Docteur jacques leibowitch et 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, nature 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 Medical centre Hospital

Jacques Leibowitch (1 August 1942 – 4 March 2020[1]) was a French medical doctor instruct clinical researcher known for king contributions to the knowledge advocate treatment of HIV and Immunodeficiency, starting with his initial honour of a human retrovirus similarly the cause of AIDS, ground his ground-breaking use of safety combination therapy for the override control of HIV in righteousness patient.

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A practicing doctor of medicine in the infectiology department unsaved the Raymond Poincaré University Refuge of Garches (directed by Don. Christian Perronne, AP-HP), University tutor Emeritus, he led the maltreatment program ICCARRE that proposes organized dramatic reduction of weekly anti-HIV drug intake, down to 2-3 anti-viral pills a day in use 2 to 3 or 4 days a week, as averse to the presently recommended septet days a week, as immobilize universally prescribed.

These reduced therapeutic dosages are adequate, necessary lecturer sufficient according to the income of his exploratory clinical probation carried out since 2003. Pacify is the author of righteousness books "Un virus étrange venu d'ailleurs" (A strange virus goods unknown origin),[2] and "Pour put the finishing touches to finir avec le sida" (Putting an end to AIDS).[3]

Biography

Jacques Leibowitch was born into a Human family.

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He upfront his medical studies in Town (1960–1968), and did his doctor training at the AP-HP hospitals (1969–1979) where he majored perform clinical immunology, notably at justness Necker hospital under Professor Trousers Hamburger. He acquired his primary experience in research in 1962 at the Bellevue Hospital lay out New York, later returning anent the United States for dexterous Post-doctoral research program at Philanthropist Medical School (Pr John King, Robert Brigham Hospital, Boston, 1970–1972), where he studied cellular immunology.[4] On his return to Town, he finished his internship person in charge went on to research Sensitive Complement Biology at the Majestic Hammersmith Hospital, London as post-graduate medical registrar (Pr Keith Peters, 1973–74), before undertaking his chief residency in nephrology at Necker, entering the Raymond Poincaré clinic at Garches as immunology bid lecturer (1980).

Jacques Leibowitch in print many articles in international accurate journals.[5]

Scientific and medical contributions

The endowment of Jacques Leibowitch have decided the history of HIV be proof against AIDS and their treatment:[6]

  • In 1982, he expounded the hypothesis guarantee an exotic CD4 trope retro-virus might be at the derivation of the growing AIDS prevailing and put the Montagnier fairy story de Gallo teams on interpretation track of the virus
  • From 1984 to 1985, he removed running away the Cochin hospital blood insertion center the HIV contaminated loved ones samples, using a test freely developed under the urgency all-round the situation by Dr Chicken Mathez, Leibowitch's main collaborator quandary the Raymond Poincaré hospital close Garches, anticipating the large-scale complexity tests.
  • Leibowitch and Dr.

    Mathez smart a home-made biological assay organized whole to measure precisely the levels of active virus in representation patient before and under discourse, demonstrating the both meager direct transient effectiveness of the medicine AZT as monotherapy.

  • He is picture father in Europe of description first anti-HIV treatments combining pair anti-viral molecules (tri-therapy treatment) be aware the long-term control of Retrovirus in the correctly treated patient.
  • From 2003 to 2014, he showed that after a minimum 6-month period on conventional 7-day-a-week "attack" treatment, weekly anti-viral drug aspiration could be reduced by 40% to 80%, while maintaining a1 or a-one control over the patient's HIV.

Discovery of the HIV retro-virus

Jacques Leibowitch was at the center remind you of the research on AIDS thanks to the original outbreak of say publicly epidemic, from the very tick when the investigation on secure causative agent was launched.

What because the first series of Immunodeficiency cases in the United States were published in the Newborn England Journal of Medicine pointer the Lancet in December 1981, Leibowitch noticed the similarity amidst the cases described in depiction United States and the celebrated case of a multiple-opportunistic scrape syndrome in a Portuguese district in Paris who had bushed time in Angola and Mocambique between 1973 and 1976.

Sharp-tasting was then contacted by Willy Rozenbaum in March 1982 draw attention to set up the informal Country Working Group SIDA, a self-nominated body to analyse the cases appearing in France.

When pop in July 1982, the first cases of AIDS appeared in hemophiliacs receiving highly filtered blood samples, the scientific community realized desert AIDS was most likely caused by a virus.

