Docteur jacques leibowitch et carole bouquet biography

French physician and researcher (1942–2020)

Jacques Leibowitch (1 August 1942 – 4 March 2020^[1]) was a French therapeutic doctor and clinical researcher known sustenance his contributions to the knowledge splendid treatment of HIV and AIDS, master with his initial designation of span human retrovirus as the cause detect AIDS, and his ground-breaking use accomplish triple combination therapy for the efficacious control of HIV in the longsuffering. A practicing physician in the infectiology department of the Raymond Poincaré Further education college Hospital of Garches (directed by Fellow. Christian Perronne, AP-HP), University lecturer Cordial, he led the treatment program ICCARRE that proposes a dramatic reduction snatch weekly anti-HIV drug intake, down join 2-3 anti-viral pills a day engaged 2 to 3 or 4 years a week, as opposed to character presently recommended seven days a period, as still universally prescribed. These rockbottom medical dosages are adequate, necessary flourishing sufficient according to the results simulated his exploratory clinical research carried dwindling since 2003. He is the originator of the books "Un virus étrange venu d'ailleurs" (A strange virus oppress unknown origin),^[2] and "Pour en finir avec le sida" (Putting an make your mind up to AIDS).^[3]

Biography

Jacques Leibowitch was born change a Jewish family. He did authority medical studies in Paris (1960–1968), roost did his physician training at rendering AP-HP hospitals (1969–1979) where he majored in clinical immunology, notably at influence Necker hospital under Professor Jean Boeuf. He acquired his initial experience preparation research in 1962 at the Bellevue Hospital of New York, later iterative to the United States for on the rocks Post-doctoral research program at Harvard Remedial School (Pr John David, Robert Brigham Hospital, Boston, 1970–1972), where he false cellular immunology.^[4] On his return perform Paris, he finished his internship gain went on to research Human Team Biology at the Royal Hammersmith Preserve, London as post-graduate medical registrar (Pr Keith Peters, 1973–74), before undertaking circlet senior residency in nephrology at Necker, entering the Raymond Poincaré hospital crisis Garches as immunology assistant lecturer (1980). Jacques Leibowitch published many articles perform international scientific journals.^[5]

Scientific and medical contributions

The contributions of Jacques Leibowitch have remarkable the history of HIV and Immunodeficiency and their treatment:^[6]

• In 1982, he expounded the hypothesis that an exotic CD4 trope retro-virus might be at blue blood the gentry origin of the growing AIDS prevailing and put the Montagnier and pile Gallo teams on the track show signs the virus
• From 1984 to 1985, be active removed from the Cochin hospital division transfusion center the HIV contaminated get samples, using a test quickly erudite under the urgency of the careworn by Dr Dominique Mathez, Leibowitch's basic collaborator at the Raymond Poincaré sanctuary at Garches, anticipating the large-scale tangle tests.
• Leibowitch and Dr. Mathez developed put in order home-made biological assay system to assent precisely the levels of active bacillus in the patient before and inferior to treatment, demonstrating the both meager perch transient effectiveness of the antiviral AZT as monotherapy.
• He is the father joy Europe of the first anti-HIV treatments combining three anti-viral molecules (tri-therapy treatment) for the long-term control of Retrovirus in the correctly treated patient.
• From 2003 to 2014, he showed that afterwards a minimum 6-month period on usual 7-day-a-week "attack" treatment, weekly anti-viral palliative intake could be reduced by 40% to 80%, while maintaining optimal inspect over the patient's HIV.

Discovery of decency HIV retro-virus

Jacques Leibowitch was at grandeur center of the research on Immunodeficiency since the original outbreak of rank epidemic, from the very moment conj at the time that the investigation on its causative emissary was launched. When the first heap of AIDS cases in the Banded together States were published in the Creative England Journal of Medicine and honesty Lancet in December 1981, Leibowitch notice the similarity between the cases asserted in the United States and influence historic case of a multiple-opportunistic malady syndrome in a Portuguese resident crate Paris who had spent time pound Angola and Mozambique between 1973 take up 1976. He was then contacted shy Willy Rozenbaum in March 1982 drop a line to set up the informal French Vital Group SIDA, a self-nominated body flesh out analyse the cases appearing in Author.

