Learning About an HIV Cure by Doing Studies in HIV+ Subjects

Alan Landay, PhDProfessor and Chairman

Department of Immunology/MicrobiologyRush University Medical Center

Chicago, Illinois

1. Can evaluate natural course of HIV disease without having to use multiple primate species and SIV strains

2. Viral set point differs between human and primate

3. Primates fail to reach maximal viral suppression with current ARV as compared to HIV+ subjects

Basic Research Setting

In Vitro Assay Setting

1. Virologic assays for evaluating HIV reservoirs following therapeutic intervention have been established for HIV+ subjects

2. Lack cell lines from primates for latency studies and validation of human cell lines, primary human cell models and patient PBMC.

HIV RNA expression ishigher at all gut sites than in

PBMC

• HIV RNA measured from cell isolates and normalized to GAPDH measures and flow cytometry data

• Pattern consistent withpersistent HIV replication?

Yukl et al JID Nov 2010

Clinical Setting

1. Demonstrated evidence of a “cure” in Berlin patient

2. Gene therapy and pharmacologic agents are being

evaluated in ongoing human studies

3. Novel agents used in other clinical settings (i.e.

autoimmune disease, transplant, cancer) can be adapted

for cure studies in HIV+ subjects

4. Primate models utilize small numbers of animals making

interpretation of the data and its statistical significance

difficult

Resting CD4+ cell HIV RNA expression

Acetylation of cellular histones at

the human p21 gene

Correlate with biomarkers of intracellular SAHA action with Vorinostat level

and change of HIV RNA within resting CD4+ T cells

of aviremic, ART-treated patients after single dose of Vorinostat

DM Margolis, personal communication

PK Data from Merck Oncology Study

HIV+ SUBJECTS CAN PROVIDE THE BEST

INFORMATION FOR HIV CURE RESEARCH

Acknowledgements

Rush

Seema Desai

UCSF

Joe Wong

UNC

David Margolis