The ACTG congratulates the 2021 Tuberculosis Transformative Science Group Special Contributions Award recipients: Nishi Suryavanshi, PhD, from the Byramjee Jeejeebhoy Medical College CRS and Yvetot Joseph, MD, from the GHESKIO Institute of Infectious Diseases and Reproductive Health CRS. This award was developed to recognize the many site team members and investigators that go above and beyond to help implement TB Studies at their sites. The TB TSG recognized there are no current ACTG awards for these individuals and believe it is important to recognize their efforts. Congratulations, Drs. Suryavanshi and Joseph!!
Last month, the ACTG announced the initiation of A5355, a clinical trial studying a new CMV vaccine in adults with both HIV and CVM. Congratulations to the study team! Read more HERE.
The ACTG applauds the FDA approval of cabotegravir, the first long-acting injection to HIV and congratulates HPTN study leadership & ACTG investigators Raphael Landovitz, MD, Beatriz Grinzstejn, MD, PhD and Mina Hosseinipour, MD who each played leadership roles in these landmark HPTN trials, 083 and 084! The approval of this new HIV prevention option, an injection given once every two months, was based on the results of two large studies that enrolled men who have sex with men, transgender women, and cisgender women. Read more HERE.
High Rates of Coronary Artery Plaque Among People Living with HIV with Controlled Viremia: Results from the REPRIEVE Mechanistic Substudy (A5333s)
Myocardial infarction and other atherosclerotic cardiovascular disease (ASCVD) events occur 1.5 to 2 time more often among people living with HIV than in the general population, but the prevalence of ASCVD among people living with HIV is not well understood. In this analysis from the mechanistic sub-study of the REPRIEVE Trial, investigators performed cardiac CT scans to determine the prevalence and composition of coronary artery disease among 755 REPRIEVE participants. They then assessed the findings to determine associations with traditional risk factors and biomarkers of immune activation and vascular and systemic inflammation.
The median age of the participants in this cohort was 51 years. Sixteen percent were female, 35 percent were Black, and 97 percent had a plasma HIV viral load <400cp/mL. Overall, 49 percent showed evidence of atherosclerotic plaque in imaging, with significant plaque found even among participants who had the lowest ASCVD risk scores. Coronary artery plaque was more commonly detected among people who were older, male, White, had a family history of premature CVD, had hypertension, had elevated fasting glucose, and had higher LDL cholesterol levels. Markers of immune activation and vascular inflammation were also higher in people with detectable plaque. These data confirm that people living with HIV, including those with well-controlled viremia, have a significant coronary artery plaque burden and that inflammation and immune activation are important drivers of this excess cardiovascular disease risk. REPRIEVE will determine whether pitavastatin can prevent cardiovascular events in this at-risk population and whether the effect is mediated through cholesterol lowering or the anti-inflammatory effects of statins that is important for patient populations with ongoing inflammation as has been described for PWH.
Evaluating Underlying Causes of Brain Impairment in People Who are Aging with HIV (NWCS 447)
NWCS 447 investigated a possible biological mechanism that may be an underlying factor causing brain impairment in people who are aging with HIV. This mechanism is triggered by persistent activation of a particular type of immune cell and results in accumulation of citrate and succinate in blood, reflecting a shift in cellular metabolism that may adversely affect the nervous system. Researchers evaluated the hypothesis that this metabolic shift would be linked to reduced walking speed and poorer performance on tests of memory and thinking. To do this, they measured citrate and succinate along with walking speed and memory in participants in the ACTG HAILO study who generously donated their time and samples to enable the research. The study included 957 people living with HIV who ranged in age between 40–78 years. On average, those with higher citrate and succinate levels had slower walking speeds and poorer memory than those with lower levels. This was particularly true for participants older than 60 years. These results confirmed the research hypothesis and suggest that this shift in metabolism may underpin age-related brain impairment. Medications, supplements, and other interventions that affect this metabolic shift may benefit walking speed and memory and thinking in people living with HIV.
HIV and its medications affect the metabolite and lipid profile of a person (NWCS 412)
While the field has made huge strides in HIV treatment, HIV and its treatment can cause metabolic complications and the distinct effects of HIV itself and antiretroviral therapy (ART) on specific metabolic pathways are not known. A5260s aimed to better understand whether HIV or HIV medications affect metabolism in the body and whether HIV or its treatment affects how the body handles metabolites, lipids, and sugar.
NWCS 412 utilized a novel technology (metabolomics and lipidomics) to assess several hundred metabolites and lipid subspecies that are involved in pathways of cholesterol, sugar control, and fat storage. The study measured these metabolites and lipid subspecies in HIV-seronegative individuals from the Multicenter AIDS Cohort Study/Women’s Interagency HIV Study Combined Cohort Study (MACS/WIHS) and in people living with HIV from the A5260s before and after initiating ART [tenofovir/emtricitabine plus atazanavir/ritonavir (ATV/r) or darunavir/ritonavir (DRV/r) or raltegravir (RAL)].
