University of �鶹��ý at ����ԴDz� (JABSOM) physician-scientist Dominic Chow has been selected for the 2026 Emerging Leaders in Health and Medicine Forum at the National Academy of Medicine.

The invitation-only program brings together emerging leaders in health care, research and policy from across the country.

“It’s a real honor,” Chow said. “To be able to interact with members of the National Academy of Medicine and contribute to discussions that help guide health policy is something I don’t take lightly.”

Chow’s career spans global public health, including training at Johns Hopkins Bloomberg School of Public Health and work in Guyana, where he helped lead a yellow fever outbreak investigation.

At JABSOM, he has advanced HIV research through the �鶹��ý Center for AIDS and serves as program director of Ola HAWAII, an NIH-funded initiative expanding clinical research access in underserved communities and supporting studies including Long COVID.

“I think bringing clinical trials to various populations across �鶹��ý helps create more equity,” Chow said.

The forum connects participants to address major health challenges and inform national policy. Chow said he hopes to ensure �鶹��ý’s health needs are represented.

“We have a responsibility to address health disparities here in �鶹��ý and beyond,” he said.

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Since HIV was linked to AIDS in 1983, researchers have struggled to develop a vaccine due to the virus’s rapid mutation, which makes it difficult to create an immune response that can prevent infection. Iain MacPherson, assistant professor at the University of �鶹��ý at ����ԴDz�’s (JABSOM), is tackling this problem with a promising new approach. He recently received a $410,813 grant from the National Institutes of Health to develop a vaccine targeting a stable part of the virus.

“Developing an HIV vaccine is one of the most difficult, complex problems in medicine,” MacPherson said. “We’re aiming to engineer an immunogen better capable of protecting people against diverse strains of HIV so we can help stem the spread of HIV.”

MacPherson explained that HIV’s rapid mutations make vaccine development tough. Researchers are focusing on a stable region of the virus’s spike protein to create broadly neutralizing antibodies (bnAbs) that can fight multiple strains of the virus.

“If an antibody can bind to that part of the HIV spike protein, it would block the interaction, neutralize the virus, and prevent it from being able to infect someone,” MacPherson said.

More effective vaccine design

MacPherson’s research focuses on accelerating the production of these bnAbs by targeting specific B-cells. The new vaccine design aims to direct the immune system to target specific B-cells that can produce a key antibody, helping them develop it more effectively.

Working with JABSOM Professor Axel Lehrer, MacPherson is using molecular engineering and AI tools to test the vaccine design on humanized mouse models. If successful, the approach could improve vaccines for other viruses like influenza and COVID-19.

A �鶹��ý native, MacPherson began HIV vaccine research during his postdoctoral studies and joined UH in 2017.

“There’s been a lot of amazing work done in HIV vaccine development and we’re hoping that we can contribute part of the solution to the HIV vaccine problem,” he said.

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HIV/AIDS continues to be an ongoing health issue internationally, nationally and locally as dozens of people are diagnosed each year with the virus in �鶹��ý, according to the �鶹��ý State Department of Health (DOH). Since 2021, 64 people have been diagnosed with HIV/AIDS in the state.

We want to do everything that’s possible to drive HIV to zero, which means zero stigma and zero deaths
—Cecilia Shikuma

Inspirational stories from people who have lived with the virus and discussions on finding a cure were among the highlights at the 5th annual (H20) sponsored by various �鶹��ý health partners including DOH, (HICFA) at the (JABSOM) and DOH in September. It was the first time the conference has been held in person since the COVID-19 pandemic.

“The HIV epidemic is not over,” said Cecilia Shikuma, director of HICFA, who has been working for more than three decades to combat HIV/AIDS. “We want to do everything that’s possible to drive HIV to zero, which means zero stigma and zero deaths.”

Since its opening in 1991 under the �鶹��ý AIDS Clinical Trials Unit, HICFA has serviced more than 700 patients who are either infected or at-risk with HIV/AIDS. The clinic opened its current location in December 2015 at JABSOM, where clinical trials and research also take place.

“We participated in a lot of the advances, certainly in antiretroviral therapy,” Shikuma said. “So to us, it’s important that our HIV community participates in being the solution.”

