ACTG Newsletter - June 2022

HIV Long Term Survivors Awareness Day

ACTG Salutes the Efforts of Long-Term Survivors

Over the past 40 years, having an HIV diagnosis has transitioned from a severe, life-threatening disease to a chronic medical condition that, in some cases, can be managed by bimonthly injections. For many, successful therapy confers a lifespan that now approaches that of people without HIV. This inspirational progress could have only been accomplished with the dedication and struggle of the global community of people living with HIV. In the setting of unprecedented and tragic losses of friends, family, lovers, and children to HIV, people living with HIV fearlessly spoke out against discrimination; volunteered to take experimental therapies with toxic side effects; and demanded their HIV providers treat them as whole people who deserve to be fully involved in their medical decisions. People living with HIV and their allies also came together to form chosen families so no one would have to die alone. Their advocacy resulted in the Denver Principles and other recommendations that have forever changed the practice of medicine. Advocacy also changed the medical research field, resulting in accelerated access to life-saving medication and other advancements that have benefitted people living with HIV. These changes have been so valuable that other fields have adopted them as a guide.

On HIV Long-Term Survivor Awareness Day, we honor the sacrifices and fierce spirit that led to real change. We acknowledge the trauma of heartbreaking losses that to this day continue to impact so many lives. Long-term survivors include both people living with HIV and allies without HIV who are diverse in race, gender, and age but share these unique experiences.

We also celebrate long-term survivors who refuse to become the forgotten majority (San Francisco Principles 2020) and continue to advocate for their voice in advancing HIV research, care, and policy beyond 90-90-90. Because they survived, many long-term survivors are now older adults (50+ years) who demand research and programs that promote healthy aging, preserve independence, and enhance quality-of-life. They courageously combat the intersecting impact of HIV stigma, ageism, racism, sexism and unrelentingly insist on improvements in the diagnosis and management of the non-AIDS conditions and geriatric syndromes that continue to occur in people living with HIV, including cardiovascular disease, metabolic syndromes, frailty, and dementia. They point the way toward the necessity of expanding the provision of essential services (e.g., mental healthcare, poverty, transportation, nutrition, housing) and the development of opportunities for socialization beyond the dating scene.

On this Long-Term Survivors Awareness Day, we as allies, HIV clinicians, and researchers pledge to withhold “Nothing about you, without you” by continuing to listen and amplify your voices.

Maile Young Karris expresses deep gratitude for her Uncle’s New York chosen family: I never knew you, but you were there when we couldn’t be and I’m eternally grateful.

Scott Letendre honors the memory of his many friends and patients who left us before they could benefit from antiretroviral therapy as well as those who continue to enrich his life today.

Orbit Clanton, long-term survivor for 40 years gives thanks to all the other long-term survivors who despite the many challenges over the decades continue to advance the effort to Ending the HIV Epidemic.

- Orbit Clanton, Maile Young Karris, MD, and Scott Letendre, MD

Many Challenges Remain for HIV Long-Term Survivors

HIV Long Term Survivor’s Awareness Day is important because many elderly people living with HIV face enormous problems of health decline that can be life threatening, including the inability to function normally mentally and physically. Indeed, I know too many elderly people living with HIV over 65 or 70 with physical and mental disability, who cannot walk well, cannot shop for food, who struggle to physically function and get around, and who suffer cognitive mental decline.

It is crucial to raise awareness about this group in order to bring full attention to this problem to the ACTG research community, to federal authorities and leaders at NIAID and the OAR, HHS, CDC, ONAP, and HRSA. It’s important for leaders at these agencies to get a real picture of what is going on with these elderly people living with HIV. I think they do not fully grasp the real-life situations and conditions these people living with HIV are experiencing. We must make it real to them. We need to make it clear how important it is that the HIV research agenda reflect the needs of these folks. Not only do people living with HIV over 50 represent more than 50 percent of the US HIV population right now but by 2030 (in only eight years) that number is expected to grow to 75 percent.

