UNC to Test Therapeutic HIV Vaccine

Nilu Goonetilleke, Ph.D., will lead the study testing a therapeutic vaccine for HIV.

Nilu Goonetilleke, Ph.D., will lead the study testing a therapeutic vaccine for HIV.

A multidisciplinary research team at the University of North Carolina at Chapel Hill has been awarded more than $5.6 million from the National Institutes of Health (NIH) to test a therapeutic vaccine in people living with HIV. Strengthening and redirecting the immune system’s anti-HIV response are the primary goals of the five-year study.

“The first generation of this vaccine produced an impressive immune response in people living with HIV,” said Nilu Goonetilleke, Ph.D., an assistant professor in the Departments of Medicine, Microbiology and Immunology at UNC. “Here we will test the second generation of this vaccine that we hope will be even better at targeting HIV reservoirs in the body.”

A challenge to achieving an HIV cure is that the virus enters a resting state in the body. Latency-reversing agents have shown promise in awaking these dormant reservoirs. If the vaccine proves successful in boosting and controlling the immune system’s response to HIV, it could eventually be paired with latency-reversing agents to clear the virus.

“The next step would be a combination study investigating a latency-reversing agent and the vaccine,” Goonetilleke said. “Ultimately, we want to improve clearance of these reactivated cells and reduce the viral reservoir.”

The study will recruit patients at UNC who are living with HIV, but who are virally suppressed due to antiretroviral therapy. Goonetilleke will work with colleagues across campus, including the Center for AIDS Research, the Division of Infectious Diseases and the Department of Biostatistics. The University of Oxford will provide the vaccine.

Vorinostat Dosing Exposes Latent HIV

Nancie Archin, PhD

Nancie Archin, Ph.D.

Exposing hidden HIV reservoirs so that they can be cleared is a strategy being tested in efforts to develop therapies to cure the nearly 40 million people worldwide living with HIV. Researchers at the University of North Carolina at Chapel Hill have shown that interval dosing of the drug Vorinostat reverses HIV latency and is well-tolerated in people living with HIV. However, while Vorinostat makes latent HIV easier to detect, it does not clear or deplete infection, meaning additional advances will be needed to achieve a cure. These results were published in the Journal of Clinical Investigation on July 17.

The team studied Vorinostat in 16 patients living with HIV whose viral load was controlled through standard antiviral therapy. Doses of Vorinostat were administered at 48 or 72-hour intervals. The team found that HIV could be more easily detected within latently infected CD4+ T cells when Vorinostat was administered once every three days, even though control of viral load in the blood was maintained.

“We showed that a single dose of Vorinostat could expose the hidden virus several years ago, but it has taken two studies over the last five years to define the proper interval dosing strategy to use Vorinostat safely and effectively,” said Nancie Archin Ph.D., lead author of this study and an assistant professor in the Division of Infectious Diseases at UNC. “Now we can attempt to chip away the viral reservoir.”

Over a month of treatment with Vorinostat few side effects and no serious toxicities were seen, but depletion of latent infection was not found. The team believes pairing a latency reversing agent, like Vorinostat, with an antiviral immune therapy, such as a vaccine or an antibody capable of recognizing and clearing the latent cells, will be needed to achieve a cure.

David Margolis, M.D.

David Margolis, M.D.

“We have now been able to begin two small, intensive studies pairing Vorinostat with an anti-HIV vaccine produced by Argos Therapeutics, or with an infusion of antiviral immune cells prepared by Cath Bollard’s laboratory at Children’s National Medical Center, in an attempt to test combined approaches to clearing HIV infection,” said David Margolis, M.D., director of the UNC HIV Cure Center at the UNC Institute for Global Health & Infectious Diseases. “We do not expect immediate success, but hope to make progress towards the goal of developing treatments that someday might clear HIV infection.”

The team at the HIV Cure Center collaborated with researchers in the Departments of Medicine, and Microbiology and Immunology in the School of Medicine, the Gillings School of Global Public Health, and the Eshelman School of Pharmacy on this study. Merck Sharpe & Dohme provided Vorinostat, and the National Institutes of Health funded this research.

Connecting the Community with Research

The UNC ROPE Team held a drag race in June at the Durham LGBTQ Center, offering free HIV testing and information about enrolling prevention studies.

The UNC ROPE Team held a drag race in June at the Durham LGBTQ Center, offering free HIV testing and information about enrolling prevention studies.