Finding hope, a cure for HIV

When Adam Castillejo found out about his HIV diagnosis in 2003, doctors told him that he only had a few years to live.

“It’s kind of challenging for anyone,” said Castillejo, who shared his story at the H20 conference.

Castillejo was also diagnosed with stage 4 cancer in 2012 with Hodgkin’s lymphoma disease and underwent a vigorous chemotherapy regime for years, while being denied a bone marrow transplant due to his HIV/AIDS diagnosis.

“Being HIV, you are three times more likely to develop cancer,” he added. “I was diagnosed terminally ill in 2015. There were not many choices for me—and I realized that HIV was stigmatizing me.”

Although the circumstances seemed dire for Castillejo, he received overwhelming support from his partner, who helped him to resume to normal life.

Eventually, things looked up for Castillejo. A new medical team stepped in and allowed him to have the transplant he needed. The operation proved successful, and in 2016, Castillejo was confirmed to be cured of HIV.

“We want to give hope to people living with HIV today,” Castillejo said. “Don’t allow HIV to define you. I know it’s difficult, but people around the world are trying to find a cure for you out there. Stay strong and be positive.”

Solutions for neighbor island patients

Shikuma continues to look for solutions for those living with HIV/AIDS, particularly for those on the neighbor islands, many of whom also have underlying health conditions and have limited access to resources in their areas. She hopes that in the next year or so, the efforts will start to build momentum. HICFA sends a team to Maui and �鶹��ý Island each month to provide these services as more start to develop.

“We talked about transportation being an issue,” said Shikuma, who also sees the stigma on HIV/AIDS as a concern. “As the HIV population ages, we’re going to face more issues—increases in heart attacks, dementia, heart disease, liver disease. But we’re also going to proactively have to think about how to support this community. Curing HIV is the final frontier of this research endeavor. And I’m hoping to be able to have some thoughts as to how to make this a reality.”

The nursing staff of the University of �鶹��ý at ����ԴDz� John A. Burns School of Medicine’s (HICFA) were recognized with the 2021 Suzanne Richard-Crum Award at the annual on December 1. The virtual event took place at 6 p.m.

The award is presented by the �鶹��ý Department of Health (DOH)-Harm Reduction Services Branch to recognize those who have made “outstanding contributions in providing HIV/AIDS services.” In honor of the HICFA nurses, Gov. David Ige has also proclaimed December 1, 2021 as “Nurses of the �鶹��ý Center for AIDS �ٲ���.”

Under the leadership of its director Cecilia Shikuma, HICFA conducts research to evaluate optimal therapies for HIV infection and AIDS-associated complications, increase understanding of the disease, and transfer research findings to improve the quality of life for those living with HIV. HICFA operates the Clint Spencer Clinic on Oʻahu, Maui and �鶹��ý Island, and provides care to about 500 patients living with HIV statewide.

For more than 30 years, HICFA nurses have been dedicated to ending HIV and its stigma. They stepped forward to uphold the values of the nursing profession in the early days of the AIDS epidemic when fear and discrimination were widespread. They have provided essential medical care to hundreds of people living with HIV/AIDS.

The group has contributed to important research in numerous clinical trials for effective treatments and toward finding a cure. Their work with AIDS service organizations and HIV housing programs has also elevated the level of health care among people living with HIV in �鶹��ý.

“The current COVID pandemic reminds us of the challenges we faced when the HIV epidemic began four decades ago,” said Glenn Wasserman, chief of the DOH’s Communicable Disease and Public Health Nursing Division. “Our former Department of Health colleague, Suzanne Richard-Crum, would be proud of the HICFA nurses, who have worked tirelessly on the frontlines, providing direct patient care and taking the time to build meaningful bonds with their patients, seeing the whole person, not just the disease.”

The entire nursing staff of HICFA, past and present, are being honored for their dedication and self-sacrifice. The HICFA nursing team includes: Debbie Ogata-Arakaki (retired), Nancy Hanks (retired), Cris Milne, Lorna Nagamine, Maya Barney and Mary Lichota. The past nurses whose dedication and commitment left long lasting impacts include: Paul Coelho, Nicole Valcour, Joanne Frederick Auskern, Jo McKeague, Lyle Oshita, Monica Millard, James Cairl, Sandra Akina and Sue Congdon.

