Jacques Leibowitch

Source: Wikipedia, the free encyclopedia.

Jacques Leibowitch
Born(1942-08-01)1 August 1942
Clermont-Ferrand, France
Died4 March 2020(2020-03-04) (aged 77)
Massy, France
Known forIdentification of HIV as retro-virus, world pioneer use of tri-therapy treatment
Spouse
​
​
(m. 1992; div. 1996)​
AwardsChevaliers of the Légion d'honneur
Scientific career
FieldsHIV research
InstitutionsRaymond Poincaré University Hospital

Jacques Leibowitch (1 August 1942 – 4 March 2020

infectiology department of the Raymond Poincaré University Hospital of Garches (directed by Prof. Christian Perronne, AP-HP), University lecturer Emeritus, he led the treatment program ICCARRE that proposes a dramatic reduction of weekly anti-HIV drug intake, down to 2-3 anti-viral
pills a day taken 2 to 3 or 4 days a week, as opposed to the presently recommended seven days a week, as still universally prescribed. These reduced medical dosages are adequate, necessary and sufficient according to the results of his exploratory clinical research carried out since 2003. He is the author of the books "Un virus étrange venu d'ailleurs" (A strange virus of unknown origin),[2] and "Pour en finir avec le sida" (Putting an end to AIDS).[3]

Biography

Jacques Leibowitch did his medical studies in

Necker hospital under Professor Jean Hamburger
. He acquired his initial experience in research in 1962 at the Bellevue Hospital of New York, later returning to the United States for a Post-doctoral research program at Harvard Medical School (Pr John David, Robert Brigham Hospital, Boston, 1970–1972), where he studied cellular immunology.[4] On his return to Paris, he finished his internship and went on to research Human Complement Biology at the Royal Hammersmith Hospital, London as post-graduate medical registrar (Pr Keith Peters, 1973–74), before undertaking his senior residency in nephrology at Necker, entering the Raymond Poincaré hospital at Garches as immunology assistant lecturer (1980). Jacques Leibowitch published many articles in international scientific journals.[5]

Scientific and medical contributions

The contributions of Jacques Leibowitch have marked the history of HIV and AIDS and their treatment:[6]

  • In 1982, he expounded the hypothesis that an exotic CD4 trope retro-virus might be at the origin of the growing AIDS epidemic and put the Montagnier and de Gallo teams on the track of the virus
  • From 1984 to 1985, he removed from the Cochin hospital blood transfusion center the HIV contaminated blood samples, using a test quickly developed under the urgency of the situation by Dr Dominique Mathez, Leibowitch's main collaborator at the Raymond Poincaré hospital at Garches, anticipating the large-scale screening tests.
  • Leibowitch and Dr. Mathez developed a home-made biological assay system to measure precisely the levels of active virus in the patient before and under treatment, demonstrating the both meager and transient effectiveness of the antiviral
    AZT
    as monotherapy.
  • He is the father in Europe of the first anti-HIV treatments combining three anti-viral molecules (tri-therapy treatment) for the long-term control of HIV in the correctly treated patient.
  • From 2003 to 2014, he has shown that after a minimum six-month period on conventional 7-day-a-week "attack" treatment, weekly anti-viral drug intake could be reduced by 40% to 80%, while maintaining optimal control over the patient's HIV.

Discovery of the HIV retro-virus

Jacques Leibowitch was at the center of the research on AIDS since the original outbreak of the epidemic, from the very moment when the investigation on its

SIDA
, a self-nominated body to analyse the cases appearing in France.

When in July 1982, the first cases of AIDS appeared in

Franco-American literary author Gilles Barbedette of the announcement by Robert Gallo in Medical World News
(1 August 1982) that an HTLV type retro-virus could be the cause of AIDS, found in that most succinct brief the profile matching his CD4-tropic exotic viral suspect (in Grasset, Ballantine Books, works cited). The retro-viral inspiration was thus consolidated and opened between Bethesda (Gallo) and Paris (Leibowitch et al.) from August 1982 onwards. Failing to find in the Paris team of Professor Jean-Paul Lévy
Nobel Prize for Medicine in 2008 for their work. In a letter to the prestigious magazine Nature Medicine in 2003, as well as in his Nobel Prize acceptance speech in 2008, Luc Montagnier recognized Jacques Leibowitch as being the initiator of the retro-virus hypothesis in France[11].[12] However, the patented list of the discoverers of AIDS and HIV do not take Jacques Leibowitch into account for his contribution in the initial phases of the discovery. The scientific historian Mirko Grmek reflects back on the details of the stages that led to the discovery of the AIDS virus in his work "the History of AIDS" and the Jon Cohen AIDS Research Collection contains numerous archived documents on the subject. The book "Sida.O" (AIDS.O) written by D. Lestrade and G.Pialoux contains also many details on the history of AIDS.[13]

