Poster Exhibition - International AIDS Society

International AIDS Society’s Pre-Conference Symposium
“Towards An HIV Cure”
20-21 July 2012
POSTER EXHIBITION
Rapporteurs: Lachlan Gray, Burnet Institute, Australia (themes 2, 3, 4 & 7)
María Buzón, Ragon Institute of MGH, MIT and Harvard, USA (themes 1, 5 & 6)
During the International AIDS Society’s Pre-Conference Symposium “Towards an HIV
Cure” (July 20-21, 2012, Washington DC USA), a total of 32 abstracts were presented
during the poster session. The posters were divided into seven themes based on the
main priority areas that were identified by the IAS Global Scientific Strategy Working
Group. These themes set the agenda for HIV cure and eradication research efforts
moving forward.
1. Determine cellular and viral mechanisms that maintain HIV persistence
HIV persists despite antiretroviral therapy through cellular mechanisms determining
viral latency. Understanding the molecular processes implicated in viral latency is
important in order to design new strategies to purge HIV reservoirs. In this regard,
poster 1 showed a putative link between selective dietary restriction and the
epigenetic regulation of HIV latency. Limitation of essential amino acids, such as
methionine and cysteine, caused upregulation of HIV-1 expression most likely via
selective downregulation of histone deacetylase 4 (HDAC4). Poster 2 presented the
humanized bone marrow-liver-thymus (BLT) mouse as a model for HIV latency. After
HIV infection, they showed the presence of latently infected cells that were
successfully stimulated using novel anti-latency drugs and the production of
competent virus after ART. Poster 3 highlighted the important role of HIV integration
sites in determining proviral latency. Knockout of LEDGF/p75, a cellular co-factor of
HIV integrase, shifted the integration site distribution pattern away from genes and
towards CpG islands, suggesting that LEDGF/p75 is a pivotal protein determining HIV
integration. The role of HIC1 (tumor suppressor hypermethylated in cancer 1) in viral
transcription was presented in poster 4. Overexpression of HIC1 in microglia cells led
to a decrease in p24 production and tat-mediated transcription, suggesting it is
implicated in CNS HIV-1 reservoirs. Finally, poster 6 studied the role of RNA
processing controlling tat expression. The authors showed that alternative RNAsplicing
inserted HIV tat exon4 into cellular mRNAs, facilitating expression of Tat and
supporting the hypothesis that alternative splicing after HIV integration might
control viral latency.
2. Determine the tissue and cellular sources of persistent HIV in long-term ARTtreated
individuals
It’s well established that the major cellular reservoir of HIV exists in naïve and central
memory CD4+ T-cells. However, in order to eliminate the cellular reservoirs of HIV

we need to comprehensively characterize all cell types that may contribute to it, as
each cell type may have unique mechanisms of latency and persistence.
In poster 7, Zink et al., identify macrophages as another potential cell type that may
be contributing to the HIV reservoir within the CNS. In poster 8, Ruel et al., studied
pediatric cART cases in Uganda and identified that the HIV reservoir is most
pronounced in naïve CD4+ T-cells and is predominantly established by CXCR4-tropic
virus. This work highlights important considerations for strategies aimed at virus
eradication because of the differences that may exist between viral reservoirs in
adults and children. Finally, in poster 9, Donahue et al., proposed superinfection of
latently infected cells as a potential mechanism for the emergence of multi-drug
resistant virus.
3. Determine the origins of immune activation and inflammation in the presence of
ART and their consequences for HIV persistence
It’s well known that chronic immune activation and inflammation caused by HIV
plays a central role in premature ageing, bone disease, heart disease and several
other debilitating conditions. However, their role in the establishment and
maintenance of viral reservoirs is less well understood. In posters 10-14, the authors
identify several new immune mediators that may play a key role in HIV persistence.
In poster 11, Naicker et al., propose polymorphisms in IL-10 as a potential mediator
of altered cytokine production that may act as a driver of chronic HIV infection and
HIV persistence. In poster 13, Reece et al., studied an SIV model confirming that viral
reservoirs are established early and highlighting the need for early interventions to
restrict their expansion. Additionally, they suggested that eliminating cells while
under high turnover would achieve the greatest impact in reducing viral reservoirs.
4. Determine host and immune mechanisms that control infection but allow viral
persistence
Numerous studies have investigated the correlates of protection and viral control
against HIV, highlighting strong CTL responses and broad neutralizing antibodies.
However, their relationship to viral persistence remains to be determined. In posters
15-16, the authors attempt to dissect this relationship and in the process uncover
some interesting findings. In poster 16, Conceicao et al., undertook genome wide
expression studies of patients pre- and post-cART and compared these against a
panel of long-term non-progressors (LTNP). Their findings suggest that LTNP have a
block in apoptosis pathways which in turn favors strong immune responses that
assists in controlling viremia.
5. Study, compare and validate assays to measure persistent infection
Poster 17 studied viral replication in human M1-MDM (monocyte-derived
macrophage). They showed a transient but robust restriction of HIV replication in
those cells compared to M2-MDM. In Poster 18 the role of Vacc-4x, a p24 peptidebased
HIV therapeutic vaccine, was evaluated in 135 patients. The authors showed

