About The Study
To compare the antiviral effect and safety of a once daily investigational four-drug regime (IDR) that includes adefovir to a standard triple-drug regimen (SDR) consisting of two nucleosides and a protease inhibitor (selected by the treating physician).
This was an open label study. Participants were HIV-positive, antiretroviral (ARV)-naïve adults with a viral load above 10,000 copies/mL and CD4 counts above 70 cells/mm3. They were randomly assigned to receive either an IDR or an SDR for 28 weeks (including four weeks follow-up). At baseline and every four weeks, a physical exam, viral load (VL), CD4 cell count, blood work, biochemistry analysis and urinalysis were done.
Beginning in March 1999, 27 patients were recruited at seven sites. Median viral load and CD4 cell count were not significantly different between the two arms (VL: 4.59 and 4.76, CD4: 303 and 265). The arms were also similar in age.
Health Canada requested that the study be discontinued in November 1999 due to concerns over potential renal toxicity with adefovir dipivoxil. Sixteen participants (nine in the IDR arm and seven in the SDR) completed the study.
Viral load decreased in both groups over the 24 weeks of the trial. Slightly more that one half of the patients achieved non-detectable levels at week 12. Although the numbers are small, it appears that viral suppression was sustained in those who responded at week 12. CD4 count increased in both groups. Proportionally, more adverse events were reported in the IDR arm, but the proportion of those rated moderate to severe were similar in the arms. Serum creatinine (measure of kidney function) was unchanged and significant abnormalities were not seen in either treatment arm.
A once daily ARV regimen of adefovir, ddI, 3TC and nevirapine was as effective and well tolerated as a standard PI-containing regimen in a small group of ARV-naïve patients over 24 weeks.