Reports for NATAP

1st International AIDS Society (IAS) Conference on HIV Pathogenesis and Treatment

July 7-11, 2001 Buenos Aires, Argentina

Clinical Trials Presentations:

Abacavir+Combivir vs Indinavir+Combivir

CNA3014 – Randomized, open-label, multicenter, equivalence trial.

Brief summary by Jules Levin: Abacavir appears to perform as well as indinavir in this study, as evaluated by percent below 50 copies/ml and 400 copies/ml, because abacavir is easier to tolerate and adhere to. Indinavir appears to be more potent, but is less tolerable and less easy to adhere to. In patients with >100,000 copies/ml abacavir may be less potent than other more potent HIV drugs, but for some individuals Trizavir (one pill twice a day containing abacavir, AZT and 3TC) appears to be easier to tolerate, may have less side effects & toxicities, and for some patients may be easier to adhere to.

Entry Criteria:

ARV naïve
T-cells > 100 cells/mm3
VL > 5000 copies/ml

Design:

• 2 arms:
       ABC 300 bid + COM bid
       IDV 800 q 8 hrs + COM bid
  
  
• Stratification on screening plasma VL > 5000 – 100,000 copies/ml or >100,000 copies/ml
  
  
• Subjects who were >400 copies/ml on two separate occasions at least 1 week apart after week 16 were able to switch therapies.
  
  
• Adherence data collected by self-report questionnaire administered at study visits.

Baseline Characteristics:

N = 342
Males approximately 60%
Randomized but did not initiate treatment = 13 (5 in ABC arm, 8 in IDV arm)
Median VL = 4.78 log/copies/ml in the ABC arm, 4.82 log copies/ml in the IDV arm

HIV RNA >100,000 copies/ml – 36% of ABC arm, 38% of IDV arm
Median T-cells = 331 cells/mm3 in the ABC arm, 299 cells/mm3 in the IDV arm

Final 48 Week Results:

Completed Randomized Therapy = 77% of ABC arm, 60% of IDV arm
Lost to follow up = 10 in ABC arm, 18 in IDV arm
ITT < 50 copies: ABC 60%, IDV 50%
ITT < 50 copies among those whose baseline VL was >100,000: ABC 48%, IDV 46%; ITT <400 ABC 60%, IDV 51% (ABC did better due to IDV dropouts).
As Treated < 50 copies: ABC 79%, IDV 81%
As Treated < 50 copies among those whose baseline VL was >100,000: ABC 59%, IDV 73%
ABC hypersensitivity was reported at 6%
Adherence data for last month of study or last collected data (Week 44-48): 72% of ABC arm reported taking > 95% of doses, 45% of IDV arm reported taking > 95% of doses.
Grade 3 or 4 lab abnormalities 2 times greater in IDV arm or 14% vs. 7% for ABC arm.

Commentary: This study was a follow-up to CNA3005, which was a cumbersome double blinded, placebo controlled, 16 pills, with tid dosing study. That study raised questions about the potency of ABC/COM in patients with higher viral loads. This study offers some reassurance, still questions persist. This study had high drop out rates from the originally randomized arms, 23% in the ABC arm and 40% in the IDV arm. Self-reported adherence showed significantly poor adherence to IDV. One could argue that poor adherence to an IDV/COM regimen almost equals the efficacy of good adherence to an ABC/COM regimen. Or one could argue that ABC/COM was tremendously easier for patients to adhere to. In the real world, patients must individually weigh a number of factors when choosing a HAART regimen. Number of pills, number of times during the day the pills must be taken, side effects, virologic efficacy, and etc. Given that ABC/COM is now in one tablet (Trizivir) twice per day, has made this choice attractive for many patients in the clinic where I practice.

The number of lab abnormalities in the IDV arm is concerning and we await further data from this study regarding these issues. Of specific interest will be lipid comparisons.

In order to fully weigh the results of this study, we will also need to examine the genetic mutations of virologic failures, and if among the viral loads >100,000 did the ABC/COM fail more rapidly.