ASHM Report Back

Clinical posts from members and guests of the Australasian Society for HIV, Viral Hepatitis and Sexual Health Medicine (ASHM) from various international medical and scientific conferences on HIV, AIDS, viral hepatitis, and sexual health.

Attending my first CROI in Boston, I am amazed by two things. Firstly, how cold it is during the day. I'm sure my eyeballs were going to freeze walking to the conference venue. More of that to come - it's only reaching a maximum of 0 degrees Celsius all week. At least the locals are warm and friendly.

Secondly, the scale of CROI is enormous. Over 4000 delegates this year and the main auditorium is imposing for any speaker. Thankfully there are large screens and excellent amplification. You can still sit way down the back and still see/hear what's going on.

This evening, Dr Paul D. Bieniasz from the Aaron Diamond AIDS Research Center presented the Bernard Fields Lecture on "Making and Breaking Barriers to Cross-Species HIV-1 Transmission". 

The lecture centred on the role of intrinsic host cell factors that directly inhibit viral replication. They work through a diverse mechanism of actions on invariant or genetically fragile viral features. For HIV these defences are called restriction factors. A number of restriction factors have been studied as potential inhibitors of HIV replication. Tetherin was used as an example - the expression of which causes retention of mature, fully formed infectious HIV-1 on surface of infected cells. Tetherin works by inserting its c-terminal anchor into viral envelope, trapping nascent HIV-1 virions by a direct tethering mechanism, leading to endocytosis and signalling.

The Research Center had created an artificial tetherin that was structurally similar but not the same protein sequence as the human protein. Remarkably, this artificial tetherin had action (not as good as real tetherin) to trap virions on the cell surface, preventing release of the virus and further viral replication.

However, viruses have evolved defence mechanisms to counteract these restriction factors. HIV has the Vpu protein that binds tetherin to overcome the cell's defence mechanism. The HIV-1 Vpu protein specifically evolved to work against human tetherin.

These defences are largely species specific, making it difficult to use animal models to study the actual HIV-1 virus. Many Simian immunodeficiency viruses (SIVs) do not encode a Vpu protein, and evolved a different mechanism - the Nef protein which interacts with simian tetherin via the protein's cytoplasmic tail.

Another HIV-1 restriction factor discussed was APOBEC3. APOBEC3 is antagonised by HIV-1 Vif proteins, which also has species specific action like Vpu. The researchers developed an HIV-1 strain with SIV Vif inserted that allowed the virus to replicate in pig-tailed macaque lymphocytes. Infecting successive groups of macaques, the researchers generated a terminal AIDS defining illness in phase 4 animals, when they artificially caused CD8 depletion at the time of infection using anti-CD8 antibodies. The phase 4 macaques developed a B cell lymphoma which showed marked CD4 depletion.

Interestingly, the HIV-1 Vpu in this modified strain adapted to antagonise the pig-tailed macaque tetherin, at the expense of the ability to antagonise human tetherin, providing an insight into viral mutation and cross-species infectivity.

Although Dr Bieniasz was hopeful on the ability to develop more realistic animal models for HIV-1, he cautioned against the use of such models for more advanced research such as vaccine development. While this adapted HIV-1 strain can cause AIDS in a non-hominid species, the adaptation is incomplete. Notably, in this experiment the researches needed to induce CD8 depletion at the time of infection, as the animal quickly adapted and post-infection depletion of CD8 was ineffective at inducing an AIDS defining illness.

 

Tagged in: CROI2014 IAS2013

The day held many highlights. There was ongoing discussion on the importance of the international community continuing to partner in the continuing challenges related to the epidemic. This is a time where national governments will be expected to continue to increase local contributions to local programs, however external assistance is a valuable and essential element in continuing to turn the tide. A great deal has been achieved. Yet there is much more to do. A way of contributing to this process is by signing the DC declaration.

Please could you consider signing this document. This is an important contribution you can make. Consider sharing it also with other friends and colleagues. 

Some of the world's leading HIV researchers have signed the D.C. Declaration. Community advocates have signed.  Have you?

The possibility of beginning to end the AIDS epidemic in our lifetimes is now a reality, but it requires a scale up of resources and efforts using the tools we have today to curb new infections and improve the health of tens of millions of people with HIV/AIDS. Turning the tide will take concerted leadership at all levels of government, health systems, and academic and non-governmental organizations. The Washington, D.C. Declaration calls for:

  • An increase in targeted new investments
  • Access for all to evidence-based HIV prevention, treatment and care
  • An end to stigma, discrimination, legal sanctions and human rights abuses against those living with and at risk for HIV
  • Marked increases in HIV testing, counselling and linkages to services
  • Treatment for all pregnant and nursing women living with HIV and an end to peri-natal transmission
  • Access to antiretroviral treatment for all in need
  • Identification, diagnosis and treatment of TB
  • Accelerated research on new HIV prevention and treatment tools
  • Mobilization and meaningful involvement of affected communities.
  • Sign the declaration online at www.dcdeclaration.org or www.2endaids.org
  • You too can lend your name before the final number of endorsements is announced at the Closing Session!
Tagged in: AIDS 2012

Lots of excitement at CROI this year about some new studies demonstrating an initial signal of disrupting latency. See my overview of these studies presented at CROI on Wednesday 4-6pm, Archin et al on Thursday 10am and the current story in nature.

 

Tagged in: CROI2012

Please join us for a memorial event celebrating the life of one of Australia’s leading HIV advocates, Levinia Crook… https://t.co/N7dof5xaGa

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