7th IAS Conference on HIV Pathogenesis, Treatment and Prevention (IAS 2013)


TUSA03 ANRS Satellite Symposium: What Can We Learn from Post-Treatment Controllers?
  Non-Commercial Satellite
Venue: Mini Room 3
Time: 02.07.2013, 18:30 - 20:30
Co-Chairs: Jean-Francois Delfraissy, France
Sharon Lewin, Australia
Cécile GOUJARD, France
Carl Dieffenbach, United States
Jean-Pierre Routy, Canada
Organiser: ANRS, The French National Agency for Research on AIDS and Viral Hepatitis
Long-term control of HIV replication has been observed in patients from France who initiated cART during primary infection, then stopped the treatment. The ANRS VISCONTI study of 14 post-treatment controllers (PTC) shows that these patients present low levels of HIV reservoirs, like natural HIV controllers (HIC), but have different immune-genetic characteristics. Moreover, the probability of viral control after interruption of a durable treatment initiated early in primary infection appears higher (5-15%) than the frequency of spontaneous control (<1%). Once off treatment, PTCs presented a skewed distribution of the reservoir, which was further reduced over time. In recent reports, early treatment initiation also appears a key factor to achieve this status. The goal of this meeting is to discuss the frequency and the mechanisms underlying post treatment control in both acutely and chronically treated PTCs. The ultimate goal is to promote international collaborative research.

18:30
Introduction
J. Delfraissy, France

18:40

Powerpoint
Long-term clinical and viro-immunologic outcomes of post-treatment controllers in the VISCONTI study
L. Hocqueloux, France

18:55
PHI, ART and viral control: insights from SPARTAC
J. Frater, United Kingdom

19:10

Powerpoint
Should we treat HIV controllers?
O. Lambotte, France

19:25

Powerpoint
Natural and induced control of HIV infection: differences and similarities
A. Sáez-Cirión, France

19:40

Powerpoint
HIV reservoirs in post-treatment controllers and HIV controllers
C. Rouzioux, France

19:55

Powerpoint
Early treatment initiation: the case of RV254/Search 010 Study Group
J. Ananworanich, Thailand

20:10
Antiviral immune responses in natural and induced control of HIV infection
M. Altfeld, United States

20:25
Conclusion
F. Barré-Sinoussi, France

20:28

Powerpoint
International Post-Treatment Controllers
A. Sáez-Cirión, France

Powerpoints presentations
Long-term clinical and viro-immunologic outcomes of post-treatment controllers in the VISCONTI study - Laurent Hocqueloux

Should we treat HIV controllers? - Olivier Lambotte

Natural and induced control of HIV infection: differences and similarities - Asier Sáez-Cirión

HIV reservoirs in post-treatment controllers and HIV controllers - Christine Rouzioux

Early treatment initiation: the case of RV254/Search 010 Study Group - Jintanat Ananworanich

International Post-Treatment Controllers - Asier Sáez-Cirión



Rapporteur report

Track B report by Jürgen Rockstroh


A special ANRS satellite symposium was dedicated to individuals who are maintaining non-detectable viral loads in the absence of ART after initiation of treatment during early primary HIV infection (PHI). These so-called post treatment controllers (PTC, VISCONTI cohort) are rare and comprise app. 5-15% of patients treated early during acute infection for 3-5 years before treatment interruption. In most cases these patients experience severe symptoms during acute infection. Unlike elite controllers they do not carry protective HLA alleles (e.g. HLA-B52/27) in the majority of cases. Consequently T cell responses are much weaker in PTC compared to elite controllers (EC). French virologists reported a very low reservoir size in PTC. However, cell bound DNA can be detected in almost all cases when large amounts of PBMC are investigated indicating a functional cure rather than eradication. One of the most pertinent remaining questions, namely how PTC manage to control viral replication remains to be elucidated and will not only be crucial for the cure arena but also for vaccine development. During the workshop researchers from Thailand extended their earlier reports of their very early acute infection cohort from Bangkok. Patients who have been treated as early as possible during PHI (Fiebig stage I) show considerable restriction in the initial seeding of the viral reservoirs. In these patients cell bound DNA will rapidly decline during treatment and will be absent in most cases during treatment. However, further studies are needed to assess the remaining reservoir size. Of note there was no difference in viral loads or T cell recovery in patients treated with intensified five drug regimens including maraviroc and raltegravir compared to those treated with standard three drug regimens. This amazing cohort will now serve as a platform to conduct randomized clinical trials including therapeutic vaccines and HDAV inhibitors before initiating treatment interruption.

Another case of functional cure comparable to the VISCONTI patients was reported during the conference by German researchers from Hamburg. This patient was treated during PHI and for five consecutive years with standard ART. No plasma viral load and proviral DNA was detected in this patient after nine years of treatment interruption using standard techniques. Moreover, no virus was found in gut biopsies and CSF. However, virus could be recovered after prolonged co-culture and proved to be pathogenic in a humanized mouse model indicating infection with a replication competent virus. Again this argues for a functional cure which was associated with broad HIV specific T cell responses in this case. At the end of this crowded session ANRS researchers announced the creation of a platform where they want to collect more PTC from all around the world and co-ordinate research performed on these rare but very important individual cases.     




   

    The organizers reserve the right to amend the programme.