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A randomized placebo-controlled trial of adefovir dipivoxil in advanced HIV infection: the ADHOC trial
Insights
Adding adefovir dipivoxil (ADV) to antiretroviral therapy (ART) in advanced HIV disease did not improve outcomes. The study found no significant immunological or virological benefits, and ADV increased serious adverse events.
Area of Science:
- Infectious Diseases
- Immunology
- Pharmacology
Background:
- Advanced HIV disease presents significant challenges in treatment.
- Stable background antiretroviral therapy (ART) is crucial for managing HIV.
- Assessing novel therapeutic additions is vital for improving patient outcomes.
Purpose of the Study:
- To evaluate the efficacy of adefovir dipivoxil (ADV) when added to ART.
- To determine the safety profile of ADV in HIV-infected individuals.
- To assess ADV's impact on immunological and virological markers in advanced HIV disease.
Main Methods:
- A randomized, double-blind, placebo-controlled, international multicenter trial (ADHOC).
- Inclusion criteria: CD4 counts < 100 or < 200 cells/microL with specific nadir.
- Participants received either ADV (120 mg then 60 mg) or placebo daily.
Main Results:
- No significant difference in AIDS events or mortality between ADV and placebo groups.
- A lower incidence of herpes events was observed in the ADV group (P = 0.009).
- No significant improvements in CD4 cell count or viral load (RNA) were noted.
- Increased serious adverse events (SAEs) and proximal renal tubular dysfunction were associated with ADV.
Conclusions:
- ADHOC trial was terminated early, limiting assessment of clinical disease progression.
- Adding ADV to ART in advanced HIV disease did not yield immunological or virological benefits.
- ADV, at the doses studied, was linked to a higher incidence of serious adverse events.
Objectives:
To assess the efficacy and safety of adefovir dipivoxil (ADV) added to stable background antiretroviral therapy (ART) in HIV-infected individuals with advanced HIV disease.
Methods:
ADHOC was a randomized, double-blind, placebo-controlled, international multicentre trial. Three hundred and one individuals with CD4 cell counts < 100 cells/microL or < 200 cells/microL with nadir < 50 cells/microL were allocated to receive either 120 mg ADV (subsequently 60 mg) (n = 161) or matching placebo (n = 140) once daily.
Results:
Over a median follow-up of 76 weeks, 23 (14%) and 18 (13%) participants assigned ADV and placebo, respectively, developed a new AIDS event or died (hazard ratio = 1.23, 95% confidence interval 0.66-2.29, P= 0.51). There was a lower incidence of new or recurrent herpes events in the ADV group (P = 0.009). The mean increase in CD4 cell count from baseline to week 24 was 23.0 and 24.4 cells/ micro L in ADV and placebo groups, respectively (P = 0.89), and the mean decrease in RNA was 0.32 and 0.35 log10 copies/mL at week 24 (P = 0.87) in a subset of participants. There was greater weight loss in the ADV group during the trial (P = 0.007). One hundred and twenty-four participants (41%) had stable background ART in the 8 weeks prior to and the 24 weeks after randomization. There was no significant imbalance in background ART regimens between the two treatment groups. Ninety-seven serious adverse events (SAEs) occurred, 65 and 32 in the ADV and placebo groups, respectively, with significantly shorter time to first SAE in the ADV group (P = 0.002). A total of 33 participants developed proximal renal tubular dysfunction during the trial, all but one in the ADV group.
Conclusions:
Due to the early termination of recruitment, ADHOC was unable to assess the original objective of clinical disease progression. Adding ADV to background antiretroviral therapy in advanced HIV disease did not provide immunological or virological improvement compared with placebo. Furthermore, at the doses used in this trial, ADV was associated with a significantly higher incidence of SAEs.
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