Suzanne Richmond-Crum served for more than a decade as director of the �鶹��ý Seropositivity and Medical Management Program of the �鶹��ý Department of Health’s Harm Reduction Services Branch and passed away in August 2004. The award was established in honor of the competence and compassion she demonstrated in her HIV/AIDS work and is presented each year in �鶹��ý for outstanding contributions in providing HIV/AIDS services. 2021 will mark the 18th annual bestowing of this honor.

This recognition is an example of UH ����ԴDz�’s goal of (PDF), one of four goals identified in the (PDF), updated in December 2020.

A student from the University of �鶹��ý at ����ԴDz� (JABSOM) will earn his doctorate in tropical medicine this month as he works to help solve the mystery of why the human immunodeficiency virus (HIV) “rebounds” when treatment is stopped or interrupted.

Brooks Mitchell, a Kamehameha Schools Kapālama graduate of Kamuela on �鶹��ý Island, has poured himself into the research. “Understanding where HIV hides, and what cells are involved in its persistence, remains a topic of intense interest in the field and has become a current focus of my research,” Mitchell said. The study of viral reservoirs in HIV infection is motivated by the fact that the virus is not eradicated by current treatment, although it can be reduced to undetectable levels in the blood.

Mitchell, with other researchers at the �鶹��ý Center for AIDS, is investigating which types of blood cells may harbor HIV despite optimal antiretroviral therapy. He uses a method that he developed during his PhD studies to assess different types of cells isolated from HIV-positive individuals who are on treatment.

“I determine the number of cells that are infected and produce HIV, as well as estimate the amount of HIV produced by each infected cell,” he said. Mitchell believes that greater understanding of these HIV reservoirs may inform targeted approaches in future curative treatments.

“The opportunity to work with healthcare providers and patients has been an important experience because it is a reminder that the research being conducted should be relevant to both the investigators and, more importantly, the people living with HIV.”

Mitchell developed an interest in infectious diseases and immunology as an undergraduate while majoring in microbiology and working in a clinical microbiology laboratory. Some of his professors and the technical director of the lab where he worked were affiliated with JABSOM’s . “After talking to some of the faculty, the tropical medicine department seemed like a great fit since its curriculum focused on areas of research that I wanted to further pursue during my graduate studies.”

Mitchell is expected to earn his PhD in tropical medicine in fall 2019. He previously earned a BS in microbiology and an MS in tropical medicine from UH ����ԴDz�.

“After my PhD, I plan to continue on to receive medical training and become a physician-scientist,” added Mitchell.

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About a third of us are walking around with the bacteria that causes tuberculosis (TB) in our bodies, but most don’t actually end up with TB. For children living with HIV—about 2 million at last estimate—it’s a different story. They’re much more likely to develop TB, and about 40,000 HIV-positive children die from it each year.

To explore how HIV puts children at greater risk of contracting and dying from TB, an international team of scientists, led by researchers at the , University of Pittsburgh, and the University of Wisconsin-Madison and have secured a five-year, $6.2 million grant from the .

The grant will fund nonhuman primate experiments to understand disease mechanisms and explore a potential therapeutic approach. Then, extending from the laboratory to the field, Lishomwa Ndhlovu, professor of tropical medicine in the UH ����ԴDz� will investigate whether the same findings are true for children living in Myanmar, where rates of HIV and TB are both high.

“Children with HIV are very vulnerable to TB, and anything we can do to try to better understand the pathology of the disease and potentially develop new interventions would make a great dent in the morbidity and mortality of the two diseases,” Ndhlovu said.

Children have distinct immune responses

“Kids are not small adults. They have distinct immune responses. You can’t necessarily extrapolate results from adults to kids,” said principal investigator Charles Scanga, research associate professor of microbiology and molecular genetics at the University of Pittsburgh.

In collaboration with the Yangon Children’s Hospital, Ndhlovu and his team will look at blood samples from children in Myanmar. The idea is to see whether children living with HIV have the same T cell deficiencies and immune exhaustion markers as the laboratory animals do, and whether those markers correlate with TB coinfection rates.

