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Press Releases and Announcements
On August 26, the ACTG announced the positive data for the monoclonal antibody combination therapy BRII-196/BRII-198 from the ACTIV-2 study. Read more HERE. Congratulations to the team on this important accomplishment!

Want to become a member of one of the many ACTG committees? ACTG committee nominations are now open for general membership positions. The application and eligibility requirements can be found here. The deadline for nominations is September 20. 
 
Publications
 
Initiating ART Is Associated With Decreased Fat Density in People Living With HIV
 
Fat changes are common in people living with HIV. When people gain fat, their bodies can either make new fat cells (hyperplasia), or their existing fat cells can take up more fat (hypertrophy). Hypertrophy results in fat cells becoming less dense, and is associated with inflammation, poorer fat cell function, and metabolic diseases such as diabetes and cardiovascular disease. This study assessed changes in fat density after antiretroviral therapy (ART) initiation among participants enrolled in A5260s, in which ART-naïve people living with HIV were randomized to start tenofovir-emtricitabine plus either ritonavir-boosted atazanavir, ritonavir-boosted darunavir, or raltegravir. Fat in and around the organs (visceral fat) and underneath the skin (subcutaneous fat) were measured using abdominal CT scans. Of the 228 participants, 89 percent were male and 44 percent were white non-Hispanic. The median age was 36 years old, baseline HIV-1 RNA was 4.6 log10 copies/mL, and CD4+ T-cell count was 344 cells/μL. Over 96 weeks, visceral and subcutaneous fat cells became less dense on all three ART regimens, suggesting that people living with HIV who initiate ART experience fat cell hypertrophy. Following virologic suppression, lower visceral and subcutaneous fat density were associated with more inflammation, more insulin resistance (a precursor to diabetes), and worse cholesterol, independent of how much fat the person had, suggesting that changes in fat density with ART may contribute to adverse health outcomes in people living with HIV.


Debroy P, Lake JE, Moser C, Olefsky M, Erlandson KM, Scherzinger A, Stein JH, Currier JS, Brown TT, McComsey GA. Antiretroviral Therapy Initiation Is Associated With Decreased Visceral and Subcutaneous Adipose Tissue Density in People Living With Human Immunodeficiency Virus. Clin Infect Dis. 2021 Mar 15;72(6):979-986. doi: 10.1093/cid/ciaa196. PMID: 32107532; PMCID: PMC7958728.

Early Chemotherapy Plus ART Prevents Early Worsening of AIDS-related Kaposi Sarcoma: A5264/AMC-067

People with mild-to-moderate AIDS-related Kaposi sarcoma (AIDS-KS) often experience improvements after starting ART, but in some people, it worsens within a short period. This deterioration may reflect either a natural course of AIDS-KS worsening while on ART or what is referred to as KS immune reconstitution inflammatory syndrome (KS-IRIS), a paradoxical worsening of the AIDS-KS despite ART. There is little research on how well people with early worsening of AIDS-KS (including those who have had KS-IRIS) fare during treatment for HIV and AIDS-KS.

A5264/AMC-067 evaluated the efficacy of etoposide, a type of chemotherapy used to treat AIDS-KS, and assessed early worsening (defined as worsening that occurred within three months of starting ART) of AIDS-KS after starting ART. Participants with mild-to-moderate AIDS-KS initiated ART together with etoposide (“immediate etoposide” group) or initiated ART alone and waited to start etoposide if their AIDS-KS worsened (“as-needed etoposide” group).
 
A5264 found that early worsening of AIDS-KS was common: out of 190 people in the trial, 50 (27%) had early worsening of AIDS-KS, including 28 of whom were confirmed to have had KS-IRIS. Early worsening of AIDS-KS and KS-IRIS occurred more frequently in people who were in the as-needed etoposide group than in the immediate etoposide group. In addition, people who had early worsening of AIDS-KS were worse off in terms of AIDS-KS after 48 weeks and 96 weeks of follow up in the study than people who did not have early worsening of AIDS-KS. Having early worsening of AIDS-KS was a predictor of poor clinical outcomes during treatment.

These findings support starting chemotherapy and ART together to treat mild-to-moderate AIDS-KS but the decision must consider the added toxicities of the chemotherapy.


