New HIV Reservoir Identified by UNC Team

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HIV cure research to date has focused on clearing the virus from T cells, a type of white blood cell that is an essential part of the immune system. Yet investigators in the Division of Infectious Diseases at the University of North Carolina School of Medicine have found the virus persists in HIV-infected macrophages. Macrophages are large white blood cells found in tissues throughout the body including the liver, lung, bone marrow and brain. The discovery of this additional viral reservoir has significant implications for HIV cure research. These findings were published in Nature Medicine on Monday, April 17.

“These results are paradigm changing because they demonstrate that cells other than T cells can serve as a reservoir for HIV,” said Jenna Honeycutt, Ph.D., lead-author and postdoctoral research associate in the UNC Division of Infectious Diseases. “The fact that HIV-infected macrophages can persist means that any possible therapeutic intervention to eradicate HIV might have to target two very different types of cells.”

Last spring, this laboratory lead by J. Victor Garcia, Ph. D., professor of medicine, microbiology and immunology at UNC School of Medicine, demonstrated the ability of tissue macrophages to support HIV replication in vivo in the total absence of human T cells. But how macrophages would respond to antiretroviral therapy (ART) and whether macrophages represented a reservoir for HIV after treatment were unknown.

Macrophages are myeloid lineage cells that have been implicated in HIV pathogenesis and in the trafficking of virus into the brain. Using a humanized myeloid-only mouse (MoM) model devoid of T cells, Garcia and his team showed that ART strongly suppresses HIV replication in tissue macrophages. Yet when HIV treatment was interrupted, viral rebound was observed in one third of the animals. This is consistent with the establishment of persistent infection in tissue macrophages.

“This is the first report demonstrating that tissue macrophages can be infected and that they respond to antiretroviral therapy,” Honeycutt said. “In addition, we show that productively infected macrophages can persist despite ART; and most importantly, that they can reinitiate and sustain infection upon therapy interruption even in the absence of T cells – the major target of HIV infection.”

Now that Garcia and his team know HIV persists in macrophages, the next step will be to determine what regulates HIV persistence in tissue macrophages, where in the body persistently infected macrophages reside during HIV treatment and how macrophages respond to possible therapeutic interventions aimed at eradicating HIV from the body.

The UNC School of Medicine team collaborated with scientists in UNC’s Department of Biostatistics, the Theoretical Division at Los Alamos National Laboratory, Veterans Affairs San Diego Healthcare System, and the Departments of Medicine and Pathology at the University of California at San Diego. This study was funded by the National Institute of Mental Health and the National Institute of Allergy and Infectious Diseases of the U.S. National Institutes of Health.

UNC to Test Injectable Long-Acting Implant to Prevent HIV

Researchers at the University of North Carolina at Chapel Hill have received a three-year, $1.8 million grant from the National Institutes of Health to develop a new implantable drug delivery system for long-lasting HIV-prevention.

Scientists in the UNC School of Medicine’s Division of Infectious Diseases and the UNC Eshelman School of Pharmacy are developing an injectable drug delivery system that forms an implant that steadily releases anti-HIV medication over long periods of time.

The injectable formulation includes an anti-HIV drug, a polymer and a solvent. The three-compound liquid will solidify once injected under the skin. As the polymer slowly degrades, the drug is released. Efficacy of the new formulation to prevent HIV transmission will be evaluated using state of the art pre-clinical models developed at UNC.

Currently, a once-daily pill exists to prevent HIV infection. However, adherence to this daily regimen can be challenging for some people.

“This long-acting injectable formulation could provide a discrete and efficient method to protect against HIV infection and improve adherence, which is one of the major challenges of oral pre-exposure prophylaxis, or PrEP,” said Rahima Benhabbour, Ph.D., assistant professor in the UNC Eshelman School of Pharmacy and one of the study’s co-principal investigators. “The formulation is adaptable to a number of drugs alone or in combination and can be fine tuned to meet a targeted release regimen.”

Read more here..

Dr. Kevin Robertson honored for his work to understand the neurological effects of HIV

fb842458-2788-4812-b4c4-612385ac37fcKevin Robertson, PhD, is a professor of neurology and the director of the AIDS Neurological Center. He has led global research initiatives, and trained clinicians and researchers all over the world to establish research centers in Uganda, South Africa, Malawi, Nigeria, India, Thailand, Peru, and Zimbabwe. This summer, Robertson was recognized for his role in training the next generation of AIDS researchers across the globe by the American Psychological Association as the 2016 Distinguished Leader in Psychology and AIDS.