Compared to HIV-seronegative individuals, ART-naïve people living with HIV exhibited an altered metabolome that suggests increased lipid production and increased inflammation. This indicates that HIV itself can change metabolism in the body. People living with HIV taking RAL vs. ATV/r or DRV/r also had more inflammation and alterations in fat metabolism. These finds suggest that people living with HIV could benefit from closer monitoring for metabolic complications after starting HIV treatment, including newer HIV treatments. More studies are needed to further understand the cardiometabolic consequences of HIV and its treatment.
Kelly Dooley, MD, PhD, Johns Hopkins University CRS
Kelly Dooley, MD, PhD is a Professor of Medicine & Pharmacology at Johns Hopkins University with appointments in Clinical Pharmacology and Infectious Diseases. She grew up in West Virginia and went to Northwestern University for her undergraduate degree. After obtaining her undergraduate degree, she spent two years in the Peace Corps in Chad. She earned her medical degree at Duke University, an MPH at UNC Chapel Hill, and a PhD at the Bloomberg School of Public Health at Johns Hopkins. She maintains an active outpatient HIV clinical practice and attends on the inpatient HIV service as well. Her research focuses on tuberculosis (TB) therapeutics with an emphasis on clinical trials of TB drugs and HIV/TB co-treatment, as well as clinical pharmacology of TB and HIV drugs. She is lead investigator for trials of therapeutics for drug-sensitive and drug-resistant TB, TB meningitis, and TB prophylaxis and has been honored to be a consultant to WHO and a member of Guidelines Development Committees for TB therapeutics. Within the ACTG, Kelly is the Chair of the Tuberculosis Transformative Science Group (TB TSG), working alongside her close colleagues, Vidya Mave, Md, TM, MPH, from Pune, India, and Payam Nahid, MD, MPH, from University of California, San Francisco. She is looking forward to the opportunities through the TB TSG to improve treatment options for patients with TB, including those with HIV and those with hard-to-treat forms of TB that have few treatment options. She is also the Clinical Research Site (CRS) leader of the Baltimore /Johns Hopkins site, and is proud to be part of the wonderful and dedicated Positive Choices Unit team there (shout-out to Becky, Denise, Dezi, Taknesha, Tisha, Adaliah, Terri, Ilene, Lindsay, Pat, and Charlie). Kelly lives in Baltimore with her husband David (who is currently based in Benin), son Luke (who will be graduating from high school this year), and daughter Ava (who is a sophomore at University of Virginia), plus their German shepherd, Lola.
New Jersey Medical School CRS, Newark, New Jersey, USA
The New Jersey Medical School CRS, located in Newark, New Jersey, has been making contributions to the ACTG since 2014. The site is currently participating in seven ACTG clinical trials: A5359, A5379, A5332 (REPRIEVE), A5322 (HAILO), A5366, A5357, and A5128. In addition, the New Jersey Medical School CRS is co-located within the largest HIV treatment clinic in the state of New Jersey, providing care to approximately 1,600 people living with HIV.
The site is most proud of their amazing team of individuals who love to work together and serve their community. The team is led by women of color who each have more than 10 years of clinical research experience across NIH- and industry-sponsored trials. The site has a team of 25 diverse and dynamic individuals that serve administrative, clinical, and non-clinical research roles. Some of the team has been together for 10 years, while others have joined more recently due to the increased demand the COVID-19 pandemic placed on the department. The CRS collectively shares the belief that their community and participants are their number one priority. Increasing research literacy through education, support recruitment, and retention efforts ensures that individuals feel confident to make decisions about participating in clinical trials. This is at the core of all that the team does in a genuine way.
While the CRS has a great team, they also pride themselves on the real-world impact they make through the ACTG. Throughout their time as an ACTG site, they have offered cutting-edge research opportunities that have not only provided novel HIV treatment options, but also prevention and treatment of associated diseases as well as cure research. These studies have ensured that the site consistently connects, educates, and engages with the community and equip their community advisory board (CAB) with the knowledge and resources to be ambassadors to this special work. From a local, regional, national, and international lens, this work is transformative. It has changed people’s lives, both at the participant and team level and will continue to do so on the road to curing HIV. The site intentionally celebrates their ACTG participants in many ways, including sending birthday, holiday, and thank you cards and providing other milestone items. The New Jersey Medical School CRS also celebrates Participant Appreciation Day – something born out of ACTG’s Outreach, Recruitment, and Retention Subcommittee.
“Closing out HAILO has been one of the most bittersweet experiences,” said CRS leader, Shobha Swaminathan, MD. “These participants’ dedication and commitment to the study and to our team continues to be something I am amazed by. It has been about eight years since we’ve started the HAILO study plus the time on A5257 and A5001-what a truly remarkable group of people have become part of the Research With A Heart family!”
The site has been especially impressed by the ACTGs Global CAB and the structure that supports it. At a local level, the CTU Joint CAB and Site Leaders were instrumental in petitioning for protocol teams to provide summaries of the CAB draft feedback with responses back to the CABs and the sites.
You can keep up with the CRS on their social media channels: Facebook/Instagram: @researchwithaheart and Twitter: @RWAHNewark!
ACTG Member Website Announcement
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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 ACTG Communications Manager Aisha Patel.