Learning About an HIV Cure by Doing Studies in HIV+ Subjects Alan Landay, PhD Professor and Chairman Department of Immunology/Microbiology Rush 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 is higher at all gut sites than in PBMC HIV RNA measured from cell isolates and normalized to GAPDH measures and flow cytometry data Pattern consistent with persistent 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