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 Hawaiʻi, according to the Hawaiʻi 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 Hawaiʻi 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 Hawaiʻi 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 Hawaiʻi 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 Hawaiʻi at Mānoa 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 Hawaiʻi 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 Hawaiʻi 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 Hawaiʻi 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 Hawaiʻi.

“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 Hawaiʻi Seropositivity and Medical Management Program of the Hawaiʻi 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 Hawaiʻi for outstanding contributions in providing HIV/AIDS services. 2021 will mark the 18th annual bestowing of this honor.

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

Fourth-year medical student Kalei Hosaka of the University of Hawaiʻi at Mānoa (JABSOM) is a recipient of the 2020 Excellence in Public Health Award from the U.S. Public Health Service (USPHS) Physician Professional Advisory Committee.

The award recognizes medical students across the nation who advance public health in their communities and exemplify the USPHS mission to protect, promote and advance health and safety.

Hosaka, who grew up in Hawaiʻi and graduated from Hawaii Baptist Academy, credits the concern he has for underserved populations to his family’s Christian faith and challenging childhood experiences of bullying. He says he is keenly aware of the disparities and the commonalities he shares with others.

Hosaka was an intern with Shalom [AIDS] Delhi as part of Wheaton’s Human Needs and Global Resources program. “For six months, I worked in a community health clinic that serves neglected HIV patients from the Delhi slums,” he said. “As a result, the HIV community became important to me. When I began medical school, I made efforts to work on important HIV research and public health topics with the .”

In recent years, he has been involved in promoting indigenous and migrant health. Hosaka praised his mentors and JABSOM faculty members for encouraging him to pursue research and public health.

“I do not think I know of a medical student who has contributed so much to clinical medicine and public health,” said Paul Kitsutani, captain of the USPHS Physicians Professional Advisory Committee. “This award emphasizes program implementation, research, community service, impact and a commitment to public health. As a JABSOM graduate, I couldn’t be more impressed or proud of Kalei.”

In January 2021, pushed back from July 2020 due to COVID-19, Hosaka will begin a year of research funded by the National Institutes of Health Fogarty Program in Tanzania. His focus is youth with HIV, their mental health and antiretroviral therapy resistance patterns. Hosaka’s wife, Leah, a ����Vlog�ٷ� Mānoa graduate alumna, will also join him.

“For me, solidarity is the driving principle for the kind of work I involve myself in and the kind of physician I aspire to be, following JABSOM’s model of obtaining optimal health for all. It’s why I went into medicine,” Hosaka said. “I believe that being a physician is my calling and my vocation, just as my interests in public health, research and writing.”

Elisabeth Young (JABSOM 2019) and Brandyn Dunn (JABSOM 2016) are the only other JABSOM students who have earned the USPHS recognition.

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Scientists at the have discovered a novel method of diagnosing non-Hodgkin lymphoma, a group of cancers that start in cells called lymphocytes, which are part of the body’s immune system.

Currently, there are no widely recommended screening tests for non-Hodgkin lymphoma, which is usually diagnosed through invasive surgical or needle biopsies, or removal of living tissue for examination.

This new study, published in , suggests the use of Raman spectroscopy technology as an initial step to determine if and when a biopsy would be necessary.

The study is led by Bruce Shiramizu, pediatrician researcher at the (JABSOM) and senior author of the paper. Shiramizu describes their findings as a repurposing of technology that has been used for the Department of Defense in remotely identifying chemicals such as explosives using a laser technique.

“We partnered with an investigator with a physics background to design a way to use a hand-held probe to identify different types of pediatric non-Hodgkin lymphoma tissues,” said Shiramizu. He adds, “the importance of this work is to be able to use the hand-held probe as a screening or diagnostic tool for real-time assessment of a mass that might be a tumor.”

“This work in characterizing malignant cells has future diagnostic implications as a non-invasive initial tissue assessment in children with potential malignancies,” said Melissa Agsalda-Garcia, researcher at JABSOM’s and first-author of the paper.

This study is being supported by the St. Baldrick’s Foundation, the largest private funder of childhood cancer research grants, through multiple grants totaling $113,000.

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

Researchers at the University of Hawaiʻi at Mānoa ’s Hawaiʻi 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 ����Vlog�ٷ� Cancer Center.

For more information, (PDF).

—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 Hawaiʻi 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 Hawaiʻi 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 Hawaiʻi 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 ����Vlog�ٷ�’s Department of Tropical Medicine and Hawaiʻi 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