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ACTG AND COVID-19
ACTG Investigators Pivot to COVID-19 Work

Investigators and clinicians in HIV/AIDS know how to respond nimbly and compassionately to a pandemic. Many of our ACTG investigators are using their expertise and leveraging existing structures to quickly research COVID-19 and potential treatments. We have highlighted some of our ACTG investigators’ work on COVID-19 below. This is by no means complete and this will be a recurring feature each month moving forward. For a fuller description of our efforts, please check out our newly launched webpage, COVID-19. If you have work you’d like to share, please email krhoffman@mednet.ucla.edu.
  • A number of ACTG investigators were chosen to be part of the new NIH COVID-19 guidelines panel, which issued initial guidelines on April 21, 2020 (these will be updated on an ongoing basis). ACTG investigators on the expert U.S. panel include Drs. Roger Bedimo, Ann Collier, Eric Daar, Rajesh Gandhi, Roy (Trip) Gulick,  Jeffrey Lennox, Susanna Naggie, Susan Swindells, and Pablo Tebas.
  • From the University of Washington CTU, Dr. Bob Coombs’ lab (ACTG VSL and the UW ACTU processing lab) has been repurposed and is performing SARS-Co-2 RNA testing as an extension of the UW Department of Laboratory Medicine efforts. Dr. Ann Collier is leading a UW-wide COVID-19 Clinical Research Review Working Group to help prioritize COVID-19 research requiring access to patients, specimens, and data at UW facilities. Dr. Rachel Bender-Ignacio is working locally to implement COVID-19 randomized clinical trials for inpatients.
  • From the Boston-based ACTG sites, Dr. Paul Sax has authored a number of articles, including one on gratitude on the COVID-19 service and the IDSA COVID-19 treatment guidelines, to answer questions and to bring an informed perspective to the continued discussions surrounding everyday life and “what to know” about COVID-19. Drs. Rajesh Gandhi from the Massachusetts General Hospital CTU and Carlos del Rio from the Emory ACTG co-authored a piece on mild to moderate coronavirus in the New England Journal of Medicine (NEJM) published Friday, April 24.
  • From the University of California at San Francisco CTU, Drs. Monica Gandhi and Diane Havlir co-authored a piece on universal population-level masking in Open Forum Infectious Diseases and an editorial in the NEJM on mass asymptomatic testing in Skilled Nursing Facilities. Dr. Annie Luetkemeyer and main UCSF CTU ACTG CRC, Jay Dwyer, are setting up all of the randomized clinical trials for inpatients getting experimental COVID-19 therapy.
  • At the Alabama CTU (where several members of the research team have recovered from COVID-19), investigators are involved in clinical and public health work, including Dr. Sonya Heath leading efforts to develop antibody testing; Dr. Turner Overton (below on the right) assisting with employee health issues; Dr. Mike Saag and Dr. Overton leading an outpatient COVID-19 clinic. Dr. Turner is also sending out a daily “pandemic song of the day” to Alabama CRS investigators. Please see the fully recovered Dr. Saag (below on the left) in full PPE prepared to swab!
  • At the Weill Cornell-New Jersey Medical School CTU, investigators initially turned almost completely to clinical work in the context of New York being the epicenter of the U.S.-based epidemic. ACTG investigators have now pivoted to leading the COVID-19 clinical research efforts at our hospitals, implementing experimental treatment protocols (with remote electronic consents to minimize risk to research staff), and ensuring healthcare worker safety. Cornell/New Jersey investigators are Zooming away with a picture below!
  • The Byramjee Jeejeebhoy Government Medical College–Johns Hopkins University (BJGMC – JHU) CRS in Pune is applying creative solutions to continue ACTG-related studies during governmental lockdown, including a “drop and run” protocol (to minimize personal interaction) by study team members in Pune and Pimpri-Chinchwad city to deliver PHOENIx protocol study medications to participants. 
  • The Stellensbosch University CTU’s Dr. Mark Cotton co-authored an article in the South African Medical Journal describing their early response as a designated COVID-19 provincial hospital. 
  • The Socios En Salud Sucursal CRS in Peru has provided a comprehensive guide to their response to COVID-19, which can be found here.
  • ACTG investigator Dr. Babafemi Taiwo, Chief of Infectious Diseases at Northwestern University, was interviewed by CNN about the early results of a study evaluating the drug remdesivir to treat COVID-19. ACTG investigators continue to be on the frontlines of research across the country and the globe. Watch here!
PUBLICATION
A5263 in The Lancet
 
Dr. Susan E. Krown and colleagues published “Treatment of advanced AIDS-associated Kaposi sarcoma in resource-limited settings: a three-arm, open-label, randomized, non-inferiority trial” from the A5263 trial in The Lancet on April 11, 2020. Optimal treatment regimens for AIDS-associated Kaposi sarcoma (KS) have not been systematically evaluated in low and middle-income countries (LMIC), where the disease is most common. A5263 aimed to study optimal treatment strategies for advanced-stage disease in these settings. Participants with HIV and advanced-stage AIDS-associated KS were recruited from 11 ACTG sites in Brazil, Kenya, Malawi, South Africa, Uganda, and Zimbabwe. Eligible participants were randomly assigned (1:1:1) to receive either intravenous bleomycin and vincristine or oral etoposide (the investigational arms), or intravenous paclitaxel (the control arm), together with standard EFV-based ART.

