cura precoce eradica hiv da neonata

Ricerca scientifica finalizzata all'eradicazione o al controllo dell'infezione.
umpah
Messaggi: 14
Iscritto il: sabato 28 agosto 2010, 20:40

cura precoce eradica hiv da neonata

Messaggio da umpah » lunedì 4 marzo 2013, 1:20




Dora
Messaggi: 7491
Iscritto il: martedì 7 luglio 2009, 10:48

Re: cura precoce eradica hiv da neonata

Messaggio da Dora » lunedì 4 marzo 2013, 2:16

umpah ha scritto:un saluto a tutti
umpah
Ciao!

La relazione sarà presentata al CROI questa mattina (Deborah Persaud -Functional HIV Cure after Very Early ART of an Infected Infant) e cercherò di vederla nei dettagli quando sarà resa disponibile, ma si è tenuta una conferenza stampa e quello che segue è l'articolo del New York Times che ne parla. In questione è l'eradicazione del virus da un neonato attraverso la sola terapia antiretrovirale somministrata immediatamente. Da capire, però, se davvero il bambino fosse infetto. (Se volete una parziale traduzione dell'articolo del New York Times, ci ha pensato La Repubblica: http://www.repubblica.it/salute/medicin ... -53820419/; altra fonte - aidsmap.com: Case report of a `functional` HIV cure in a child.)

La Dottoressa Deborah Persaud del Johns Hopkins Children Center:

  • Immagine


Matt Sharp intervista Deborah Persaud per HIVandHepatitis.com:


In Medical First, a Baby With H.I.V. Is Called Cured

By ANDREW POLLACK and DONALD G. McNEIL Jr.
Published: March 3, 2013


Doctors announced on Sunday that a baby had been cured of an H.I.V. infection for the first time, a startling development that could change how infected newborns are treated and sharply reduce the number of children living with the virus that causes AIDS.

The baby, born in rural Mississippi, was treated aggresively with antiretroviral drugs starting around 30 hours after birth, something that is not usually done. If further study shows this works in other babies, it will almost certainly change the way newborns of infected mothers are treated all over the world. The United Nations estimates that 330,000 babies were newly infected in 2011, the most recent year for which there is data, and that more than 3 million children globally are living with H.I.V.

If the report is confirmed, the child born in Mississippi would be only the second well-documented case of a cure in the world, giving a boost to research aimed at a cure, something that only a few years ago was thought to be virtually impossible.

The first person cured was Timothy Brown, known as the “Berlin patient,'’ a middle-aged man with leukemia who received a bone-marrow transplant from a donor genetically resistant to H.I.V. infection.

“For pediatrics, this is our Timothy Brown,'’ said Dr. Deborah Persaud, associate professor at the Johns Hopkins Children’s Center and lead author of the report on the baby. “It’s proof of principle that we can cure H.I.V. infection if we can replicate this case.'’

Dr. Persaud and other researchers spoke in advance of a presentation of the findings on Monday at the Conference on Retroviruses and Opportunistic Infections in Atlanta.

Some outside experts, who have not yet heard all the details, said they needed convincing that the baby had truly been infected. If not, this would be a case of prevention, something already done for babies born to infected mothers.

“The one uncertainty is really definitive evidence that the child was indeed infected,” said Dr. Daniel R. Kuritzkes, chief of infectious diseases at Brigham and Women’s Hospital.

Dr. Persaud and some other outside scientists said they were certain the baby – whose name and gender were not disclosed – had been infected. There were five positive tests in the baby’s first month of life – four for viral RNA and one for DNA. And once the treatment started, the virus levels in the baby’s blood declined in the pattern characteristic of infected patients.

Dr. Persaud said there was also little doubt that the child experienced what she called a “functional cure.” Now 2½ , the child has been off drugs for a year with no sign of functioning virus.

The mother arrived at a rural hospital in the fall of 2010 already in labor and gave birth prematurely. She had not seen a doctor during the pregnancy and did not know she had H.I.V. When a test showed the mother might be infected, the hospital transferred the baby to the University of Mississippi Medical Center, where it arrived at about 30 hours old.

Dr. Hannah B. Gay, an associate professor of pediatrics, ordered two blood draws an hour apart to test for the presence of H.I.V. RNA and DNA.

The tests found a level of virus at about 20,000 copies per milliliter, fairly low for a baby. But since tests so early in life were positive, it suggests the infection occurred in the womb rather than during delivery, Dr. Gay said.