that the vaccinated group experienced a significant reduction in viral load compared
to placebo. Poster 19 assessed the size and decay of the resting CD4+ T cell reservoir
over the first two years of life in 17 infected infants initiating early therapy. The size
of the reservoir was associated with the time to first undetectable viral load.
6. Develop and test therapeutic agents or immunological strategies to safely
eliminate latent infection in individuals on ART
Developing novel therapeutic interventions that might potentially clear latent
infection is important for achieving sterilizing or functional cure. In this regard,
poster 20 presented the potential of tre-recombinase to reverse in vivo HIV-1
infection using a humanized mouse model. Tre-recombinase was efficiently delivery
into cells using a lentiviral vector, and excised HIV-proviral DNA from chromosomal
integration sites. Poster 21 presented delivery systems for targeting specifically CD4
T cells. They showed activation of latent infection using liposomes containing
bryostatin, and they introduce a new nanoparticle called “Vault” with enhanced
means to deliver therapeutic agents with minimal cell activation. Poster 22
presented an interesting observation regarding the lack of re-emergence of CXCR4
variants in the “Berlin Patient” after stem cell transplantation. Those CXCR4 variants
depended on CCR5 co-receptor for viral replication in functional assays. The
potential of Rapamycin, an immunosuppressant, was evaluated in poster 24 after
kidney transplantation. The authors observed a trend to towards higher plasma HIV
RNA and lower HIV DNA over time after the transplant. In poster 25, the efficacy of
multidrug ART and anti reservoir drugs (mega ART) in a range of viremic conditions
in macaques was evaluated. Complete reduction of viral load was achieved, with a
reduction of the viral set point after therapy interruption. In addition, they observed
a spontaneous control of low level viremia strictly dependent on CD8+ T cells. Poster
26 showed that CD4-AsiCs (CD4 aptamer-siRNA chimera), intravaginally applied in
solution or in a gel formulation in a BLT mouse, knocked down CCR5 expression
reducing viral load and delaying CD4 decline after HIV infection.
7. Develop and test strategies to enhance the capacity of the host response to
control active viral replication (Lachlan)
Targeting viral reservoirs will not be sufficient on it’s own to eradicate HIV. In
addition to eliminating latently infected cells, the patient’s immune system will also
need to be enhanced so that it can effectively clear any residual viral replication. In
posters 27-32, the authors suggest new ways of boosting and reinvigorating the
immune system to effectively target HIV replication. In poster 27, Vanham et al.,
propose dendritic cells as a potential mediator to enhance potent immune
responses. In poster 28, Pavlakis et al., describe a DNA vaccine encoding p55gag that
maximizes anti-Gag responses. In poster 29, Yi et al., describe the induction of
broadly neutralizing antibodies against the HIV-1 Env membrane proximal region. All
of these strategies of boosting immune response show promise and could play a role
in future efforts to enhance anti-HIV immunity.