“We are very fortunate to have an ongoing study of HIV in children in Yangoon and we have leveraged that opportunity to see how we can investigate how we can prevent TB in this vulnerable HIV population in children,” said Ndhlovu.

Read more about the study on the .

—By Tina Shelton

For same-sex male couples, the first few months of a new relationship are a crucial time to communicate about sexual health and HIV prevention, according to new findings from public health researchers at the . The research may ultimately help to lower new HIV infections for this group.

For the study, same-sex male couples were sought through advertising on Facebook. A total of 722 men (representing 361 couples) were enrolled in the study, and completed a questionnaire asking about the timing of when they first discussed their HIV status, had sex without a condom, and if and when they had reached an agreement about whether or not they would have sex with anyone else.

The results showed that more than half of the men had talked about their HIV status on the first day of their relationship, and more than 80 percent had talked about it during the first two weeks. The results also showed that about one quarter of the men reported having sex without a condom on the first day of their relationship, and about 60 percent reported doing so during the first three months. However, there were some differences based on the men’s and couples’ HIV-status.

“In our study, we wanted to look at same-sex males couples and determine, within their relationships, when they start having conversations about their HIV status, when they start having sex without a condom, and deciding what kind of relationship they want,” said , lead author of the study and an assistant professor with the UH Mānoa in the Myron B. Thompson School of Social Work. “Knowing this timeline could give the public health research community ideas for ways to intervene to help improve HIV prevention efforts for same-sex male couples in the U.S. and abroad.”

Research shows that men who have sex with men (a group that includes men who are gay, bisexual, questioning their sexual identity or orientation, or heterosexual but having sexual encounters with other men) have elevated rates of HIV infection. Epidemiological estimates from other studies indicate that between 33 to 66 percent of men who have sex with men acquire HIV while in a same-sex relationship, and that this risk is attributed to the sexual behaviors they engage in with their primary partner.

“The new findings suggest that many couples find it important to communicate about their HIV status before they first engage in sex without a condom,” Mitchell said. The new data provide researchers with a good summary of the timing of when these events occur within same-sex male couple relationships, he said.

Mitchell and his research team secured funding from the National Institute of Mental Health via an R21 grant, which is intended to encourage exploratory/developmental research. Their goal is to apply these findings toward the development of a web-based “decision aid” aimed at helping same-sex male couples in new relationships create a plan on how best to reduce their risk for HIV. The researchers will also test this decision aid to determine whether couples find it useful and effective.

The was published on October 8 in The Journal of Sex Research. Mitchell’s co-authors on the study include , an assistant professor of public health at UH, and Kristi E. Gamarel, an assistant professor with the University of Michigan School of Public Health.

—By Theresa Kreif

Native Hawaiians and Pacific Islanders are in the top three ethnicities with the highest rates of HIV diagnoses in the country according to .

In response to the alarming rates, Associate Professor Misty Pacheco has begun researching health disparities experienced by �鶹��ý Island HIV/AIDS patients.

“Native Hawaiians and Pacific Islanders, behind African-Americans, behind Hispanics, have the third-highest rate for HIV diagnoses, even though we are such a small population,” said Pacheco.

Pacheco’s research primarily looks at the disparities or differences in experiences that HIV/AIDS-diagnosed Native Hawaiians and Pacific Islanders living in �鶹��ý have in comparison to other ethnicities living elsewhere in the country.

“I am specifically looking at the satisfaction with the care they receive, and viral suppression, which basically means they have control of their disease, they are on [effective] medication and regularly seeing a provider,” said Pacheco. “I’m looking to see, with those two outcomes, does it differ with Native Hawaiians and Pacific Islanders [from] all other race groups?”

UH Hilo students have contributed to HIV/AIDS research through gathering background information. “I usually recruit students to do things that I’ve introduced in my classes [such as] where they can gather evidence-based data,” said Pacheco.

Through community-based research, Pacheco hopes to further develop programs and interventions for the Native Hawaiian and Pacific Islander HIV/AIDS population in a culturally effective way.

