aids cure research- moving into the clinic
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AIDS Cure Research-Moving Into the
ClinicMatt Sharp
Long-term Survivor and AIDS Cure ActivistSan Francisco
OutlinePerspective
Cure-related clinical trial issues
Cure-related clinical enrolling
Zinc finger nuclease approach
My clinical experience
Results
SB-728
Issues
Remaining questions
PerspectiveHIV cure-related research has progressed relatively quickly since the first clinic case report of Timothy Brown, who is considered now functionally cured after five years
Despite many unknowns the field is moving rapidly towards remarkable advances in HIV
Eradication/functional cure has become a new direction in HIV research and is already moving into the clinic requiring study volunteers
New drugs, vaccines, gene therapy, drug intensification trials and immune-based therapies are now being studied in humans
Cure-related clinical trial issues
Recruitment in the age of effective ARV therapy
Are trials ethical?
What risks are reasonable? Protection from research injury
Informed consent
Challenging trial designs-ATI, invasive procedures
Reimbursement
Product continuation after trial completion
Grass-roots outreach and education
Community Advisory Boards to provide input into informed consents
Cure-related clinical trials now enrollingTrials now enrolling as of June 2012*
6 immune-based or cell therapeutic8 therapeutic vaccine8 reservoir-related
Several others are being planned (ACTG, industry, etc.)
*clinicaltrials.govhttp://survivinghiv.blogspot.com/2012/05/hiv-cure-related-studies-currently.html
Clinical background Dx in 1988 with HIV w/ 409 CD4
Sequential monotherapy throughout 90’s
Consented to be in dozens of clinical trials
Salvage patient developing multi-drug resistance
First reached undetectable 2007 w/ RAL+DRV/r yet T-cells never rebounded
Currently virally suppressed on stable HAART
Immunologic non-responder
ZFN approachA kinder, gentler approach to making HIV-resistant
Gene modification through zinc finger nuclease technology
Disrupts the CCR5 gene in leukapheresised CD4 cells
Cells modified with zinc finger nuclease introduced with adeno virus vector
Modified CD4 cells; then expanded and frozen
Infusion
SB-728 phase 1 safety trial First safety trial in virally suppressed immunologic non-responders
Screened and consented for SB-728 in June 09
Apheresis procedure July 09
“product” development-aprx. 6 weeks
Single infusion September 09
Monthly blood draws, urine
6 rectal biopsies-20 snips each procedure
One lymph node biopsy-off protocol
My results
Results after one year:Baseline CD4 294; CD4% 14.7; CD4/CD8; Month 12 CD4 458; CD4% 21.2; CD4/CD8;Average annual CD4 488; CD4% 21.2; CD4/CD8; Month 18 CD4 350; CD4%; CD4/CD8
CD4 CD4% CD8 CD4/CD8
Baseline 8/09 294 14.7 1144 .26
12 mo 458 21.2 1096 .42
Average 610 26.4 1563 .49
21 mo 355 15.2 1341 .26
• 6% of total cells were modified CCR5 cells
• Modified cells found in gut• No clinical events (not analyzed)• No upper respiratory infections
apheresis
IssuesRectal biopsies
Reimbursed $2000 over the course of one year
5 protocol amendments w/new lengthy informed consents
No drug continuation for study volunteers
yet
No safety issues
Immune system benefit?
Science 13 May 2011: Vol. 332 no. 6031 pp. 784-789
Remaining questionsCure-related clinical trials will require many patients
Will healthy HIV+ people participate and enroll?If so, will participants understand informed consents?
Will product continuation be built into protocols if a benefit is found in the absence of a cure?
What is the best way to inform the community of complex and rapidly evolving scientific information?
On the road to the goal of a cure, will immunologic non-responders, long-term survivors and others be forsaken?
While there are risks there also may be benefits for INR
We must not see any person as an abstraction.
Instead, we must see in every person a universe with its own secrets, with
its own treasures, with its own sources of anguish, and with some
measure of triumph.-Elie Wiesel
The Nazi Doctors and the Nuremberg Code
Henrietta Lacks
Imagine a World without AIDS
mattsharpster@gmail.com
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