• Two-Year Follow-Up of ABT-378/Ritonavir (ABT-378/r) in Antiretroviral Naive HIV+ Patients
  Poster 546
  Authored by C. Benson, S. Brun, M. King, K. Real, R. Murphy, C. Hicks, J. Eron, J. Thommes, R. Gulick, M. Glesby, M. Thompson, C. White, M. Albrecht, H. Kessler, J. Poddig, E. Sun, A. Japour
• Time to Treatment Success: 24 weeks is Not Enough in Patients Starting with High Viral Load (VL) in DP-006
  Poster 547
  Authored by G. J. Moyle, M. Nelson, N. Ruiz, D. Manion, D. Farina

Two-Year Follow-Up of ABT-378/Ritonavir (ABT-378/r) in Antiretroviral Naive HIV+ Patients (Poster 546)

This abstract presents a two-year follow up data on the clinical experience of ABT-378/ritonavir (ABT-378/r) in drug naive patients. The study involved 100 patients with baseline viral loads >5,000 and no CD4 cell restriction. The first group evaluated two doses of ABT-378 for three weeks followed by the addition D4T/3TC for a total of 48 weeks. The second group stated all drugs at the same time and continued for 48 weeks. After 48 weeks patients were converted to open label (ABT-378/r) and followed for an additional 48 weeks. The baseline characteristics of the study cohort revealed a medium viral load (4.8 logs) and a CD4 count of 326 (96 men, 4 women). Viral load suppression at 96 weeks was presented for both the <400 and <50 copy viral load assays. At 96 weeks there were 86 evaluable patients. In the intent-to-treat analysis, 78% had less than 50 copies. In the on-treatment analysis 92% had an undetectable viral load at 96 weeks. An additional on-treatment analysis was presented that looked at the viral load response in patients < or > 100,000 copies at baseline. There was no difference in the number of patients who maintained a viral load of <400 at 96 weeks when the level of baseline viral load considered. However, it took significantly longer for patients with a baseline viral load >100,000 to achieve a viral load of <50 when compared to the those patients who had baseline viral loads of <100,000. The mean CD4 increase after 96 weeks of treatment was 290 cells. The most common side effects were gastrointestinal. Elevated cholesterol (>300) and triglycerides (>750) were seen in 14 and 12 patients respectively. Fourteen patients discontinued the study for various reasons.

This study presented long-term follow up on the recently FDA-approved ABT-378/r in combination with D4T and 3TC. The study shows the potency and long-term durability of response in drug-naive patients that have received this compound. In addition, ABT-378/r-containing regimen was well tolerated. Several previous studies have presented data on the use of ABT-378/r in patients who have failed prior regimens, including protease inhibitor failures. Although changing to a ABT-378/r regimen in patients who have experience PI failure has resulted in significant and sustained viral load reductions in many patients, the percentage of patients with undetectable viral loads in this population was not as significant as the drug-naive patients presented in this study.

Time to Treatment Success: 24 weeks is Not Enough in Patients Starting with High Viral Load (VL) in DP-006 (Poster 547)

This poster presents a re-analysis of the DuPont 006 study that specifically addresses the question of the time to achieve a viral load of <50 copies/ml. The DPC006 study was a three-arm efficacy and safety study that compared efavirenz/ZDV/3TC and efavirenz/indinavir and ZDV/3TC/indinavir. The treatment arms were evaluated through week 72. Subjects were stratified for the purpose of this analysis by baseline viral load. The baseline viral loads were divided into the following quartiles: <50,000; 50,000-99,999; 100,000-299,999; and >300,000. In addition, the population was analyzed for both observed data (missing viral load and CD4 were not accounted for) and intent-to-treat analysis (where a non-completer equaled failure). Intent-to-treat methodology is a much more rigorous way to analyze the data.

Observed data out to 72 weeks was presented for each arm and by quartile of baseline viral load. Overall, more than 2/3 of patients in each arm, irrespective of baseline viral load, achieved an undetectable viral load by week 24. The medium time to achieve an undetectable viral load for the efavirenz/ZDV/3TC arm was 16 weeks irrespective of baseline viral load. In the other two arms, the medium time to achieve an undetectable viral load in patients with >300,000 copies at baseline was 24 weeks. A number of variables (age, gender, race, baseline CD4 count etc.) were analyzed to identify what predicts achieving an undetectable viral load in <24 or >24 weeks. The only significant variable that was a predictor of response was baseline viral load. A number of patients in all three arms were found to require over 36 weeks in order to achieve an undetectable viral load.

The observations in this study are important because current national guidelines suggest that treatment should be modified or changed if an undetectable viral load (<50) is not achieved by 24 weeks. This study identified a subset of patients that may, in fact, be late responders (i.e. requiring greater than 24 weeks to achieve an undetectable viral load). The number one factor associated with this response was a baseline viral load of >300,000 irrespective of whether the regimen contained a protease inhibitor or a non-nucleoside reverse transcriptase inhibitor. In conclusion, patients with very high viral loads may take longer to achieve undetectable viral load levels than national guidelines would indicate and still have a successful treatment outcome.