Nyirenda M, Ngongondo M, Kang M, Umbleja T, Krown SE, Godfrey C, Samaneka W, Mngqibisa R, Hoagland B, Mwelase N, Caruso S, Martinez-Maza O, Dittmer DP, Borok M, Hosseinipour MC, Campbell TB; A5264/AMC-067 team. Early Progression and Immune Reconstitution Inflammatory Syndrome During Treatment of Mild-To-Moderate Kaposi Sarcoma in Sub-Saharan Africa and South America: Incidence, Long-Term Outcomes, and Effects of Early Chemotherapy. J Acquir Immune Defic Syndr. 2020 Aug 1;84(4):422-429. doi: 10.1097/QAI.0000000000002361. PMID: 32265361; PMCID: PMC7365262.

Risk Factors for Weight Gain Following Switch to Integrase Inhibitor-Based Antiretroviral Therapy

Some people with HIV have gained more weight than expected with integrase strand transfer inhibitor (INSTI)- or tenofovir alafenamide (TAF)-based ART regimens. This weight gain is especially apparent among Black people and women, suggesting that it may be due, in part, to genetic factors. Mitochondrial haplogroup  (groups of genes from a common ancestor) are linked to migration patterns (i.e., European, African ancestry) and are associated with some disease risks in other populations. This study used existing data on mitochondrial haplogroups and weight change after switching to INSTI with or without TAF from A5001 and A5322 studies. Two hundred and ninety-one participants switched to INSTI and had haplogroup data. Although the numbers of participants within each group were small, the study did find that certain haplogroups were associated with significantly greater weight gain. Interestingly, in one of the African haplogroups, this weight-gain was most apparent in the participants also switching to TAF. Although these findings need to be confirmed in larger, more diverse populations, ultimately haplogroup data could help clinicians identify those individuals who would be at highest risk for weight gain with a switch to INSTI and/or TAF, and could use that information to determine the most appropriate treatment regimen.


Lake JE, Wu K, Bares SH, Debroy P, Godfrey C, Koethe JR, McComsey GA, Palella FJ, Tassiopoulos K, Erlandson KM. Risk Factors for Weight Gain Following Switch to Integrase Inhibitor-Based Antiretroviral Therapy. Clin Infect Dis. 2020 Dec 3;71(9):e471-e477. doi: 10.1093/cid/ciaa177. PMID: 32099991; PMCID: PMC7713693.

 
 
National HIV/AIDS and Aging Awareness Day
ACTG and National HIV/AIDS and Aging Awareness Day
By Carl Fichtenbaum, M.D., Cincinnati CRS

Diseases linked to aging (including cardiovascular disease, diabetes, hypertension, dyslipidemia, chronic kidney disease, obesity, liver disease, cognitive impairment, and impaired physical function) appear to occur at higher rates in people living with HIV compared to the general population. The ACTG is committed to investigating the interplay between aging and HIV and has prioritized efforts to identify interventions that will help prevent, treat, and slow conditions associated with aging in people living with HIV.
 
In honor of National HIV/AIDS and Aging Awareness Day, the ACTG is highlighting several research areas of focus around aging:
  • Because bone strength declines as we age and because this process can be accelerated by HIV and antiretroviral therapy (ART), the ACTG is undertaking research into bone disease.
    • A5142 and A5303 both demonstrated that bone strength loss was greater with tenofovir disoproxil fumarate.
    • A5280 showed that starting HIV therapy at the same time as vitamin D prevented some loss in bone strength.
  • The ACTG is a leader in increasing knowledge about the ways that ART affects the development of cardiovascular disease.
    • A5260s compared cardiovascular markers, body composition, and immune activation among ART-naïve participants in A5257 who were randomized to receive atazanavir/ritonavir, darunavir, or raltegravir and highlighted the potential effect of gut dysfunction on metabolic comorbidities in HIV.
    • A5322 or HAILO is examining the relationship between HIV therapy and frailty
    • A5332/A5333s/A5361s (REPRIEVE and its sub-studies) are evaluating the role of statins in preventing cardiovascular disease and the development of frailty in people living with HIV. 
 
These are just several examples of the research that the ACTG is undertaking to support the needs of people who are aging with HIV. The organization will continue to advance research into the ways that HIV affects aging, in the hopes of identifying new ways to slow the onset of these comorbidities, lower their impact, and identify treatments that will improve the lives of people who are aging with HIV.


