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