The ACTG is happy to announce that Global Community Advisory Board (GCAB) and Community Scientific Subcommittee (CSS)’s They Became My Family is back! They Became My Family is a portrait gallery celebrating the diverse community of the ACTG. The project aims to preserve the community’s voices and their experiences and honor individual activist legacies. The profiles include portraits and stories that describe advocacy journeys and future hopes for the ACTG. You can check out the project and submit your own story here!
Last month, the ACTG and Shionogi announced that the FDA has cleared the investigational new drug application for S-217622, a novel COVID oral antiviral therapy, enabling the global phase 3 trial to proceed as part of the ACTIV-2 program for COVID-19. You can read the full press release here!
Both Standard and Double-Dose NRTI Regimens had Acceptable PK, Safety, and TB Outcomes but Unacceptable HIV Outcomes
TB is the most common opportunistic infection among people living with HIV globally. While co-administration of HIV antiretroviral therapy (ART) and TB therapy reduces both the risk of HIV progression or death and improves TB outcomes, there are many drug-drug interactions between those used for TB treatment and HIV protease inhibitors (PIs). Rifampicin (RIF) markedly decreases the plasma concentrations of PIs, though doubling lopinavir/ritonavir (LPV/r) doses can overcome that effect. Rifabutin (RBT) may be an effective alternative to RIF in many high-burden TB settings since it’s on the WHO Essential Medicines list, but PIs markedly increase its plasma concentrations.
A5290 aimed to find the best approach to HIV treatment in individuals who require PI-based ART in the setting of TB co-treatment. The study enrolled people living with HIV and drug-sensitive TB co-infection who failed or were intolerant of a prior nonnucleoside reverse transcriptase inhibitor regimen. The study equally randomized 71 adults from nine sites in Brazil, Peru, Haiti, Kenya, and South Africa. In addition to receiving one of the following three regimens, all participants received two nucleoside reverse transcriptase inhibitors and other TB drugs outside of the study.
Standard-dose LPV/r + RBT
Double-dose LPV/r + RIF
Standard-dose LPV/r + RBT + raltegravir (added to increase HIV activity).
While accrual prematurely ended due to low recruitment, the study gathered enough data to reach several key conclusions. Double-dose LPV/r + RIF had acceptable pharmacokinetic, safety, and TB outcomes. Standard-dose LPV/r + RBT also had acceptable pharmacokinetic and TB outcomes, but RBT-related uveitis and neutropenia were observed. An unexpected drug-drug interaction between raltegravir and RBT was noted, wherein RBT exposure was lower in the presence of raltegravir; further study is recommended. HIV viral suppression at 48 weeks was not optimal in any arm, but this outcome did not appear related to adverse pharmacokinetics/pharmacodynamics.
The KISS (Keep it Simple and Safe) Approach to Managing HCV infection
Globally, there are about 58 million people living with hepatitis C. Despite advances in therapeutics, as of 2020, only about 4 million of them had been treated. Barriers to scale-up include access to diagnostic and monitoring tests, healthcare infrastructure and requirement for frequent visits during treatment. ACTG 5360 (MINMON) was conducted to determine whether an approach using minimal face-to-face contact and reduced laboratory tests was an efficacious and safe way to deliver hepatitis C treatment. The MINMON approach comprised four components:
No pre-treatment genotyping
The entire treatment course (84 tablets of sofosbuvir/velpatasvir) was dispensed at treatment initiation
No on-treatment clinical or laboratory visits
Two virtual visits at week 4 to assess adherence and week 22 to schedule an evaluation assessment.
The study enrolled 400 participants across 38 sites in five countries across four continents; 399 initiated treatment. Overall, 379 (95%) had no detectable virus at the end of the study period, implying that they had been “cured” of HCV. Additionally, only 14 (3.5%) participants reported serious adverse events; importantly, none were related to study medication or led to treatment discontinuation or death. These findings suggest that the MINMON approach with sofosbuvir and velpatasvir was safe and achieved “cure” rates comparable to standard hepatitis C treatment delivery, which requires a lot more testing and more frequent in-person visits. The MINMON approach could play a critical role in achieving the ambitious global hepatitis C elimination agenda by removing key barriers to treatment and maximizing efficiency of healthcare infrastructure.
Debika Bhattacharya, MD, MSc, University of California, Los Angeles CARE Center CRS
Debika Bhattacharya, MD, MSc is an Associate Clinical Professor of Medicine at the University of California, Los Angeles (UCLA) David Geffen School of Medicine, with a joint appointment at the Greater Los Angeles Veterans Affairs Health System. She grew up in the suburbs of Chicago and spent her elementary school years in Indonesia. She went to the Boston University Seven-Year Medical Program, did her residency at Baylor College of Medicine-Houston, and her infectious diseases fellowship at Stanford University before coming to UCLA as faculty. She is an Associate Program Director for the Infectious Diseases Fellowship Program and the co-director of the Viral Hepatitis Program for the Greater Los Angeles Veterans Affairs Health System. She sees inpatients and outpatients at both UCLA (the CARE Center) and GLAVAHS. Her research focuses on viral hepatitis therapeutics and clinical outcomes, with a focus on HIV/viral hepatitis coinfection. She is the co-chair of the AASLD/IDSA Hepatitis C Guidance Panel and a panel member on both the DHHS Opportunistic Infection Guidelines Panel and DHHS Pediatric Opportunistic Infection Guidelines Panel. She is also the Co-Chair of A5368, the CHECK-HBV trial, which is investigating an immune checkpoint inhibitor in hepatitis B infection.