Aging with HIV: Shifting the Narrative
By Kristine Erlandson, M.D., University of Colorado Hospital CRS

Over the past thirty years, HIV has been transformed from a near uniformly fatal virus to a chronic condition, driven in part by the tremendous efforts of advocates, dedication of scientists, and determination of providers and people living with HIV. Those who survived the early days of HIV are now living well into their 50s, 60s, 70s, and beyond. The Centers for Disease Control and Prevention estimate that nearly 50 percent of people living with HIV in the United States are aged 50 years and older. 
 
The healthcare of older adults living with HIV can be very complex and difficult to navigate. They experience a greater burden of comorbidities and medications than many of their peers who are aging without HIV. Adherence to the screening and management recommendations for the general population, in addition to HIV-specific guidelines, has become overwhelming for providers and people living with HIV.  Data from HIV cohorts and feedback from the HIV community suggest that the current model of care is not meeting the needs of older adults living with HIV. 
 
Rather than a singular focus on how we can most effectively suppress HIV, the care of older adults living with HIV needs to shift to improve the quality of life and health span (or years of healthy living) of older adults living with HIV.  This change in focus will require adapting the current model of HIV clinical care and research approach. The “6Ms” provide a framework for prioritizing clinical care and research of older adults living with HIV. They emphasize:
1) Multi-complexity of care of older adults living with HIV
2) Medications
3) Mind (cognitive function and mood)
4) Mobility through physical activity and rehabilitation (and fall prevention)
5) Modifiable aspects of care such as physical activity, diet, or reduction in substance use
6) What matters most  
 
As those with HIV continue to grow older, many unanswered questions exist: what is the safest and most effective ART for older adults? What are the best treatments/interventions for decreasing frailty, falls, and managing multiple problems in older adults living with HIV? Do senolytics (anti-aging) drugs work and are they safe? Should screening and treatments differ for older adults living with HIV compared to the general population? Do geriatric clinics or consultations decrease costs and improve quality of life in older adults living with HIV?

As we’ve all learned over the last year, we can accomplish great things together. With input from the community, the HIV and aging agenda can shift to address the most relevant issues of those who have paved the way for HIV.
SPOTLIGHTS
Investigator Spotlight
Karine Dubé, DrPH, MPhil, Chapel Hill CRS


Karine Dubé, DrPH, MPhil is a socio-behavioral researcher and experienced clinical research manager with more than 15 years of experience in infectious disease-related work, including HIV prevention, treatment, and cure-related research. Her current research focuses on integrating socio-behavioral sciences as part of ongoing HIV cure trials in the United States and South Africa. Dr. Dubé bridges biomedical research, socio-behavioral sciences, ethics, patient and community engagement, and public health in infectious diseases research. She has worked in nine African countries, including Mozambique, South Africa, Zambia, Kenya, Uganda, Tanzania, Liberia, Benin, and Burkina Faso, and has managed large research consortia.
 
Born and raised in Canada, Dr. Dubé came to the United States in 1999. After completing her Bachelors’ degree in International Studies at the University of North Carolina (UNC) Chapel Hill, she studied International Development and Global Health at Oxford University in England in 2005. She completed her DrPH at UNC Chapel Hill in 2016. She worked with FHI 360 (formerly Family Health International and FHI) and the U.S. Military HIV Research Program (MHRP) to build clinical research capacity for HIV prevention trials. She also served as research program manager for the Collaboratory of AIDS Researchers for Eradication (CARE) at UNC Chapel Hill and helped build a CUREiculum (https://www.avac.org/cureiculum) to make HIV cure science accessible to the community and the HIV research field (under revision).
 
Dr. Dubé has been an active member of the ACTG since 2017, serving as socio-behavioral scientist on HIV cure research protocols. She is a member of the Behavioral Science Subcommittee (BSS), led by Dr. Jane Simoni and Dr. Ivan Balán. With Dr. John Sauceda (UCSF), she was recently awarded an R01 from the National Institute of Mental Health to investigate psychosocial experiences of HIV cure trial participants undergoing extended analytical treatment interruptions within the ACTG and at the University of California at San Francisco. Dr. Dubé is also a co-investigator on the BEAT-HIV Collaboratory and volunteers for several community advisory boards focused on HIV cure research.