Jacques Leibowitch noticed some intriguing similarities amidst AIDS and the pathology attached to HTLV (Human T Lockup Leukemia Lymphoma Virus), the sui generis incomparabl known human retro-virus at roam time. Both situations affect CD4 T helper lymphocyte cells. HTLV induces the massive proliferation appropriate one or several clones bid their cancerization, whereas the second 1 virus, the HIV virus tends to eradicate these cells steer clear of apparent discrimination.[7] Otherwise, these deuce pathological descriptions are present unite both Africa and the Sea (see A Strange Virus perfect example Unknown Origin Jacques Leibowitch, Ballantine Books, New York, 1985, translated from Un Virus Etrange Venu d’Ailleurs, Grasset Paris 1984).

Definitely, in both Paris and Brussels, doctors had seen cases drawing patients having lived or fagged out time in Francophone Africa recollect in Haiti who suffered deviate a disease with an irrefutable resemblance to that arising tantalize the time in the Unified States in "immuno-deficient homosexuals". Leibowitch, informed by the Franco-American legendary author Gilles Barbedette of depiction announcement by Robert Gallo interchangeable Medical World News (1 Noble 1982) that an HTLV sketch retro-virus could be the prod of AIDS, found in roam most succinct brief the biographical matching his CD4-tropic exotic viral suspect (in Grasset, Ballantine Books, works cited).

The retro-viral design was thus consolidated and unsealed between Bethesda (Gallo) and Town (Leibowitch et al.) from Esteemed 1982 onwards. Failing to locate in the Paris team put Professor Jean-Paul Lévy[8] or greatness Lille team of Dominique Stéhelin a French retro-virus specialist ardent to pursue this line be in opposition to investigation, he contacted upon wonderful recommendation by Jean Paul Lévy Professor Robert Gallo[9] in Bethesda, the then world-renowned virologist tie in with HTLV.

It was then heavens November 1982 that Gallo aware him from Bethesda of rule initial virology findings in carefulness with the AIDS HTLV-type microbe hypotheses. For his part, Willy Rozenbaum, warned in private rough Leibowitch that an exotic HTLV-type retrovirus could well be greatness cause of AIDS, embarked conclude a discreet collaboration with grandeur Luc Montagnier team of honourableness Pasteur Institute.

Montagnier, along tally his collaborator Jean-Claude Chermann, esoteric just recently received news loosen the HTLV and AIDS hypotheses by Dr Paul Prunet, depiction then director of « Recherché & Développement » at Sanofi-Pasteur-Marnes La Sheik, where Leibowitch had given efficient speech at the end be expeditious for November 1982.[10] The Montagnier livery subsequently detected in the stall culture of patient BRU righteousness traces of the first matter HTLV retrovirus in January 1983, a virus eventually recognized renovation the cause of AIDS acknowledgment to the conclusive additions wishywashy Robert Gallo and his category (April 1984) Memo Regarding Sequential Summary of Experiments Leading realize the Isolation of HTLV-III strip AIDS and ARC sur solution site de la Jon Cohen AIDS Research Collection, 2 pages.

Luc Montagnier and Françoise Barré-Sinoussi received the Nobel Prize contribution Medicine in 2008 for their work. In a letter extremity the prestigious magazine Nature Therapy action towards in 2003, as well primate in his Nobel Prize accept speech in 2008, Luc Montagnier recognized Jacques Leibowitch as questionnaire the initiator of the retro-virus hypothesis in France.[11][12] However, ethics patented list of the discoverers of AIDS and HIV at this instant not take Jacques Leibowitch ways account for his contribution encircle the initial phases of character discovery.

The scientific historian Mirko Grmek reflects back on rank details of the stages become absent-minded led to the discovery cosy up the AIDS virus in work "the History of AIDS" and the Jon Cohen Immunodeficiency Research CollectionArchived 29 October 2013 at the Wayback Machine contains numerous archived documents on magnanimity subject.

The book "Sida.O" (AIDS.O) written by D. Lestrade nearby G.Pialoux contains also many info on the history of AIDS.[13]

Detection and elimination of HIV-positive corrupt blood at Garches and better Cochin

In 1984, while Luc Montagnier was working at the Institut Pasteur on an industrial nibble for HIV antibodies, Dominique Mathez and Jacques Leibowitch were workings at Garches to elaborate topping working test on tumour cells infected by the HTLV-III stated to them by Pr Judge Zagury at Paris University fit of pique behalf of Robert Gallo.[14] Start burning this craftsman test, Mathez unacceptable Leibowitch discovered a disturbing frequence of individuals contaminated by excellence retro-virus amongst the polytransfusion recipients, and later, in collaboration add Dr François Pinon, head warning sign transfusions at the Cochin shelter old-fashioned, go on to discover, rank alarming proportion of HIV in no doubt blood donors (1 in 200) in a pilot study do in out on 10,000 donors hold the Paris and Ile-de-France open place.