Kareem Greene believes the once daily pill to prevent HIV has kept him virus-free on at least two occasions. It is a fact he shared candidly during an outreach event at the LGBTQ Center in Durham the last Friday in June.

“I know two former partners who are living with HIV,” Greene said. “But I have remained HIV-negative and I owe that to PrEP.”

Greene, who participated in the clinical trial at UNC that proved Truvada could be used as pre-exposure prophylaxis or PrEP to guard against HIV infection, now educates the community about this option as a member of the ROPE Team. ROPE, which stands for Research, Outreach, Education and Prevention, is the advocacy arm of the UNC Global HIV Treatment and Prevention Clinical Trials Unit.

“We are the bridge to the community,” said Noshima Darden-Tabb, MSW, LCSW, community engagement manager. “The goal is through our visibility, community programs and partnerships that we increase knowledge about research and reduce stigma, leading to more people wanting to be involved in research.”

Launched in the fall of 2015, the ROPE Team is made up of ambassadors who have undergone training on the unit’s prevention studies, PrEP, research and confidentiality. Ambassadors talk with people in their social networks who may be at risk for HIV as well as host community events. The ROPE Team attended Out! Raleigh in May and organized a drag show at the LGBTQ Center in Durham in June.

ROPE Team member Kenneth Freeman emceed the drag show. Like Greene, he participated in the PrEP trial and remains committed to keeping his community HIV-free.

“I’ve lost 20 people to HIV,” Freeman said. “Black, gay men are especially affected by this disease. I am a black, gay man and it makes sense for me to approach my community about this. I have a dog in this fight, too. I can say ‘I’m just like you.’”

The team attends community events like Out! Raleigh to spread the word about HIV prevention. (Photo courtesy of Mary Lide Parker)

The team attends community events like Out! Raleigh to spread the word about HIV prevention. (Photo courtesy of Mary Lide Parker)

The event at the LGBTQ Center mixed fun with education. During breaks between drag show contestants dancing and lip-syncing to Tina Turner and Prince songs were announcements about free HIV testing. ROPE Team member JT Williams gave an overview of the current HIV prevention trials at UNC, including a long-acting injection and an infusion of antibodies.

“I’m enrolled in a prevention trial; so when I talk with people about the research options available to them, I am more relatable and credible,” Williams said. “HIV doesn’t discriminate. But through unity and community, we can win this fight.”

The ROPE Team is having an impact. Five people inquired about being pre-screened for an HIV prevention trial during the drag show. And Darden-Tabb said approximately 8-10 people have joined research studies after attending a ROPE Team event over the past year and a half.

“I certainly believe that we have created a culture among the members, and this has fostered conversations about HIV research and general HIV prevention among ambassadors and the community at outreach events as well as in their individual social networks,” Darden-Tabb said. “I believe these conversations have decreased stigma about HIV testing and research with those we have engaged. We have received a lot of positive praise for just ‘being there.’ People are generally grateful that UNC participates in Out! Raleigh, PRIDE and other community events.”

Connect with the ROPE Team at https://www.facebook.com/uncropeteam/. To learn more about the HIV prevention trials enrolling at UNC, visit prevention4me.org.

Biostatistics Core presents work at Summer Conferences

Yinyan & Ilana

Ilana Trumble from the CFAR Biostatistics Core presented a poster at the Collaboratory of AIDS Researchers for Eradication (CARE) Annual Meeting in June 2017, together with Yinyan Xu. This work from the Goonetilleke Lab (G lab) is entitled “Longitudinal assessment of baseline variation in HIV-1 specific T cell responses in HIV-1 infected, durably suppressed individuals.” For more information on the G lab, click here.

Wang Cheng Poster

Wang Cheng, visiting scholar from UNC Project China, is researching the generalizability of online randomized control trials. His work was presented at the Atlantic Causal Inference Conference, Chapel Hill, NC, May 2017. This work was a joint collaboration between UNC Project China, the Chinese Center for Disease Control (C-CDC), and the UNC CFAR Biostatistics Core. For more information about UNC Project China, click here.

10th Annual InWomen’s Conference

The 10th annual conference on new and significant findings about the consequences of substance use, abuse, and risk behaviors, hosted by the International Women’s and Children’s Health and Gender Group. The group aims to identify and promote innovative research that helps to empower women across the lifespan, foster gender-based analyses in research, and promote the benefits of prevention, intervention, and treatment.

