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THE FOTOSTUDY
48 week Results to assess durability of the strategy of taking Efavirenz, Tenofovir and Emtricitabine Five-days-On, Two-days-Off each week in virologically suppressed patients
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Reported by Jules Levin
IAS Capetown July 19-22 2009
C. Cohen1, A. Colson1, G. Pierone2, E. Dejesus3, F. Kinder4, R. Elion5, D. Skiest6, A. Habel1, J. Jensen1, J. Garb7, H. Schrager1, D. Back81CRI New England, Boston, United States, 2AIDS Research and Treatment Center of the Treasure Coast, Fort Pierce, United States, 3Orlando Immunology Center, Orlando, United States, 4Kinder Medical Group, Miami, United States, 5Whitman-Walker Clinic, District of Columbia, United States, 6CRI New England, Springfield, United States, 7Baystate Medical Center, Springfield, United States, 8University of Liverpool, Liverpool, United Kingdom
Community Research Initiative of New England, Boston USA
From Jules: One concern raised is regarding adherence, that patients get into a routine and stopping & starting ARTs as in this study might be difficult to maintain. Forgetting Monday's dose might be just enough to cause virologic failures. The study does not report if higher rates of AEs in the FOTO arm were due to stopping & starting and study doesn't report the types of AEs reported. In a clinical study like this it is easier to control patients while in the clinic it is much easier for patients to be non-adherent or not stick to such a strict protocol as in the FOTO arm.
In response Dr Cal Cohen sent me an email -
As you know - adherence can be difficult for some people to maintain when given meds every day - challenges to maintaining adherence are not unique to the FOTO strategy of course. We found a very strong pt preference for the FOTO and preference in general correlates with adherence (see poster pix). While I agree that adherence to FOTO was likely optimal in our study population - it is also possible that there might be other non-study pts who might similarly do better on this schedule than they now do on daily medication. If daily med adherence was perfect for everyone our study would only be addressing cost savings - but we did see strong pt preference for this indicating this has additional merit. He also said that on the poster they reported that about 10% of pts did occasionally miss a Monday dose (e.g. took three days off) and there was no failure even with a 3-day holiday in the small number who did so. Agreed it could happen but we did not see any, and referred to Dybul/Fauci study a few years ago where they did a week on/week off and did not see viral rebound so a third day off may not lead to failure based on their study. We did report all AEs in the poster - anything that was considered at least mild related to the study procedure was reported. These were all patients in the study who were tolerating Atripla - so the control arm had no AEs in 24 weeks as they were all OK to start with. And you summarized the few events that occurred all on the FOTO arm - 3 people reported some sleep insomnia and 2 resolved by the next study visit without any Rx - one person started on a med Rx. There were only 2 other AEs noted - one night sweats, and one feeling intoxicated both of which were mild/transient. The cost saving issue - which is not trivial - if Atripla is 20000 per year and as FOTO saves about 5500 per year - for every 100 people who did FOTO instead of daily - there would be a savings of 550,000 - and I am pretty convinced that more than one hundred people would do well on this schedule. Indeed, if just 200 people do it successfully - over one million dollars now spent on drug could be spent on something else.
From Jules:
- 60 patients on Atripla with HIV RNA <75 for at least 90 days, <50 at screening were randomized equally to FOTO regimen 5 days on ART, 2 days off or to daily regimen. This poster reported adherence data (self-reported) and there appeared to be no difference between the 2 groups.
- Authors report at week 24 100% (n=25) As -Treated analysis <50 c/ml in FOTO, 86% (n=28) <50 c/ml on DAILY. No subject on either arm who continued experienced virologic failure during the entire 48 week study. Extension Phase 48 wks: week 36 90% on FOTO, week 48 90% on FOTO <50 c/ml.
- The EFV drug concentrations were higher in the daily vs FOTO: EFV >1000 ng/ml on FOTO (mean 60 hrs post last dose) 48%, while 90% on daily (mean 12 hrs post last dose) had >1000 ng/ml. Authors reported - PK: while nearly half of the trough concentrations were below the standard MEC used for EFV, there was no virologic rebound observed.
- In slide 12 authors report missed 1 or more doses in 5 day period on FOTO: 3/29 (1%) at week 4, 4/26 (15%) at week 12, and 2/25 (8%) at week 24; on DAILY: 5/30 (17%) at week 4, 2/28 (7%) at week 12, 3/28 (11%) at week 24
- At week 24 25/30 on FOTO completed (5 discontinued), while on daily 28/30 completed week 24 (2 discontinued): that's 17% vs 8% discontinued, although this is a small study. Of those 25 continuing to week 48 on FOTO 23 completed and on daily 27/28 completed.
- Reasons for discontinuation (n=10): 5 lost to follow-up, 4 withdrew consent, 1 pregnancy (n=5 on FOTO, n=4 on daily).
- ADVERSE EVENTS judged at least possibly related to study intervention: no AEs on daily through week 24; on FOTO: n=5 through 48 weeks, 'all mild in severity', n=3 with sleep related AEs: all resolved with one month (1 additional Rx), 1 night sweats, 1 with intoxicated feeling for 1 day. (from Jules: the higher number of AEs reported on FOTO could be due to stopping & starting).
- % who took 1 extra day dose during 2 days off: 3/29 at week 4 (10%) , 1/26 at week 12 (4%), 2/24 (8%) at week 24
- COST SAVINGS: the authors concluded: This strategy has the potential to conserve 28% of the cost of this three-drug regimen
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