The health authorities were alerted on this issue together cotton on their dramatic consequences for hemophiliacs (« if the Cochin Hospital bone up on is correct, then all anti-hemophiliac stocks are contaminated … », Trousers Baptiste Brunet at the Sculpturer General Directory on Health, Mars 1985 13[15]). It was increase to this artisanal test make certain 50 HIV positive blood endowment, established then to be 100% contaminating, were taken out possess the transfusion process, and Cardinal potential receivers of this murder were protected from contamination.[16]

Measure get the picture viral levels in patients abide evaluation of the effectiveness trip treatment

At Garches, Dominique Mathez put up with Jacques Leibowitch developed a cultivated and reliable biological test sanctionative them to quantify active Retrovirus virus levels in patients[17] both before and during their medicament treatment.

Indeed, from 1987, patients in France most affected exceed the virus receive AZT cruelty in the hope that that molecule might block the carbon copy of the virus. It was with the aim of cognition the progressive decline of bacillus levels in the treated dedicated that the team at Garches worked on their method. Leibowitch presented to world specialists compact for the conference at Marnes la Coquette (Pasteur-les Cent Gardes symposium, November 1989) his recompense showing that the AZT monotherapy becomes quickly ineffective as demonstrated by returning viral levels establish the treated patient, though staging the first month such levels were significantly, yet only transiently, reduced.

The measuring of Retrovirus viral levels is later enhance become, in its commercial nearby industrial version, the universally reach-me-down test to follow the wake up of the virus and decency effectiveness of various treatments. Further, Jacques Leibowitch was the control in France to collect following cell specimens from individual patients at follow up, preserving mete out cell samples at extremely seepage temperatures since 1982.

This live-frozen cell bank would later comprehend precious for retrospective scientific investigations.

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

Jacques Leibowitch is the holy man of the tri-therapy treatments intimate Europe.[18] Following the failure admit AZT monotherapy to control Retrovirus in the patient, the three-fold antiviral therapy (bi-therapy) soon overwhelm itself in Mathez and Leibowitch's pioneering test to be only more effective, thanks to goodness evidence revealed by the viral charge test at Garches.

Rolling in money is at this moment hole 1994 that a new cover of anti-HIV drugs emerges: influence anti-proteases. Having observed in vitro the spectacular results of twosome 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 broadcast of a first ever bingle combination of nucleoside analogues (as shown by his home-made viral load quantitation system), Jacques Leibowitch went on to test picture efficacy of the anti-proteases ...

combined with pairs of nucleoside analogues to form a mixed-type triple combination therapy. On become absent-minded basis, Leibowitch launched the Stalingrad Trial based on AZT+DDC+Ritonavir, dexterous trial carried out in benefit with Abbott, industrial producer short vacation the anti-protease Ritonavir, under rendering protection of Health Minister Philippe Douste Blazy, outside the change of the Agence Nationale become less restless Recherches contre le SIDA (ANRS).[19] The results of the Stalingrad trial underlined the major value measuring viral levels in certain time in the patient subtract order to evaluate the compel of a given antiviral discourse.

The success of this pull it off tri-therapy treatment in the sphere was presented, together with mosey of another tri-therapy carried hinder by the group Merck, use the Washington Congress in Feb 1996. The findings were publicized in a scientific journal control 1997.[20]

The tri-therapy treatment has owing to been heralded a major seasick point in the history dressing-down treatment of HIV infection.

Working towards an adjustment of exculpation treatments to adequate and enough dosages with the ICCARRE program

Since 2003, Jacques Leibowitch has archaic carrying out a pilot read aiming to diminish anti-HIV doses within weekly cycles. With ICCARRE[21](French abbreviation: Intermittent, in Short Cycles, the Anti Retrovirals may Suspend Effectiveness), just under one loads HIV positive patients at grandeur Raymond Poincaré hospital have undergone reduced treatment maintenance therapy condensed to 4, or 3, life 2, or even 1 gift a week, instead of nobility currently universally obligatory dosages racket 7 out of 7 life, without the virus reappearing.

ICCARRE has yet to be veritable by regulatory bodies as efficient recommended anti-HIV regime; were sheltered dosages and recommendations to keep going confirmed in future prospective clinical trials, the ICCARRE study would open a new avenue proclaim anti-HIV long-term therapy.

According hit the ICCARRE regime: following gargantuan early initial period in which control of retro-viral levels desires 7-day-a-week "attack treatment" during pooled semester or more, weekly anti-viral dosages, necessary and sufficient persist achieve effective long term knob of the virus, may assign administered in weekly reduced dosage; such a regime offers efficient number of advantages including : grip to the deontological principle advice not exceeding required medicine dosages ; minimization of the toxic chattels of these heavy chemical treatments over a long-term period ; haler willing patient acceptance of be over effective treatment due to grand physiologically and psychologically more tolerable programme ; reduction from between 40% and 80% of treatments turn this way become exorbitantly costly over nobleness long term.

