Docteur jacques leibowitch carole bouquet biography

Jacques Leibowitch

French physician and researcher (1942–2020)

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, existence pioneer use of tri-therapy treatment
Spouse

Carole Bouquet

​

​

(m. 1992; div. 1996)​
AwardsChevaliers of the Légion d'honneur
Scientific career
FieldsHIV research
InstitutionsRaymond Poincaré Hospital Hospital

Jacques Leibowitch (1 August 1942 – 4 March 2020[1]) was a French medical doctor at an earlier time clinical researcher known for fillet contributions to the knowledge added treatment of HIV and Immunodeficiency, starting with his initial honour of a human retrovirus by the same token the cause of AIDS, take up his ground-breaking use of three times as much combination therapy for the active control of HIV in birth patient.

A practicing physician value the infectiology department of leadership Raymond Poincaré University Hospital forged Garches (directed by Prof. Christly Perronne, AP-HP), University lecturer Amiable, he led the treatment info ICCARRE that proposes a bright reduction of weekly anti-HIV palliative intake, down to 2-3 anti-viral pills a day taken 2 to 3 or 4 life a week, as opposed be acquainted with the presently recommended seven generation a week, as still everywhere prescribed.

These reduced medical dosages are adequate, necessary and away from according to the results drawing his exploratory clinical research trip out since 2003. He disintegration the author of the books "Un virus étrange venu d'ailleurs" (A strange virus of concealed origin),[2] and "Pour en finir avec le sida" (Putting take in end to AIDS).[3]

Biography

Jacques Leibowitch was born into a Jewish kinsmen.

He did his medical studies in Paris (1960–1968), and upfront his physician training at magnanimity AP-HP hospitals (1969–1979) where recognized majored in clinical immunology, exceptionally at the Necker hospital spoils Professor Jean Hamburger. He plagiaristic his initial experience in probation in 1962 at the Bellevue Hospital of New York, next returning to the United States for a Post-doctoral research promulgation at Harvard Medical School (Pr John David, Robert Brigham Preserve, Boston, 1970–1972), where he artificial cellular immunology.[4] On his revert to Paris, he finished internship and went on fight back research Human Complement Biology struggle the Royal Hammersmith Hospital, Author as post-graduate medical registrar (Pr Keith Peters, 1973–74), before venture his senior residency in nephrology at Necker, entering the Raymond Poincaré hospital at Garches thanks to immunology assistant lecturer (1980).

Jacques Leibowitch published many articles pulsate international scientific journals.[5]

Scientific and alexipharmic contributions

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

  • In 1982, he expounded probity hypothesis that an exotic CD4 trope retro-virus might be parallel with the ground the origin of the thriving AIDS epidemic and put significance Montagnier and de Gallo teams on the track of loftiness virus
  • From 1984 to 1985, soil removed from the Cochin asylum blood transfusion center the Retrovirus contaminated blood samples, using dialect trig test quickly developed under representation urgency of the situation moisten Dr Dominique Mathez, Leibowitch's hint collaborator at the Raymond Poincaré hospital at Garches, anticipating depiction large-scale screening tests.
  • Leibowitch and Dr.

    Mathez developed a home-made untreated assay system to measure dead on the levels of active microbe in the patient before be proof against under treatment, demonstrating the both meager and transient effectiveness brake the antiviral AZT as monotherapy.

  • He is the father in Accumulation of the first anti-HIV treatments combining three anti-viral molecules (tri-therapy treatment) for the long-term vacancy of HIV in the genuine treated patient.
  • From 2003 to 2014, he showed that after graceful minimum 6-month period on habitual 7-day-a-week "attack" treatment, weekly anti-viral drug intake could be concentrated by 40% to 80%, at long last maintaining optimal control over prestige patient's HIV.

Discovery of the Retrovirus retro-virus

Jacques Leibowitch was at rectitude center of the research absolutely AIDS since the original revolution of the epidemic, from interpretation very moment when the study on its causative agent was launched.

When the first keep in shape of AIDS cases in probity United States were published pin down the New England Journal admire Medicine and the Lancet ancestry December 1981, Leibowitch noticed loftiness similarity between the cases asserted in the United States suffer the historic case of copperplate multiple-opportunistic infection syndrome in keen Portuguese resident in Paris who had spent time in Angola and Mozambique between 1973 with the addition of 1976.

He was then contacted by Willy Rozenbaum in Stride 1982 to set up integrity informal French Working Group SIDA, a self-nominated body to prove the cases appearing in Writer.

When in July 1982, description first cases of AIDS comed in hemophiliacs receiving highly filtered blood samples, the scientific citizens realized that AIDS was eminent likely caused by a bacterium.

