 |
|
|
| |
GigHAART Study: treatment interruption with advanced HIV
|
| |
| |
Reported by Jules Levin
"Treatment Interruptions in Patients with Multiple Failures to ARV Therapy: can the controversy be solved?"
Reported by Jules Levin
For two years now there has been ongoing controversy regarding the conflicting results from two studies of treatment interruption in patients with advanced HIV and extensive HIV drug resistance: the GigHAART Study and the Reverse Study. Here is a further study analysis presented at the Resistance Workshop by the French research group. It is this French group that performed the GigHAART Study. In the GigHAART study patients with few treatment options remaining had an 8 week treatment interruption and benefit was reported for these patients; patients in this study received MegaHAART after the interruption. This is compared to the Reverse Study in which patients received a longer interruption (170 days) but no benefit was found for patients. For two years researchers have been questioning the results and the explanations for these results the French researchers reported in this study. MegaHAART is not used anymore since the advent of more drugs following the GigHAART study. We may never understand why these two studies find differences in response to interruption. The general consensus currently among thought leaders is that treatment interruptions certainly in patients with advanced disease such as the patients in these two studies will not yield benefit in terms of providing a better response as measured by CD4 & viral load change to patients after they restart HAART following the interruption.
Dominique Costagiola (INSERM, Universitie Pierre et Marie Curie, Paris) reported this study at the XIII HIV Drug Resistance Workshop (June 8-12, 2004, Tenerife, Canary Islands, Spain). Here is her report.
Treatment interruptions (TI) remain a controversial issue in the management of patients with multiple failures. In very advanced treatment-failing patients (VL 5.3 log, 27 CD4), the GigHAART study has shown the benefit of an 8-week TI with a median reduction in VL of --1.91 log versus --0.37 log at week 12 in patients with TI versus no TI (p=0.008) and a benefit of +54 versus +7 CD4s respectively at week 24. By contrast, the Reverse Study had evaluated in 23 patients (VL 5.14 log, CD4 43) a longer duration of TI (median 170 days) with multitherapy started after reversion of resistance mutations (RM) in >2 classes and showed no benefit of TI (+0.06 log in VL, -27 CD4) at week 24.
The objective of the study was to explain the apparent discrepancy by comparing the number of RM at baseline and after TI, and the number of ARV sensitive at baseline among those available and after TI among those prescribed.
RESULTS
In GigHAART, median baseline RM was 5, 2 and 7 for NRTI, NNRTI, PI; 5 patients (17%) had virus sensitive to <2 drugs; after TI, there was no change in the median RM; 23 patients (68%) had virus sensitive to >2 drugs.
In Reverse, the RM were 6, 2, and 9 and 17 patients (74%) had no more than one sensitive drug; TI induced a change in median RM with 0 major for PI, 0 NNRTI and 2 TAMs; 16 patients (70%) had virus sensitive to >2 drugs.
Only 1 complete shift to wild-type viruses were seen in GigHAART versus 6 complete and 7 partial shifts (57%) in Reverse. In reverse, the resistance profile was the same at week 24 after treatment re-institution and at baseline, this was observed in most patients less than 2 months after treatment re-institution. Clonal analysis in GigHAART showed that the clones which are emerging or re-emerging are more susceptible to a multiple combination of ARV than the nearly monoclonal baseline viruses.
The authors conclude that in the management of multiple failures, complete re-occurrence of wild-type viruses appears deleterious. TI should not be used unless HIV has kept some sensitivity to available drugs.
|
| |
|
|
|
|
|
