ias aids conference – washington dc – july 20-27, 2012 · lohse, ann int med 2007; hogg. lancet...

IAS AIDS Conference – Washington DC – July 20-27, 2012

Robert Reinhard

OUTLINE OF TALK

CURE BASICS

CURE WITHIN THE GLOBAL PROGRAM TO END AIDS

IAS CURE RESEARCH PLAN

CURE RESEARCH PRESENTED AT CONFERENCE

WITHOUT A CURE ALMOST ALL HIV-INFECTED PATIENTS MUST ACCESS AND ADHERE TO

SAFE, EFFECTIVE cART EVERY DAY THROUGHOUT THEIR LIFETIME

HIV

RN

A

CD

4 c

ou

nt

50

Rapid rebound in virus when cART stopped

Years on cART 0

off cART 1

WHAT DO WE MEAN BY “CURE”?

• STERILIZING CURE: ALL HIV ELIMINATED FROM THE BODY – NO cART BECAUSE NO VIRUS IS PRESENT

• FUNCTIONAL CURE: HIV REMAINS IN SMALL AMOUNTS – cART MAY NOT BE NEEDED BECAUSE VIRUS DOES NOT MULTIPLY OR IS CONTROLLED

WHAT ABOUT REINFECTION OR TRANSMISSION?

Sharon Lewin http://pag.aids2012.org/session.aspx?s=150

what are the major barriers

to cure?

BARRIERS TO CURE

• HIV hides and “sleeps” for many years (latency) in resting cells where drugs do not operate.

• “Wake Up” factors are unknown.

• Viral replication continues on cART- ?

• Anatomical tissue as a location for HIV where drugs do not operate

Anatomical reservoirs

Why do we need to cure HIV?

Life expectancy remains reduced on cART

Ongoing morbidity on cART

Prevent HIV transmission

Substantial stigma and discrimination

Lifelong cART: adherence toxicity long term-cost

Lohse, Ann Int Med 2007; Hogg. Lancet 2008; Deeks & Phillips, BMJ 2009; May, BMJ 2011 Viral Eradication: The Cure AgendaJ. Martinez-Picado, Spain- http://pag.aids2012.org/session.aspx?s=679#2

Estimated 2015 AIDS investment for universal prevention, treatment, care and

support

22 billion USD

CURRENT – OR EVEN HOPED FOR - GLOBAL SPENDING IS NOT ENOUGH TO END AIDS

: The Lancet 2011; 377:2031-2041

WE HAVE A NEED BUT WHY IS CURE RESEARCH POSSIBLE

Françoise Barré-Sinoussi

says so

The Berlin Patient

Critical mass of scientific advances

Seven key scientific priorities for HIV cure research

• Determine why HIV remains even with cART

• Determine the sources of hidden HIV

• Study immune activation effects

• Determine how HIV replication can be controlled by the body

• Study ways to measure persistent HIV infection and hidden HIV.

• Test therapeutic agents or immunological strategies

• Test strategies to enhance immune response. http://www.iasociety.org/Web/WebContent/File/HIV_Cure_Full_recommendations_J

uly_2012.pdf

STERILIZING OR FUNCTIONAL CURE

GENE THERAPY

THERAPEUTIC VACCINATION

TREATMENT OPTIMIZATION/INTENSIFICATION

REVERSAL OF LATENCY

IMMUNE-BASED THERAPIES

? REDUCING INFLAMMATION

CURE STUDIES THAT MADE NEWS HEADLINES

THE BERLIN PATIENT

TWO PATIENTS RECEIVING STEM CELL TRANSPLANT BUT STILL ON cART

“VISCONTI COHORT”

BERLIN PATIENT Effects of Leukemia Treatment and Transplant from

CCR5 mutation Donor

1. BERLIN PATIENT IS FUNCTIONALLY CURED

• Has not used cART for 5 years

• Decline in HIV antibody levels

2. EXPERIMENTAL LAB TESTS ARE NEGATIVE FOR PRESENCE OF HIV

• BUT some labs suggest presence of HIV: error, sample contamination, validity of test also possible

• Further tissue testing to to be conducted

3. BERLIN PATIENT CELLS ALSO RESISTANT TO CXCR4 HIV STRAINS?

• WE DON’T KNOW WHY BERLIN PATIENT IS CURED[CHEMOTHERAPY? TRANSPLANT ALONE? GRAFT/HOST DISEASE?]