Debika is the Chair of the Hepatitis Transformative Science Group (Hep TSG), working alongside Arthur Kim, MD from Massachusetts General Hospital. They are excited to develop novel HBV cure strategies and explore new opportunities for the TSG and ACTG in hepatitis B therapeutics. Ultimately, they hope to improve long-term hepatitis B treatment options for people living with both HIV and HBV. She is proud to be part of the amazing UCLA CARE CRS team.
Debika lives in Los Angeles with her husband, Ram, two children, and their pandemic puppy, Cutester. She loves to travel with her family and all things science fiction.
University of Pittsburgh CRS, Pittsburgh, Pennsylvania, USA
The University of Pittsburgh CRS (Pitt CRS), originally established in 1987, prides themselves on excellence in clinical research. The site is comprised of investigators, clinicians, study coordinators and support staff, pharmacy personnel, community educators, lab personnel, and administrative staff. Everyone plays an integral part and works together to reach their research goals. In addition to the day-to-day research, the team comes together for Pittsburgh PRIDE every year to support the community. One way they strengthen their bond is by celebrating achievements and special occasions together. Every year, the whole team is invited to celebrate with the community advisory board over the holidays.
The Pitt CRS has been part of a number of ACTG studies over the years and is currently participating in A5128, A5321, A5332, A5355, A5361s, A5357, A5359, A5379, A5383, A5401, and A5391. Recently, A5321 (Decay of HIV-1 Reservoirs in Participants on Long-Term ART) reached its accrual goal of 30 participants into its Group 5, which studies people who continue to have low-level viremia while on ART. The Pitt laboratories support A5321, and the Pitt CRS team stepped up its efforts to identify potential candidates. Led by Deborah McMahon, MD, A5321 co-chair, and Sharon Riddler, MD, MPH, CRS leader, and Madhu Choudhary, MD, CRS investigator, the site’s collective efforts resulted in enrolling more than 25 percent of the total Group 5 participants. The CRS team achieved this through local provider education about clonal expansion, strong communication about potential candidates with providers, careful prescreening by site staff, and willing and engaged participants.
It is difficult to pinpoint the most meaningful part of the site’s work with the ACTG. “If I had to summarize everything into a single aspect, it would be knowing that I am a link in the chain of care aimed at improving the quality of life/life expectancy of PLWH,” says William Louth, MD, MPH, research coordinator at the Pitt CRS. “Oftentimes, when we read scholarly papers, we do not usually think of the individuals participating in these studies; instead, we conceptualize them as a single entity - ‘the participants’. Having the opportunity to interact with the individuals, getting to know them, and understanding their motives to participate in ACTG studies is priceless; mostly because—in my limited experience—the motivation has been to contribute to a cause greater than themselves: to help find a cure. The participants’ selflessness and commitment to other people living with HIV, as well as the hope they place on ACTG studies, are the engine that propels me to deliver the best way I can in my capacity as a research coordinator.”
When Patricia Peters, RPh, BS, began her career as the regulatory coordinator for the Pitt CRS, her daughter was three years-old and her twin sons were just one. “As my children grew, they would tell family and friends that their mom worked on studies to help people living with HIV and that her boss was Tony Fauci. Although this explanation seemed to appease most folks’ curiosity, I did not realize my children truly understood its meaning until I found this note on my desk one morning in late 2021: ‘Thank you so much for working for us and to help people you will never meet.’”
Vijaya Jori, Byramjee Jeejeebhoy Medical College (BJMC) CRS, India
Vijaya started her journey in the field of HIV/ AIDS in 2000 and has been active member of the CAB at BJMC, and John Hopkins University Clinical Trial University since 2008. Beginning with her training in social work in 1998, her dream has been to serve people living with HIV. In 2002, she became associated with the NGO Prayas, a Pune-based non-profit organization in India working on HIV/AIDS and sexual health. Looking back, she feels that starting her work with Prayas was a turning point in her career and personal life. Vijaya feels that the founders of Prayas have played a significant role in her personal and professional career for cultivating values and developing her perspective towards HIV work and her life.
Vijaya is an active member of the GCAB and has served on several sub-committees (Protocol Development and Implementation Subcommittee and Site Management and Clinical Care Committee) and working groups (Field Representatives Working Group) as a GCAB representative. She has been an active member of CAB Women’s Working Group for the last three years. Vijaya has also worked as a mentor for new GCAB members from around the world. She is known for explicitly sharing her input in CAB and GCAB meetings. Her intense experience with the HIV community provides critical insights for protocol review and developing training/educational material for research participants, ultimately helping recruitment and retention of participants in ACTG HIV and TB studies. During the COVID-19 pandemic, she became involved in conducting capacity-building sessions for counsellors and outreach staff working for the BJMC clinical trial unit, focused on developing dialogue with the community and motivating them to take part in clinical trials. She hopes that the ACTG will be able to advance comprehensive care for people aging with HIV and increased inclusivity of women living with HIV in research.
Vijaya enjoys her life with her mother (Sudha) and her younger brother (Milind), an entrepreneur in Pune, her greatest supporters. Her hobbies include cycling, physical fitness, trekking, and staying in tune with nature.
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