Abstracts are now being accepted!

Abstracts with a focus or component on women, children, youth, LGBT+ individuals, and/or gender differences in areas pertaining to substance use will be considered.

Submission Deadline: January 06, 2017 at 11:59 PM EST
Abstract and Travel Award Notifications will be sent by: February 24, 2017
Visa Letters Issued: February 24 – March 24, 2017

Click here for the Abstract Submission Form.

2nd Annual CFAR HIV in the Southeast Workshop

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In the decades since the first AIDS cases were reported in Los Angeles and New York City in 1981, the epicenter of the nation’s HIV epidemic has shifted from urban centers along the coasts to the 16 states and District of Columbia that make up the South. The South now experiences the greatest burden of HIV infection, illness, and deaths of any U.S. region, and lags behind in providing quality HIV prevention and care to its citizens.

Southern states today account for an estimated 44 percent of all people living with an HIV diagnosis in the U.S., despite having only about one-third (37%) of the overall U.S. population. Eight of the 10 states with the highest rates of new HIV diagnoses are in the South, as are the 10 metropolitan statistical areas (MSAs) with the highest rates (CDC HIV Surveillance Report, 2014). Diagnosis rates for people in the South are higher than for Americans overall: In 2010, the region had the highest rates of HIV and AIDS diagnoses in the country, as well as the highest number of people living with HIV compared to all other regions (SAS Report, 2015).

2017 marked the second year of the CFAR HIV in the Southeast Workshop, at gathering of researchers and community organizers from CFARs across the country. This year’s event was held in the Cal Turner Family Center at Meharry Medical College in Nashville, Tennessee on March 24, 2017.  The Tennessee CFAR hosted the workshop.

CFAR investigators and staff, along with public health workers and community representatives, collaboratively addressed the nature of the shifting HIV epidemic at the workshop. Discussions and panels identified shared resources and strategies to combat the epidemic, ways to engage the community and methods to influence public health policy to better serve people living with or at risk for HIV in the Southeast. Attendees had the opportunity to hear plenary speakers present on NIH priorities and initiatives relevant to HIV/AIDS in the South, necessary components for collaboration between health departments and CFARs, and use of molecular surveillance data to identify clusters of HIV infection.

The UNC CFAR was well-represented in panel discussions as leaders in the field: Erika Samoff  spoke on the panel “Working with Health Departments, including Rapid HIV Transmission Networks/Phylogenetics”,  Heidi Swygard spoke on the panel “PrEP Implementation, Linkage, Retention, and Rapid ART Initiation”, Bill Zule shared on the panel “HIV and the Opioid Epidemic”, and Caressa White led a discussion on “Effective Approaches to Community Engagement”. Following the panel discussions, attendees joined in conversation about priorities and action items for the future.

Workshop planners are now collecting information from participants in the Southeast CFAR Workshops (Atlanta 2016 and/or Nashville 2017) to assist all participating CFARs, justify supplemental funding for a potential third workshop, and maintain momentum for the organization. The work to address the epidemic in the Southeast is essential to the health of people in the region and to our nation’s long-term goal of ending the epidemic. – Caressa White, SCEED Office Director

UNC CFAR Spring 2017 Networking Event

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Congressman David Price

On May 8, 2017, the UNC CFAR Social and Behavioral Sciences Research Core hosted the Spring 2017 Networking Event. The theme of this month’s event was “HIV Research that Reaches Policymakers: Part I with Congressman David Price D-NC-04”.

David Price represents North Carolina’s Fourth District – a rapidly growing, research-and-education-focused district that includes parts of Orange, Durham, and Wake counties. He received his undergraduate degree at UNC-Chapel Hill and went to Yale University to earn a Bachelor of Divinity and Ph.D. in Political Science. Before he began serving in Congress in 1987, Price was a Professor of Political Science and Public Policy at Duke University. He is the author of four books on Congress and the American political system. Price currently serves on the House Appropriations Committee and is the ranking member of the Transportation, Housing and Urban Development Appropriations Subcommittee. He is also a member of the Appropriations subcommittees covering homeland security, State Department, and foreign operations funding.

Congressman Price addresses attendees at the Networking Event

Congressman Price addresses attendees at the Networking Event

Congressman Price shared his perspective on how researchers can best focus their outreach efforts to inform policy makers about their research findings and shared personal examples of how he used research to inform policy.  He also shared the importance of having a broad viewpoint on health issues and working as a coalition to advocate for funding.