Detection and elimination of HIV-positive contaminated blood at Garches and at Cochin

In 1984, while Luc Montagnier was working at the Institut Pasteur on an industrial test for HIV antibodies, Dominique Mathez and Jacques Leibowitch were working at Garches to elaborate a working test on

hemophiliacs (« if the Cochin Hospital study is correct, then all anti-hemophiliac stocks are contaminated … », Jean Baptiste Brunet at the French General Directory on Health, Mars 1985 13[15]). It was thanks to this artisanal test that 50 HIV positive blood donations, established then to be 100% contaminating, were taken out of the transfusion process, and 150 potential receivers of this blood were protected from contamination.[16]

Measure of viral levels in patients and evaluation of the effectiveness of treatment

At Garches, Dominique Mathez and Jacques Leibowitch developed a sophisticated and reliable biological test enabling them to quantify active HIV virus levels in patients[17] both before and during their antiviral treatment. Indeed, from 1987, patients in France most affected by the virus receive AZT treatment in the hope that this molecule might block the reproduction of the virus. It was with the aim of monitoring the progressive decline of virus levels in the treated patient that the team at Garches worked on their method. Leibowitch presented to world specialists assembled for the conference at Marnes la Coquette (Pasteur-les Cent Gardes symposium, November 1989) his results showing that the AZT monotherapy becomes quickly ineffective as demonstrated by returning viral levels in the treated patient, though in the first month such levels were significantly, yet only transiently, reduced. The measuring of HIV viral levels is later to become, in its commercial and industrial version, the universally used test to follow the development of the virus and the effectiveness of various treatments. Also, Jacques Leibowitch was the first in France to collect sequential cell specimens from individual patients at follow up, preserving living cell samples at extremely low temperatures since 1982. This live-frozen cell bank would later become precious for retrospective scientific investigations.

First tri-therapy trials based on viral end-point levels, "Stalingrad trials, the besieged retrovirus" (Libération, August 2013)

Jacques Leibowitch is the father of the tri-therapy treatments in Europe.

anti-proteases
. Having observed in vitro the spectacular results of three combined anti-HIV nucleoside analogues (AZT +3TC +DDI) available for clinical use at the time (July 1994) and seen in patients the most effective antiviral impact of a first ever triple combination of nucleoside analogues (as shown by his home-made viral load quantitation system), Jacques Leibowitch went on to test the efficacy of the anti-proteases ... combined with pairs of nucleoside analogues to form a mixed-type triple combination therapy. On that basis, Leibowitch launched the Stalingrad Trial based on AZT+DDC+Ritonavir, a trial carried out in collaboration with Abbott, industrial producer of the anti-protease Ritonavir, under the protection of Health Minister Philippe Douste Blazy, outside the influence of the Agence Nationale de Recherches contre le SIDA (ANRS).[19] The results of the Stalingrad trial underlined the major importance measuring viral levels in real time in the patient in order to evaluate the impact of a given antiviral treatment. The success of this first tri-therapy treatment in the world was presented, together with that of another tri-therapy carried out by the group Merck, at the Washington Congress in February 1996. The findings were published in a scientific journal in 1997.[20]

The tri-therapy treatment has since been heralded a major turning point in the history of treatment of HIV infection.

Working towards an adjustment of maintenance treatments to adequate and sufficient dosages with the ICCARRE program

Since 2003, Jacques Leibowitch has been carrying out a

pilot study aiming to diminish anti-HIV doses within weekly cycles. With ICCARRE[21](French abbreviation: Intermittent, in Short Cycles, the Anti Retrovirals may Retain Effectiveness), just under one hundred HIV positive patients at the Raymond Poincaré
hospital have undergone reduced treatment maintenance therapy reduced to 4, or 3, or 2, or even 1 day a week, instead of the currently universally obligatory dosages of 7 out of 7 days, without the virus reappearing. ICCARRE has yet to be validated by regulatory bodies as a recommended anti-HIV regime; were its dosages and recommendations to be confirmed in future prospective clinical trials, the ICCARRE study would open a new avenue in anti-HIV long-term therapy.

According to the ICCARRE regime: following an early initial period in which control of retro-viral levels requires 7-day-a-week "attack treatment" during one semester or more, weekly anti-viral dosages, necessary and sufficient to achieve effective long term control of the virus, may be administered in weekly reduced dosage; such a regime offers a number of advantages including : adhesion to the deontological principle of not exceeding required medicine dosages ; minimization of the toxic effects of these heavy chemical treatments over a long-term period ; improved willing patient acceptance of an effective treatment due to a

NIAID
in the United States.

