AAPS RMDC invited Dr Ho to lecture on Targeted Therapy at the 2018 American Association of Pharmaceutical Scientists – Rocky Mountain Discussion Group Annual Meeting (AAPS-RMDG). The RMDG provides a forum for interacting with scientists from industry and academia to promote basic and pharmaceutical sciences in the Rocky Mountain and Pacific Northwest regions. Dr. Ho spoke on, “Systems Approach to Targeted Drug Combination Therapy: Integrating Medical and Pharmaceutical Sciences”.
This past March, Drs. Rodney Ho and Ann Collier attended the Long-Acting/Extended Release (LA/ER) Antiretroviral Research Resource Program (LEAP) in Boston, MA. Dr. Ho spoke on, “Phase 0 development of combination LA ART delivered subcutaneously”. Select TLC-ART scientists also attended, displaying their research at poster sessions.
The objective of the behavioral section of the TLC-ART program is to measure preferences among potential end users for long-acting regimens. These preferences will be used to guide the TLC-ART drug development process. Conducting focus groups with key populations in Sub-Saharan African was recommended by the external advisory committee as an important component of the acceptability research. Under the auspices of Dr. Susan Graham’s “Key Challenges” protocol and Dr. Scott McClelland’s “Exploring Women’s Lifecourse Events & HIV Transmission Potential: A Qualitative Study” protocols, Dr. Jane M. Simoni, along with Zahra Mohamed and George Wanje, completed collecting additional acceptability data in Mombasa, Kenya through a series of focus groups with study participants in the Ganjoni HIV care facility.
The target populations for the focus groups were persons living with HIV, characterized as follow:
The focus group discussions were conducted in June 2017; each lasted ~90 minutes, and were recorded for later translation and transcription. Participants also completed a short socio-demographic questionnaire. The discussion guide explored domains hypothesized to influence TLC-ART acceptability including:
The team also explored current experiences with ART and other factors influencing acceptability. Analysis is ongoing.
The team gratefully acknowledge the generous collaboration of UW colleagues Drs. Graham and McClelland, as well as the participation of the patients and assistance with recruitment and administration from the expert clinic staff.
In the AIDS journal, the TLC-ART team reported that a dose of HIV drug combination, targeted to the residual virus in lymph nodes-exhibiting drug insufficiency, persisted with high levels over 2 weeks. Currently HIV patients take multiple pills daily and do not have drug levels high enough to clear the virus in the nodes. The results, improved lymph node drug levels over two weeks, was demonstrated in monkeys and will be published in the March 2017 issue of AIDS, one of the most respected HIV/AIDS journals. John Kraft, Lisa McConnachie, Josefin Koehn, Loren Kinman, Carol Collins, Danny Shen, Ann Collier and Rodney Ho lead the research team. The linked article is entitled, “Long-acting combination anti-HIV drug suspension enhances and sustains higher drug levels in lymph node cells than in blood cells and plasma”
A pre-print version of this article is available online
This study is sponsored by NIH Grant UM1 AI120176.
The University of Washington (UW) Population Health Initiative is a 25-year program which intends to help treat disease and afflictions to improve the health and well-being of the UW community. More information can be found through the link: http://www.washington.edu/president/populationhealth/
UW President Ana Mari Cauce and Provost Jerry Baldasty announced today the selection of the 30-member Executive Council for the University’s new Population Health Initiative. TLC-ART’s Dr. Jane Simoni has been appointed to be on the executive council of this program!
Dr. Jane Simoni is a licensed clinical psychologist specializing in the development and evaluation of health promotion interventions and a behavioral scientist for the TLC-ART program. Most of her research involves persons living with HIV/AIDS and other populations at risk for health disparities, including sexual and ethnic minorities.
original article: Executive Council selected for the UW’s Population Health Initiative
Sharon Nachman (IMPAACT Network Chair) and James McIntyre (IMPAACT Network Vice Chair) invited Dr. Rodney Ho (TLC-ART Principal Investigator) to give a 25-minute talk at the 2016 International Maternal Pediatric Adolescent AIDS Clinical Trials Network (IMPAACT) Annual Meeting on April 21st, 2016. Dr. Rodney Ho (Principal Investigator) presented at the 2016 IMPAACT meeting’s plenary session on Wednesday, June 15, 2016 in Arlington, VA, USA. He represented the program in a presentation entitled, “Targeted Long-Acting Combination Antiretroviral Therapy” and discussed overcoming drug insufficiency in lymphatic tissues and cells.
