Adherence and Viral Load >100,000 copies/ml: Abacavir/Combivir vs Indinavir/Combivir in Therapy NaÔve (CNS3014)- preliminary week 24  data of 48 week study

This study was reported in Durban and can be read in the NATP Durban Reports section, and is a multi-center international study.  This report will address the new information reported at ICAAC on adherence to the two regimens. The overall study data reported by Pedro Cahn, MD, from Buenos Aires is preliminary 24 week results of a 48 week open-label, randomized study comparing a triple NRTI twice daily regimen to a regimen in which indinavir is taken every 8 hours while Combivir is taken twice daily. As you will see there is a difference in adherence reported by patients between the two regimens. This explains in part the study results. Overall baseline viral load and CD4s were comparable in both arms: median 60,000 copies/ml and 300-324 CD4s. In the lower viral load group (5,000-100,000 c/ml) median baseline VL was 29,000 in both arms, while in the higher VL group (>100,000 c/ml) VL was comparable in both arms (about 220,000 copies/ml). About 37% (n=126) had >100,000 copies/ml at baseline in both arms, about 340 participants in total in study.

Patients were asked if they took all their doses in the past 4 weeks, and at week 24 or the last assessment while on therapy 56% reported yes in the abacavir arm and 25% in the indinavir arm. Patients were also asked if  they missed < 1 dose per week in the last month or 4 doses in total over the last month, 74% in the abacavir arm said yes while 45% in the indinavir arm.

The patients were asked if none of the drugs in their regimen were difficult to take, and 94% in the abacavir arm and 62% in the indinavir arm said yes.

Patients were asked what was the longest time elapsed where all ARTs were missed:

169 patients were randomized to ABC and 173 to IDV arms. 8% discontinued from the study from ABC arm and 12% from IDV arm. 4 patients in the ABC arm met the protocol switch criteria (>400 copies/ml) in the ABC arm and 15 in the IDV arm prior to week 24. Patients were permitted to switch to other arm for intolerance or if they had two consecutive viral loads >400 c/ml, and 4 did so in the ABC arm and 24 in the IDV arm.

Reporting any drug related AE were 59% of patients in ABC arm and 75% in the IDV arm; any grade 3/4 AE- 4% in ABC arm 12% in IDV arm; 6% reported ABC hypersensitivity. But, about the same were reported discontinuing due to AE: 9% (ABC) and 10% (IDV).

% <400 copies/ml

87% in the abacavir arm and 83% in the indinavir arm (As Treated) had <400 c/ml at week 24. Using an ITT analysis 68% (ABC) and 57% (IDV) had <400 c/ml at week 24.

When looking at the group with >100,000 c/ml at baseline, and using an ITT analysis, 66% in ABC arm and 54% in IDV had <400 c/ml.

% <50 copies/ml (ITT)

In the overall study group, 63% in the ABC arm and 50% in the IDV arm had <50 c/ml at week 24. In those who had 5,000-100,000 viral load at baseline 68% (ABC) vs 53% (IDV) had <50 c/ml. For those with >100,000 viral load at baseline, 55% (ABC) and 45% (IDV) had <50 c/ml. There were over 100 individuals in each of the arms for the lower viral load group analysis, and there were about 60 persons in each of the arms for the higher viral load analysis.

Predictors of HIV Viral Load <50 copies/ml at Week 24

This was a sub-analysis of 257 individuals (ABC=133, IDV=124). It was sub-sample analysis of subjects who had completed 24 week adherence questionaire and had 24 week <50 copies/ml test result available. Baseline HIV-RNA was a predictor. For every 1 log increase in viral load the odds of being >50 at week 24 was severely increased regardless of the treatment arm. Adherence was also reported to be a factor. For every 5% increase, odds of 24-week test result <50 c/ml increased by 17% regardless of treatment group. ABC subjects were 1.9 times more likely than IDV subjects to have 24-week test result <50 c/ml.