In his interview of 1 December 2011, on

Vivement dimanche 24 May 2013[26]) and Laurent Ruquier (On n'est pas couchés 15 June 2013[27]), Jacques Leibowitch has presented his programme of « canny short cycles », which distinguish themselves from current recommendations, which advocate the intake of medications on 7 days out of 7[28].[29]

Distinctions

  • Knight of the
    Legion of Honor
    , 1993

Publications

  • Un virus étrange venu d'ailleurs Jacques Leibowitch, Grasset, 1984 ; translated for Ballantine Books, New-York, 1985 as : A Strange Virus of Unknown Origin
  • Pour En Finir Avec Le SIDA (Putting an end to AIDS), Jacques Leibowitch, Plon, 2011

References

  1. ^ "Le docteur Jacques Leibowitch, un des pionniers de la lutte contre le sida, est mort" [Dr. Jacques Leibowitch, one of the pioneers of the fight against AIDS, has died]. Le Monde (in French). 5 March 2020. Retrieved 8 March 2020.
  2. ^ Pour en finir avec le sida, Jacques Leibowitch, 2011, sur le site de l'édition Plon. Consulté le 1/10/2013
  3. ^ "Un virus étrange venu d'ailleurs", Grasset 1984
  4. ^ Entretien avec Jacques Leibowitch réalisé par J.-F. Picard en mai 2001 sur le site histrecmed
  5. ^ International scientific journals
  6. ^ Les contributions de Jacques Leibowitch Pour en finir avec le sida, sur le site de Patrick Vallas. Consulté le 1/10/2013
  7. ^ Un entretien avec le Docteur J. Leibowitch, Le Panorama du médecin n°1507, 8 octobre 1982
  8. ^ Entretien avec Jean-Paul Lévy réalisé par Anne Lévy-Viet&Jean-François Picard, janvier 1992-décembre 2001, paragraphe "Mais vous-même, vous aviez reçu la visite des cliniciens à Cochin" sur le site histrecmed
  9. ^ Interview with Robert Gallo réalisé par Victoria A. Harden et Dennis Rodrigues le 4 novembre 1994 sur le site de l'Office of NIH History
  10. ^ Paul Prunet,Comprendre la vie et ou comprendre les maladies. Avec petit retour sur l'histoire de la recherche sur le sida en France sur le site de Patrick Valas
  11. ^ Luc Montagnier, 2003, Historical accuracy of HIV isolation, Nature Medicine 9
  12. ^ Luc Montagnier, Nobel lecture, 2008
  13. ^ Didier Lestrade et Gilles Pialoux, Sida 2.0, Regards croisés sur 30 ans d'une pandémie
  14. S2CID 6181443
    .
  15. ^ Retour sur l'affaire du sang contaminé par Catherine Manuel et Pascal Auquier, 1/06/1996, site de La recherche Archived 13 October 2013 at the Wayback Machine
  16. ^ Le procès du sang contaminé. 5e jour par Eric Favereau et Armelle Thoraval, Libération le 17/02/1999
  17. ^ Productive human immunodeficiency virus infection levels correlate with AIDS-related manifestations in the patient, Proc Natl Acad Sci U S A. , 1990, Mathez et al.
  18. ^ Essai "Stalingrad", le virus assiégé par Eric Favereau, Libération du 3 et 4 août 2013
  19. ^ Sida : la course aux molécules. Sébastien Dalgalarrondo,2004; Editions EHESS
  20. PMID 11322272
    .
  21. ^ En savoir plus sur le protocole ICCARRE sur le site dédié
  22. ^ Short cycles of antiretroviral drugs provide intermittent yet effective therapy: a pilot study in 48 patients with chronic HIV infection, FASEB J., 2010, Leibowitch et al.
  23. ^ Short-cycle structured intermittent treatment of chronic HIV infection with highly active antiretroviral therapy:effects on virologic, immunologic, and toxicity parameters, PNAS, 2001, Dybul et al.
  24. ^ A proof-of-concept study of short-cycle intermittent antiretroviral therapy with a once-daily regimen of didanosine, lamivudine, and efavirenz for the treatment of chronic HIV infection, JID, 2004, Dybul et al.
  25. ^ A randomized, controlled, trial of short cycle intermittent compared to continuous antiretroviral therapy for the treatment of HIV infection in Uganda, PLOS ONE, 2010, Reynolds et al.
  26. ^ "Emission Vivement dimanche du 24 mai 2013 sur le site de France2". Archived from the original on 17 March 2014. Retrieved 17 March 2014.
  27. ^ Video France 2-Ruquier/le Pr Jacques Leibowitch "On n'est pas couchés"(15 juin 2013), sur le site Le mediascope, consulté le 1/10/2013
  28. ^ "BFM Business : Professeur Jacques Leibowitch". Archived from the original on 21 September 2013. Retrieved 2 August 2013.
  29. ^ "Leibowitch chez Drucker. Retranscription sur le site sero-on-line". Retrieved 7 August 2013.

External links

Retrieved from "https://en.wikipedia.org/w/index.php?title=Jacques_Leibowitch&oldid=1177336256"