ACTG Newsletter - May 2022

Press Releases and Announcements

Last month, the ACTG announced the initiation of study A5383, a clinical trial evaluating whether the anti- cytomegalovirus (CMV) drug letermovir reduces inflammation when given to people who have well-controlled HIV and CMV without symptoms. Congratulations to the study team! Read more here.

HPV Test and Treat for Cervical Cancer Prevention Underperforms in Women Living with HIV

Women living with HIV are at high risk for developing cervical cancer, especially in areas of the world where screening like PAP smears are not readily available. The standard approach in places where PAP smears are available consists of screening for precancerous cells and then evaluation by colposcopy (looking at cervix closely with a specialized scope) and treatment with a local surgery to remove the cancer cells. ACTG A5282 evaluated a simpler approach to cervical cancer screening, called HPV test-and-treat, in which women are tested for HPV (which causes cervical cancer) in the cervix. If HPV is found, they undergo cervix cryosurgery to freeze and destroy the abnormal cells in the cervix that are at risk for turning into cancer.

The study found that HPV test-and-treat did not perform better than PAP smear screening, and that one quarter of women who had freezing of the cervix went on to develop pre-cancers of the cervix. Freezing of the cervix did not clear HPV from women in this study. While HPV test-and-treat was straightforward and easier to implement than PAP smear screening, the outcomes were not as good as hoped. This suggests that further research is needed to improve prevention options for cervical cancer, a leading cause of cancer death for women living with HIV.

Wilkin T, Chen H, Sahasrabuddhe V, et al. A randomized clinical trial of HPV test-and-treat as compared to cytology-based screening for prevention of cervical cancer among women living with HIV: AIDS Clinical Trials Group Protocol A5282 [published online ahead of print, 2022 Mar 16]. Clin Infect Dis. 2022;ciac213. doi:10.1093/cid/ciac213

Fall Risk among HAILO Participants is Highest in the Midwest and South

Prior studies have suggested that the region where someone lives may impact aging outcomes, such as falls. As the ACTG HAILO cohort includes participants across many different regions of the US, investigators sought to determine how falls might differ by geographic region and if any regional differences could be explained by differences in physical activity or obesity.

980 participants were grouped into the following US regions: Northeast (22%), Midwest (29%), South (20%), and West (28%). The study team found that people in the Midwestern and Southern regions had a greater risk of falls than people in the Western and Northeastern regions.

Among the more physically active participants, those in the Midwestern region had a greater risk of recurrent falls compared to participants in the Western region. There are a number of possible explanations for this: those in the Midwest may be more likely to encounter snowy or rainy conditions while exercising outdoors. Active participants might also be provided with more opportunities for falls (tripping while walking or jogging) compared to participants who are less physically active.

Among obese individuals, those in the Southern region were more likely to fall than those in the Western region. It could be that obese individuals in the Southern region have a greater burden of other health conditions than those in the Western region. Indeed, HAILO sites in the South have a higher proportion of smokers and participants with high blood pressure.

While falls occurred in all age groups, factors that impact falls suggest that younger participants may experience physical activity-related falls, while factors among older adults may be more traditional fall-related risk factors. We can use this information to target the highest-risk groups for interventions to decrease falls. This study highlights the importance of falls. Patients should have conversations with health care providers to assess how best to prevent falls; like make floors even in the home and not having objects in the way where you walk, etc. Fall prevention is important for everyone as we age.

Abdo M, Wu X, Sharma A, et al. Regional Differences in Risk of Recurrent Falls Among Older U.S. Women and Men with HIV in the HIV Infection, Aging, and Immune Function Long-Term Observational Study [published online ahead of print, 2022 Feb 2]. AIDS Res Hum Retroviruses. 2022;10.1089/AID.2021.0162. doi:10.1089/AID.2021.0162

Overall Positive Participant Experiences in A5345 Biomarker Study

ACTG A5345 included an intensively monitored antiretroviral pause (IMAP), during which participants with HIV temporarily stopped antiretroviral treatment (ART) to identify biomarkers (signals) that could predict when HIV would return in the blood. Investigators evaluated the potential psychosocial impact of the IMAP on A5345 study participants in the United States by questioning them immediately after the IMAP and at the end of the study.

The study found that participant reactions to the IMAP were positive, with some variability in curiosity, satisfaction, and frequency of feeling good about contributing to science. While the study found elevated rates of anxiety in a minority of participants throughout the study, participants reported an overwhelming sense of satisfaction: nearly all (28/29) respondents indicated they would complete a similar study in the future. Further, most respondents reported either not having sexual partners during that time or using some form of protection (e.g., PrEP, condoms). However, one respondent reported difficulty with implementing protection measures because their partner(s)’ dislike of them. Finally, half of the participants would be willing to tolerate a high viral load (higher amount of virus in the blood) during a treatment interruption, which partially supports the movement towards longer analytical treatment interruptions permissive of higher viral loads to figure out how the body can achieve post-treatment control.