“If it comes from the community, and they identify their needs and priorities and the best way in addressing them, it will be more accepted by them. Whatever intervention or program that comes out of that, will be more sustainable,” said Pacheco. “Empowering the community and building that capacity through community-based research projects is the greatest benefit. Not only do they learn but they take ownership of what’s in their community.”

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—A �鶹��ýHilo Stories article written by Alyssa Mathews, a freshman at the University of Hawai‘i at Hilo

A researcher is investigating why people with human immunodeficiency virus (HIV) are living longer with antiretroviral treatment yet experiencing more chronic complications as they age. was awarded the 2018 Koenig Foundation Award in Medicine by the .

Mitchell, a PhD candidate at UH ����ԴDz�’s (JABSOM), received the award that includes a $5,000 prize on May 7.

At JABSOM, Mitchell is part of a team at the that is examining why those with HIV suffer earlier from diseases related to aging than those who are not infected with HIV.

“HIV has been around for decades, but there is still a lot of work to be done,” said Mitchell. “This recognition of the work that our group is doing is an honor.”

About his research

“One of the projects that I’ve been working on is looking at lymph node fibrosis,” said Mitchell. “We excised the lymph nodes from 10 volunteers and conducted various immunoassays to understand the immunological mechanisms that may be driving fibrosis within these tissues.”

Fibrosis is not normal and interferes with the functionality of the tissue, Mitchell explains.

“Lymph nodes are important in the immune response, so when you have a lot of collagen deposits—which is the definition of fibrosis—occurring within these tissues, it interferes with normal immune processes that may result in persistent inflammation,” he said. “It may be a reason why we see a lot of chronic complications within our (HIV) patients.”

See the on the JABSOM website.

—By Tina Shelton

A mobile app that aims to encourage getting tested for HIV on a regular basis among men who have sex with men should include an HIV test location finder and help them track their sexual activities, according to research by the (OPHS) in collaboration with the University of Minnesota.

Public health researchers conducted in-depth interviews with Spanish-speaking men who are homosexual, bisexual, questioning their sexual identity or orientation, or heterosexual but have sexual encounters with other men. The researchers asked the men what features they look for in apps, and what aspects of an app would make them likely to use it.

“We know from previous research that there is a need to improve HIV prevention efforts, including testing rates, for Latino men who have sex with men in the U.S., and to help these men get tested for HIV and other sexually transmitted infections,” said lead author , an OPHS assistant professor. “Mobile apps are a great way to get information and resources out to people but, prior to our research, there weren’t any studies that asked these men what they wanted in an app, and what might motivate them to download an app and keep using it over time.”

Using Facebook ads and flyers the researchers recruited men in the Miami area whose primary language was Spanish. They interviewed 15 men and then analyzed the transcripts of the interviews, looking for common themes.

When asked what they looked for in apps in general, all of the study participants said that it was very important to keep their personal information secure and confidential. Most said they were willing to pay for apps that were useful to them. The men also said they tended to download apps that their friends had used and liked.

As for an HIV testing app, almost all of the men said they would like an app to send them reminders to get tested for HIV on certain dates and to show them the nearest location where they could get tested. Most also said they would like the app to send them information about HIV prevention, either through text messages or alerts, and that they would want a feature in the app that would help them keep track of how many sexual partners and encounters they had.

“These findings have applications for prevention, and could be used to help guide future efforts toward developing HIV testing apps for Spanish-speaking men who have sex with men,” Mitchell said.

The study is in the . Mitchell’s co-authors include Maria Beatriz Torres of Gustavus Adolphus College in Minnesota, Lucy Asmar of the University of Miami Miller School of Medicine in Florida, and Thu Danh and Keith Horvath, both at the University of Minnesota.

—By Theresa Kreif

Over the past five years approximatley 80 to 100 newly diagnosed cases of HIV have been reported annually in �鶹��ý. On World AIDS Day, December 1, the will host the , which will detail how the state might realize a �鶹��ý to Zero goal.

Researchers at the University of �鶹��ý at Mānoa ’s �鶹��ý Center for AIDS (HICFA) and community partners will lead discussions updating local efforts to prevent, treat and cure AIDS.

