February 6, 2001
Dr. V. Miller and her colleagues in several European clinical sites were among the first to report that stopping treatment in those not fully suppressed may somehow improve the success of the next regimen, as compared to just switching from one combination to another. While this is still uncertain, and is the focus of two U.S. randomized studies, this follow-up poster presented an analysis of factors observed in those who do interrupt.
These data reflect the outcomes of those who chose to stop a regimen not fully suppressive, and who stopped this regimen for at least two months before starting a new combination. In all, 252 people fit this category. Of note, however, is that there are risks associated with interruptions, as this group had a CD4 drop of about 100 cells. The lowest CD4 that a patient had experienced was one predictor of how low the CD4 count would go during this interruption. In addition, those whose CD4 counts had increased the most over time prior to the interruption were at risk for losing a higher number of CD4 cells during the interruption. Together these suggest something somewhat fragile about the degree of immune reconstitution we get with antivirals.
On average, there was an increase in the viral load for those who stopped medication of between a half and one log -- however the peak viral load during the interruption did not appear to have an impact on the success of the next regimen. After a restart, the group experienced about a 1.5 log drop, and about 60% achieved a viral load below 500 copies on this next regimen. The CD4 counts did slowly increase, but it appeared to take many months to do so -- about 70% got back their CD4 counts lost during the interruption after about two years. On average there was a 50 cell increase in the CD4 counts over the next year.
From this data set, some have used treatment interruption as one way to potentially improve the response when going from one failing regimen to another, hopefully more active, regimen. While stopping may ultimately be shown to improve virus suppression rates, it may also be associated with significant drops in the CD4 counts, the clinical impact of which is as yet undefined but suggests caution. Based on these data, those with a very low CD4 in their history should be especially cautious if undergoing a treatment interruption, as they may wind up closer to this count shortly after stopping antivirals.