Even more important is the number of people living with HIV right now over 60. In 2018, the CDC reported that 200,000 people living with HIV in the US were over 60, a number that is expected to double by 2030. Right now in New York and San Francisco, 35 percent are over 60. They do not get the care they need as the HIV healthcare system is not configured to meet their needs. Our current HIV healthcare system is designed to focus on viral suppression. That is no longer what the complete focus should be. The system imposes a 20-minute medical visit with HIV doctors or specialists; this too does not meet the needs of the elderly people living with HIV with complex multimorbidity and mental and physical disabilities who for sure need more attention and time. Mental health services and physical therapy are all too often very inaccessible and difficult to secure. Navigating the healthcare system for disabled or impaired elderly people living with HIV is a very difficult challenge. We need to reconfigure the HIV care system to be patient-centered and meet the needs of the majority of people living with HIV. We need a research agenda that focuses on their needs. We need a mechanism whereby we can implement research studies that address real-world clinical needs for the aging and elderly population. We need a “fast-track” mechanism to get these studies funded, designed, and implemented quickly.

Furthermore, women and HIV has been a neglected problem since the beginning of the epidemic. Women living with HIV have more inflammation and immune activation, suffer higher rates of comorbidities, and appear to experience worse mental and physical function than men living with HIV. We need care and research that reflects this inequity and provides women living with HIV with the confidence that we are recognizing their health problems and are in fact addressing them fairly and equitably.

- Jules Levin, CAB member

New Way to Measure Low Amounts of HIV Correlates Well with Other Methods

Researchers need better laboratory tools to measure the effects of cure strategies on the HIV reservoir. The new intact proviral DNA assay (IPDA) costs less than a commonly used measure of the HIV reservoir called the quantitative viral outgrowth assay (QVOA), and unlike the QVOA, the IPDA does not require a large number of cells. Proviruses refer to HIV that have incorporated themselves into a person’s DNA. The reason intact HIV proviruses are important is that they can lead to HIV rebound when antiretroviral therapy (ART) is stopped, whereas defective HIV proviruses do not.

The aim of the ACTG HIV Reservoirs Cohort study was to see how IPDA corresponds with other ways to measure low amounts of HIV, using blood samples. We used samples from 25 people living with HIV who were taking long-term HIV treatment and participated in A5341s, the sub-study of the ACTG HIV Reservoirs Cohort study A5321. Like recent findings by other research groups, we found a strong positive correlation between IPDA and QVOA; participants who had higher levels of intact HIV proviruses tended to also have higher HIV levels by QVOA. There was also a positive correlation between IPDA and assays measuring total HIV in cells. These results add to our knowledge about the IPDA, which has been an important addition to HIV cure research since it was first published in 2019.

This advance was made possible by the study volunteers, some with more than 20 years of follow-up in A5321 and prior ACTG studies, and in particular the sub-study participants who contributed additional blood and tissue samples. The strong association between IPDA and other measures of HIV supports the use of this new assay in cure-related research studies.

Bosch RJ, Gandhi RT, Mar H, et al. Associations between multiple measures of HIV-1 persistence on suppressive antiretroviral therapy [published online ahead of print, 2022 Feb 4]. J Infect Dis. 2022;jiac030. doi:10.1093/infdis/jiac030

Reduced Inflammation with ART is Associated with Improved Arterial Health in PWH

The purpose of this study was to investigate novel grayscale ultrasound characteristics (such as brightness, contrast, and signal variation) of the carotid and brachial arteries that previously have been shown to predict future cardiovascular disease events in people living with HIV before and after starting initial ART.

A5260s performed ultrasound image analyses of the common carotid and brachial arteries prior to and after receipt of one of three randomly allocated ART regimens. Researchers measured arterial wall echogenicity (brightness), contrast, and entropy (a measure of signal variation). These measures and their changes were compared to cardiovascular disease risk factors, measures of HIV disease severity, and inflammatory biomarkers before and after ART.