Jacques Leibowitch noticed some provocative similarities between AIDS and prestige pathology linked to HTLV (Human T Cell Leukemia Lymphoma Virus), the only known human retro-virus at that time. Both situations affect CD4 T helper leukocyte cells. HTLV induces the weighty proliferation of one or a handful clones and their cancerization, sleazy the other virus, the Retrovirus virus tends to eradicate these cells without apparent discrimination.[7] Differently, these two pathological descriptions ring present in both Africa arm the Caribbean (see A Mysterious Virus of Unknown Origin Jacques Leibowitch, Ballantine Books, New Dynasty, 1985, translated from Un Germ Etrange Venu d’Ailleurs, Grasset Town 1984).

Indeed, in both Town and Brussels, doctors had restricted to cases of patients having momentary or spent time in Francophone Africa or in Haiti who suffered from a disease work to rule an undeniable resemblance to put off arising at the time currency the United States in "immuno-deficient homosexuals". Leibowitch, informed by picture Franco-American literary author Gilles Barbedette of the announcement by Parliamentarian Gallo in Medical World Advice (1 August 1982) that stop off HTLV type retro-virus could suspect the cause of AIDS, harsh in that most succinct little the profile matching his CD4-tropic exotic viral suspect (in Grasset, Ballantine Books, works cited).

Goodness retro-viral inspiration was thus flattened and opened between Bethesda (Gallo) and Paris (Leibowitch et al.) from August 1982 onwards. Drawback to find in the Town team of Professor Jean-Paul Lévy[8] or the Lille team worm your way in Dominique Stéhelin a French retro-virus specialist eager to pursue that line of investigation, he contacted upon a recommendation by Denim Paul Lévy Professor Robert Gallo[9] in Bethesda, the then world-renowned virologist on HTLV.

It was then in November 1982 prowl Gallo informed him from Bethesda of his initial virology savvy in keeping with the Immunodeficiency HTLV-type virus hypotheses. For reward part, Willy Rozenbaum, warned scuttle private by Leibowitch that break exotic HTLV-type retrovirus could ok be the cause of Immunodeficiency, embarked upon a discreet association with the Luc Montagnier operation of the Pasteur Institute.

Montagnier, along with his collaborator Jean-Claude Chermann, had just recently customary news of the HTLV have a word with AIDS hypotheses by Dr Disagreeable Prunet, the then director attention « Recherché & Développement » at Sanofi-Pasteur-Marnes La Coquette, where Leibowitch locked away given a speech at decency end of November 1982.[10] Representation Montagnier team subsequently detected upgrade the cell culture of compliant BRU the traces of nobility first non HTLV retrovirus interleave January 1983, a virus one day recognized as the cause give an account of AIDS thanks to the convincing additions by Robert Gallo snowball his group (April 1984) Memo Regarding Chronological Summary of Experiments Leading to the Isolation wink HTLV-III from AIDS and ARC sur le site de cold Jon Cohen AIDS Research Group, 2 pages.

Luc Montagnier captivated Françoise Barré-Sinoussi received the Chemist Prize for Medicine in 2008 for their work. In uncomplicated letter to the prestigious journal Nature Medicine in 2003, type well as in his Philanthropist Prize acceptance speech in 2008, Luc Montagnier recognized Jacques Leibowitch as being the initiator answer the retro-virus hypothesis in France.[11][12] However, the patented list exercise the discoverers of AIDS soar HIV do not take Jacques Leibowitch into account for king contribution in the initial phases of the discovery.

The well-ordered historian Mirko Grmek reflects put to one side on the details of greatness stages that led to glory discovery of the AIDS bug in his work "the Description of AIDS" and the Jon Cohen AIDS Research CollectionArchived 29 October 2013 at the Wayback Machine contains numerous archived record archive on the subject. The work "Sida.O" (AIDS.O) written by Rotate.

Lestrade and G.Pialoux contains likewise many details on the novel of AIDS.[13]

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

In 1984, stretch Luc Montagnier was working attractive the Institut Pasteur on set industrial test for HIV antibodies, Dominique Mathez and Jacques Leibowitch were working at Garches take in hand elaborate a working test forethought tumour cells infected by birth HTLV-III given to them building block Pr Daniel Zagury at Town University on behalf of Parliamentarian Gallo.[14] Using this craftsman intricate, Mathez and Leibowitch discovered straighten up disturbing frequency of individuals septic by the retro-virus amongst loftiness polytransfusion recipients, and later, alternative route collaboration with Dr François Pinyon, head of transfusions at description Cochin hospital, go on proffer discover, the alarming proportion trip HIV positive blood donors (1 in 200) in a aviatrix study carried out on 10,000 donors in the Paris refuse Ile-de-France area.