Robertson shared, “Even in 1987, there was a real interest in establishing an infrastructure here in infectious diseases and other disciplines. Things really took off when the Global HIV Prevention and Treatment Clinical Trials Unit was established to test the drugs that were in development and determine how effective they were.

Joe Eron led a number of those studies, and he’s just been a great collaborator and wonderful scientist and clinician and researcher. Mike Cohen has always been very supportive of my research in HIV in the brain. There’s always been really wonderful, collaborative, cutting-edge, leading scientists here at UNC doing this work. And it shows.

It shows in Mike Cohen’s work – showing that the virus can be suppressed and not transmitted to partners if you’re taking your antiretrovirals –  and Ron Swanstrom’s work. Dr. Swanstrom, who’s head of the Center for AIDS Research, and I have had a long collaboration, as well, studying virus in the brain and comparing that to systemic virus and looking for compartmentalization.”

Read more here…

Early HIV Treatment Can Prevent Transmission to Uninfected Partners

cohenAntiretroviral therapy (ART) for HIV infection provides consistent protection against the sexual transmission of the HIV virus from infected men and women to their HIV-uninfected sexual partners.

These findings were announced on Monday, July 20 by researcher Dr. Myron Cohen at the 8th International AIDS Society (IAS) Conference on HIV Pathogenesis, Treatment & Prevention in Vancouver, Canada. Cohen, UNC’s chief of the Institute for Global Health & Infectious Diseases, has headed the HPTO 052 global research project for a decade and studied more than 1,700 couples.

HPTN 052 began in 2005 and enrolled 1,763 HIV sero-discordant couples – where one person is HIV-infected and the other is not – at 13 sites in nine countries. The majority of the couples were heterosexual (97 percent). HIV-infected partners were assigned to start ART at the beginning of the study, called the “early” arm, or later in the study, called the “delayed” arm. Those on the delayed arm started ART when their bodies’ immune systems were declining. HPTN 052 was funded primarily by the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health (NIH).

The IAS 2015 Conference

The IAS 2015 Conference

“These findings demonstrate that antiretroviral therapy, when taken until viral suppression is achieved and sustained, is a highly effective, durable intervention for HIV prevention,” said Myron Cohen, Principal Investigator for HPTN 052. “The HPTN 052 trial was designed to address two questions: whether providing antiretroviral therapy to an HIV-infected person would prevent HIV transmission to a sexual partner, and whether earlier antiretroviral therapy offered long-lasting health benefits, and the answer to both is a
resounding yes.”

The significance of the research findings cannot be understated – when used consistently, medication can break the chain of HIV transmission and has the potential to eradicate the virus when all infected people die natural deaths. For the foreseeable future, however, such a medical strategy will disproportionately benefit industrialized countries whose residents have wider, though far from universal, access to modern health care.

Read the full article from the News and Observer Newspaper here.

Click here to see all the UNC IAS coverage.

Dr. David Margolis featured on NPR’s The State of Things

CFAR Investigator Dr. David Margolis has been featured on NPR’s The State of Things talking about how studies led by UNC investigators continue to make progress in HIV prevention, treatment and eradication research. He also discusses in layman’s terms all of the HIV news to come out of the International AIDS Society (IAS) meeting in Vancouver last month.

Listen to the conversation here.

International Conference on HIV Treatment and Prevention Adherence

IAPACThe International Association of Providers of AIDS Care (IAPAC) is hosting the 10th annual International Conference on HIV Treatment and Prevention Adherence.

June 28-30, 2015
Eden Roc Miami Beach Hotel, Miami, FL

The conference provides an annual forum for the presentation and discussion of state-of-the-science HIV treatment and biomedical prevention adherence research, as well as current behavioral and clinical perspectives in practicum, within the context of achieving the maximum therapeutic and preventative benefit of antiretroviral therapy across the continuum of care.

Early registration is available until January 9th.

More information can be found on the event page.

Registration will be open through May 8. IAPAC offers reduced rates for your hotel stay, as well as flights through several airlines.