Rapporteur reports
Track A report by Guido Silvestri
In his plenary lecture Dr. Robert Siliciano (USA) reminded us that when ART was first introduced it was thought that in 2-3 years of treatment the virus will be completely eradicated. Needless to say, that prediction was wrong, as HIV continues to replicate although below the clinically detectable level in cellular reservoirs that sustain this residual replication. In this view, HIV infects CD4+ T cells that normally are activated to fight various infections and then becomes latent as a fraction of these cells return to a resting state. This latent phase may last for decades with a minute fraction of these latently infected cells being reactivated at any give time, thus producing virus (and often dying as a result). Mathematical modeling predicted that natural eradication of these HIV-infected memory cells will take ~70 years. Seminal work from Dr.Siliciano’s laboratory provided experimental proofs for this model by showing that virus that is reactivated out of memory cells has the genetic signatures of the initial virus (as it did not undergo evolution during latency). An appealing strategy to eliminate this latent virus (and thus possibly eradicate the infection) is to activate these resting memory cells and let them die out. Currently there is no way to activate these cells specifically, i.e., without massive activation of uninfected cells, which would again increase the pool of latently infected cells. In summary, three steps are needed to eradicate the reservoir of latently infected cells: (i) stop ongoing replication, (ii) identify virus reservoirs and (iii) eradicate these reservoirs by selectively activating the HIV-infected cells. While the first two stes have been accomplished, the third has been beyond our reach.
Community report by Terje Anderson
Sex workers are not the part of the problem; they are the part of the solution asserted Elena Reynaga, executive secretary of AMMAR, the Argentine Association of Female Sex Workers. Speaking last at the Plenary on Wednesday, Elena said:
Evidence from across the world shows that the best HIV prevention work among sex workers has been done by organizations managed and run by sex workers. Giving the example of the sex worker-run Sonagachi Project of Kolkata, she said they have contained HIV prevalence among sex workers to around 5%, when it was 54% among sex workers in other parts of the country. Yet, evidence like this was ignored by international agencies that base program support on ideologies and impose sanctions on sex worker projects.
It was also evident from interventions across the world that addressing human rights, law and stigma were vital for impacting on HIV prevalence among sex workers; however violations of rights of sex workers, violence against them from law enforcement agencies continued unabated and unpunished.
She concluded by saying sex workers per se were not vulnerable: it is their unfavourable working conditions that make them so. Countries where sex work is recognized as work and where sex workers are invited to contribute to designing national HIV/AIDS strategies, have done much better in terms of containing the epidemic.
Averring that we have failed the children because perhaps they are ‘too small to count’, Linda Richter of the Human Sciences Research Council of South Africa said HIV response is failing children. She also pointed out that lot of resources were misspent by focusing attention on children orphaned by AIDS when their vulnerabilities were no different from other children in their own contexts. Programmes should focus on making services available to children infected and affected by HIV and also their surviving parents. Focussing almost exclusively on the generalized epidemic in Sub-Saharan Africa, she recommended that children affected by HIV needs to be supported through family-centred services; and emphasised that it was important for countries to increase their social protection/social security programmes to reach the poorest families to enable them to do so.
Youth report by Annelies Mesman
Robert Silicano, professor of Medicine, Molecular Biology and Genetics presented the latest findings of his department. Although much more research is needed, the results give promising insights for Highly active anti-retroviral therapy (HAART) for HIV-1.
Finding a cure for HIV demands three things:
1.Stop viral replication. This can be done with anti-retro virals (arv).
2. Identify characteristics of reservoirs: latent memory T cells can survive for decades and contain virus particles.
When active T cells are induced to latent T cells, virus replication (gene expression) stops because this is dependent on host cell transcription factor NF-kB. However, sometimes these particles are freed from the resting cells.
During HAART these cells persist. According to the hypothesis of Professor Silicano’s team, HAART stops every virus replication. This implies that free HIV from latent T cells is not dangerous.
-This hypothesis was supported by the inhibition of further evolving of virus RNA in patients receiving HAART, the lack of new drug resistance in the patients and the fact that intensification of HAART does not further decrease viremia.
By using slope parameters of a log dose-response curves, they developed an index to calculate replication inhibition of separate arv’s. Their models indicate that protease inhibitors indeed have the potential to stop replication.
3. Eliminate reservoirs
The research group has generated new realistic in vitro model systems to identify latency T cell attack mechanisms and to obtain information about factors that can induce latency.
The next step will be to screen these cells with drugs libraries to search for candidates of non-toxic drugs.
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