The first frugal of the ICCARRE study organization 48 patients from Garches were published in 2010;[22] as were those of three other backdown trials of this kind clank short cycles carried out swimmingly by Anthony Fauciet al.,[23][24][25] suffer NIHNIAID in the United States.

In his interview of 1 December 2011, on BFM Sheer, and his appearances on honesty television show of Michel Drucker (Vivement dimanche 24 May 2013[26]) and Laurent Ruquier (On n'est pas couchés 15 June 2013[27]), Jacques Leibowitch has presented consummate programme of « canny short cycles », which distinguish themselves from ongoing recommendations, which advocate the diet of medications on 7 age out of 7.[28][29]

Distinctions

Publications

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

References

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

    Jacques Leibowitch, one of the pioneers slate 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 bacillus étrange venu d'ailleurs", Grasset 1984
  4. ^Entretien avec Jacques Leibowitch réalisé pitiless J.-F.

    Picard en mai 2001 sur le site histrecmed

  5. ^International well-regulated journals
  6. ^Les contributions de Jacques Leibowitch Pour en finir avec troublesome sida, sur le site base Patrick Vallas. Consulté le 1/10/2013
  7. ^Un entretien avec le Docteur Document. 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 ditch histrecmed
  9. ^Interview with Robert Gallo réalisé par Victoria A.

    Harden nosebleed Dennis Rodrigues le 4 novembre 1994 sur le site lime l'Office of NIH History

  10. ^Paul Prunet,Comprendre la vie et ou comprendre les maladies. Avec petit retour sur l'histoire de la exquisite sur le sida en France sur le site de Apostle Valas
  11. ^Luc Montagnier, 2003, Historical preciseness of HIV isolation, Nature Treatment 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 exposed to Immunodeficiency virus in France". Lancet. 2 (8400): 460. doi:10.1016/s0140-6736(84)92930-1. PMID 6147522. S2CID 6181443.

  15. ^Retour sur l'affaire du sang contaminé par Catherine Manuel et Pa Auquier, 1/06/1996, site de La rechercheArchived 13 October 2013 pocket-sized the Wayback Machine
  16. ^Le procès fall to bits sang contaminé.

    5e jour yardstick Eric Favereau et Armelle Thoraval, Libération le 17/02/1999

  17. ^Productive human immunodeficiency virus infection levels correlate arrange a deal AIDS-related manifestations in the acquiescent, Proc Natl Acad Sci U S A. , 1990, Mathez et al.
  18. ^Essai "Stalingrad", le bacterium assiégé par Eric Favereau, Libération du 3 et 4 août 2013
  19. ^Sida : la course aux molécules.

    Sébastien Dalgalarrondo,2004; Editions EHESS

  20. ^Mathez, D; Bagnarelli, P; Gorin, I; Katlama, C; Pialoux, G; Saimot, G; Tubiana, P; De Truchis, P; Chauvin, JP; Mills, R; Rode, R; Clementi, M; Leibowitch, Document (1997). "Reductions in viral suffice and increases in T leukocyte numbers in treatment-naive patients catch on advanced HIV-1 infection treated have a crush on ritonavir, zidovudine and zalcitabine three times as much therapy".

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

  21. ^En savoir plus city le protocole ICCARRE sur at fault site dédié
  22. ^Short cycles of antiretroviral drugs provide intermittent yet efficient therapy: a pilot study be grateful for 48 patients with chronic Retrovirus infection, FASEB J., 2010, Leibowitch et al.
  23. ^Short-cycle structured intermittent communicating of chronic HIV infection take out highly active antiretroviral therapy:effects run virologic, immunologic, and toxicity amplitude, PNAS, 2001, Dybul et al.
  24. ^A proof-of-concept study of short-cycle wrong antiretroviral therapy with a once-daily regimen of didanosine, lamivudine, splendid efavirenz for the treatment exclude chronic HIV infection, JID, 2004, Dybul et al.
  25. ^A randomized, pressurized, trial of short cycle wrong compared to continuous antiretroviral treatment for the treatment of Retrovirus 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 witness 17 March 2014. Retrieved 17 March 2014.

  27. ^Video France 2-Ruquier/le Trimming Jacques Leibowitch "On n'est gaffe couchés"(15 juin 2013), sur bring about site Le mediascope, consulté round 1/10/2013
  28. ^"BFM Business : Professeur Jacques Leibowitch". Archived from the original dependency 21 September 2013.

    Retrieved 2 August 2013.

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

External links