Speakers, including keynoter Julie Dombrowski of the University of Washington, will provide updates on the latest research in HIV prevention. Also speaking will be HICFA Director and center scientists including Lishomwa Ndhlovu, who was awarded top-tier funding from the National Institutes of Health this year to test his  in the body.

The event is free and is being held in the John A. Burns School of Medicine’ Sullivan Conference Center and the UH Cancer Center.

For more information, (PDF).

—By Tina Shelton

The laboratory of Associate Professor , has been awarded two new grants from the , including prestigious R01 level funding, to advance his strategy to cure HIV.

The new awards to Ndhlovu, of the (JABSOM) and , comes on the heels of the discovery his lab, in collaboration with the , published this month in . The researchers located an epigenetic footprint for brain related problems in HIV infected persons. The �鶹��ý Center for AIDS, also launched its in 2015 to raise funds to prevent new infections and find an HIV cure.

“We are excited with funding for these studies as it builds on our recent work on HIV and the impact on the brain and is line with our �鶹��ý 2 Zero Initiative,” said Ndhlovu.

Eliminating HIV-infected cells

With these new grants in hand, Ndhlovu will seek to facilitate the elimination of HIV-infected cells that persist despite anti-HIV drugs by flushing the virus out of its hiding place and trying to poison the virus on its way out. An alternate approach he is testing is to clear the virus by restoring the disabled immune system killing function.

“We propose to achieve this through a concerted study of a novel immune regulatory pathways that when blocked restores T cell function capable of depleting latently HIV infected T cells,” he explained.

is funding the new grant (R21AI122393-01). has also awarded the Ndhlovu lab a multi-principal investigator R01 grant (R01MH112457-01) with from the in San Francisco, on the “Effects of Human Galectin-9 on the CNS HIV Reservoir.”

“While the advent of antiretroviral therapy (ART) has significantly decreased the morbidity and mortality associated with HIV infection, the virus is never completely eliminated from the body of the infected individual, necessitating lifelong drug treatment,” said Ndhlovu. “The central nervous system (CNS) in particular is an important sanctuary site for the virus during ART, due to the relative lack of antiviral immune surveillance in the CNS and poor penetration of many antiretroviral drugs across the blood-brain barrier. In this project, we investigate the ability of a to control and clear virus in the CNS compartment, with the ultimate goal of utilizing this protein as a tool to cure HIV infection.”

—By Tina Shelton

University of �鶹��ý researchers have identified a unique epigenetic footprint in specific types of immune cells from blood that can identify individuals with HIV that have a range of impairments in cognitive function.

Reliable biomarkers such as that identified by the researchers offer insight into how HIV associated cognitive impairment develops but also promises improved diagnostic testing and improved treatment decisions.

The findings are published in the September 2016 issue of (PDF) by scientists and at the (JABSOM) and collaborators at the University of �鶹��ý at Mānoa and the .

“These results offer the first significant window into the mechanisms driving HIV-related brain damage and how to track the disease,” said Ndhlovu, an associate professor in the , JABSOM.

Combination antiretroviral therapies have improved HIV survival. If started early and taken daily for life, antiretroviral therapies can result in fewer non-AIDS related complications. However, HIV still impacts the brain. Around 40 percent of individuals even on antiretroviral therapy still suffer HIV-related neurocognitive disorders that can affect living activities.

It has long been suspected that changes to cells of the monocyte/macrophage lineage, a type of immune cell, influence the development of cognitive impairment in HIV. Since HIV infection itself alters epigenetic processes in the immune system, the research team wondered whether a distinct DNA methylation profile, a major epigenetic modification where methyl groups are added to DNA, occurs in those with HIV associated-cognitive impairment and whether it exists in distinct immune cell populations from the blood.

By evaluating DNA methylation, the researchers discovered differences in gene networks and gene expression linked to the central nervous system and interactions with HIV that appeared uniquely in monocytes of HIV infected study participants with cognitive impairment.

“Strikingly, further analysis showed a strong association between DNA methylation levels of these markers in monocytes and neuropsychological test function, measured using a composite score of multiple cognitive domains” said Maunakea, an assistant professor in JABSOM’s and co-senior author of the study.

