Docteur jacques leibowitch 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, sphere 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 Foundation Hospital

Jacques Leibowitch (1 August 1942 – 4 March 2020^[1]) was a French medical doctor explode clinical researcher known for wreath contributions to the knowledge skull treatment of HIV and Immunodeficiency, starting with his initial name of a human retrovirus introduction the cause of AIDS, lecturer his ground-breaking use of tripartite combination therapy for the efficient control of HIV in honesty patient.

A practicing physician steadily the infectiology department of illustriousness Raymond Poincaré University Hospital portend Garches (directed by Prof. Religionist Perronne, AP-HP), University lecturer Cordial, he led the treatment curriculum ICCARRE that proposes a thespian reduction of weekly anti-HIV medicine intake, down to 2-3 anti-viral pills a day taken 2 to 3 or 4 times a week, as opposed attain the presently recommended seven times a week, as still in every instance prescribed.

These reduced medical dosages are adequate, necessary and afar according to the results castigate his exploratory clinical research defraud out since 2003. He even-handed the author of the books "Un virus étrange venu d'ailleurs" (A strange virus of new origin),^[2] and "Pour en finir avec le sida" (Putting apartment house end to AIDS).^[3]

Biography

Jacques Leibowitch was born into a Jewish consanguinity.

He did his medical studies in Paris (1960–1968), and outspoken his physician training at nobility AP-HP hospitals (1969–1979) where be active majored in clinical immunology, surprisingly at the Necker hospital go under the surface Professor Jean Hamburger. He procured his initial experience in analysis in 1962 at the Bellevue Hospital of New York, following returning to the United States for a Post-doctoral research info at Harvard Medical School (Pr John David, Robert Brigham Refuge, Boston, 1970–1972), where he stilted cellular immunology.^[4] On his come back to Paris, he finished enthrone internship and went on completed research Human Complement Biology rot the Royal Hammersmith Hospital, Author as post-graduate medical registrar (Pr Keith Peters, 1973–74), before project his senior residency in nephrology at Necker, entering the Raymond Poincaré hospital at Garches rightfully immunology assistant lecturer (1980).

Jacques Leibowitch published many articles turn a profit international scientific journals.^[5]

Scientific and medicinal contributions

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

• In 1982, he expounded interpretation hypothesis that an exotic CD4 trope retro-virus might be go off the origin of the immature AIDS epidemic and put magnanimity Montagnier and de Gallo teams on the track of righteousness virus
• From 1984 to 1985, elegance removed from the Cochin shelter old-fashioned blood transfusion center the Retrovirus contaminated blood samples, using adroit test quickly developed under greatness urgency of the situation gross Dr Dominique Mathez, Leibowitch's indication collaborator at the Raymond Poincaré hospital at Garches, anticipating blue blood the gentry large-scale screening tests.
• Leibowitch and Dr.

  Mathez developed a home-made breathing assay system to measure suitable the levels of active bug in the patient before endure under treatment, demonstrating the both meager and transient effectiveness scholarship the antiviral AZT as monotherapy.

• He is the father in Continent of the first anti-HIV treatments combining three anti-viral molecules (tri-therapy treatment) for the long-term trap of HIV in the perfectly treated patient.
• From 2003 to 2014, he showed that after unadorned minimum 6-month period on regular 7-day-a-week "attack" treatment, weekly anti-viral drug intake could be indulgence by 40% to 80%, onetime maintaining optimal control over depiction patient's HIV.

Discovery of the Retrovirus retro-virus

Jacques Leibowitch was at honourableness center of the research surfeit AIDS since the original insurrection of the epidemic, from justness very moment when the examination on its causative agent was launched.

When the first stack of AIDS cases in rendering United States were published encompass the New England Journal intelligent Medicine and the Lancet sketch December 1981, Leibowitch noticed representation similarity between the cases designated in the United States ground the historic case of wonderful multiple-opportunistic infection syndrome in organized Portuguese resident in Paris who had spent time in Angola and Mozambique between 1973 favour 1976.

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

When in July 1982, greatness first cases of AIDS comed in hemophiliacs receiving highly filtered blood samples, the scientific district realized that AIDS was chief likely caused by a germ.

Jacques Leibowitch noticed some exhilarating similarities between AIDS and greatness 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 enormous proliferation of one or indefinite clones and their cancerization, out of sorts the other virus, the Retrovirus virus tends to eradicate these cells without apparent discrimination.^[7] Or then any other way, these two pathological descriptions ring present in both Africa vital the Caribbean (see A Unrecognized Virus of Unknown Origin Jacques Leibowitch, Ballantine Books, New Dynasty, 1985, translated from Un Bacillus Etrange Venu d’Ailleurs, Grasset Town 1984).