Among 201 ART-naïve people living with HIV, higher systolic blood pressure, higher body-mass index, lower CD4+ T-cells, and non-Hispanic white race/ethnicity were associated independently with lower carotid artery echogencity. Changes in each carotid artery grayscale measure from baseline to 144 weeks correlated with changes in soluble CD163, a marker of macrophage activation. Within the atazanavir/ritonavir arm, carotid artery entropy increased but no other within-arm changes in grayscale measures were seen. Correlations of brachial artery grayscale measures were weaker.

We concluded that in ART-naïve people living with HIV, carotid artery grayscale ultrasound measures were associated with cardiovascular disease risk factors and lower echogencity was associated with lower CD4+ T-cells. Reductions in sCD163 with initial ART were associated with improvements in all three carotid artery grayscale measures, suggesting that reductions in macrophage activation with ART initiation may lead to less arterial injury. These findings add to the body of literature suggesting that reduced inflammation with ART is associated with improved arterial health in people living with HIV.

Hughey, C. M., Vuong, B. W., Ribaudo, H. B., Mitchell, C. C., Korcarz, C. E., Hodis, H. N., ... & Stein, J. H. (2022). Grayscale Ultrasound Texture Features of Carotid and Brachial Arteries in People With HIV Infection Before and After Antiretroviral Therapy. Journal of the American Heart Association, 11(5), e024142.

Investigator Spotlight

Katharine "Katie" Bar, MD, Penn Therapeutics CRS, Philadelphia, Pennsylvania

Katie Bar is an Infectious Disease physician, clinical trialist, and physician-scientist who studies the basic mechanisms and translational impact of virus transmission, pathogenesis, and persistence of HIV-1 and other viral pathogens.

Much of her recent work focuses on the translation of basic science discovery through preclinical testing in the nonhuman primate (NHP) model and human clinical trials. Her lab currently has three main areas of interest: characterizing the viral dynamics and host immune responses during ART suppression and analytical treatment interruption (ATI); developing NHP models that faithfully recapitulate HIV-1 latency and rebound following ATI; and determining the mechanisms and effects of broadly neutralizing antibody (bNAb)-based interventions.

Katie is an investigator and holds leadership positions within the ACTG and HVTN. She is currently the vice chair of the ACTG Cure TSG and a member of the HVTN Concept Committee, and serves as a chair or investigator on several studies in each network. Outside of work, Katie is kept busy by her three not-yet-completely feral school-age children. When they can tolerate her, she enjoys time with her husband coaching their soccer, basketball, and softball/baseball teams.

Chapel Hill CRS, Chapel Hill, North Carolina, USA

The Chapel Hill CRS, originally established in 2005, currently participates in eleven ACTG studies and looks forward to contributing to as many ACTG trials as they can. COVID-19 significantly diverted their efforts over the last two years and they have been extremely grateful to re-dedicate their efforts to the ACTG agenda. In the last few weeks, the site enrolled a woman for A5357 (“CAB LA+VRC07-523LS for HIV Suppression”) and re-initiated screening for A5359 (The LATITUDE Study) with upcoming enrollments planned.

The site has been fortunate to have a cadre of long term staff members that work alongside some of their newest team members. They have a large group made up of nurse coordinators, research specialists, research assistants, data staff, regulatory and lab members, as well as their investigators. The site’s CRS coordinator position was vacant for a short time earlier this year and they recently filled it with two long term team members that have a combination of nearly 25 years of experience at the site and will be sharing responsibilities. The site team works very hard to foster a sense of family among the staff while remembering why their work is important.

If you look at the HIV prevalence maps in the United States, the Chapel Hill CRS sits in one of the areas that shows up as the darkest shade. The site staff views this as their responsibility to bring ACTG’s research to the communities that are most affected. A few years ago, at the Annual ACTG Meeting in Washington, DC, a group of the site staff were out at a restaurant for lunch on the patio. A gentleman walked up to the group and asked about their nametags as he noticed the HIV awareness ribbons on them. The group explained that they were in town for a conference and about the work of the ACTG. The gentleman shared that he had lost his partner to AIDS and thanked the group profusely for their work. In that moment, it was a sobering reminder of how important the work is and why they were all there.

