

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.

INTERVENTION:

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.

MAIN OUTCOME MEASURES:

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.

RESULTS:

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).

CONCLUSIONS:

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.

PMID:
10612317
DOI:
10.1001/jama.282.24.2305
[Indexed for MEDLINE]

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