“The IMPAACT Network is a global collaboration of investigators, institutions, community representatives and other partners organized for the purpose of evaluating interventions to treat and prevent HIV infection and its consequences in infants, children, adolescents and pregnant/postpartum women through the conduct of high quality clinical trials.” (source: http://impaactnetwork.org/about-us/index.htm)
As noted in the invitation letter, “This meeting typically includes over 500 participants from around the world, including leading scientists, representatives from industry, government, and other research groups, and provides unique opportunities to exchange ideas and information regarding cutting edge research in HIV treatment and prevention as well as co-morbidities such as tuberculosis, particularly in pediatric populations and pregnant and postpartum women.” More information on IMPAACT and its partnering organization, the HIV Prevention Trials Network (HPTN) can be found through the embedded links.
Dr. Rodney Ho (TLC-ART principal investigator) presented at the 2016 BioEngage Symposium: Imaging Tools Delivering on the Promise of Precision Cancer Treatment on May 25th, 2016 at the University of Washington Foege Hall Conference Room in Seattle, WA. The University of Washington Bioengineering Department invited Dr. Ho to speak for 15 minutes on, “High-resolution MRI and IR diagnostic imaging enabled by a novel biocompatible & biodegradable nano-platform,” during an hour long session chaired by Matt O’Donnell. This biodegradable, nano-platform supports TLC-ART as well as other related research programs that Dr. Ho is involved in. Specifically for TLC-ART, it allows for high-resolution, lymphatic and blood vessel MRI imaging. This imaging technique, as noted in Dr. Ho’s presentation, improves diagnostic functionality through greater contrast, higher resolutions, longer image acquisition times and is safer with lower dose requirements compared to more commonly used imaging techniques.
The purpose of BioEngage Symposium is to, “…explore new and existing imaging technologies helping guide surgeries, drive interventional procedures, and optimize personalized therapeutics. Faculty, post-docs, and students at all levels at UW…join[ed] with researchers from industry and selected clinicians to discuss current trends in the field, learn about each other’s research expertise, and promote potential research collaborations, development/translation projects, student projects, internships, and targeted recruiting.” More information on this symposium can be found through the linked source: http://uwbioengage.wix.com/symposium#!about/fun5o
Dr. Rodney Ho delivered an invited presentation at the Long-Acting/Extended Release (LA/ER) Antiretroviral Drugs Workshop at the Westin Copley Plaza Hotel in Boston, MA on February 21st, 2016. His speech, entitled “Lymphatic Targeting of combination HIV drugs– TLC ART” and sponsored by The Long-Acting/Extended Release Antiretroviral Resource Program (LEAP), covers new strategies proven to provide long-acting behaviors and improve drug acceptance in the lymphatics (Presentation: Rodney Ho: Lymphatic Targeting – TLC ART). “…lectures, conferences and workshops…help move the field of LA/ER drugs forward.” (source: http://longactinghiv.org/resource-categories/conference-and-workshop-proceedings).
The LEAP program is publicly funded by the National Institute of Health (NIH) and serves, “…to support established investigators and encourage new investigators entering this field by 1) providing access to a centralized group of subject matter experts, 2) establishing a communications and data hub for dissemination of important results and resources, and 3) developing a modeling and simulation core to aid investigators in assigning priority to drugs and formulations in development.” (source: http://longactinghiv.org/content/who-we-are). For more information, click through the embedded links.