Findings underscore the relevance of the psychosocial aspects of participating in studies that involve ART interruptions. Findings also support current efforts to develop partner protection measures during ART pauses. Treatment interruption studies are expected to remain a vital tool for the evaluation of HIV strategies for cure and post-intervention control. Understanding how participants experience these studies is invaluable for informing the design of future similar research aimed at sustained ART-free virologic suppression. Finding a cure for HIV is a big challenge. In the end, the only way we will know if a cure works is by removing effective treatment. Partnerships with patients and researchers are essential to making this work. This study helps us better understand how people feel about stopping treatment.

Dubé K, Eskaf S, Barr L, et al. Participant Perspectives and Experiences Following an Intensively Monitored Antiretroviral Pause in the United States: Results from the AIDS Clinical Trials Group A5345 Biomarker Study [published online ahead of print, 2022 Apr 21]. AIDS Res Hum Retroviruses. 2022;10.1089/AID.2021.0170. doi:10.1089/AID.2021.0170

Investigator Spotlight

Beau Ances, MSc, PhD, MD, Washington University Therapeutics CRS, St. Louis, Missouri

Beau Ances, MSc, PhD, MD is the Daniel J Brennan MD Professor in the Departments of Neurology, Radiology, and Biomedical Engineering at Washington University in Saint Louis (WUSTL). He is an expert in neurodegenerative and neuroinfectious diseases. Clinically, he evaluates HIV associated neurocognitive disorders (HAND), and post acute sequelae of COVID19 (PASC). His research laboratory focuses on 1) Developing novel neuroimaging biomarkers to differentiate “healthy” aging from neurodegenerative and neuro-infectious diseases. 2) Evaluating therapeutic interventions that will improve neurocognitive deficits and biomarkers associated with neurodegenerative disorders. The Ances lab utilizes state-of-the-art techniques and analytical approaches to address how neurodegeneration spreads through the brain by coupling neuroimaging (magnetic resonance imaging (MRI) and positron emission tomography (PET)) with blood and cerebrospinal fluid biomarkers, and psychometrics measures.

Within the ACTG, Dr. Ances is chair of the Neuro CSG. The Neuro CSG aims to continue to 1) support ongoing neuro focused ACTG studies, develop strong collaborations with other Transformative Science Groups (TSGs), and develop the next leaders in Neuro CSG. Outside of work, he enjoys running and coaching his children’s soccer and basketball teams.

University of the Witwatersrand Helen Joseph Hospital (WITS HJH) CRS, Johannesburg, South Africa

In 2003, under the careful guidance of Professor Charles van der Horst, the University of the Witswatersrand Helen Joseph Hospital (WITS HJH) CRS became the ACTG’s first international site. It is thus befitting that the site is often approached to facilitate mentorship to newly appointed ACTG CRSs.

Located at an academic and provincial institution in Johannesburg, South Africa the CRS has conducted more than 36 ACTG studies since inception. They have developed extensive clinical trials experience in HIV, TB, women’s health and more recently COVID-19 treatment trials (A5401).

Although CoVID-19 has had a tremendous impact on the site’s effort over the last two years, they have continued to see great progress in the research agenda. They are currently working on A5381, A5300B, A5332, A5401, A5379, and A5243.

Over the years, the CRS has continued to perform outstandingly in various areas such as data management and the recruitment and retention of participants. The CRS has consistently maintained a loss-to-follow-up rate of less than 1 percent.

As a result of the continued research expansion particularly in response the increased number of XDR/MDR studies conducted, they have modified their infrastructure to include a new XDR/MDR clinic equipped with an automated, mechanical air filtration system providing complete air changes every 2 minutes, which ensures infection control. Simultaneously, an infusion center was built for oncology infusion trials (A5263) and more recently for the administration of vaccines in COVID-19 vaccine trials. This clinic houses a certified Class II TypeA2 Biological Safety Cabinet which makes it ideal for conducting monoclonal antibody trials for the treatment of COVID-19(ACTIV-2/ A5401).

The WITS HJH CRS site staff have worked closely to constantly improve and enhance clinical trial processes by placing the safety of all participants first as well as considering the public health sector relevance of the research agenda. The CRS has adopted a centralized approach ensuring that procedures and peer-review quality-control processes are standardized. Innovative approaches have enabled them to introduce technology within the protocol operations and this has strengthened the site’s ability to adapt to any new technological requirements.

“We are proud that together with the ACTG, we have been able to contribute to the global research agenda and changed the South African national guidelines for the treatment of HIV and TB,” said [insert name and title]. “Many of us recall the days when the national government’s reluctance to provide antiretroviral therapy treatment to people living with HIV and yet today HIV is considered a chronic illness.”

The CRS’s involvement with the ARV / TB protocols has resulted in many participants visiting to thank them for the treatment and support that they received. They report that the most meaningful experience has been the ability to have made such a huge impact on participants’ lives and livelihood and being able to see their children grow up to become adults with healthy parents.

ACTG Member Website Announcement

We hear you!

Our survey about the ACTG Member Website continues throughout the year. So far we have received nearly 100 responses about using the website, trainings, and suggested improvements. The team reviews every response and is working hard to address all comments. You may have already noticed some updates to the website.

When you get the survey, please take a moment to complete it and provide feedback about your experience with the website. We are listening.

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 Aisha Patel.

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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 ACTG Communications Manager Aisha Patel.