According to Michael Corley, a junior researcher in JABSOM’s Department of Native Hawaiian Health and lead author of the study, the field of epigenetics has ushered in a new era of discovery in immunology and neuroscience. “Combined with the advancement of

Currently there is no treatment for individuals with HIV associated cognitive impairment. “The advancement in epigenetic therapeutics also affords promising new interventions that should be considered for the management of HIV associated cognitive impairment, provided they are selective to the appropriate immune cell target,” added Ndhlovu.

“There is still much we need to understand about how HIV affects the brain and several findings from this study are highly relevant to this field of neuroAIDS,” said Ndhlovu.

—By Tina Shelton

Neurologist Beau Nakamoto, associate professor of medicine at the John A. Burns School of Medicine, received a two-year, $421,313 grant from the National Institute of Neurological Disorders and Stroke (National Institutes of Health) to examine whether a new magnetic resonant imaging (MRI) contrast dye can be used to detect the inflammation that is believed to signal decline in memory and thinking. The contrast dye that Nakamoto will be studying will specifically target the immune system’s white blood cells, which are believed to play a key role in the development of HIV-associated cognitive impairment.

About 2,900 people in �鶹��ý live with HIV/AIDS, and there continue to be new cases every year. In the last two decades, as people live longer under a daily regimen of anti-viral HIV-fighting medicine, the �鶹��ý Center for AIDS has noticed that HIV patients are suffering dementia at rates greater than people without the virus.

While severe HIV dementia is uncommon with effective combination antiretroviral therapies, milder degrees of cognitive impairment continues to affect up to 50 percent of HIV-infected individuals. Even mild cognitive impairment can have a big impact on important parts of a person’s daily life. Employment difficulties arise because of fatigue, driving is difficult or dangerous and people forget to take their medications (without daily doses of life-sustaining HIV antivirals, HIV patients will die).

Nakamoto, a neurologist at Straub Clinic and Hospital, is a member of an elite team of researchers at the �鶹��ý Center for AIDS who suspect one of the main types of cells which protect the body against infection also play a key role in causing HIV-associated dementia. It is believed that once these infection-fighting cells (monocytes) have switched on to battle HIV, an unintended consequence is the production of toxic chemicals in the brain that cause uncontrolled inflammation and ultimately cognitive impairment.

Nakamoto is one of few researchers in the nation to utilize novel MRI contrast agents to track those infection-fighting cells in the brains of HIV-infected patients. If successful, this technique could potentially be used in future clinical trials aimed at targeting the HIV-infection fighting monocytes with the hope of finding a treatment for HIV-associated dementia.

—By Tina Shelton

Researchers at the and have revealed a novel new immune pathway that can be targeted to increase the immune systems’ ability to eliminate HIV, the virus that can lead to AIDS.

The research team led by at the (JABSOM) , and Jonah Sacha, from OSHU, identified a novel negative checkpoint receptor on T cells, TIGIT, which may be responsible for making immune cells dysfunctional and unable to control or eliminate the HIV virus.

The discovery, , will give new directions to vaccines and therapies that will potentially reverse these exhausted cells and allow them to control HIV-1 replication, but also serve in “Shock and Kill” HIV curative strategies.

Background

When a person becomes infected with HIV, starting combination antiretroviral drug treatment will, in most cases, successfully suppress HIV in the blood. However, the treatment is powerless to clear infection and restore full health. Furthermore, if people with HIV stop taking antiretroviral drugs, they experience a rapid, aggressive rebound of the virus in the blood. This indicates that HIV has found a way to hide and establish a “dormant reservoir”, but more importantly, evade elimination by the immune system.

In the absence of treatment, HIV infection is brought partially under control by the infected person’s immune system, specifically by an immune system cell called a CD8+ Killer T cell. The response of these CD8+ T cells and HIV during the early stages of infection is crucial and will determine how the disease will progress. Over time, however, the immune damage mediated by HIV infection will affect the function of the CD8+ T cells even if with the addition of antiretroviral drugs.