• TWO LYMPHOMA PATIENTS GIVEN TRANSPLANT, NO RADIATION, BUT REMAIN ON cART

• HIDDEN/LATENT HIV CANNOT BE DETECTED IN BLOOD OF THESE PATIENTS; HIV ANTIBODY DECLINES

• MORE STUDY NEEDED BEFORE REMOVING cART

OTHER PATIENTS RECEIVING STEM CELL TRANSPLANT Timothy Henrich study

http://pag.aids2012.org/session.aspx?s=274

VISCONTI COHORT “Virological and Immunological Studies in CONtrollers after Treatment Interruption”

Asier Saéz-Cirión

• 14 patients treated with cART w/in 10 weeks of infection • Treatment interruption after an average of 3 years on cART • Controlling VL to <50 copies/ml - median of 6.6 years, range 4-9.5 years • Other French studies have found controllers among very early treaters: “HIV-1 control after transient antiretroviral treatment initiated in primary infection: role of patient characteristics and effect of therapy” Antiviral Therapy journal- http://www.intmedpress.com/journals/avt/abstract.cfm?id=2273&pid=88

CURES ARE FOR KIDS: WHY SHOULD WE STUDY PEDIATRIC POPULATIONS?

• Infants are more like people than mice or

monkeys

• Historically, 15% of new infections worldwide were in individuals <15 years old (most from MTCT); new infections still high

• Lessons from a developing immune system

• Identification during very early infection possible

• Ethics experience available from multiple studies

TWO DEVELOPMENTS IN INFANTS

• Published: Amount of hidden/latent HIV is reduced in 17 infants who achieved viral control with cART more quickly compared to others

AIDS 2012, 26:000–000; IAS ABSTRACT 12206

• Off the record discussion: In the next year, results will be presented of functional cure in infants treated very early.

STERILIZING OR FUNCTIONAL CURE FOR WHOM? KIDS, EARLY INFECTION, CHRONIC

GENE THERAPY

THERAPEUTIC VACCINATION

TREATMENT OPTIMIZATION/INTENSIFICATION

REVERSAL OF LATENCY

IMMUNE-BASED THERAPIES

? REDUCING INFLAMMATION

OTHER CURE RESEARCH AT IAS

• SOURCES OF HIDDEN HIV – IAS studies in tissue, central nervous system, and a new class of Tcells

• TESTING THERAPEUTIC AGENTS – early research with drugs that can “wake up” sleeping HIV

• MEASURING HIDDEN HIV – Infected resting cells may be identified by their differences. Measurement tests improving.

CURE: The point of view of people living

with HIV

Fred Verdult

Amsterdam, The Netherlands

Your logo

RESOURCES

• IAS PRECONFERENCE SYMPOSIUM – includes detailed presentations

http://www.iasociety.org/Default.aspx?pageId=606

• TOWARDS AN HIV CURE: A GLOBAL SCIENTIFIC STRATEGY

http://www.nature.com/nri/journal/v12/n8/full/nri3262.html

• IAS SCIENTIFIC STRATEGY – FULL SET OF RECOMMENDATIONS

http://www.iasociety.org/Web/WebContent/File/HIV_Cure_Full_recommendations_July_2012.pdf

ACKNOWLEDGEMENTS

Canada

Mario Ostrowski ICAD/Nicci Stein

Rupert Kaul

Colin Kovacs

Shariq Mujib

Sonya MacParland

Ron Rosenes

OHTN – Towards HIV Eradication

US

Richard Jefferys

Travel Funding

Treatment Action Group, NY

IAS