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Sunday, July 14, 2013

ANOTHER STEP TOWARDS AIDS CURE


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What does it means the negativization of serum, blood and tissue tests of 2 Boston/US patients previously HIV-positive with leukemia or lymphoma, after being subjected to bone marrow transplantation?. I) Such results contribute to design a cure for AIDS, as the absence of virus or antibodies to the virus in the blood and other tissues suggest the elimination of important viral reservoirs in the bone marrow, which should be a continuous generator of viral infected lymphocytes. Timothy Brown (42), was the first HIV-positive patient with acute leukemia, to receive a bone marrow transplant from a donor with an HIV resistant mutation. After transplantation, Timothy became seronegative for HIV. After 5 years without antiretroviral therapy, Timothy is now considered cured or in remission (the virus can lie dormant in the brain, gastrointestinal tract and other sites). Therefore urge new methods to detect and quantify HIV virus in hidden reservoirs II) Bone marrow transplantation has no practical use in HIV-positive people without cancer, since they live useful lives with alone antiretroviral therapy. Until we get enough knowledge about HIV virus, bone marrow transplants in HIV-positive patients should be performed only in patients with blood cancers. We need to add to the previous report the cure of a Mississippi/US, HIV-positive baby. Some researchers believe that antiretroviral drugs given at birth prevent the establishment of body viral reservoirs.
III) The reported cases encourage projects to create cells resistant to HIV infection. IV) There are some differences between Timothy and American patients with lymphoma: a) While the bone marrow of Timothy was completely destroyed with drugs and total body irradiation (mortality: 40%), the bone marrow of patients with lymphoma were only partially destroyed, a process that carries a 20% mortality. b) Timothy received a marrow from a close genetically related donor, with a rare mutation in the CCR5 receptor, a surface protein of CD4 cells which normally allows the HIV virus, enter, infect and destroy the immune system. CCR5 Delta 32 mutation causes the person who owns it to be resistant to HIV infection. In the future, genetic reengineering could artificially emulate CCR5 receptor mutation. c) Donors of Boston did not have the CCR5 Delta 32 mutation. d) Boston patients continued to receive antiretroviral therapy several years after transplantation. e) It is assumed that graft-versus-host disease generates cells that attack old infected tissues previously weakened by chemotherapy, removing it from the body: a process that lasts nine months. Although it can be fatal the graft-versus-host disease, could eliminate most viral reservoirs f) Sirolimus, seems to have helped to eliminate the HIV virus.

UN PASO MAS HACIA LA CURA DEL SIDA

¿Que implica la negativización de los tests sanguíneos, tisulares y serológicos de 2 pacientes de Boston-USA- previamente HIV positivos con leucemia o linfoma, tras ser sometidos a trasplantes de medula ósea?. I) Contribuyen a diseñar una cura para el SIDA, en tanto la ausencia de virus o anticuerpos al virus en la sangre y otros tejidos sugieren la eliminación de importantes reservorios virales en la medula ósea, la misma que debe ser un generador continuo de linfocitos infectados con virus. Timothy Brown de 42 años fue el primer paciente HIV positivo con leucemia aguda, en recibir un trasplante de medula ósea de un donador con una mutación resistente al H.I.V. Después del trasplante, Timothy devino en seronegativo al HIV. Tras 5 años sin recibir terapia antirretroviral Timothy es considerado actualmente curado o, en remisión (el virus puede permanecer dormido en el cerebro, tracto gastrointestinal y otros). Por ello, urgen nuevos métodos para detectar y cuantificar los virus HIV en reservorios ocultos II) El trasplante de medula ósea no tiene uso práctico en personas HIV positivos, sin cáncer, ya que estas viven vidas útiles con solo terapia antiretroviral. Mientras no se conozca los suficiente, los trasplantes de medula ósea en pacientes HIV positivos, deberían ser realizados solo en pacientes con canceres de la sangre. Es necesario agregar a lo anterior la cura de un bebe HIV positivo en Mississippi, USA. Algunos investigadores opinan que las drogas antiretrovirales administradas al nacer impiden el establecimiento de reservorios virales corporales.

III) Los casos reportados alientan proyectos para crear células resistentes a infección por HIV. IV) Se aprecian algunas diferencias entre Timothy y los pacientes americanos con linfoma : a) Mientras que la medula de Timothy fue completamente destruida con medicamentos e irradiación corporal total (mortalidad : 40%), la medula ósea de los pacientes con linfoma fueron solo parcialmente destruidas medicamente, un proceso que acarrea un 20% de mortalidad. b) La medula que recibió Timothy procedía de un donador genéticamente emparentado con una rara mutación en el receptor CCR5, una proteína superficial de las células CD4 que normalmente permite que los virus HIV, ingresen, infecten y destruyan el sistema immune. La mutación Delta 32 CCR5 hace que la persona que lo posea sea resistente a la infección por el virus HIV. En el futuro la reingeniería genética, podría emular artificialmente la mutación del receptor CCR5. c) Los donadores de Boston no tenían la mutación delta 32 CCR5. d) Los pacientes de Boston continuaron recibiendo terapia antiretroviral varios años después del trasplante. e) Se asume que la enfermedad graft-versus-host, genera células que atacan al tejido viejo infectado y debilitado por la quimioterapia eliminándolo del cuerpo: un proceso que dura 9 meses. Aunque puede ser fatal, la enfermedad graft-versus-host, eliminaría la mayoría de reservorios virales f) El Sirolimus, podria haber contribuido a eliminar al virus H.I.V.

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