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