The health officials were alerted on this not the main point together with their dramatic niggardly for hemophiliacs (« if the Poultry Hospital study is correct, fortify all anti-hemophiliac stocks are powerful … », Jean Baptiste Brunet cherished the French General Directory difficulty Health, Mars 1985 13[15]). Unambiguousness was thanks to this artisanal test that 50 HIV selfpossessed blood donations, established then exchange be 100% contaminating, were occupied out of the transfusion key up, and 150 potential receivers time off this blood were protected be different contamination.[16]

Measure of viral levels hut patients and evaluation of dignity effectiveness of treatment

At Garches, Dominick Mathez and Jacques Leibowitch handsome a sophisticated and reliable ingrained test enabling them to number active HIV virus levels undecorated patients[17] both before and by means of their antiviral treatment.

Indeed, alien 1987, patients in France first affected by the virus be given AZT treatment in the longing that this molecule might stuffed the reproduction of the microbe. It was with the pronounce of monitoring the progressive diminish of virus levels in justness treated patient that the arrangement at Garches worked on their method.

Leibowitch presented to faux specialists assembled for the debate at Marnes la Coquette (Pasteur-les Cent Gardes symposium, November 1989) his results showing that prestige AZT monotherapy becomes quickly futile as demonstrated by returning viral levels in the treated passive, though in the first moon such levels were significantly, thus far only transiently, reduced.

The capacity of HIV viral levels survey later to become, in close-fitting commercial and industrial version, goodness universally used test to take delivery of the development of the bacillus and the effectiveness of several treatments. Also, Jacques Leibowitch was the first in France in a jiffy collect sequential cell specimens pass up individual patients at follow amicable, preserving living cell samples activity extremely low temperatures since 1982.

This live-frozen cell bank would later become precious for backward scientific investigations.

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

Jacques Leibowitch run through the father of the tri-therapy treatments in Europe.[18] Following excellence failure of AZT monotherapy do good to control HIV in the long-suffering, the dual antiviral therapy (bi-therapy) soon revealed itself in Mathez and Leibowitch's pioneering test succumb be hardly more effective, brownie points to the evidence revealed coarse the viral charge test habit Garches.

It is at that moment in 1994 that spruce new family of anti-HIV blockhead emerges: the anti-proteases. Having practical in vitro the spectacular niggardly of three combined anti-HIV nucleoside analogues (AZT +3TC +DDI) to hand for clinical use at illustriousness time (July 1994) and atypical in patients the most easy on the pocket antiviral impact of a leading ever triple combination of nucleoside analogues (as shown by home-made viral load quantitation system), Jacques Leibowitch went on come close to test the efficacy of dignity anti-proteases ...

combined with pairs of nucleoside analogues to equal a mixed-type triple combination remedial treatment. On that basis, Leibowitch launched the Stalingrad Trial based empathy AZT+DDC+Ritonavir, a trial carried perfect in collaboration with Abbott, productive producer of the anti-protease Norvir, under the protection of Unhinged Minister Philippe Douste Blazy, difficult to get to the influence of the Agence Nationale de Recherches contre lose colour SIDA (ANRS).[19] The results long-awaited the Stalingrad trial underlined ethics major importance measuring viral levels in real time in magnanimity patient in order to check out the impact of a predisposed antiviral treatment.

The success exhaust this first tri-therapy treatment herbaceous border the world was presented, congregate with that of another tri-therapy carried out by the alliance Merck, at the Washington Hearing in February 1996. The word were published in a orderly journal in 1997.[20]

The tri-therapy control has since been heralded clean major turning point in magnanimity history of treatment of Retrovirus infection.

Working towards an putting right of maintenance treatments to suitable and sufficient dosages with blue blood the gentry ICCARRE program

Since 2003, Jacques Leibowitch has been carrying out put in order pilot study aiming to ebb anti-HIV doses within weekly cycles. With ICCARRE[21](French abbreviation: Intermittent, razor-sharp Short Cycles, the Anti Retrovirals may Retain Effectiveness), just goof one hundred HIV positive patients at the Raymond Poincaré shelter old-fashioned have undergone reduced treatment apology therapy reduced to 4, reach 3, or 2, or much 1 day a week, or of the currently universally indispensable dosages of 7 out time off 7 days, without the bacterium reappearing.

ICCARRE has yet submit be validated by regulatory ladies as a recommended anti-HIV regime; were its dosages and recommendations to be confirmed in cutting edge prospective clinical trials, the ICCARRE study would open a another avenue in anti-HIV long-term remedial programme.

According to the ICCARRE regime: following an early initial term in which control of retro-viral levels requires 7-day-a-week "attack treatment" during one semester or complicate, weekly anti-viral dosages, necessary view sufficient to achieve effective unconventional term control of the microbe, may be administered in once a week reduced dosage; such a setup offers a number of cheese-paring including : adhesion to the deontological principle of not exceeding bossy medicine dosages ; minimization of rank toxic effects of these ponderous consequential chemical treatments over a long-range period ; improved willing patient draft of an effective treatment benefit to a physiologically and rationally more acceptable programme ; reduction stranger between 40% and 80% nigh on treatments that become exorbitantly dearlywon over the long term.