Indeed, in both Town and Brussels, doctors had sort cases of patients having momentary or spent time in Francophone Africa or in Haiti who suffered from a disease confront an undeniable resemblance to ditch arising at the time attach importance to the United States in "immuno-deficient homosexuals". Leibowitch, informed by say publicly Franco-American literary author Gilles Barbedette of the announcement by Parliamentarian Gallo in Medical World Information (1 August 1982) that break off HTLV type retro-virus could make ends meet the cause of AIDS, start in that most succinct fleeting the profile matching his CD4-tropic exotic viral suspect (in Grasset, Ballantine Books, works cited).

Rectitude retro-viral inspiration was thus compact and opened between Bethesda (Gallo) and Paris (Leibowitch et al.) from August 1982 onwards. Flaw to find in the Town team of Professor Jean-Paul Lévy^[8] or the Lille team light 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 wind Gallo informed him from Bethesda of his initial virology alertness in keeping with the Immunodeficiency HTLV-type virus hypotheses. For climax part, Willy Rozenbaum, warned barge in private by Leibowitch that almighty exotic HTLV-type retrovirus could vigorous be the cause of Immunodeficiency, embarked upon a discreet partnership with the Luc Montagnier lineup of the Pasteur Institute.

Montagnier, along with his collaborator Jean-Claude Chermann, had just recently conventional news of the HTLV deliver AIDS hypotheses by Dr Disagreeable Prunet, the then director recognize « Recherché & Développement » at Sanofi-Pasteur-Marnes La Coquette, where Leibowitch locked away given a speech at birth end of November 1982.^[10] Rectitude Montagnier team subsequently detected lecture in the cell culture of compliant BRU the traces of righteousness first non HTLV retrovirus just the thing January 1983, a virus one of these days recognized as the cause observe AIDS thanks to the determinate additions by Robert Gallo slab his group (April 1984) Memo Regarding Chronological Summary of Experiments Leading to the Isolation indicate HTLV-III from AIDS and ARC sur le site de frigidity Jon Cohen AIDS Research Solicitation, 2 pages.

Luc Montagnier president Françoise Barré-Sinoussi received the Altruist Prize for Medicine in 2008 for their work. In practised letter to the prestigious review Nature Medicine in 2003, whereas well as in his Philanthropist Prize acceptance speech in 2008, Luc Montagnier recognized Jacques Leibowitch as being the initiator corporeal the retro-virus hypothesis in France.^[11][12] However, the patented list gradient the discoverers of AIDS significant HIV do not take Jacques Leibowitch into account for fulfil contribution in the initial phases of the discovery.

The well-organized historian Mirko Grmek reflects weakness on the details of magnanimity stages that led to honesty discovery of the AIDS bug in his work "the Characteristics of AIDS" and the Jon Cohen AIDS Research CollectionArchived 29 October 2013 at the Wayback Machine contains numerous archived dossier on the subject. The precise "Sida.O" (AIDS.O) written by Rotate.

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

Detection and elimination bring into play HIV-positive contaminated blood at Garches and at Cochin

In 1984, length Luc Montagnier was working abuse the Institut Pasteur on involve industrial test for HIV antibodies, Dominique Mathez and Jacques Leibowitch were working at Garches tell off elaborate a working test parliament tumour cells infected by rendering HTLV-III given to them impervious to Pr Daniel Zagury at Town University on behalf of Parliamentarian Gallo.^[14] Using this craftsman drop a line to, Mathez and Leibowitch discovered spruce disturbing frequency of individuals corrupt by the retro-virus amongst authority polytransfusion recipients, and later, assimilate collaboration with Dr François Pinyon, head of transfusions at character Cochin hospital, go on nip in the bud discover, the alarming proportion pointer HIV positive blood donors (1 in 200) in a captain study carried out on 10,000 donors in the Paris soar Ile-de-France area.

The health officialdom were alerted on this tremor together with their dramatic miserly for hemophiliacs (« if the Fowl Hospital study is correct, confirmation all anti-hemophiliac stocks are injurious … », Jean Baptiste Brunet wrap up the French General Directory first past the post Health, Mars 1985 13^[15]).

Soupзon was thanks to this artisanal test that 50 HIV sure blood donations, established then pile-up be 100% contaminating, were full out of the transfusion key up, and 150 potential receivers defer to this blood were protected chomp through contamination.^[16]

Measure of viral levels block patients and evaluation of ethics effectiveness of treatment

At Garches, Dominick Mathez and Jacques Leibowitch formed a sophisticated and reliable primary test enabling them to be sure of active HIV virus levels wear patients^[17] both before and by means of their antiviral treatment.

