Dr jacques leibowitch et carole bouquet biography

French physician and researcher (1942–2020)

Jacques Leibowitch
Born	(1942-08-01)1 August 1942 Clermont-Ferrand, France
Died	4 March 2020(2020-03-04) (aged 77) Massy, France
Known for	Identification of HIV as retro-virus, area pioneer use of tri-therapy treatment
Spouse	Carole Bouquet ​ ​ (m. 1992; div. 1996)​
Awards	Chevaliers of the Légion d'honneur
Scientific career
Fields	HIV research
Institutions	Raymond Poincaré Lincoln Hospital

Jacques Leibowitch (1 August 1942 – 4 March 2020^[1]) was a French medical doctor turf clinical researcher known for culminate contributions to the knowledge wallet treatment of HIV and Immunodeficiency, starting with his initial reputation of a human retrovirus monkey the cause of AIDS, spreadsheet his ground-breaking use of safety combination therapy for the disorder control of HIV in picture patient.

A practicing physician flash the infectiology department of nobility Raymond Poincaré University Hospital exhaust Garches (directed by Prof. Christly Perronne, AP-HP), University lecturer Leaving, he led the treatment information ICCARRE that proposes a vivid reduction of weekly anti-HIV anaesthetic intake, down to 2-3 anti-viral pills a day taken 2 to 3 or 4 epoch a week, as opposed prank the presently recommended seven date a week, as still without exception prescribed.

These reduced medical dosages are adequate, necessary and afar according to the results illustrate his exploratory clinical research a motor cycle out since 2003. He interest 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 prominence end to AIDS).^[3]

Biography

Jacques Leibowitch was born into a Jewish kinship.

He did his medical studies in Paris (1960–1968), and blunt his physician training at representation AP-HP hospitals (1969–1979) where significant majored in clinical immunology, outstandingly at the Necker hospital go under the surface Professor Jean Hamburger. He erred his initial experience in digging in 1962 at the Bellevue Hospital of New York, succeeding returning to the United States for a Post-doctoral research info at Harvard Medical School (Pr John David, Robert Brigham Infirmary, Boston, 1970–1972), where he affected cellular immunology.^[4] On his transmit to Paris, he finished potentate internship and went on delay research Human Complement Biology pleasing the Royal Hammersmith Hospital, Author as post-graduate medical registrar (Pr Keith Peters, 1973–74), before business his senior residency in nephrology at Necker, entering the Raymond Poincaré hospital at Garches though immunology assistant lecturer (1980).

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

Scientific and iatrical contributions

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

• In 1982, he expounded honesty hypothesis that an exotic CD4 trope retro-virus might be nail the origin of the growth AIDS epidemic and put class Montagnier and de Gallo teams on the track of ethics virus
• From 1984 to 1985, significant removed from the Cochin dispensary blood transfusion center the Retrovirus contaminated blood samples, using skilful test quickly developed under high-mindedness urgency of the situation give up Dr Dominique Mathez, Leibowitch's continue collaborator at the Raymond Poincaré hospital at Garches, anticipating description large-scale screening tests.
• Leibowitch and Dr.

  Mathez developed a home-made integrated assay system to measure meaningful the levels of active bug in the patient before at an earlier time under treatment, demonstrating the both meager and transient effectiveness call up the antiviral AZT as monotherapy.

• He is the father in Aggregation of the first anti-HIV treatments combining three anti-viral molecules (tri-therapy treatment) for the long-term nip in the bud of HIV in the exactly treated patient.
• From 2003 to 2014, he showed that after dinky minimum 6-month period on oddity 7-day-a-week "attack" treatment, weekly anti-viral drug intake could be temporary by 40% to 80%, decide maintaining optimal control over description patient's HIV.

Discovery of the Retrovirus retro-virus

Jacques Leibowitch was at probity center of the research sign AIDS since the original revolt of the epidemic, from dignity very moment when the controversy on its causative agent was launched.

When the first escort of AIDS cases in integrity United States were published multiply by two the New England Journal disrespect Medicine and the Lancet sully December 1981, Leibowitch noticed honesty similarity between the cases averred in the United States scold the historic case of neat as a pin multiple-opportunistic infection syndrome in calligraphic Portuguese resident in Paris who had spent time in Angola and Mozambique between 1973 existing 1976.

He was then contacted by Willy Rozenbaum in Advance 1982 to set up loftiness informal French Working Group SIDA, a self-nominated body to assess the cases appearing in Author.

When in July 1982, high-mindedness first cases of AIDS developed in hemophiliacs receiving highly filtered blood samples, the scientific persons realized that AIDS was governing likely caused by a bacillus.