Dr. Dubé is leading the socio-behavioral and ethics component of the Last Gift program (http://lastgift.ucsd.edu/) at UCSD (whose principal investigators are fellow ACTG members: Drs. Davey Smith and Sara Gianella), which enrolls people living with HIV at the end of life to investigate HIV reservoir dynamics in deep body compartments. In addition to the ACTG, she also closely collaborates with the amfAR Institute for HIV Cure Research, BEAT-HIV Collaboratory (Wistar Institute), the defeatHIV Collaboratory (Fred Hutch), and the City of Hope/California Institute of Regenerative Medicine (CIRM) and the Ragon Institute of MGH, Harvard and MIT.

Dr. Dubé adopts a lifespan approach to her research, engaging diverse youth in HIV cure research, as well as aging and terminally ill people living with HIV. In addition, Dr. Dubé’s research aims to reduce disparities in access to HIV clinical trials – including increasing the engagement of women, racial and ethnic, and sexual and gender minorities in research. Dr. Dubé led an empirical ethics supplement to investigate groundbreaking areas of HIV cure research, such as interventional HIV cure research at the end of life, cell and gene therapy towards a global HIV cure, combinatorial approaches towards an HIV cure, and partner protection measures during extended analytical treatment interruptions. In 2018 – 2019, Dr. Dubé helped define research priorities related to the behavioral and social sciences of HIV cure research (https://pubmed.ncbi.nlm.nih.gov/31665568/). Dr. Dubé is also part of the 2021 International AIDS Society (IAS) Global Scientific Strategy team and the IAS Research-for-Cure Academy, led by Drs. Steven Deeks and Sharon Lewin.
 
Dr. Dube remains incredibly passionate about giving patients and communities a voice in HIV cure research. She is most grateful to her HIV research mentors, Drs. David Wohl, Mallory Johnson, Tor Neilands, Davey Smith, Sara Gianella, Judy Auerbach, Jane Simoni, Brandon Brown, Jeremy Sugarman, Steve Deeks, and Michael Peluso among others.
 
In her spare time, she loves to travel to beautiful places on planet Earth. Her recent destinations have included Iceland and New Zealand, which she most highly recommends.
 
Site Spotlight
Greensboro CRS, Greensboro, North Carolina, USA


The Greensboro CRS is located in Greensboro, North Carolina and has been part of the ACTG network since the early 1990s. The site is actively conducting seven ACTG clinical trials: A5321, A5322, A5332, A5379, A5380, and A5391 as well as HPTN 083 and several industry-sponsored studies. They are nearing the completion of A5322, which addresses issues of aging, HIV infection, and inflammation and scheduling last visits for participants who have been part of the study for at least seven years.

The Greensboro CRS team is small but mighty, consisting of seven key players. The site’s PI, Cornelius “Kees” Van Dam, M.D., has been their fierce leader for 10 years. In the last month, Kelly Phillips, PA-C, joined the team as a new sub-investigator/research clinic manager, bringing with her 10 years of research experience. For more than 20 years, Marlene Allen has been the site’s regulatory and laboratory manager. She maintains a near flawless laboratory and meticulous records. The CRS coordinator, Kim Epperson, R.N., has been wearing multiple research hats and managing the CRS seamlessly since 2004. In 2017, Lisa Dasnoit, R.N., rejoined the team as a research nurse. Samira Dixon and Luwam Debru joined the CRS almost a year ago as research assistants and are flourishing in their roles, becoming vital team members. The CRS hopes to continue to grow and learn as a team.

Throughout the years, the Greensboro CRS has created many fond memories with their participants and community members. Their journey features many stories, some of happiness and some of profound sadness and loss.

“The Greensboro CRS feels that working with the ACTG has been especially meaningful through our relationships with participants over the years, as we provide a safe medical home and alternative treatment modalities for those who face treatment barriers and serve as the face of hope to those who at one time thought HIV was unmanageable,” says Dr. Van Dam.

The site is honored to have contributed to transforming the treatment of this once untreatable and universally fatal virus. The site has witnessed the era of HAART, of single-tablet regimens, and now long-acting antivirals for the treatment and prevention of HIV. The Greensboro CRS knows only too well that HIV continues to carry an enormous stigma. Furthermore, the site recognizes the specter of inequality that accompanies this virus, including classism, racism, homophobia, and xenophobia. The site recognizes the fight against inequality as an important element of their work.

Moving forward, the site will continue to pursue the most important milestones for the ACTG  -- working consistently to advance HIV treatment and prevention research to improve HIV-related health outcomes; finding a cure; and allying themselves in the fight against HIV stigma and inequity.
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