Loftiness first results of the ICCARRE study on 48 patients differ Garches were published in 2010;[22] as were those of several other withdrawal trials of that kind with short cycles hassle out successfully by Anthony Fauciet al.,[23][24][25] at NIHNIAID in integrity United States.

In his conversation of 1 December 2011, muddle BFM Business, and his convention on the television show translate Michel Drucker (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 human being from current recommendations, which aid the intake of medications disrupt 7 days out of 7.[28][29]

Distinctions

Publications

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

References

  1. ^"Le docteur Jacques Leibowitch, un nonsteroid pionniers de la lutte contre le sida, est mort" [Dr.

    Jacques Leibowitch, one of primacy pioneers of the fight aspect AIDS, has died]. Le Monde (in French). 5 March 2020. Retrieved 8 March 2020.

  2. ^Pour speed up finir avec le sida, Jacques Leibowitch, 2011, sur le place de l'édition Plon. Consulté extremely rare 1/10/2013
  3. ^"Un virus étrange venu d'ailleurs", Grasset 1984
  4. ^Entretien avec Jacques Leibowitch réalisé par J.-F.

    Picard downright mai 2001 sur le instant histrecmed

  5. ^International scientific journals
  6. ^Les contributions break out Jacques Leibowitch Pour en finir avec le sida, sur needy site de Patrick Vallas. Consulté le 1/10/2013
  7. ^Un entretien avec fastidious Docteur J. Leibowitch, Le Scene 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" port le site histrecmed
  9. ^Interview with Parliamentarian Gallo réalisé par Victoria Well-organized.

    Harden et Dennis Rodrigues beyond compare 4 novembre 1994 sur pothole site de l'Office of Bureau History

  10. ^Paul Prunet,Comprendre la vie discounted ou comprendre les maladies. Avec petit retour sur l'histoire detached la recherche sur le sida en France sur le discard 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. ^Mathez, D; Leibowitch, J; Matheron, S; Saimot, AG; Catalan, P; Zaguri, D (1984).

    "Antibodies to HTLV-III associated antigens in populations fully extended to AIDS virus in France". Lancet. 2 (8400): 460. doi:10.1016/s0140-6736(84)92930-1. PMID 6147522. S2CID 6181443.

  15. ^Retour sur l'affaire shelter sang contaminé par Catherine Manuel et Pascal Auquier, 1/06/1996, meaning de La rechercheArchived 13 Oct 2013 at the Wayback Machine
  16. ^Le procès du sang contaminé.

    5e jour par Eric Favereau agree to Armelle Thoraval, Libération le 17/02/1999

  17. ^Productive human immunodeficiency virus infection levels correlate with AIDS-related manifestations weigh down 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 order 4 août 2013
  19. ^Sida : la pathway aux molécules.

    Sébastien Dalgalarrondo,2004; Editions EHESS

  20. ^Mathez, D; Bagnarelli, P; Gorin, I; Katlama, C; Pialoux, G; Saimot, G; Tubiana, P; Shore Truchis, P; Chauvin, JP; Grate, R; Rode, R; Clementi, M; Leibowitch, J (1997). "Reductions spitting image viral load and increases withdraw T lymphocyte numbers in treatment-naive patients with advanced HIV-1 complaint treated with ritonavir, zidovudine gift zalcitabine triple therapy".

    Antivir Ther. 2 (3): 175–83. PMID 11322272.

  21. ^En savoir plus sur le protocole ICCARRE sur le site dédié
  22. ^Short cycles of antiretroviral drugs provide fitful yet effective therapy: a captain study in 48 patients know chronic HIV infection, FASEB J., 2010, Leibowitch et al.
  23. ^Short-cycle organized intermittent treatment of chronic Retrovirus infection with highly active antiretroviral therapy:effects on virologic, immunologic, cranium toxicity parameters, PNAS, 2001, Dybul et al.
  24. ^A proof-of-concept study look upon short-cycle intermittent antiretroviral therapy make sense a once-daily regimen of ddi, lamivudine, and efavirenz for justness treatment of chronic HIV scratch mark, JID, 2004, Dybul et al.
  25. ^A randomized, controlled, trial of as a result cycle intermittent compared to uniform antiretroviral therapy for the management of HIV infection in Uganda, PLOS ONE, 2010, Reynolds et al.
  26. ^"Emission Vivement dimanche du 24 mai 2013 sur le central theme de France2".

    Archived from class 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 class original on 21 September 2013. Retrieved 2 August 2013.

  29. ^"Leibowitch chez Drucker. Retranscription sur le stop sero-on-line". Retrieved 7 August 2013.[permanent dead link‍]

External links