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Despite long-term treatment, HIV remains in spinal fluid, associated with cognitive problems



PITTSBURGH, July 15, 2019 – Even after nearly a decade of strict HIV treatment, viral-resistant cells can be found in the cerebrospinal fluid of half of the participants in a national clinical trial of HIV-positive people. Moreover, these participants had a greater likelihood of cognitive deficits than their HIV-free sperm cells in spinal fluid, according to an analysis published today Journal of Clinical Research.

The study, conducted by scientists from the University of Pittsburgh, Yale University and North Carolina University of Medicine, can help answer questions about why people with well-controlled HIV still have problems with memory, concentration, and ability to perform complex tasks. , It also points to an important reservoir for a brain virus that can not be overlooked in clinical trials testing the drug.

"I do not even know about a contagious disease that is easier to cure when it's in the brain than when it's anywhere else in the body," said senior author John Mellors, a professor and head of Pitt's Division of Infectious Diseases. "It's hard to target brain trauma, and HIV is probably not an exception to the rules. Our job is cut for us in search of HIV, but knowledge is half the battle, so I'm cautiously optimistic."

Many people who have received long-term treatment still have HIV DNA in several blood cells. These cells may cause re-emergence of active infection when the treatment is stopped, so cleaning the entire HIV DNA is a focus of effort to develop the drug. However, the stability of HIV cells in the central nervous system – particularly in cerebrospinal fluid surrounding the brain and spinal cord – was not well-known.

With funding from the National Institute of Health (NIH), a group for clinical trials of AIDS, the research team tested a 69-person cerebrospinal fluid, all of which were on anti-HIV therapy for an average of nine years. Very sensitive HIV detection methods revealed that nearly half of the participants had viral DNA in the cells in the cerebrospinal fluid. Of these, 30% met the criteria for cognitive impairment, compared with 11% of those who did not have HIV cells in their cerebrospinal fluid.

The researchers emphasized that the presence of these cells did not clearly cause cognitive impairment and that there may be several explanations for the findings. For example, it is possible that the level of native infection in the nervous system was higher in the group of HIV-infected cells or that the development of cognitive problems may be initiated at an early stage of HIV infection before anti-HIV infection. therapy started.

Mellors noted that although treatment is not yet available for removing HIV from cerebrospinal cells, findings still have potential clinical uses. Awareness of a possible link between HIV infection, even when well controlled, and cognitive problems can help doctors track down patients who may need additional monitoring.

Co-author of Dr. Sc. Serena Spudich, Dr. Harry M. Zimmerman and Dr. Nicholas, and Professor of Violence Spinelli, University of Yale, have noted that clinical trials will be needed in the future to determine the cause of cerebrospinal HIV infection. associated with declining cognitive abilities and to determine whether it is possible to remove this reservoir and if this improves the neurocognitive function of people living with HIV.

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The late Kevin Robertson, Ph.D., from the University of North Carolina, is the second head of this paper. Additional authors are Dr. Ronald J. Bosch, Hanna Mar, M.P.H. and Christina M. Lalama, all at Harvard University; Dr. Rajesh T. Gandhi, Massachusetts General Hospital; Dr. Sc. Joshua C. Cyktor, mr. Sc. Bernard J. Macatangay, Dr. Charles Rinaldo, Dr. Deborah McMahon, Ph.D. Jana L. Jacobs and Dianna Koontz, all Pitt; Ann C. Collier, mr. From the University of Washington; Mr. Catherine Godfrey of NIH; Evelyn Hogg, of Social & Scientific Systems, Inc.; and mr. Sc. Alyssa Vecchio from the University of North Carolina.

This research is supported by NIH grants UM1 AI068634, UM1 AI068636, UM1 AI106701, UM1 AI069481 and R21MH110260.

To read this edition online or share it, visit http: // www.UPMC.com /Media /news/Mellors-071 519 HIV-spinal [when embargo lifts].

About the University of Pittsburgh Medical School

The University of Pittsburgh School of Medicine, as one of the leading academies in biomedical research in the country, integrates advanced science-leading technology into a wide range of disciplines in a continuous effort to utilize the power of new knowledge and improve the human condition. Driven mainly by the Faculty of Medicine and its affiliates, Pitt ranked among the top 10 recipients of funding from the National Institute of Health since 1998. In the ranking list recently announced by the National Science Foundation, Pitt ranked fifth among all American universities in the overall federal science and engineering research and development support.

Likewise, the Medical School is equally committed to improving the quality and strength of its medical and graduate education programs, which has been recognized as an innovative leader, and training highly qualified, compulsive clinicians and creative scientists who are well equipped to participate in world class research. The Medical School is an academic partner of UPMC who has collaborated with the University to raise the standard of medical excellence in Pittsburgh and position health care as the driving force of the economy of the region. For more information about Medical School, see http: // www.medschool.Pitt.edu.

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