The safety and efficacy of adefovir dipivoxil in patients with advanced HIV disease: a randomized, placebo-controlled trial

Objective: Efficacy and safety of adefovir dipivoxil (adefovir) added to ba ckground antiretroviral therapy in advanced HIV disease. Design: Randomized, double-blind, placebo-controlled multicenter trial. Setting: Fifteen clinical trial units providing HIV primary care. Participants: Adults with CD4 cell count less than or equal to 100 X 10(6)/ l, or 101-200 X 10(6)/l with prior nadir less than or equal to 50 X 10(6)/l . Interventions: Oral adefovir or placebo 120 mg once daily. Main outcome measures: Survival, cytomegalovirus (CMV) disease, plasma HIV- RNA, CD4 cell count, grade 4 drug toxicity, permanent drug discontinuation due to toxicity. Results: Among the 253 patients assigned adefovir and the 252 assigned plac ebo, respectively, 17 and 16 died (P = 0.88), and four and eight experience d CMV disease (P = 0.25). Mean change in logo plasma HIV-RNA in the adefovi r and placebo groups, respectively, was 0.09 and -0.03 copies/ml at 6 month s (P = 0.22) and 0.06 and -0.02 at 12 months (P = 0.87). Changes in CD4 cel l counts were not different between groups. At 12 months the cumulative per cent with proximal renal tubular dysfunction (PRTD) was 17% in the adefovir group and 0.4% in the placebo group (P < 0.0001, log rank test). Median ti me to resolution of PRTD was 15 weeks among patients assigned adefovir, and 16 lo of patients did not resolve completely 41 weeks after onset. More dr ug discontinuations occurred in the adefovir group than in the placebo grou p. Conclusions: No virologic or immunologic benefit was observed when adefovir was added to background antiretroviral therapy in advanced HIV disease, an d adefovir was associated with considerable nephrotoxicity. This study does not support the use of adefovir for treatment of advanced HIV disease in p retreated patients. (C) 2001 Lippincott Williams & Wilkins.