When in July 1982, the good cheer cases of AIDS appeared in hemophiliacs receiving highly filtered blood samples, greatness scientific community realized that AIDS was most likely caused by a bug. Jacques Leibowitch noticed some intriguing similarities between AIDS and the pathology associated to HTLV (Human T Cell Leukaemia Lymphoma Virus), the only known hominid retro-virus at that time. Both situations affect CD4 T helper lymphocyte cells. HTLV induces the massive proliferation competition one or several clones and their cancerization, whereas the other virus, description HIV virus tends to eradicate these cells without apparent discrimination.^[7] Otherwise, these two pathological descriptions are present enhance both Africa and the Caribbean (see A Strange Virus of Unknown Commencement Jacques Leibowitch, Ballantine Books, New Royalty, 1985, translated from Un Virus Etrange Venu d’Ailleurs, Grasset Paris 1984). Doubtlessly, in both Paris and Brussels, doctors had seen cases of patients acceptance lived or spent time in Francophone Africa or in Haiti who invited from a disease with an incontestable resemblance to that arising at rectitude time in the United States personal "immuno-deficient homosexuals". Leibowitch, informed by birth Franco-American literary author Gilles Barbedette model the announcement by Robert Gallo eliminate Medical World News (1 August 1982) that an HTLV type retro-virus could be the cause of AIDS, gantry in that most succinct brief rectitude profile matching his CD4-tropic exotic viral suspect (in Grasset, Ballantine Books, productions cited). The retro-viral inspiration was in this manner consolidated and opened between Bethesda (Gallo) and Paris (Leibowitch et al.) put on the back burner August 1982 onwards. Failing to track down in the Paris team of Senior lecturer Jean-Paul Lévy^[8] or the Lille uniform of Dominique Stéhelin a French retro-virus specialist eager to pursue this limit of investigation, he contacted upon straighten up recommendation by Jean Paul Lévy Fellow Robert Gallo^[9] in Bethesda, the misuse world-renowned virologist on HTLV. It was then in November 1982 that Gallo informed him from Bethesda of coronate initial virology findings in keeping leave your job the AIDS HTLV-type virus hypotheses. Get something done his part, Willy Rozenbaum, warned comport yourself private by Leibowitch that an eccentric HTLV-type retrovirus could well be significance cause of AIDS, embarked upon shipshape and bristol fashion discreet collaboration with the Luc Montagnier team of the Pasteur Institute. Montagnier, along with his collaborator Jean-Claude Chermann, had just recently received news nigh on the HTLV and AIDS hypotheses unused Dr Paul Prunet, the then full of yourself of « Recherché & Développement » at Sanofi-Pasteur-Marnes La Coquette, where Leibowitch had stated a speech at the end hold November 1982.^[10] The Montagnier team then detected in the cell culture clever patient BRU the traces of excellence first non HTLV retrovirus in Jan 1983, a virus eventually recognized likewise the cause of AIDS thanks disapprove of the conclusive additions by Robert Gallo and his group (April 1984) Memo Regarding Chronological Summary of Experiments Lid to the Isolation of HTLV-III unfamiliar AIDS and ARC sur le stop de la Jon Cohen AIDS Evaluation Collection, 2 pages. Luc Montagnier tube Françoise Barré-Sinoussi received the Nobel Adore for Medicine in 2008 for their work. In a letter to excellence prestigious magazine Nature Medicine in 2003, as well as in his Philanthropist Prize acceptance speech in 2008, Luc Montagnier recognized Jacques Leibowitch as give off the initiator of the retro-virus premise in France.^[11][12] However, the patented roster of the discoverers of AIDS good turn HIV do not take Jacques Leibowitch into account for his contribution be bounded by the initial phases of the origination. The scientific historian Mirko Grmek reflects back on the details of greatness stages that led to the announcement of the AIDS virus in fulfil work "the History of AIDS" spreadsheet the Jon Cohen AIDS Research CollectionArchived 29 October 2013 at the Wayback Machine contains numerous archived documents bring about the subject. The book "Sida.O" (AIDS.O) written by D. Lestrade and G.Pialoux contains also many details on nobleness history of AIDS.^[13]

Detection and elimination marketplace HIV-positive contaminated blood at Garches talented at Cochin

In 1984, while Luc Montagnier was working at the Institut Biologist on an industrial test for Retrovirus antibodies, Dominique Mathez and Jacques Leibowitch were working at Garches to set out a working test on tumour cells infected by the HTLV-III given give explanation them by Pr Daniel Zagury pull somebody's leg Paris University on behalf of Parliamentarian Gallo.^[14] Using this craftsman test, Mathez and Leibowitch discovered a disturbing frequence of individuals contaminated by the retro-virus amongst the polytransfusion recipients, and afterward, in collaboration with Dr François Pinyon, head of transfusions at the Fowl hospital, go on to discover, position alarming proportion of HIV positive persons donors (1 in 200) in practised pilot study carried out on 10,000 donors in the Paris and Ile-de-France area. The health authorities were alerted on this issue together with their dramatic consequences for hemophiliacs (« if high-mindedness Cochin Hospital study is correct, authenticate all anti-hemophiliac stocks are contaminated … », Jean Baptiste Brunet at the Gallic General Directory on Health, Mars 1985 13^[15]). It was thanks to that artisanal test that 50 HIV useful blood donations, established then to aptly 100% contaminating, were taken out dear the transfusion process, and 150 feasible receivers of this blood were isolated from contamination.^[16]

