The Body Covers: The 39th Annual Meeting of the Interscience Conference on Antimicrobial Agents and Chemotherapy
Session 93.I: Late-Breaker Slide Session II
September 27, 1999
Abstract: The Atlantic Study: A Randomized, Open-Label Trial Comparing Two Protease Inhibitor (PI)-Sparing Antiretroviral Strategies Versus A Standard PI-Containing Regimen, 48 Week Data (Paper LB-22)
Dr. Rob Murphy reported the 48 week data on the Atlantic trial, a randomized, open-label, multinational trial comparing ddI/d4T/indinavir to ddI/d4T/nevirapine to ddI/d4T/3TC. The trial is ongoing.
All patients were antiretroviral naive, with CD4 <200 and HIV RNA >5000 copies. 298 patients were randomized, with 235 patients now completing 48 weeks. Plasma viral loads are available in 181 patients at this time.
The baseline viral load in this study was 4.36 log, or ~24,000 copies. This is higher than the baseline reported at the January Retrovirus conference in Chicago for the 24 week timepoint, due to the inclusion of data missing at that time. At 48 weeks, the median change in CD4 from baseline is 140 to 167 cells. All arms of the study appear to be doing well, with a slightly higher CD4 increase in the triple nucleoside arm.
An intent-to-treat analysis shows that overall, approximately 55% of patients have HIV RNA <500 copies. There is a suggestion that the triple nucleoside arm is faring less well, although there is no statistically significant difference among the treatment arms.
A post-hoc analysis has been done, looking at patients with baseline viral loads >51,286 copies, a stratification not designed into the study originally. There is no difference in endpoints for those achieving <500 copies in the three arms. When assessed for the number of patients achieving <50 copies, the triple nucleoside arm does not look as good as the PI or NNRTI arms, but this difference does not reach statistical significance (p=0.08). There are no unexpected toxicities seen. There has been a dropout rate of 24% at 48 weeks, 24 patients for adverse events and 15 by patient request.
This study shows no difference between a PI/2NRTI regimen and a NNRTI/2NRTI regimen. The big question here is the fate of the triple nucleoside arm. Several people I spoke to at the conference said that the most current analysis of patients with high viral loads on the triple nucleoside arm does show a drop-off compared to the other two arms that reaches statistical significance. This has not been reported officially yet. This, along with data reported in patients on adefovir/AZT/3TC with high viral loads, seems to indicate that the triple nucleoside combination may not be potent enough for use on its own in patients with high viral loads. However, the combination used in Atlantic may be somewhat problematic. It is well known that 3TC resistance with the M184V mutation can decrease sensitivity to ddI, so this particular triple combination might not be the best choice.
We must wait for further data from these studies before making any definitive statement, but for now, most of the doctors I spoke with prefer not to use triple nucleoside regimens in patients with high viral loads ( >50,000 or >100,000 depending on who you speak to). This study does confirm the long-term utility of the triple nucleoside combination in patients with lower baseline viral loads and also the potency of an NNRTI-containing regimen. This is good news for those who choose a PI-sparing regimen.
Authored by: R. L. Murphy, et al.
This article was provided by The Body PRO. Copyright © Body Health Resources Corporation. All rights reserved.