Two more PI-sparing regimens were assessed in the international Atlantic study, which also featured amongst Monday's Late Breakers at the 39th ICAAC in San Francisco. This open-label study randomised treatment naive patients to receive d4T/ddI plus either indinavir, nevirapine or 3TC. 235 patients have now completed 48 weeks on study medication, representing 79% of the full cohort.
When preliminary data were presented at this year's Retrovirus meeting in February, the low median baseline viral load (around 12,000 copies) amongst participants led some observers to question their relevance in clinical practice, given the trend away from aggressive early treatment. With additional recruits and longer follow-up however, the median baseline viral load was a higher 4.36 log copies (or around 23,000 copies). Median CD4 count was 408 cells.
The overall virological efficacy was unchanged. At 48 weeks, there was no difference in the proportions with viral load below either 500 or 50 copies in the as treated analysis (95% and 90% for indinavir, 91% and 82% for nevirapine, and 90% and 78% for 3TC respectively). By intent to treat analysis, which includes data on all participants regardless of whether they remained on study medication, the figures are 59% and 57% for indinavir, 55% and 51% for nevirapine, and 57% and 49% for 3TC. Again, there is no significant difference between these values. All arms experienced a median gain in CD4 cells of between 140 and 170 cells by the end of the 48 week period.
Participants were stratified at entry into four sub-groups according to their viral load. In the upper quartile who began with values above 51,000 copies there was no difference between arms with respect to suppression of viral load below 500 copies. However, using a below 50 copies cut-off there was a suggestion that the 3TC arm may have performed less well than the other two. This difference did not reach significance however (p=0.08), and the numbers of patients in this analysis were small.
These findings, (along with data on abacavir/AZT/3TC presented at ICAAC yesterday), may fuel the perception that some PI-sparing regimens appear to have inadequate potency for those who begin treatment with high viral load.
Murphy RL et al. 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. 39th ICAAC, San Francisco, abstract LB-22, 1999.
Staszewski S et al. Comparison of antiviral response with abacavir/Combivir to indinavir/Combivir in therapy-naive adults at 48 weeks (CNA3005). 39th ICAAC, San Francisco, abstract 505, 1999.