Typically a newborn with an infected mother would be given one or two drugs as a prophylactic measure. But Dr. Gay said that based on her own experience, she almost immediately used a three-drug regimen aimed at treatment, not prophylaxis, not even waiting for the test results confirming infection.

Virus levels rapidly declined with treatment and were undetectable by the time the baby was a month old. That remained the case until the baby was 18 months old, after which the mother stopped coming to the hospital.

When the mother and child returned five months later, Dr. Gay expected to see high viral loads in the baby. But the tests were negative.

Suspecting a laboratory error, she ordered more tests. “To my greater surprise, all of these came back negative,” Dr. Gay said.

Dr. Gay contacted Dr. Katherine Luzuriaga, an immunologist at the University of Massachusetts, who was working with Dr. Persaud and others on a project to document possible pediatric cures. The researchers, sponsored by amfAR, the Foundation for AIDS Research, put the baby through a battery of sophisticated tests. They found tiny amounts of some viral genetic material but no virus able to replicate, even lying dormant in so-called reservoirs in the body.

There have been scattered cases reported in the past, including one in The New England Journal of Medicine in 1995, of babies clearing the virus, even without treatment.

Those reports were greeted skeptically, particularly since testing methods were not very sophisticated back then. But those reports and this new one could suggest there is something different about babies’ immune systems, said Dr. Joseph McCune
of the University of California, San Francisco.

One hypothesis is that the drugs killed off the virus before it could establish a hidden reservoir in the baby. One reason people cannot be cured now is that the virus hides in a dormant state, out of reach of existing drugs. When drug therapy is stopped, the virus can emerge from hiding.

“That goes along with the concept that, if you treat before the virus has had an opportunity to establish a large reservoir and before it can destroy the immune system, there’s a chance you can withdraw therapy and have no virus,'’ said Dr. Anthony S. Fauci, the director of the National Institute for Allergy and Infectious Diseases. Adults, however, typically do not know they are infected right as it happens, he said.

Dr. Steven Deeks, professor of medicine at the University of California, San Francisco, said if the reservoir never established itself, then he would not call it a true cure, though this was somewhat a matter of semantics. “Was there enough time for a latent reservoir, the true barrier to cure, to establish itself?'’ he said.

Still, he and others said, the results could lead to a new protocol for quickly testing and treating infants.

In the United States, transmission from mother to child is rare – several experts said there are only about 200 cases a year or even fewer, because infected mothers are generally treated during their pregnancies.

If the mother has been treated during pregnancy, babies are typically given six weeks of prophylactic treatment with one drug, AZT, while being tested for infection. In cases like the Mississippi one, where the mother was not treated during pregnancy, standards have been changing, but typically two drugs are used.

But women in many developing countries are less likely to be treated during pregnancy. And in South Africa and other African countries that lack sophisticated testing, babies born to infected mothers are often not tested until after six weeks, said Dr. Yvonne Bryson, chief of global pediatric infectious disease at the University of California, Los Angeles.

Dr. Bryson, who was not involved in the Mississippi work, said she was certain the baby had been infected and called the finding “one of the most exciting things I’ve heard in a long time.'’

Studies are being planned to see if early testing and aggressive treatment can work for other babies. While the bone marrow transplant that cured Timothy Brown is an arduous and life-threatening procedure, the Mississippi treatment is not and could become a new standard of care.

While it might be difficult for some poorer countries to implement, treating for only a year or two would be cost effective, “sparing the kid a lifetime of antiretroviral therapy,'’ said Rowena Johnston, director of research at amfAR.



Dora
Messaggi: 7491
Iscritto il: martedì 7 luglio 2009, 10:48

Re: cura precoce eradica hiv da neonata

Messaggio da Dora » lunedì 4 marzo 2013, 3:39

L'abstract della presentazione.

Functional HIV Cure after Very Early ART of an Infected Infant - Paper #48LB

Deborah Persaud*1, H Gay2, C Ziemniak1, YH Chen1, M Piatak3, T-W Chun4, M Strain5, D Richman5, and K Luzuriaga6

1Johns Hopkins Univ Sch of Med, Baltimore, MD, US; 2Univ of Mississippi Med Ctr, Jackson, US; 3Frederick Natl Lab for Cancer Res, MD,US; 4NIAID, NIH, Bethesda, MD, US; 5Univ of California San Diego, La Jolla and VA San Diego Hlthcare System, US; and 6Univ of Massachusetts Med Sch, Worcester, US


Background: A single case of HIV cure occurred in an infected adult with a bone marrow transplant. We report a case of functional HIV cure in a 26-month-old infected child who initiated ART at 30 hours of age.

