NIH HIV CURE 2014 MEETING
The NIH organized on October 15-17, 2014 a meeting intitled 'Strategies for an HIV Cure'.
This is the second edition of the meeting, the first one being held in November 2012. Its main instigator is Karl Salwedel from the NIH.
We propose below a summary of the main presentations. This is not an exhaustive report and we have had to make choices due to the quantity of data often presented in a very short time. Although, we did not insist on presentation which were quite the same as those shown a month ago at the Baltimore meeting (regarding them, please refer to the corresponding report).
You initially had to go to the high level security check of the NIH and them you could enter the 'inner sancutum'.
This year more than 600 people were registered and the meeting was moved to the Natcher Building.
Everyone was febrile when the 'Boss' shown, Professor Antony Fauci, same as always with his charism and calm, although that morning he was in the front row with another thing: the second Dallas case of Ebola infection...
As if HIV kept only his attention, he riminded us that the number of infections has decreased of 38% since 2001, but that it looks not economically nor logistically feasible to deliver ART to more than 35 millions individuals infected worldwide.
A seach with PubMed showed that there were 43 papers published in 2000 on the topic of 'HIV CURE' and 227 in 2013. Regarding the topic of 'HIV Latecgy or Reservoirs', 100 papers were published in 2000 and 237in 2013.
NIH spent 75.4 millions of dollars in 2013 for HIV cure research; NIAID 54.1 miliions with a total of 372 millions between 2005 and 2013.
Recently, the Obama adminsitration promized to add 100 Million dollars on the table.
In his conclusions, A. Fauci mentionned that a HIV cure must be:
The first part of the morning was then dedicated to the presentation of the different collaborations.
Hans-Peter Kiem talked about defeatHIV. He focused on 3 projects:
-project 1 studies the effect of the conditionning regimen intensity during autologus BMT (BEAM regimen or TBI Cy regimen). Patients with undetectable viremia were included and showed that the progression of full donor chimerism correlates with loss of proviral DNA.
The project also tries to establish a non human primate model ('SHIV-C' receiving 6 months of ART and either no transplant, transplant with stem cells, or delta 32 CCR5 transplant.
Twenty four animals were included but a rebound of viremia was observed in all.
-projects 2 and 3 study CCR5-Zinc Finger Nucleases disruption in 4 macaques. The disruption reached was only 5%.
-project 4 targets disruption of integrase
-and project 5 studies the in vivo delivery of mRNA targeting eithet CCR5 or integrase.
David Margolis gave an overview of the CARE collaboration.
He hopes that new anti latency agents will reach clinical testing in 2016.
He particularly focused that 66.5% of the compounds screened so far are of unknown mode of action.
He called for improving animal models, measures of the 'real' reservoirs, and DC vaccines.
Joseph McCune talked about the DARE collaboration.
His work focuses on modulation of PD-1 and cell proliferation. More broadly, he called for a change in Academic promotion process in order to have more efficient research.
The second part of the morning was dedicated to gene editing and cell-based strategies.
Philip Gregory from Sangamo showed that ZFN can disrupt up to 35.9% of cells at 30°C and more than 40+ of adult CD34+ stem cells.
Keith Jerome talked about endonucleases for provirus disruption but agreed that in vivo delivery is challenging.
Kevin Morris addressed the use of 2 types of vectors: with intact LTR or delta 362 LTR.
The afternoon began with a refreshing talk given by Philip Murphy on the WHIM syndrome.
This syndrome (acronim for Warts, Hypogammaglobulinemia, Infections, Myelokatesis) is rare (100 cases diagnosed), old (first described in 1962, and due to a mutation in CXCR4 gene in chromosome 2. It is a disorder of bone marrow eggress of neutrophils. Patients, however, do not generally die from infections. The speaker reported the case of a spontaneous cure of WHIM syndrome although the mutation was still there. He also pointed at the potential use of Mozabil, a CXCR4 inhibitor.
Paula Cannon went trough already shown data on the use of humanized mouse to test endonucleases.
Pablo Tebas repeated his classic presentation on the sangamo trial involving 12 patients treated with ZFN. With chance the audiance known his data by hart as he messed with the computer and was unable to show all his slides...
Timothy Henrich emphasized the 2 Boston patients thar rebounded after 3 and 8 months post ATI. He stressed the fact that GVH disease is the cause of the decrease in the reservoir observed and that NK cells take a major role in beneficial GVH.
Melanie Ott addressed protein acetylation and stressed that BET inhibitors are latency reversing agents. HMBA and Bromosporine are BET Bromodomain inhibitors.
Jenice Clements, finally, showed that with SIV Ingenol B can prolong the time to rebound from 15 to 45 days.
Key words: Antonny Fauci, Berlin Patient, HIV DNA, HIV Functional Cure, HIV Persistence, HIV Reservoirs, HIV cure, HIV eradication, NAIAD, NIH, NIH meeting