Pharmaceutics Professor Rodney Ho
An interdisciplinary team led by Professors Rodney JY Ho of the UW School of Pharmacy and Ann Collier of the UW School of Medicine received $14M from the National Institutes of Health (NIH) to develop a long-lasting (7-day) therapy for HIV. The two co-Principal Investigators and the team will develop innovative treatments to overcome limitations of current oral drug therapies. The UM1 NIH grant is one of the first that the NIH recently awarded as part of its key initiatives to address unmet medical need in HIV/AIDS. Dr. Ho was a recipient of the Milo Gibaldi Endowed Professorship, which funded part of the research in developing this program.
The HIV virus is a formidable opponent for researchers. It constantly mutates, making it harder to create drugs for prevention and treatment. HIV lives not only in the blood stream, but in tissues, making it hard to eradicate from the body. It is possible to greatly reduce the presence of the virus in the blood, but finding a way to reduce its presence in tissues has been significantly more challenging.
While current drug combination therapies have significantly improved the length and quality of patient life, they present two main challenges: 1) they must be taken one or more times a day lifelong; and 2) they are not as effective at removing residual viruses from tissues.
Taking treatment as prescribed, known as medication adherence, can be a challenge for many patients. A 2004 study showed that while over 80 percent of HIV patients take their medications as prescribed, two-thirds of older patients who missed a dose said they ‘simply forgot.’ As former surgeon general C. Everett Koop famously said, “Drugs don’t work in patients who don’t take them.”
Dr. Ann Collier of UW Medicine
With the global, U.S. and Washington state goals to eliminate HIV transmission and end the HIV/AIDS epidemic, achieving treatment success for all infected persons is an important component. If adherence is poor, HIV can develop resistance to antiretroviral drugs, which in turn means that higher drug levels or different drugs are needed. Insufficient drug levels may also occur in some tissues. These issues may lead to treatment failure with subsequent progression of HIV to AIDS.
The UW’s new Targeted Long-Acting Combination Antiretroviral Therapy (TLC-ART) Program is an innovative, translational medicine research designed to leverage existing knowledge and a world-class interdisciplinary team of academic, NIH, and industry researchers to deliver new, safe, stable, scalable, and tolerable antiretroviral combination treatments for HIV infection.
Based on the discovery at UW that some antiretroviral medications taken by mouth do not provide sufficient drug exposure and are linked to residual HIV replication, a team led by Drs. Ho and Collier developed the TLC-ART Program that has now received support from the NIH.
The Program has multiple projects designed to interact in a coordinated and collaborative way with the focused goal of producing injectable drug combinations that will achieve effective drug levels lasting more than seven days. In addition to laboratory-based research, the Program incorporates innovative behavioral science studies that will gather information from potential users of long-acting antiretroviral treatments.
Long-acting antiretroviral treatment would provide a new option to help improve patient adherence, especially for those with adherence challenges. With the ability to direct drugs to lymphoid tissue and potentially overcome drug insufficiency in tissues, this research may also help eliminate residual virus.
“We started out very early on in the battle against HIV/AIDS to find a treatment or a vaccine, but it continued to elude us. It is more than likely that a systems approach using innovative drug targeting to cell and tissue along with boosting of patients’ immune system may lead to a cure,” said Dr. Ho. “We cannot do this work alone and I look forward to collaborating with our partners and especially Dr. Collier, who has over 25 years of clinical trials experience.”
“Collaboration among researchers with many different types of expertise and with the affected community has led to major advances in treatment for HIV and I am optimistic that the TLC-ART Program will continue to advance treatment options,” said Dr. Collier.
The TLC-ART Program has investigators from the UW Schools of Pharmacy and Medicine, Fred Hutch, Seattle Children’s Research Institute as well as Harborview Medical Center, and will leverage resources of the UW/Fred Hutch Center for AIDS Research and the UW Institute of Translational Health Sciences.
Research reported in this press release was supported by National Institute of Allergy and Infectious Diseases (NIAID) UM1 large-scale research program of the National Institutes of Health under award number UM1AI120176. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.
A version of this story also appeared in UW Health Science NewsBeat