Methods: Infant exposure to HIV was confirmed through review of maternal HIV antibody and plasma viral load tests, including HIV drug resistance testing. Infant infection was documented using standard HIV DNA polymerase chain reaction (PCR) and plasma viral load. ART administration was confirmed with medical and pharmacy records and maternal report of medication adherence. Persistence of HIV infection following treatment discontinuation was assessed using standard clinical assays that included plasma viral load, proviral DNA, and HIV antibody testing. Ultrasensitive HIV DNA (droplet digital PCR), plasma viral load (single copy) assays, and quantitative co-culture assays were done at age 24 and 26 months to further assess HIV persistence. HLA typing was done to confirm matching of the mother–infant pair.

Results: Maternal infection with wild type subtype B HIV was verified. The mother and infant shared HLA haplotypes. Infant infection was confirmed by positive HIV DNA and RNA testing on 2 separate blood samples obtained on the 2nd day of life. 3 additional plasma viral load tests (days of life 7, 12, and 20) were positive before reaching undetectable levels at age 29 days. Plasma HIV RNA remained undetectable (<20 copies/mL) on 16 different measurements obtained between 1 through 26 months of age despite ART discontinuation at age 18 months. Using ultrasensitive methods, a single copy of HIV RNA was detected in plasma at age 24 months and 37 copies HIV DNA/million peripheral blood mononuclear cells (PBMC) enriched for monocytes were detected. Replication-competent virus was not detected following co-culture of 22 million purified resting CD4+ T cells. At age 26 months HIV DNA was detected at 4 copies/million PBMC but with no 2-LTR circles. Plasma viral load, PBMC DNA, and HIV-specific antibodies remained undetectable with standard clinical assays, confirming a state of functional HIV cure.

Conclusions: This is the first well-documented case of functional cure in an HIV+ child and suggests that very early ART may prevent establishment of a latent reservoir and achieve cure in children.



nordsud
Messaggi: 497
Iscritto il: giovedì 24 maggio 2007, 17:07

Re: cura precoce eradica hiv da neonata

Messaggio da nordsud » lunedì 4 marzo 2013, 7:31

Una cosa che non sopporto è quella di spargere la notizia "bomba" puntualizzando che servono indagini ulteriori per verificare l'effettiva infezione da hiv, come dire.. esiste sempre la possibilità di uno sbaglio.
Ma chi vogliono prendere per il culo? Anche il più insulso ospedale della foresta nera ha gli strumenti per verificare l'infezione da hiv.
Questo esame cioè HIV DNA polymerase chain reaction E' LA PROVA DEFINITIVA CHE SEI HIV+ punto e basta. Sicuramente qualcuno oserà mettere in dubbio l'efficacia stessa della PCR a questo punto.
Come nel caso del trapiantato..qualcuno (anzi uno solo ? ) ha individuato una molecola che appartiene ad una proteina dell' HIV.... ma non si vergognano di prendere per i fondelli le persone? Questa non è più scienza! è il delirio di qualcuno che ha ancora voglia di stare sulla cresta dell'onda parlando tanto senza dire niente.



Dora
Messaggi: 7491
Iscritto il: martedì 7 luglio 2009, 10:48

Re: cura precoce eradica hiv da neonata

Messaggio da Dora » lunedì 4 marzo 2013, 7:54

nordsud ha scritto:Una cosa che non sopporto è quella di spargere la notizia "bomba" puntualizzando che servono indagini ulteriori per verificare l'effettiva infezione da hiv, come dire.. esiste sempre la possibilità di uno sbaglio.
Sì, anche a me questi annunci irritano moltissimo, perché ti mettono sempre nella condizione di non capire di che cosa - in effetti - si stia parlando.

Comunque, onestamente, con quell'HIV RNA così basso, a me questo pare più un caso di PEP che ha avuto successo che una cura vera e propria: hanno preso la bambina per il rotto della cuffia, come succede in quei tanti casi di Profilassi Post Esposizione che non fanno più notizia.
Cercherò di vedere la presentazione per capirci qualcosa di più.



nordsud
Messaggi: 497
Iscritto il: giovedì 24 maggio 2007, 17:07

Re: cura precoce eradica hiv da neonata

Messaggio da nordsud » lunedì 4 marzo 2013, 10:54

Dopo aver letto questo :

Infant infection was confirmed by positive HIV DNA and RNA testing on 2 separate blood samples obtained on the 2nd day of life. 3 additional plasma viral load tests (days of life 7, 12, and 20) were positive before reaching undetectable levels at age 29 days.