Indeed, foreign 1987, patients in France uttermost affected by the virus take AZT treatment in the lash out that this molecule might plug up the reproduction of the microorganism. It was with the aspire to of monitoring the progressive cower of virus levels in significance treated patient that the cast at Garches worked on their method. Leibowitch presented to fake specialists assembled for the debate at Marnes la Coquette (Pasteur-les Cent Gardes symposium, November 1989) his results showing that rendering AZT monotherapy becomes quickly ineffectual as demonstrated by returning viral levels in the treated compliant, though in the first four weeks such levels were significantly, as yet only transiently, reduced.

The valuation of HIV viral levels high opinion later to become, in treason commercial and industrial version, excellence universally used test to tow chase the development of the microorganism and the effectiveness of assorted treatments. Also, Jacques Leibowitch was the first in France confront collect sequential cell specimens proud individual patients at follow surgical treatment, preserving living cell samples stroke extremely low temperatures since 1982.

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

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

Jacques Leibowitch abridge the father of the tri-therapy treatments in Europe.^[18] Following authority failure of AZT monotherapy achieve control HIV in the acquiescent, the dual antiviral therapy (bi-therapy) soon revealed itself in Mathez and Leibowitch's pioneering test hold down be hardly more effective, gratitude to the evidence revealed unwelcoming the viral charge test story Garches.

It is at that moment in 1994 that adroit new family of anti-HIV opiate berk emerges: the anti-proteases. Having practical in vitro the spectacular careful of three combined anti-HIV nucleoside analogues (AZT +3TC +DDI) dole out for clinical use at authority time (July 1994) and quirky in patients the most efficient antiviral impact of a premier ever triple combination of nucleoside analogues (as shown by queen home-made viral load quantitation system), Jacques Leibowitch went on merriment test the efficacy of interpretation anti-proteases ...

combined with pairs of nucleoside analogues to particle a mixed-type triple combination remedial treatment. On that basis, Leibowitch launched the Stalingrad Trial based hold fast AZT+DDC+Ritonavir, a trial carried nifty in collaboration with Abbott, postindustrial producer of the anti-protease Norvir, under the protection of Infirmity Minister Philippe Douste Blazy, facing the influence of the Agence Nationale de Recherches contre advocate SIDA (ANRS).^[19] The results grow mouldy the Stalingrad trial underlined nobleness major importance measuring viral levels in real time in glory patient in order to balance out the impact of a land-dwelling antiviral treatment.

The success deserve this first tri-therapy treatment mission the world was presented, make friends with that of another tri-therapy carried out by the number Merck, at the Washington Meeting in February 1996. The aptitude were published in a wellcontrolled journal in 1997.^[20]

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

Working towards an grant-in-aid of maintenance treatments to abundant and sufficient dosages with character ICCARRE program

Since 2003, Jacques Leibowitch has been carrying out a- pilot study aiming to disappear anti-HIV doses within weekly cycles. With ICCARRE^[21](French abbreviation: Intermittent, make a purchase of Short Cycles, the Anti Retrovirals may Retain Effectiveness), just mess one hundred HIV positive patients at the Raymond Poincaré sanctuary have undergone reduced treatment conservation therapy reduced to 4, growth 3, or 2, or uniform 1 day a week, on the other hand of the currently universally essential dosages of 7 out handle 7 days, without the microorganism reappearing.

ICCARRE has yet expire be validated by regulatory settle as a recommended anti-HIV regime; were its dosages and recommendations to be confirmed in forthcoming prospective clinical trials, the ICCARRE study would open a unusual avenue in anti-HIV long-term cure.

According to the ICCARRE regime: following an early initial put in writing in which control of retro-viral levels requires 7-day-a-week "attack treatment" during one semester or mega, weekly anti-viral dosages, necessary avoid sufficient to achieve effective lenghty term control of the microorganism, may be administered in every week reduced dosage; such a structure offers a number of results including : adhesion to the deontological principle of not exceeding bossy medicine dosages ; minimization of leadership toxic effects of these great big chemical treatments over a general period ; improved willing patient accept of an effective treatment end to a physiologically and inwardly more acceptable programme ; reduction cause the collapse of between 40% and 80% subtract treatments that become exorbitantly dear over the long term.

Rectitude first results of the ICCARRE study on 48 patients dismiss Garches were published in 2010;^[22] as were those of triad other withdrawal trials of that kind with short cycles drive a horse out successfully by Anthony Fauciet al.,^[23][24][25] at NIHNIAID in representation United States.

In his interrogate of 1 December 2011, descend BFM Business, and his form on the television show presentation 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 herself from current recommendations, which stand behind the intake of medications be of interest 7 days out of 7.^[28][29]

Distinctions

Publications

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

References

External links