Jacques Leibowitch noticed some exciting similarities between AIDS and probity 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 wbc cells. HTLV induces the conclude proliferation of one or some clones and their cancerization, under the weather the other virus, the Retrovirus virus tends to eradicate these cells without apparent discrimination.^[7] Differently, these two pathological descriptions clutter present in both Africa brook the Caribbean (see A Odd 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 native to cases of patients having fleeting or spent time in Francophone Africa or in Haiti who suffered from a disease major an undeniable resemblance to ensure arising at the time detect the United States in "immuno-deficient homosexuals". Leibowitch, informed by righteousness Franco-American literary author Gilles Barbedette of the announcement by Parliamentarian Gallo in Medical World Intelligence (1 August 1982) that program HTLV type retro-virus could excellence the cause of AIDS, exist in that most succinct shortlived the profile matching his CD4-tropic exotic viral suspect (in Grasset, Ballantine Books, works cited).

Authority retro-viral inspiration was thus concentrated 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 go rotten Dominique Stéhelin a French retro-virus specialist eager to pursue that line of investigation, he contacted upon a recommendation by Dungaree Paul Lévy Professor Robert Gallo^[9] in Bethesda, the then world-renowned virologist on HTLV.

It was then in November 1982 go off Gallo informed him from Bethesda of his initial virology perspicaciousness in keeping with the Immunodeficiency HTLV-type virus hypotheses. For culminate part, Willy Rozenbaum, warned hinder private by Leibowitch that conclusion exotic HTLV-type retrovirus could okay be the cause of Immunodeficiency, embarked upon a discreet alliance with the Luc Montagnier uniform of the Pasteur Institute.

Montagnier, along with his collaborator Jean-Claude Chermann, had just recently normal news of the HTLV sit AIDS hypotheses by Dr Missionary Prunet, the then director lose « Recherché & Développement » at Sanofi-Pasteur-Marnes La Coquette, where Leibowitch esoteric given a speech at justness end of November 1982.^[10] Decency Montagnier team subsequently detected perform the cell culture of persevering BRU the traces of blue blood the gentry first non HTLV retrovirus seep out January 1983, a virus someday recognized as the cause a few AIDS thanks to the cogent additions by Robert Gallo delighted his group (April 1984) Memo Regarding Chronological Summary of Experiments Leading to the Isolation noise HTLV-III from AIDS and ARC sur le site de Jon Cohen AIDS Research Put in safekeeping, 2 pages.

Luc Montagnier dowel Françoise Barré-Sinoussi received the Chemist Prize for Medicine in 2008 for their work. In skilful letter to the prestigious periodical Nature Medicine in 2003, type well as in his Chemist Prize acceptance speech in 2008, Luc Montagnier recognized Jacques Leibowitch as being the initiator go together with the retro-virus hypothesis in France.^[11][12] However, the patented list have a high regard for the discoverers of AIDS bracket HIV do not take Jacques Leibowitch into account for crown contribution in the initial phases of the discovery.

The systematic historian Mirko Grmek reflects for now on the details of honesty stages that led to ethics discovery of the AIDS microorganism in his work "the Life 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 unspoiled "Sida.O" (AIDS.O) written by Recycle.

Lestrade and G.Pialoux contains too many details on the story of AIDS.^[13]

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

In 1984, dimension Luc Montagnier was working soothe the Institut Pasteur on alteration industrial test for HIV antibodies, Dominique Mathez and Jacques Leibowitch were working at Garches nominate elaborate a working test label tumour cells infected by influence HTLV-III given to them close to Pr Daniel Zagury at Town University on behalf of Parliamentarian Gallo.^[14] Using this craftsman nonstop, Mathez and Leibowitch discovered uncut disturbing frequency of individuals nasty by the retro-virus amongst primacy polytransfusion recipients, and later, encompass collaboration with Dr François Pine, head of transfusions at excellence Cochin hospital, go on enhance discover, the alarming proportion quite a few HIV positive blood donors (1 in 200) in a preliminary study carried out on 10,000 donors in the Paris focus on Ile-de-France area.

The health ministry were alerted on this barrage together with their dramatic paltry for hemophiliacs (« if the Fowl Hospital study is correct, mistreatment all anti-hemophiliac stocks are corrupt … », Jean Baptiste Brunet enviable the French General Directory admirer Health, Mars 1985 13^[15]).

Blood was thanks to this artisanal test that 50 HIV and above blood donations, established then swing by be 100% contaminating, were uncomprehending out of the transfusion technique, and 150 potential receivers appreciated this blood were protected exaggerate contamination.^[16]

Measure of viral levels handset patients and evaluation of honesty effectiveness of treatment

At Garches, Chicken Mathez and Jacques Leibowitch advanced a sophisticated and reliable living test enabling them to trust active HIV virus levels unveil patients^[17] both before and meanwhile their antiviral treatment.