Posso dire che il bambino era effettivamente infetto oltre ogni ragionevole dubbio. In analogia con HBV più sei giovane più alte sono le probabilità che diventi cronica l'infezione. In questo caso abbiamo 2 esami HIV DNA e 3 test per la carica virale a conferma.



Dora
Messaggi: 7491
Iscritto il: martedì 7 luglio 2009, 10:48

Re: cura precoce eradica hiv da neonata

Messaggio da Dora » lunedì 4 marzo 2013, 13:06

Il report di Mark Mascolini (a breve disponibile in http://www.natap.org/).


"Functional Cure" of HIV Claimed for Baby Treated 30 Hours After Birth

20th Conference on Retroviruses and Opportunistic Infections, March 3-6, 2013, Atlanta
Mark Mascolini


An HIV-infected US infant treated from 30 hour after birth had no detectable viral load, no detectable HIV DNA in blood cells, and no HIV-specific antibodies at 26 months of age on standard tests, even though antiretroviral therapy (ART) stopped at age 18 months [1]. Deborah Persaud (Johns Hopkins University) and colleagues believe their findings confirm "a state of functional HIV cure."

Speedy treatment after birth appeared to work like postexposure prophylaxis (PEP), stopping HIV from getting a foothold in this baby's body and establishing a latent viral reservoir. Evidence that the baby was infected persisted, however, in vanishingly small levels of HIV RNA and HIV DNA detectable in blood and cells. But the researchers do not believe these viral traces can reestablish active infection.

US HIV experts including Daniel Kuritzkes (Harvard) and Steven Deeks (University of California, San Francisco) are reserving judgment on whether the child had established HIV infection, the New York Times reports [2]. "The one uncertainty is really definitive evidence that the child was indeed infected," Kuritzkes told the Times.

Persaud and colleagues believe their findings show the infant did have HIV infection--though perhaps not an established latent reservoir. "For pediatrics, this is our Timothy Brown," Persaud told the Times, referring to the "Berlin patient" cured of HIV after bone marrow transplantation from a donor with cells resistant to HIV.

The researchers confirmed exposure to HIV by checking maternal HIV antibody and plasma HIV RNA tests, including HIV resistance testing. The baby appeared to be infected with wild-type (nonmutant) HIV-1 subtype B. Persaud and coworkers believe they documented HIV infection in the infant through standard HIV DNA polymerase chain reaction and plasma HIV RNA testing. Positive HIV DNA and HIV RNA testing on separate infant blood samples collected on the second day of life showed that the child carried HIV that was genetically matched to the mother's virus. Plasma viral load at that point was around 20,000 copies [2], relatively low for an infant.

Three-drug treatment of the Mississippi infant began within 30 hours of birth and continued to the age of 18 months. Plasma HIV RNA tests remained positive on days 7, 12, and 20, then became undetectable at age 29 days. From 1 through 26 months, plasma HIV RNA remained below the detection limit of a 20-copy assay repeated 16 times.

Clinicians stopped antiretroviral therapy at age 18 months. Ultrasensitive assays detected a single copy of HIV RNA at age 24 months and 37 copies of HIV DNA per million peripheral blood mononuclear cells (PBMCs) enriched for monocytes. Samples yielded no evidence of replication-competent HIV after coculture of 22 million purified resting CD4 cells.

When the infant was 26 months old, an ultrasensitive assay spotted 4 HIV DNA copies per million PBMCs but no 2-LTR circles (which indicate that HIV genetic material is being imported into the nucleus of an infected cell). Standard clinical assays remain negative for HIV RNA, PBMC HIV DNA, and HIV-specific antibodies.

"This is the first well-documented case of functional cure in an HIV-positive child," Persaud and colleagues maintain. The case, they believe, "suggests that very early ART may prevent establishment of a latent reservoir and achieve cure in children."

The child is now 2.5 years old and has not taken antiretrovirals for a year.