Three hundred thirty-four participants were enrolled between October 1, 2013 and March 8, 2018, when the study was closed early due to inferiority of the bleomycin and vincristine plus ART arm. The etoposide plus ART arm had previously closed due to inferiority in March 2016. Week 48 progression-free survival rates were higher in the paclitaxel plus ART arm than in both investigational arms. Rates of adverse effects were equal across arms. Non-inferiority of either investigational intervention for advanced KS in LMICs was not demonstrated. Paclitaxel plus ART should continue to be used in treating advanced AIDS-associated KS in resource-limited settings.


Krown S., Moser C., Campbell T., MacPhail A., Matining R., Godfrey C., Caruso S., Hosseinipour M., Samaneka W., Nyirenda M., Busakhala N., Okuku F., Kosgei J., Hoagland B., Mwelase N., Oliver V., Burger H., Mngqibisa R., Nokta M., Borok-Williams M. Treatment of Advanced AIDS-associated Kaposi Sarcoma in Resource-Limited Settings: A Three-Arm, Open-Label, Randomised, Non-Inferiority Trial in Five sub-Saharan African Countries and Brazil (ACTG A5263/AMC066). Lancet Vol. 395. Iss 10231. 2020 Apr 11;. doi: 10.1016/S0140-6736(19)33222-2. Epub 2020 Mar. PubMedID: 32145827

 
AIDS 2020

AIDS 2020 Virtual to Address COVID-19: Abstracts Due May 25


AIDS 2020 will now be a virtual conference and the deadline for late breaker abstracts has been pushed back to May 25, so that abstracts on the interaction of HIV and COVID-19 in each of the six tracks can be submitted. In addition, this week the International AIDS Society announced that it will host a one-day meeting on COVID-19 at the same time as AIDS 2020. The newly announced COVID-19@IAS meeting will feature plenaries on COVID-19 from Drs. Anthony Fauci and Deborah Birx.

Investigators are invited to register and submit COVID-19 abstracts for the first global health conference on SARS-CoV-2 by May 25 in one of five tracks:
  • Track A: Basic science, pathogenesis, virology, immunology, inflammation  
  • Track B: Clinical science, testing (RT-PCR and serologic) and diagnoses, natural history, clinical care, ARDS care, new therapeutics 
  • Track C: Epidemiology, transmission dynamics, prevention, vaccines 
  • Track D: Public health responses including physical distancing and community level efforts, programs, policies, lifting restrictions, modeling
  • Track E: Social, economic, political, human rights impacts of the pandemic and the response 
All COVID-19@IAS meeting content will be free to the public. Click here for more information.
SPOTLIGHTS
INVESTIGATOR SPOTLIGHT
Dr. Davey Smith

ACTG has launched ACTG 5395, which will evaluate whether the drug combination hydroxychloroquine and azithromycin can prevent hospitalization and death from SARS-CoV-2, the virus that causes COVID-19. We asked protocol chair Davey Smith, MD, of the University of California, San Diego, to describe the process and experience to us.  
 
How quickly did ACTG 5395 come together? How unusual was the timeline? 
I have worked on many ACTG protocols. They usually take months, if not more than a year, to get from concept sheet to version 1.0. Our first call for the study, which would become ACTG 5395 'HAz COVID Trial', was on March 23. We went to version 1.0 on April 13th. Crazy.
 
How did investigators and the ACTG in general work together to set up the trial so quickly? What challenges did you face? 
We had calls every day for the first week and then pretty much every other day thereafter. Everyone was engaged and pitched in. As this is the world we live in now, everything was virtual meetings and emails, lots of emails. The trial did not start off the way it ended up. At first we did not think we could get placebo so we were looking at a comparator arm to vitamin C. The Division of AIDS (DAIDS) was able to get us drug with placebo in record time. 
 
People often say that crisis brings out the best in people – did you see any examples of this as you worked to get this trial launched?
Throughout the whole process, people only wanted to help. They understood the urgency and the need for rigorous science. My co-chairs, the ACTG team, and the ACTG leadership have been amazing. They understood the importance of good and careful science. They also understood that we had to be pragmatic and make decisions in order to craft a trial that would provide clinically meaningful answers for patients. 
 
What are your hopes for the trial?
My hope for the trial is to have an answer. Do these drugs work or do they not work for COVID-19? Right now, we do not know. Care providers can only speculate and then give treatments based on speculation. If I learned anything from HIV, it is that the only way through a pandemic is stick together and work the science. That is what we need to do now.
 
