Objective: Efficacy and safety of adefovir dipivoxil (adefovir) added to background 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 < or = 100 x 10(6)/l, or 101-200 x 10(6)/l with prior nadir < or = 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 placebo, respectively, 17 and 16 died (P = 0.88), and four and eight experienced CMV disease (P = 0.25). Mean change in log(10) plasma HIV-RNA in the adefovir and placebo groups, respectively, was 0.09 and -0.03 copies/ml at 6 months (P = 0.22) and 0.06 and -0.02 at 12 months (P = 0.87). Changes in CD4 cell counts were not different between groups. At 12 months the cumulative percent 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 time to resolution of PRTD was 15 weeks among patients assigned adefovir, and 16% of patients did not resolve completely 41 weeks after onset. More drug discontinuations occurred in the adefovir group than in the placebo group.
Conclusions: No virologic or immunologic benefit was observed when adefovir was added to background antiretroviral therapy in advanced HIV disease, and adefovir was associated with considerable nephrotoxicity. This study does not support the use of adefovir for treatment of advanced HIV disease in pretreated patients.