Following the talk, Dr. Ronald Strauss, Administrative Core Consultant for the UNC CFAR, moderated a question & answer session with Congressman Price and attendees. Attendees posed questions around the future of HIV research and prevention, with a specific focus on PrEP and HIV in the South. Congressman Price emphasized the importance of community partnerships and well-developed grassroots outreach efforts. Price discussed the value of seeking funding through the ACA to promote research and further inquiry in the field of health maintenance, diagnosis and wellness. A strong emphasis was placed on developing positive working relationships with community health centers, and Price encouraged attendees to think strategically about how we support the work of those combatting health challenges outside of the HIV/AIDS field. Congressman Price articulated that the most lasting impact is made when researchers work cooperatively to address health disparities. He encouraged attendees to connect with national advocacy groups like the Non-Defense Discretionary (NDD) United, an alliance of stakeholders from across the non-defense sectors, to call for a balanced approach to deficit reduction.

Stay tuned for Part 2 of this event with Congressman Price in the fall!

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.

Self-Swabbing Increases STD Screens

 

The number of cases of syphilis, chlamydia and gonorrhea increased from 2014 to 2015 in North Carolina. This prompted a multidisciplinary group in the UNC Infectious Diseases Clinic to introduce several interventions, including self-swabbing, to screen more patients for sexually transmitted diseases.

The ID Clinic inside the NC Memorial Hospital on Carolina’s campus is one of a few clinics in the state giving patients the option to screen themselves for chlamydia and gonorrhea. Self-swabbing is one of a handful of interventions created by a multidisciplinary quality improvement group including the clinic’s nurses, social workers, a certified medical assistant and a provider.

“Sex is normal and healthy,” says Ellen McAngus, LCSWA, a social work practitioner in the ID Clinic. “But we need to give our patients the right tools to protect themselves and their partners.”

UNC ID Clinic providers manage the care for 1,800 people living with HIV. In 2015, clinic nurse Anita Holt, RN, and Associate Clinic Director Amy Heine, FNP, noticed screening rates for syphilis in patients living with HIV were down, despite there being an increase in syphilis cases in North Carolina. In fact, the number of syphilis cases in the state increased by 64 percent between 2014 and 2015, according to the NC Department of Health and Human Services.

Through photos, an infographic and a video, learn more about the team’s progress in educating their patients about sexual health.

The Role of Messaging in Reducing STI Transmission

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UNC School of Media and Journalism doctoral alumna Diane Francis ’16 (PhD),  co-investigators on a 2014 Developmental Award from the UNC CFAR, recently received the 2017 GEAB Impact Award for her work on the Role of Messaging in Reducing STI Transmission.

Women account for almost 25 percent of new HIV infections in North Carolina, with African-American women representing 71 percent of those diagnoses, according to the N.C. Department of Health and Human Services. Condoms can prevent transmission of HIV and other sexually transmitted infections. Yet young women, in particular, may experience embarrassment when accessing condoms. To improve condom access for young African-American women, Diane Francis, Ph.D., evaluated an innovative condom distribution and health communication initiative. Due to the focus on young African-American women, the study took place at an all-women’s historically black college/university (HBCU) in the state.

Dispensers featuring targeted safer sex messages were installed in dormitory bathrooms across the HBCU campus. The UNC-Chapel Hill Center for AIDS Research funded the initiative; project members were co-principal investigators Francis and Seth Noar, Ph.D., of UNC-Chapel Hill and co-investigator Deborah Fortune, Ph.D., of North Carolina Central University. Prior to launching the initiative, the team conducted extensive research to develop the messages that were placed on the dispensers.

Surveys were collected immediately before and three months after the dispensers were installed. Follow-up interviews also explored how students felt about the dispensers and messages. The initiative was found to improve perceptions of condom access and to support safer sex behaviors. The college plans to continue the campus program, even though the study has ended. Francis’ research demonstrates the effectiveness of initiatives combining health communication and condom distribution toward the goal of reducing HIV/STI transmission in North Carolina.

“Diane’s deep commitment to this project made it so successful. I am proud that her study not only contributed to the science in this area, but also changed the safer sex climate on a college campus in ways that will prevent AIDS and other STDs,” said adviser Seth Noar, Ph.D.