These immune cells are key players in eliminating HIV infected reservoir cells. One proposed strategy to eradicate HIV being considered is the ‘Shock and Kill’ approach, first to ‘Shock’ the infected cells with agents that will awaken the dormant virus and then allow the immune system to ‘Kill’ the reactivated virus. A major obstacle with this approach has been that although CD8+THIV-1 infected cells, these THIV viral reservoir.

“A preponderance of emerging evidence indicates that the functions of the HIV-specific CD8+THIV infected cells” said , a PhD candidate in immunology at JABSOM and lead author of the study.

Discovering a pathway to clearing HIV infection

The researchers observed an expansion of CD8+ T cells expressing, a negative immune checkpoint receptor, TIGIT was associated with clinical markers of HIV disease progression in a diverse group of HIV infected persons. These levels remained high even among those with undetectable virus in the blood. They also found the large fraction of the HIV-specific CD8+ T cells simultaneously express both TIGIT and another negative checkpoint receptor, PD-1 and these cells retained several features of exhausted T

Evaluating Simian Immunodeficiency Virus (SIV) infection of the rhesus macaque non-human primate, has served as an indispensible animal model for studying HIV/AIDS. The authors next defined the TIGIT pathway in this model. “We were successful in cloning rhesus TIGIT and were able to demonstrate, similar to humans, that the TIGIT pathway was active in SIV infection.” said co-author Gabriella Webb, a postdoctoral researcher in the .

“These results appear to indicate that a large fraction of HIV and SIV specific CD8+ T cells are vulnerable to negative regulation through these two pathways” said Ndhlovu, an associate professor at UH’s Department of Tropical Medicine and �鶹��ý Center for AIDS.

The research team reasoned that by interfering with the TIGIT and PD-1 pathway, they could rejuvenate the HIV-specific CD8+ T cell responses to clear HIV infection. By blocking both the TIGIT and PD-1 pathways with novel targeted monoclonal antibodies, the researchers were able to reverse the defects of these viral specific CD8+ T cells.

Read the for more information.

—By Tina Shelton

The was presented to (JABSOM) physician Dominic Chow on , December 1, at the Lutheran Church of Honolulu. The said Chow was selected for his tremendous contributions to HIV/AIDS prevention and treatment services in �鶹��ý.

“For over 15 years, Dr. Chow has dedicated himself to taking care of individuals affected by HIV/AIDS,” said the Department of Health in a news release.

Chow is an HIV expert at the , operated by the University of �鶹��ý at Mānoa medical school. It is a multi-specialty clinic focusing on the care of individuals with HIV and its complications, which now include diabetes, heart disease, dementia and cancer. The clinic has about 400 patients on Oʻahu and the neighbor islands. Some 3,000 people in �鶹��ý live with HIV/AIDS. It is believed about 25 percent of them don’t even know they are carrying the virus.

“Our HIV clinic would not exist without Dr. Chow’s hard work,” said Cecilia Shikuma, director of the .

Chow also is a board member of The Life Foundation, a non-profit organization committed to preventing the spread of HIV and assisting those who are living with HIV and AIDS.

“Dr. Chow is an active participant in the training of medical students and medical residents and has served as a mentor to other students and junior researchers,” said JABSOM Dean Jerris R. Hedges. “He provides HIV expertise through the continuing education of �鶹��ý’s practicing healthcare providers and is also an outstanding leader in the UH internal medicine and pediatric residency programs, receiving the University of �鶹��ý Pediatric Residency Program Faculty Teaching Award in 2005.”

Read the for more on Chow.

December 1 marks , a global health day first celebrated in 1988 to unite the world in the fight against HIV.

As the day approaches, news from the at the brings disturbing findings about the disease’s impact on the Native Hawaiian population.

Researchers have found that HIV/AIDS is being diagnosed in Native Hawaiians more than twice as often as Caucasians, and that Native Hawaiians with HIV/AIDS are three times more likely to need hospitalization.

Some 3,000 people in �鶹��ý live with HIV/AIDS. One in four of them, about 25 percent, don’t even realize they are carrying the virus.

Read the to learn more about how UH researchers at the �鶹��ý Center for AIDS are working to combat this disparity or read the news reports by and .