The Chapel Hill CRS is excited to see the ACTG include more and more trials aimed towards long acting suppression off daily therapy and to advance research in the cure field. Their participants are excited to see this as well and the site staff is grateful for the opportunities to educate them about this side of research.

CAB Member Spotlight

Charles Adams, GCAB Representative, University of California, San Francisco HIV/AIDS CRS

Charles Adams is 63 years old and a 38-year HIV survivor and long-term advocate for the underserved in the HIV/AIDS community. Currently Charles is the GCAB Rep for the University of California San Francisco CRS. Charles joined the CAB at UCSF in 2015. Prior to that, Charles was a member of the Stanford CRS from 2001-2013 until it was closed. Charles also volunteers at an HIV-specific Food Basket program, a nonprofit HIV/AIDS law office in SF, and is a member of the Ryan White HIV Community Council for San Francisco.

It has been a long journey to get to where Charles is at today. He became ill in November 1983 while serving in the US Army and spent 30 days in the base hospital. It did not take long for his labs lead to an assumption of being gay, which then led to dismissal from the service within six months. Moving back to Missouri, the realization hit that staying there would lead to a good chance of dying from a lack of care. Researching where HIV care was the best, he decided to move to California. Relocating to Palo Alto and gaining access to Medi-Cal and Social Security was a life changer. Stability in life allowed him the opportunity to start looking for ways to give back to the HIV community. Once the volunteering started, direct client services has always been what has kept him going.

Being a member of the Stanford/SF CABs and being able to learn about, review and give input on protocols has given him a great sense of empowerment. One of the biggest draws for the SF CAB is the amount of diversity within it and the great bank of knowledge that exist amongst its members. The majority of members are long-term survivors. Seeing the medical advancements in HIV/AIDS care due to the ATCG research has him given even more reason to stay on the CAB. “The CAB's influence on who gets to participate in research has been one of the best things to come from the past few years.”, says Charles. “Inclusion of more women, trans, and people of color would not have happened without the CAB's pushing for it. The CABs are a vital part of the ATCG. Looking at the ATCG today, research has led to great advancements in not just HIV care but also in the fields of Hepatitis, TB and even COVID-19. The HIV Cure is going to come from this research.”

What a long strange trip it has been on this life journey. Charles is grateful to be alive and able to be a long term advocate!!

ACTG Member Website Announcement

New features

There’s a new Accrual Alerts widget available for your dashboard (homepage). Studies with “Enrolling” status are listed in the new widget box with their current and projected enrollment totals along with red-highlighted alerts identifying potential accrual issues.

Remember, you can click on “Customize My Homepage” to manage your widgets.

Also, qualitative analysis information is now included in the accrual section of the study view page. It shows actual, site-anticipated, and target accrual rates, as well as alerts about the site reaching accrual/date projections.

And that’s not all…

You will discover a new Site-Study Accrual Information pop-up window by clicking the “View Site-Study Accrual Information” button within the Qualitative Analysis section.

Check it out!

Be sure to follow along for our new initiative, Fun Fact Friday. Every other Friday, we'll have a guest on our social media pages take over to talk about a topic they're passionate about! If you'd like to contribute, please reach out to the LOC at ACTGPublications@mednet.ucla.edu

Follow the ACTG on all of our social media accounts!

Like, comment, share, and retweet!

Facebook
Instagram
Twitter

Have content for posting? Tag @ACTGNetwork or email the LOC at ACTGPublications@mednet.ucla.edu.

NEWS TO SHARE?

Do you have interesting ACTG-related news to share? Has your site done something exceptional? What’s the latest news about your study? Do you have job postings or any other ACTG-related information? We want to know! Please submit your news to the LOC at ACTGPublications@mednet.ucla.edu