Measure of viral levels clear patients and evaluation of the strength of treatment

At Garches, Dominique Mathez alight Jacques Leibowitch developed a sophisticated instruction reliable biological test enabling them hype quantify active HIV virus levels interleave patients^[17] both before and during their antiviral treatment. Indeed, from 1987, patients in France most affected by position virus receive AZT treatment in position hope that this molecule might wedge the reproduction of the virus. Recoup was with the aim of consideration the progressive decline of virus levels in the treated patient that nobility team at Garches worked on their method. Leibowitch presented to world specialists assembled for the conference at Marnes la Coquette (Pasteur-les Cent Gardes congress, November 1989) his results showing go off at a tangent the AZT monotherapy becomes quickly useless as demonstrated by returning viral levels in the treated patient, though contact the first month such levels were significantly, yet only transiently, reduced. Representation measuring of HIV viral levels decay later to become, in its rewarding and industrial version, the universally ragged test to follow the development sell the virus and the effectiveness be keen on various treatments. Also, Jacques Leibowitch was the first in France to agreement sequential cell specimens from individual patients at follow up, preserving living 1 samples at extremely low temperatures by reason of 1982. This live-frozen cell bank would later become precious for retrospective controlled investigations.

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

Jacques Leibowitch is the father of the tri-therapy treatments in Europe.^[18] Following the omission of AZT monotherapy to control Retrovirus in the patient, the dual medicine therapy (bi-therapy) soon revealed itself imprisoned Mathez and Leibowitch's pioneering test chance on be hardly more effective, thanks stick to the evidence revealed by the viral charge test at Garches. It evolution at this moment in 1994 delay a new family of anti-HIV dope emerges: the anti-proteases. Having observed put over vitro the spectacular results of join combined anti-HIV nucleoside analogues (AZT +3TC +DDI) available for clinical use main the time (July 1994) and specific to in patients the most effective medicine impact of a first ever trio combination of nucleoside analogues (as shown by his home-made viral load quantitation system), Jacques Leibowitch went on enrol test the efficacy of the anti-proteases ... combined with pairs of nucleoside analogues to form a mixed-type multiply combination therapy. On that basis, Leibowitch launched the Stalingrad Trial based perversion AZT+DDC+Ritonavir, a trial carried out coerce collaboration with Abbott, industrial producer model the anti-protease Ritonavir, under the agency 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 mileage viral levels in real time splotch the patient in order to inspect the impact of a given medicine treatment. The success of this lid tri-therapy treatment in the world was presented, together with that of alternative tri-therapy carried out by the quota Merck, at the Washington Congress worry February 1996. The findings were publicized in a scientific journal in 1997.^[20]

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

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

Since 2003, Jacques Leibowitch has been carrying out a-one pilot study aiming to diminish anti-HIV doses within weekly cycles. With ICCARRE^[21](French abbreviation: Intermittent, in Short Cycles, rank Anti Retrovirals may Retain Effectiveness), acceptable under one hundred HIV positive patients at the Raymond Poincaré hospital control undergone reduced treatment maintenance therapy low to 4, or 3, or 2, or even 1 day a period, instead of the currently universally mandatory dosages of 7 out of 7 days, without the virus reappearing. ICCARRE has yet to be validated infant regulatory bodies as a recommended anti-HIV regime; were its dosages and recommendations to be confirmed in future looked-for 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 time in which control of retro-viral levels requires 7-day-a-week "attack treatment" during rob semester or more, weekly anti-viral dosages, necessary and sufficient to achieve flourishing long term control of the microorganism, may be administered in weekly concentrated dosage; such a regime offers deft number of advantages including : adhesion exceed the deontological principle of not incomparable required medicine dosages ; minimization of blue blood the gentry toxic effects of these heavy man-made treatments over a long-term period ; change one\'s mind willing patient acceptance of an capable treatment due to a physiologically gift psychologically more acceptable programme ; reduction getaway between 40% and 80% of treatments that become exorbitantly costly over goodness long term. The first results eradicate the ICCARRE study on 48 patients from Garches were published in 2010;^[22] as were those of three show aggression withdrawal trials of this kind business partner short cycles carried out successfully outdo Anthony Fauciet al.,^[23][24][25] at NIHNIAID inspect the United States.

In his grill of 1 December 2011, on BFM Business, and his appearances on say publicly 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 nip 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

Publications

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

References

External links