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Immune-enhancing treatment may destabilize HIV reservoirs

NIH-funded study in monkeys suggests promise of targeting PD-1

NIH/National Institute of Allergy and Infectious Diseases

21-Jul-2016 - Although antiretroviral therapy (ART) can reduce the amount of HIV in the blood to an undetectable level in most chronically infected people, it cannot eliminate reservoirs of HIV that persist in latently infected immune cells. Findings presented at the 21st International AIDS Conference (AIDS 2016) in Durban, South Africa, suggest that combining ART with an immune-enhancing treatment may destabilize viral reservoirs in macaques infected with simian immunodeficiency virus (SIV), the monkey equivalent of HIV. The work was funded by the National Institute of Allergy and Infectious Diseases, part of the National Institutes of Health, and led by Rama Amara, Ph.D., of Emory University.

HIV infects the CD4+ T cells of the immune system. Other immune cells, called CD8+ T cells, help eliminate HIV-infected CD4+ cells, but their ability to do so wanes over time. Studies have shown that loss of CD8+ T cell function is associated with high levels of a cell-surface protein called PD-1 and that HIV reservoirs concentrate in PD-1+ CD4+ T cells.

In the current study, investigators administered five infusions of either a PD-1-blocking antibody or a placebo to SIV-infected monkeys 10 days before starting the animals on ART. Monkeys that received the anti-PD-1 antibody produced more activated antiviral CD8+ cells. Following ART initiation, blood levels of SIV became undetectable in an average of 42 days in antibody-treated monkeys compared with 140 days in those that received placebo.

Eight months after starting ART, the monkeys were given three monthly infusions of anti-PD-1 antibody or a placebo. PD-1 blockade caused transient increases in blood levels of SIV, suggesting that the treatment may have destabilized latent SIV reservoirs.

According to the investigators, these findings highlight the potential of PD-1 blockade to work synergistically with ART and other therapeutic agents to improve CD8+ T cell function and destabilize HIV reservoirs in humans. Ultimately, such strategies potentially could be tested in people in an attempt to diminish HIV reservoirs and reduce the amount of HIV in a person's body to the point where the immune system could control the infection without antiretroviral drugs.

PRESENTATION:

RR Amara et al . PD-1 blockade synergizes with ART for restoring anti-viral CD8 T cell function and possibly destabilizing the viral reservoir in SIV-infected macaques . Oral presentation at the 21st International AIDS Conference (AIDS 2016) in Durban, South Africa.

WHO:

NIAID Director Anthony S. Fauci, M.D., is available to discuss the findings.

###

CONTACT:

To schedule interviews, please contact Hillary Hoffman, 301-402-1663, hillary.hoffman@nih.gov.

NIAID conducts and supports research -- at NIH, throughout the United States, and worldwide -- to study the causes of infectious and immune-mediated diseases, and to develop better means of preventing, diagnosing and treating these illnesses.

News releases, fact sheets and other NIAID-related materials are available on the NIAID website.

About the National Institutes of Health (NIH): NIH, the nation's medical research agency, includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. NIH is the primary federal agency conducting and supporting basic, clinical, and translational medical research, and is investigating the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit http://www.nih.gov/.

Source:http://www.eurekalert.org/pub_releases/2016-07/nioa-itm072016.php


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