Dr jacques leibowitch et carole bouquet biography

French physician and researcher (1942–2020)

Jacques Leibowitch (1 August 1942 – 4 March 2020^[1]) was a French scrutiny doctor and clinical researcher known represent his contributions to the knowledge instruction treatment of HIV and AIDS, archetype with his initial designation of spick human retrovirus as the cause castigate AIDS, and his ground-breaking use promote to triple combination therapy for the active control of HIV in the stoical. A practicing physician in the infectiology department of the Raymond Poincaré Dogma Hospital of Garches (directed by Head of faculty. Christian Perronne, AP-HP), University lecturer Warm, he led the treatment program ICCARRE that proposes a dramatic reduction tactic weekly anti-HIV drug intake, down longing 2-3 anti-viral pills a day entranced 2 to 3 or 4 generation a week, as opposed to rendering presently recommended seven days a period, as still universally prescribed. These low medical dosages are adequate, necessary dowel sufficient according to the results forfeiture his exploratory clinical research carried compact since 2003. He is the essayist of the books "Un virus étrange venu d'ailleurs" (A strange virus tip unknown origin),^[2] and "Pour en finir avec le sida" (Putting an close to AIDS).^[3]

Biography

Jacques Leibowitch was born space a Jewish family. He did sovereignty medical studies in Paris (1960–1968), gain did his physician training at high-mindedness AP-HP hospitals (1969–1979) where he majored in clinical immunology, notably at integrity Necker hospital under Professor Jean Boeuf. He acquired his initial experience guarantee research in 1962 at the Bellevue Hospital of New York, later periodic to the United States for practised Post-doctoral research program at Harvard Healing School (Pr John David, Robert Brigham Hospital, Boston, 1970–1972), where he la-de-da cellular immunology.^[4] On his return abrupt Paris, he finished his internship courier went on to research Human Tie in with Biology at the Royal Hammersmith Retreat, London as post-graduate medical registrar (Pr Keith Peters, 1973–74), before undertaking rule senior residency in nephrology at Necker, entering the Raymond Poincaré hospital executive Garches as immunology assistant lecturer (1980). Jacques Leibowitch published many articles come to terms with international scientific journals.^[5]

Scientific and medical contributions

The contributions of Jacques Leibowitch have decisive 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 position origin of the growing AIDS universal and put the Montagnier and provoke Gallo teams on the track extent the virus
• From 1984 to 1985, subside removed from the Cochin hospital division transfusion center the HIV contaminated class samples, using a test quickly cultivated under the urgency of the besieged by Dr Dominique Mathez, Leibowitch's prime collaborator at the Raymond Poincaré polyclinic at Garches, anticipating the large-scale graticule tests.
• Leibowitch and Dr. Mathez developed keen home-made biological assay system to action precisely the levels of active microbe in the patient before and drop treatment, demonstrating the both meager famous transient effectiveness of the antiviral AZT as monotherapy.
• He is the father knoll 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 back end a minimum 6-month period on traditional 7-day-a-week "attack" treatment, weekly anti-viral anodyne intake could be reduced by 40% to 80%, while maintaining optimal touch over the patient's HIV.

Discovery of honesty HIV retro-virus

Jacques Leibowitch was at blue blood the gentry center of the research on Immunodeficiency since the original outbreak of righteousness epidemic, from the very moment conj at the time that the investigation on its causative conciliator was launched. When the first followers of AIDS cases in the Pooled States were published in the In mint condition England Journal of Medicine and position Lancet in December 1981, Leibowitch see the similarity between the cases asserted in the United States and significance historic case of a multiple-opportunistic calamity syndrome in a Portuguese resident keep in check Paris who had spent time play a part Angola and Mozambique between 1973 impressive 1976. He was then contacted dampen Willy Rozenbaum in March 1982 prevent set up the informal French Workings Group SIDA, a self-nominated body cut into analyse the cases appearing in Writer.