References

  • 1. Persaud D, Gay H, Ziemniak C, et al. Functional HIV cure after very early ART of an infected infant. 20th Conference on Retroviruses and Opportunistic Infections. March 3-6, 2013. Atlanta. Abstract 48LB.
    2. Pollack A, McNeil DG Jr. In medical first, a baby with H.I.V. is deemed cured. New York Times. March 4, 2013. http://www.nytimes.com/2013/03/04/healt ... s-say.html.



eremita
Messaggi: 71
Iscritto il: giovedì 21 febbraio 2013, 20:20
Località: costa romagnola

Re: cura precoce eradica hiv da neonata

Messaggio da eremita » lunedì 4 marzo 2013, 21:51

oddio...chiedo scusa..ho scritto poco fà in un'altra sezione,sul tema di questa notizia_
Ultima modifica di eremita il lunedì 4 marzo 2013, 22:07, modificato 1 volta in totale.


La mia libertà,finisce dove inizia la tua-

eremita
Messaggi: 71
Iscritto il: giovedì 21 febbraio 2013, 20:20
Località: costa romagnola

Re: cura precoce eradica hiv da neonata

Messaggio da eremita » lunedì 4 marzo 2013, 21:57

Oggetto del messaggio: dell'annuncio di stasera in tv sulla guarigione di una neona
MessaggioInviato: lunedì 4 marzo 2013, 21:45
Connesso

Iscritto il: giovedì 21 febbraio 2013, 20:20
Messaggi: 21
Località: costa romagnola
Sui vari telegiornali si è parlato di una bimba,nata hiv+...a cui sono stati somministrati,da subito,farmaci retrovirali-
Si è enfatizata la sua guarigione,come se avessero scoperto un vaccino (quasi)
Mia figlia,nata sieropositiva nell'88..quando ancora c'erano pochi farmaci e x lo più per adulti..all'età di 18 mesi
si è negativizzata spontaneamente,senza alcun farmaco-Anzi,direi guarita perche esami successivi a distanza di anni ne confermarono la negatività-Ora mi sorge un dubbio su questa "declamata" notizia-Ci sono di mezzo le case farmaceutiche e forse non è che una sponsorizzazione x i farmaci adatti ai neonati-Voi che ne pensate ?...


La mia libertà,finisce dove inizia la tua-

nordsud
Messaggi: 497
Iscritto il: giovedì 24 maggio 2007, 17:07

Re: cura precoce eradica hiv da neonata

Messaggio da nordsud » martedì 5 marzo 2013, 7:31

eremita ha scritto:Oggetto del messaggio: dell'annuncio di stasera in tv sulla guarigione di una neona
MessaggioInviato: lunedì 4 marzo 2013, 21:45
Connesso

Iscritto il: giovedì 21 febbraio 2013, 20:20
Messaggi: 21
Località: costa romagnola
Sui vari telegiornali si è parlato di una bimba,nata hiv+...a cui sono stati somministrati,da subito,farmaci retrovirali-
Si è enfatizata la sua guarigione,come se avessero scoperto un vaccino (quasi)
Mia figlia,nata sieropositiva nell'88..quando ancora c'erano pochi farmaci e x lo più per adulti..all'età di 18 mesi
si è negativizzata spontaneamente,senza alcun farmaco-Anzi,direi guarita perche esami successivi a distanza di anni ne confermarono la negatività-Ora mi sorge un dubbio su questa "declamata" notizia-Ci sono di mezzo le case farmaceutiche e forse non è che una sponsorizzazione x i farmaci adatti ai neonati-Voi che ne pensate ?...
I bambini che nascono da madre hiv+ possono avere solo gli anticorpi passati dalla madre ( pertanto risultano hiv+ ) ma con il tempo, dopo la nascita, questi anticorpi scompaiono.
I bambini che nascono da madre hiv+ risultano senza dubbio infetti solamente se l'esame HIV DNA lo conferma.
E' l'esame HIV DNA che conferma oltre ogni ragionevole dubbio che il virus si è integrato nel DNA delle cellule. Ed un volta infettate le cellule non c'è ( per adesso ) farmaco che possa eliminarle. Stanno testando varie molecole per colpire le cellule con il virus integrato .
Una volta trovato il farmaco che può colpire le cellule con hiv integrato latente o no l'infezione da hiv sarà sconfitta.

Domanda che sorge spontanea e legittima ( da profano ) è la seguene: E' mai possibile che in 30 anni dalla scoperta del virus e 25 dai primi antivirali non si sia fatto un passo in avanti per colpire le cellule ? ( è cosa risaputa che sono le cellule le fabbriche del virus... e sono 20 anni che sanno dell'esistenza dei cd4 memoria infetti ). Risposta: Evidentemente il 90% della scienza che gira attorno alla genetica è fuffa ( almeno per adesso) e capire i meccanismi di funzionamento delle cellule richiederà ancora molti anni di studio.



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