XIX International AIDS Conference

MOLBA Late Breaker Track A
  Oral Abstract Session : Track A
Venue: Session Room 2
Time: 23.07.2012, 11:00 - 12:30
Co-Chairs: Françoise Barré-Sinoussi, France
Horacio Salomon, Argentina

Unintegrated HIV-1 generates an inducible reservoir of replication competent virus in nonproliferating CD4+ T cells
B. Trinité, E. Ohlson, S. Rana, J. Alster, D.N. Levy
New York University College of Dentistry, Basic Science, New York, United States
D. Levy, United States

Evaluation of treatment with the histone deacetylase inhibitor vorinostat (suberoylanilide hydroxamic acid; SAHA) in antiretroviral drug treated, SIVmac239-infected rhesus macaques
J. Lifson1, G. Del Prete1, R. Kiser1, C.M. Trubey1, J. Smedley2, V. Coalter1, K. Oswald1, R. Shoemaker1, R. Fast1, Y. Li1, A. Lara1, A. Wiles1, R. Wiles1, R. Macallister2, R. Sanchez3, J. Wai3, C. Tan3, B. Keele1, J. Estes1, M. Piatak, Jr.1, D. Hazuda3
1SAIC Frederick, Inc., Frederick Naitonal Laboratory for Cancer Research, AIDS and Cancer Virus Program, Frederick, MD, United States, 2SAIC-Frederick, Inc., Frederick National Laboratory for Cancer Research, Laboratory Animal Sciences Program, Frederick, MD, United States, 3Merck Research Laboratories, West Point, PA, United States
J. Lifson, United States

HIV-1 female-to-male sexual transmission: evaluation of circumcised and uncircumcised penile tissue
M. Dinh1, M. Anderson1, C. Gioia1, M. McRaven1, Z. Okocha1, G. Cianci1, T. Hirbod2, G. Kigozi3, J. Prodger4, R. Kaul4, X. Kong5, R. Gray5, T. Hope1
1Northwestern University Feinberg School of Medicine, Cell and Molecular Biology, Chicago, United States, 2Karolinska Institutet, Stockholm, Sweden, 3Rakai Health Sciences Program, Entebbe, Uganda, 4University of Toronto, Toronto, Canada, 5Johns Hopkins Bloomberg School of Public Health, Baltimore, United States
M. Dinh, United States

Comparative activity of IgA mediated antibody dependent cell-mediated cytotoxicity (ADCC) in the genital mucosa of HIV seroconverters and highly exposed seronegative women
M. Aziz1,2, M. Mata1, F. Mahmood1, H. Durkin3, C. Liu4, R. Greenblatt5, M. Nowicki6, E. Golub7, K. Anastos8, A. French1,2, L. Baum1
1Rush University Medical Center, Chicago, United States, 2Cook County Health & Hospital Systems, Chicago, United States, 3SUNY Downstate Medical Center, Brooklyn, United States, 4Georgetown University, Washington, United States, 5University of California, San Francisco, United States, 6University of Southern California Norris Hospital, Los Angeles, United States, 7Johns Hopkins University, Baltimore, United States, 8Montefiore Medical Center, Section of Infectious Diseases, Bronx, United States
L. Baum, United States

Stabilized exposure of conserved epitopes by structure guided insertion of disulfide bonds in HIV envelope glycoprotein
A. Dey1, A. Kassa1, A. Nandi1, P. Sarkar1, Y. Sun2, K. Hartog2, C. Labranche3, D. Montefiori3, I. Srivastava4, A. Carfi1, S. Barnett1
1Novartis Vaccines & Diagnostics Inc., Cambridge, United States, 2Novartis Vaccines & Diagnostics Inc., Emeryville, United States, 3Duke University Medical Center, Durham, United States, 4Vaccine Research Center / NIAID / NIH, Vaccine Production Program Laboratory/VRC/NIAID, Bethesda, United States
A. Dey, United States


Powerpoints presentations
HIV-1 female-to-male sexual transmission: evaluation of circumcised and uncircumcised penile tissue - Minh Dinh

Rapporteur report

Track A report by Hendrick Streeck

The late breaker session track A was chaired by Françoise Barré-Sinoussi and Horacio Salomon and focused on the latent reservoir, mechanisms and protection from transmission as well as a presentation by Antu Dey on recombinant envelope stabilization for vaccine design.

The session started with a presentation by David Levy demonstrating that resting CD4 T cells rendered permissive to HIV replication after stimulation with several different gamma-chain cytokines. He showed that these resting cells provide a reservoir for persistent unintegrated HIV DNA and were able to effectively produce and transmit infectious virions. He noted that while the overall contribution of infectious virus from these cells is most likely minor, it is plausible that uDNA is still a significant contributor to the overall viral diversity. He further demonstrated that the gene expression of HIV from uDNA was dependent on the presence of Vpr and could be forced in the presence of HDAC inhibitors in combination with Prostratin weeks after infection of resting T cells.

Activation of the latent reservoir using HDAC inhibitors was also a focus of the second presentation by Jeff Lifson. In six rhesus macaques infected with SIVmac239 and ART supressed viremia he showed inconclusive results on the effect of Vorinostat/SAHA on viral loads in vivo. However, SAHA had a modest effect on cell associated viral loads and a signifncant effect in an in vitro model. Despite the results on SAHA, the importance of this work was the development of a feasible, safe and well tolerated antiretroviral therapy regimen for rhesus macaques that allows the study of latent reservoir and eradication strategies in an animal model.

Mihn Dihn showed data on possible routes and localization of female to male transmission. Comparing keratinization of inner and outer foreskin she found no significant difference between the two. She also demonstrated that while more virus attaches to inner foreskin compared to outer foreskin or glans, no differences exist in the level of penetrating viruses.

Using cervical vaginal lavage samples of highly exposed seronegative females with HIV+ sex partners, Linda Baum demonstrated that high levels of HIV IgA ADCC was associated with protection from infection, while HIV IgG ADCC activity was barely detectable.

Finally, Antu Dey demonstrated data on an effective structure guided stabilization of inter-layer interactions allowing the stable exposure of conserved epitopes on the antigen to elicit improved antibody response. A single disulfid bonds between the positions Val65 and Ser 115 enhanced the stability of the receptor bound conformation of gp120.


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