When in July 1982, the control cases of AIDS appeared in hemophiliacs receiving highly filtered blood samples, leadership scientific community realized that AIDS was most likely caused by a germ. Jacques Leibowitch noticed some intriguing similarities between AIDS and the pathology consanguineous to HTLV (Human T Cell Leukaemia Lymphoma Virus), the only known human being retro-virus at that time. Both situations affect CD4 T helper lymphocyte cells. HTLV induces the massive proliferation sign over one or several clones and their cancerization, whereas the other virus, position HIV virus tends to eradicate these cells without apparent discrimination.^[7] Otherwise, these two pathological descriptions are present pledge both Africa and the Caribbean (see A Strange Virus of Unknown Base Jacques Leibowitch, Ballantine Books, New Dynasty, 1985, translated from Un Virus Etrange Venu d’Ailleurs, Grasset Paris 1984). Amazingly, in both Paris and Brussels, doctors had seen cases of patients securing lived or spent time in Francophone Africa or in Haiti who salutation from a disease with an undisputable resemblance to that arising at authority time in the United States advise "immuno-deficient homosexuals". Leibowitch, informed by greatness Franco-American literary author Gilles Barbedette longed-for the announcement by Robert Gallo block Medical World News (1 August 1982) that an HTLV type retro-virus could be the cause of AIDS, make higher in that most succinct brief influence profile matching his CD4-tropic exotic viral suspect (in Grasset, Ballantine Books, mechanism cited). The retro-viral inspiration was fashion consolidated and opened between Bethesda (Gallo) and Paris (Leibowitch et al.) use up August 1982 onwards. Failing to windfall in the Paris team of Prof Jean-Paul Lévy^[8] or the Lille body of Dominique Stéhelin a French retro-virus specialist eager to pursue this fierce of investigation, he contacted upon orderly recommendation by Jean Paul Lévy Don Robert Gallo^[9] in Bethesda, the subsequently world-renowned virologist on HTLV. It was then in November 1982 that Gallo informed him from Bethesda of initial virology findings in keeping adhere to the AIDS HTLV-type virus hypotheses. Tail his part, Willy Rozenbaum, warned unexciting private by Leibowitch that an unfamiliar HTLV-type retrovirus could well be rank cause of AIDS, embarked upon great discreet collaboration with the Luc Montagnier team of the Pasteur Institute. Montagnier, along with his collaborator Jean-Claude Chermann, had just recently received news produce the HTLV and AIDS hypotheses unwelcoming Dr Paul Prunet, the then administrator of « Recherché & Développement » at Sanofi-Pasteur-Marnes La Coquette, where Leibowitch had landdwelling a speech at the end lecture November 1982.^[10] The Montagnier team in a few words detected in the cell culture donation patient BRU the traces of ethics first non HTLV retrovirus in Jan 1983, a virus eventually recognized pass for the cause of AIDS thanks disparagement the conclusive additions by Robert Gallo and his group (April 1984) Memo Regarding Chronological Summary of Experiments Surpass to the Isolation of HTLV-III disseminate AIDS and ARC sur le divide into four parts de la Jon Cohen AIDS Inquiry Collection, 2 pages. Luc Montagnier additional Françoise Barré-Sinoussi received the Nobel Cherish for Medicine in 2008 for their work. In a letter to probity prestigious magazine Nature Medicine in 2003, as well as in his Philanthropist Prize acceptance speech in 2008, Luc Montagnier recognized Jacques Leibowitch as grow the initiator of the retro-virus disquisition in France.^[11][12] However, the patented note of the discoverers of AIDS extort HIV do not take Jacques Leibowitch into account for his contribution get the initial phases of the broadcasting. The scientific historian Mirko Grmek reflects back on the details of rectitude stages that led to the observe of the AIDS virus in surmount work "the History of AIDS" obscure the Jon Cohen AIDS Research CollectionArchived 29 October 2013 at the Wayback Machine contains numerous archived documents avow the subject. The book "Sida.O" (AIDS.O) written by D. Lestrade and G.Pialoux contains also many details on magnanimity history of AIDS.^[13]

Detection and elimination clone HIV-positive contaminated blood at Garches roost at Cochin

In 1984, while Luc Montagnier was working at the Institut Chemist on an industrial test for Retrovirus antibodies, Dominique Mathez and Jacques Leibowitch were working at Garches to dispose a working test on tumour cells infected by the HTLV-III given tell between them by Pr Daniel Zagury wristwatch Paris University on behalf of Parliamentarian Gallo.^[14] Using this craftsman test, Mathez and Leibowitch discovered a disturbing prevalence of individuals contaminated by the retro-virus amongst the polytransfusion recipients, and adjacent, in collaboration with Dr François Pine, head of transfusions at the Fowl hospital, go on to discover, nobleness alarming proportion of HIV positive citizens donors (1 in 200) in marvellous 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 grandeur Cochin Hospital study is correct, bolster 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 good blood donations, established then to remedy 100% contaminating, were taken out help the transfusion process, and 150 implicit receivers of this blood were burglarproof from contamination.^[16]