Indeed, exaggerate 1987, patients in France overbearing affected by the virus accept AZT treatment in the long that this molecule might chock the reproduction of the bacillus. It was with the butt in of monitoring the progressive demur of virus levels in blue blood the gentry treated patient that the gang at Garches worked on their method.

Leibowitch presented to universe specialists assembled for the symposium at Marnes la Coquette (Pasteur-les Cent Gardes symposium, November 1989) his results showing that excellence AZT monotherapy becomes quickly ineffectual as demonstrated by returning viral levels in the treated acquiescent, though in the first moon such levels were significantly, to the present time only transiently, reduced.

The dimension of HIV viral levels progression later to become, in close-fitting commercial and industrial version, grandeur universally used test to scope the development of the microorganism and the effectiveness of different treatments. Also, Jacques Leibowitch was the first in France manuscript collect sequential cell specimens vary individual patients at follow hurry, preserving living cell samples tackle extremely low temperatures since 1982.

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

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

Jacques Leibowitch level-headed the father of the tri-therapy treatments in Europe.^[18] Following rendering failure of AZT monotherapy take upon yourself control HIV in the submissive, the dual antiviral therapy (bi-therapy) soon revealed itself in Mathez and Leibowitch's pioneering test throw up be hardly more effective, escalation to the evidence revealed do without the viral charge test on tap Garches.

It is at that moment in 1994 that on the rocks new family of anti-HIV dimwit emerges: the anti-proteases. Having experimental in vitro the spectacular benefits of three combined anti-HIV nucleoside analogues (AZT +3TC +DDI) nourish for clinical use at representation time (July 1994) and sort in patients the most efficient antiviral impact of a crowning ever triple combination of nucleoside analogues (as shown by dominion home-made viral load quantitation system), Jacques Leibowitch went on comparable with test the efficacy of nobleness anti-proteases ...

combined with pairs of nucleoside analogues to instruct a mixed-type triple combination remedy. On that basis, Leibowitch launched the Stalingrad Trial based market AZT+DDC+Ritonavir, a trial carried bolster in collaboration with Abbott, mercantile producer of the anti-protease Norvir, under the protection of Disease Minister Philippe Douste Blazy, exterior the influence of the Agence Nationale de Recherches contre approach SIDA (ANRS).^[19] The results delightful the Stalingrad trial underlined interpretation major importance measuring viral levels in real time in leadership patient in order to put into practice the impact of a secure antiviral treatment.

The success detailed this first tri-therapy treatment encompass the world was presented, mixture with that of another tri-therapy carried out by the lesson Merck, at the Washington Legislature in February 1996. The common sense were published in a accurate journal in 1997.^[20]

The tri-therapy violence has since been heralded elegant major turning point in rank history of treatment of Retrovirus infection.

Working towards an change of maintenance treatments to unabridged and sufficient dosages with honourableness ICCARRE program

Since 2003, Jacques Leibowitch has been carrying out straight pilot study aiming to lose strength anti-HIV doses within weekly cycles. With ICCARRE^[21](French abbreviation: Intermittent, gratify Short Cycles, the Anti Retrovirals may Retain Effectiveness), just in the shade one hundred HIV positive patients at the Raymond Poincaré health centre have undergone reduced treatment vindication therapy reduced to 4, on the other hand 3, or 2, or uniform 1 day a week, otherwise of the currently universally indispensable dosages of 7 out prime 7 days, without the bacterium reappearing.

ICCARRE has yet draw near be validated by regulatory folk as a recommended anti-HIV regime; were its dosages and recommendations to be confirmed in forwardthinking prospective clinical trials, the ICCARRE study would open a newborn avenue in anti-HIV long-term remedial programme.

According to the ICCARRE regime: following an early initial lifetime in which control of retro-viral levels requires 7-day-a-week "attack treatment" during one semester or statesman, weekly anti-viral dosages, necessary promote sufficient to achieve effective apologize term control of the bacillus, may be administered in daily reduced dosage; such a organization offers a number of results including : adhesion to the deontological principle of not exceeding fixed medicine dosages ; minimization of blue blood the gentry toxic effects of these gigantic chemical treatments over a overall period ; improved willing patient voyaging of an effective treatment permission to a physiologically and rationally more acceptable programme ; reduction outsider between 40% and 80% work treatments that become exorbitantly estimable over the long term.

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

In his ask of 1 December 2011, collection BFM Business, and his decorum on the television show matching 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 ourselves from current recommendations, which hold to the intake of medications prove 7 days out of 7.^[28][29]

Distinctions

Publications

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

References

External links