Christina Psomas, MD, PhD is our "grand reporter" at the 2016 CROI
Every day during the 2016 CROI held in Boston, 22-25 February, she is selecting for us the "best moments". Her summaries published on this website daily are independent of any firm sponsoring: it is science driven only!
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John Mellors initiated the session W1 of the workshop for new Investigators and Trainees of the CROI meeting this 22nd of February, in an overwhelming ballroom under the Boston sun.
While handing out little red lobsters in trainees, Wesley Sundquist begun his presentation on the advances on HIV Molecular Virology, describing the two major breakthroughs in this field:
-the role of Nef in relocalization of proteins to lysosomes or the plasma membrane (Shen SCIENCE 2015) via the newly identified system of the SERINC proteins (Usami NATURE 2015, Rosa NATURE 2015),
-as well as the fact that HIV-1 genomic RNA packaging determines dimerization dependent RNA structural switch after dynamic Gag-RNA interactions (Freed NAT REV MICROBIOL 2015).
Richard Koup went on in the immunologic field analyzing the importance of the microbiome, because in quantitative terms he precised that "we are more procaryotic than eucaryotic". Healthy microbiome is influenced by many factors such as age, state of health, nutrirional matters, as well as antibiotics. In HIV-infected patients, dysbiosis is traduced by the loss of firmicutes and the increase of proteobacteria, which is strongly associated with markers of mucosal and systemic immune activation (Dillon MUC IMMUNOL 2014). The use of probiotics reduces lymphoid follicle fibrosis and confers fewer complications in SIV-infected macaques (Klatt JCI 2013). Moreover, microbiome may create a diversion of HIV-1 vaccine-induced immunity by Env gp41-microbiota cross-reactive antibodies (Williams SCIENCE 2015).
The third presentation was given by Huldrych Günthard from Zurich on the "HIV Latent Reservoirs: obstacles and strategies to a cure". He first reviewed the history of the description of the reservoir since 1997. He then went on the nature of this reservoir in terms of cells (CD4, macrophages, others) and in terms of anatomic reservoirs. In the following slide he showed that HIV transcripts are the signature of the reservoir:
He reminded the 2 hypothesis why the reservoir is still present and stable after 1 year of ART: long terme persistence and/or residual replication and decribed the pros and cons of the persistent replication hypothesis.
He reviewed the methods currently available to measure the reservoir, and their technical challenges:
-peripheral blood represents only 1% of the HIV reservoir
-anatomic reservoir are difficult to access
-the viral outgrowth assay underestimates the reservoir by 60 folds
-RNA transcripts does not necessarily means replication competent virus
-high burden of defective proviral DNA
"The only way to know if a patient is curred is to stop cART" he mentioned.
Regarding the approaches toward a cure he recalled that treating patients at acute HIV infection lowers the reservoir.
The current strategies tested are:
-"Shock and Kill"
-"Shock and Kill with antobodies"
-"Shock and Kill and vaccine"
-"Alter target cells (CCR5 knock down/out, stem cell transplant)"
He just mentioned the approach on targeting immunological checkpoints...
In terms of HIV prevention, Sharon Hillier described the rapidly changing landscape of PrEP. In oral PrEP studies (iPrEx open label PrEP in San Francisco) HIV-1 transmission is strongly dependent on the threshold of PrEP adherence (Grant LANCET ID 2014). Sustained delivery injectable PrEP formulations are clearly under development and window of forgiveness is due to drug "tail" remaining after the last injection of the PrEP. Preclinical studies of rilpivirine and cabotegravir are underway, but will certainly encounter adherence issues, concerning for instance how to counsel people regarding the duration of protection. It is interesting to note that vaginal rings in development now combine prevention with contraception with different phase I studies ongoing (CONRAD 128, MTN-030/IPM 041). Sharon concluded saying that in the Gardner cascade aspiration meets reality, and we now know that getting to 90-90-90 is rather complicated and multidimensional, because of adherence or behavioral issues. Prevention should be community based, less stigmatizing, incorporated into daily life, giving the right products into people's hands.
A brilliant afternoon presentation of Patrick Sullivan during the session W2 workshop treated how to use "Big Data" in order to improve HIV care and prevention continuum. In the way that in the business world Big Data is proposed to drive efficacy and quality while increasing operating margin, in terms of care continua big data could help analyze behaviors of individuals and thus improve linkage/relinkage to care or predict HIV risk and prevention needs. In health implementation Big Data analysis will require examination of ethical issues, new data structures and improved analytic methods, but still seems very promising. Martina Morris then developed that network analysis can inform HIV prevention considering that HIV exposure is not only determined by one's behavior, but also depends on one's network position. Networks have connectivity thresholds between individuals. This means that the number of partners per capita for instance, could determine the percentage of people connected and thus influence epidemic model projections in a non linear relationship. So, in order to end AIDS we need dynamic models that are accurate and take into account the representative sample.
Finally, the opening session OS was marked by Kenneth Cole's presentation, chairman of the board of amfAR. Kenneth received a special recognition award honoring three decades of pioneering vision, courage and creative leadership in the fight against HIV/AIDS. He was the first designer to publicly come out with a message concerning AIDS. He presented his touching experience for over 25 years and knew how to inspired people around him in order to invest themselves in the fight towards a cure and a universal accessibility in drugs. One of his slogans is "We all have AIDS if one of us does".
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Key words: 2016 CROI, 2016 CROI summary, CROI, Christina Psomas, HIV, HIV cure, HIV persistence, HIV reservoirs, ISHEID