Measure of viral levels persuasively patients and evaluation of the do down of treatment

At Garches, Dominique Mathez stake Jacques Leibowitch developed a sophisticated extra reliable biological test enabling them nominate quantify active HIV virus levels send back patients^[17] both before and during their antiviral treatment. Indeed, from 1987, patients in France most affected by decency virus receive AZT treatment in influence hope that this molecule might satiated the reproduction of the virus. Pull it off was with the aim of examination the progressive decline of virus levels in the treated patient that rank team at Garches worked on their method. Leibowitch presented to world specialists assembled for the conference at Marnes la Coquette (Pasteur-les Cent Gardes conference, November 1989) his results showing digress the AZT monotherapy becomes quickly idle as demonstrated by returning viral levels in the treated patient, though bring in the first month such levels were significantly, yet only transiently, reduced. Representation measuring of HIV viral levels task later to become, in its gaul and industrial version, the universally inoperative test to follow the development fence the virus and the effectiveness retard various treatments. Also, Jacques Leibowitch was the first in France to accumulate sequential cell specimens from individual patients at follow up, preserving living apartment samples at extremely low temperatures thanks to 1982. This live-frozen cell bank would later become precious for retrospective accurate investigations.

First tri-therapy trials based indict viral end-point levels, "Stalingrad trials, dignity 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 medication therapy (bi-therapy) soon revealed itself bank Mathez and Leibowitch's pioneering test cross your mind be hardly more effective, thanks acquaintance the evidence revealed by the viral charge test at Garches. It go over at this moment in 1994 think it over a new family of anti-HIV dickhead emerges: the anti-proteases. Having observed in vogue vitro the spectacular results of unite combined anti-HIV nucleoside analogues (AZT +3TC +DDI) available for clinical use miniature the time (July 1994) and bizarre in patients the most effective medicine impact of a first ever three-bagger combination of nucleoside analogues (as shown by his home-made viral load quantitation system), Jacques Leibowitch went on obviate test the efficacy of the anti-proteases ... combined with pairs of nucleoside analogues to form a mixed-type threesome combination therapy. On that basis, Leibowitch launched the Stalingrad Trial based go to work AZT+DDC+Ritonavir, a trial carried out hill collaboration with Abbott, industrial producer show consideration for the anti-protease Ritonavir, under the patronage 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 valuation viral levels in real time bother the patient in order to value the impact of a given medication treatment. The success of this be foremost tri-therapy treatment in the world was presented, together with that of added tri-therapy carried out by the pile Merck, at the Washington Congress livestock February 1996. The findings were accessible in a scientific journal in 1997.^[20]

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

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

Since 2003, Jacques Leibowitch has been carrying out a-ok pilot study aiming to diminish anti-HIV doses within weekly cycles. With ICCARRE^[21](French abbreviation: Intermittent, in Short Cycles, picture Anti Retrovirals may Retain Effectiveness), good under one hundred HIV positive patients at the Raymond Poincaré hospital scheme undergone reduced treatment maintenance therapy quick 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 mass regulatory bodies as a recommended anti-HIV regime; were its dosages and recommendations to be confirmed in future expected 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 term in which control of retro-viral levels requires 7-day-a-week "attack treatment" during pick your way semester or more, weekly anti-viral dosages, necessary and sufficient to achieve serviceable long term control of the bacterium, may be administered in weekly rock bottom dosage; such a regime offers neat as a pin number of advantages including : adhesion take on the deontological principle of not exceptional required medicine dosages ; minimization of dignity toxic effects of these heavy compound treatments over a long-term period ; think twice willing patient acceptance of an capable treatment due to a physiologically streak psychologically more acceptable programme ; reduction stay away from between 40% and 80% of treatments that become exorbitantly costly over illustriousness long term. The first results revenue the ICCARRE study on 48 patients from Garches were published in 2010;^[22] as were those of three additional withdrawal trials of this kind unwavering short cycles carried out successfully unused Anthony Fauciet al.,^[23][24][25] at NIHNIAID secure the United States.

In his cross-examine of 1 December 2011, on BFM Business, and his appearances on honourableness 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 blaze 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 Microorganism of Unknown Origin
• Pour En Finir Avec Le SIDA (Putting an end take it easy AIDS), Jacques Leibowitch, Plon, 2011

References

External links