Those leading this study all work in HIV – a field that is of tremendous import to some audiences and under the radar for others. COVID-19 is different, as it can universally affect people and is the primary driver of our news cycle. How does that shift feel for you as scientists?
It does seem that SARS-CoV-2 can infect pretty much anyone, just like HIV. But, as we learn more about this infection, we are finding that people and communities who are disadvantaged by stigma, healthcare, socioeconomics, etc. more often bear the greatest burden. We have seen this over and over in epidemics- HIV, HCV, TB, STIs. As scientists, we must be mindful that infections kill, but so do disparities, especially in the setting of a pandemic.
 
Any other thoughts you want to share?
I feel greatly privileged to be able to help bring this study together with the team at the ACTG.

 

CAB MEMBER SPOTLIGHT
Ruben Vidales, Los Angeles, CA


Ruben Vidales has been “involved with ACTG studies for a very long time – like over 20 years!” he said. He loves research and has seen the benefits hundreds of times, including for himself. He joined the ACTG to be able to assist others through his advocacy. “I never want my kids, or anyone in their generation, to go through what we have gone through and continue to go through, he added.
 
Ruben has been an ACTG CAB member for more than 12 years and was on the Community Scientific Subcommittee (CSS) for seven years. He is about to begin another term on the ACTG CSS.
 
When asked to describe his community he said, “My community is the entire world dealing with HIV, tuberculosis, and hepatitis. My local community is underrepresented and marginalized. Sometimes it is hard to reach out to the populations that make up my community, but it’s important not to give up. My community – regardless of HIV status – is hopeful for a cure. But we are also frustrated by a lack of services, especially for mental health issues. Overall my community stays positive and hopeful.” Ruben said that his community is especially interested in the medical, physical, and mental issues related to aging.
 
He hopes that he is remembered for spending ACTG resources effectively and disseminating vital information and knowledge to as many communities as possible. “I hope that the ACTG leadership continues doing a fantastic job in the field of HIV research – cure, pill burdens, side effects, new medications, identifying reservoirs, long acting treatments, aging, and most of all, continuing to involve community members at the table throughout protocol development.” 
ACTG SITE SPOTLIGHT
BJGMC-JHU Clinical Research Site, Pune, India

The Byramjee Jeejeebhoy Government Medical College–Johns Hopkins University (BJGMC-JHU) research partnership was established in 2000 to conduct the multi-country Six Weeks Extended Nevirapine (SWEN) trial to reduce HIV transmission through breastfeeding. The results of that trial led to changes in the World Health Organization’s clinical care guidelines. Capitalizing on the team’s success and the infrastructure established, the research partnership continued and has grown exponentially. With clinical operations based at BJGMC in Pune, India, the BJGMC-JHU CRS is now a member of the Baltimore-Washington-India Clinical Trials Unit (BWI-CTU), which includes a CRS at Johns Hopkins University (Baltimore) and at Whitman-Walker Health (Washington, DC). ACTG trials represent a significant portion of our research portfolio. We’re proud that our work is improving disease outcomes for patients in our own community and around the world.

With onsite leadership from Drs. Vidya Mave, Nikhil Gupte, and Nishi Suryavanshi, since 2004 the BJGMC-JHU CRS has conducted 13 ACTG studies and nine IMPAACT studies, which have had a lasting impact in Pune. A5288 and A5273 spurred our team to establish the local HIV treatment program to start second-line and third-line treatment at our site hospital, which, led by Dr. Shashi Sangle, Head of Medicine, has one of the largest ART centers in India. A5349 was another important effort to see if the long and burdensome 6-month course of TB treatment could be shortened to four months for drug-sensitive TB patients.

Our site’s current active ACTG studies are A5332 (REPRIEVE), A5349, and A5302 (B-SMART). We are very excited that the BJGMC-JHU CRS was recently activated for the PHOENIx (A5300/I2003) study, which is assessing the safety of delamanid versus isoniazid to prevent TB among high-risk household contacts of TB patients who have multidrug resistance to at least isoniazid and rifampin. This trial is of particular importance to our site, because India has the highest burden of TB and MDR-TB globally. Our hope is that this trial produces findings that can aid the Government of India and the rest of the world in eliminating TB.

Education and community building are important efforts at the BJGMC-JHU CRS. We strive to expand participant knowledge about health and the research process and provide opportunities for participants, who can be stigmatized, to come together. The BJGMC-JHU CRS team develops educational resources in local languages and in different formats and provides linkages to community resources including nutritional assistance, counselling, and income generating activities. 

Our site’s first efforts that helped establish new clinical care guidelines to reduce HIV transmission through breastfeeding remain the standard of care. We are enormously proud to continue that success by conducting high-quality research studies to address some of India’s most urgent health needs and contribute to reducing the global burden of HIV and TB.


 
 
 
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 Leadership & Operations Center Communications Specialist Karen Hoffman.
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actg.communications@fstrf.org


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