Spotlight

The AIDS Clinical Trials Group (ACTG) is excited to share the news that the REPRIEVE study was stopped early after a daily statin medication was found to reduce the risk of cardiovascular disease among people living with HIV. REPRIEVE is the first clinical trial to study a preventive approach to cardiovascular disease among people living with HIV who were considered to be at low-to-moderate risk of cardiovascular disease events, including heart attack and stroke. A planned interim analysis found that participants who took pitavastatin calcium (a daily statin pill that reduces cholesterol) lowered their risk of major adverse cardiovascular events by 35 percent compared to those who took a placebo. These findings were compelling enough that  REPRIEVE’s independent Data Safety and Monitoring Board (DSMB) recommended that it be stopped early; the National Institutes of Health (NIH) accepted this recommendation.

The ACTG played a pivotal role in REPRIEVE, which began in 2015 – 52 of our sites enrolled more than half of the total 7,769 participants and ACTG investigators played key leadership roles in the core REPRIEVE team. REPRIEVE is primarily supported by the National Institute of Allergy and Infectious Diseases (NIAID) and the National Heart, Lung, and Blood Institute (NHLBI), both part of the NIH, with additional funding from the NIH Office of AIDS Research, Kowa Pharmaceuticals America, Inc. (providers of pitavastatin calcium and placebo), Gilead Sciences, Inc., and ViiV HealthCare. REPRIEVE was conducted in 12 countries in Asia, Europe, North America, South America, and Africa.

Statins are known to prevent cardiovascular disease among those at high risk in the general population and REPRIEVE sought to understand whether they would have the same effect among people living with HIV who may not traditionally be candidates for statins. People living with HIV often experience premature cardiovascular disease and REPRIEVE was an important effort to improve cardiovascular outcomes in this community.

“It is incredibly gratifying to see these results and to know that this study has the potential to change clinical practice and thus have a meaningful impact on the experiences and health of people living with HIV,” said Carl Fichtenbaum, M.D., vice-chair of the REPRIEVE protocol. “This area of research has been a priority of the ACTG for 20 years and I want to congratulate the many individuals within the network and dedicated study participants who have contributed to making REPRIEVE such a success.”

REPRIEVE has been led by Steven Grinspoon, M.D. (Chair) and Pamela S. Douglas, M.D. (Co-chair), who led the Clinical Coordinating Center and Heather Ribaudo, Ph.D. (Lead Statistician) and Michael Lu, M.D., M.P.H. (Protocol Chair, Mechanistic Substudy of REPRIEVE), who led the Data Coordinating Center. This study leadership expressed their gratitude to the ACTG for our partnership and support, which made REPRIEVE possible.

Los Angeles, Calif. – The AIDS Clinical Trials Group (ACTG), the world’s largest HIV research network, today announced the publication of “Varied Patterns of Decay of Intact HIV-1 Proviruses over Two Decades of ART” in the Journal of Infectious Diseases. This publication found that levels of intact proviral DNA (inactive HIV DNA that may be capable of replicating) initially decay rapidly but that decay markedly slows among virally suppressed people living with HIV on long-term ART. The study also found a late increase in proviral DNA levels among some individuals. These data suggest that if the decay rates during the second phase could be accelerated to more closely approximate the first phase, it may be possible to reduce the viral reservoir to the degree needed to achieve HIV remission.

To read more:

https://www.globenewswire.com/news-release/2023/03/27/2635252/0/en/ACTG-Announces-Publication-of-New-Insights-Into-HIV-Reservoirs-and-Prospects-for-Remission-in-the-Journal-of-Infectious-Diseases.html

Los Angeles, Calif. – The AIDS Clinical Trials Group (ACTG), the world’s largest HIV research network, is announcing the publication of “Perspectives on Adherence from the ACTG 5360 MINMON Trial: A Minimum Monitoring Approach with 12 Weeks of Sofosbuvir/Velpatasvir in Chronic Hepatitis C Treatment” in the journal Clinical Infectious Diseases. This publication found that self-reported 100 percent adherence in the first four weeks of hepatitis C treatment with sofosbuvir/velpatasvir was associated with sustained virologic response (which is when no hepatitis C virus is found in the blood 12 weeks after completing treatment). Sustained virologic response is the generally accepted criteria for an individual to be considered “cured” of hepatitis C. These findings suggest that early self-reported adherence could be used to identify individuals who may be more likely to experience treatment failure and may benefit from additional support.

Read more here: https://www.eurekalert.org/news-releases/983397

We are pleased to announce that the 2023 ACTG Network Meeting will be a hybrid meeting (both in-person attendance and through webinars for virtual participation), taking place between June 13th – June 16th at the Omni Shoreham Hotel, Washington, D.C. The meeting is open to all ACTG members and the public.

To allow international members sufficient time to obtain visa appointments before the meeting, the ACTG has made the Visa Invitation Letter Request form available. Once the request is received, a letter will be prepared and forwarded to you. When submitting the visa invitation letter request form, please include your full name as written on your passport and your CRS Leader’s name and email to expedite the process.

The Annual ACTG Network Meeting online registration will open in early April. The ACTG will send an announcement when online registration is available. In the meantime, questions can be directed to ACTG Meeting Planning at actgmeetingplanning@dlhcorp.com.

Presentations focus on COVID-19; HIV cure, pathogenesis, treatment and long-term complications; tuberculosis; hepatitis C; and contraception.

Los Angeles, Calif. – The AIDS Clinical Trials Group (ACTG), the world’s largest HIV research network whose focus has expanded to include evaluating outpatient treatment for COVID-19, will present four oral presentations, two themed discussions, and 23 poster sessions at the Conference on Retroviruses and Opportunistic Infections (CROI 2022), which will be held February 19-22, 2023 in Seattle, Washington. CROI is the premier global HIV research conference and ACTG’s robust presence at the meeting demonstrates its continued leadership in HIV and related fields.

“The studies the ACTG is presenting at CROI this year represent important advances across the research agenda for the group, including HIV, COVID-19, hepatitis C, and TB, and they demonstrate that after more than 35 years, the ACTG continues to be a leader in research,” said ACTG Chair Judith Currier, M.D., MSc, of the University of California, Los Angeles. “We are especially excited to share insights in eight presentations about COVID-19, which we believe make important contributions to our understanding of SARS-CoV-2. We’re also proud to present findings on a number of long-term complications related to HIV and to highlight important findings in TB, including drug-resistant TB, and hepatitis C. Much of the work presented this year is led by a talented group of emerging investigators engaged with the ACTG. The ACTG remains committed to advancing research in these fields to ultimately improve the lives of people affected by these conditions.”

ACTG presentations are listed below by topic.

Read more here: https://www.eurekalert.org/news-releases/979658

Statement of Solidarity

The ACTG mourns with those impacted by the senseless shootings that occurred at Club Q, an LGBTQIA+ club in Colorado Springs last weekend. This attack, which fell on the eve of Transgender Day of Remembrance, is horrifying — further shattering the sense of safety of LGBTQIA+ Americans across the country.

Our network is proud to serve a diverse community of people, faculty, staff, and administrators. We are committed to fostering respect, inclusivity, and equity and to disrupting hate and bias whenever and wherever we encounter it. We must rise against hate in the strongest possible terms and stand together in solidarity and love with our LGBTQIA+ communities to demand an end to this epidemic of violence.

Los Angeles, Calif. – The AIDS Clinical Trials Group (ACTG), the world’s largest HIV research network whose focus has expanded to include evaluating outpatient treatment for COVID-19, today presented a session demonstrating that a three-dose regimen of the HEPLISAV-B vaccine fully protected people living with HIV at IDWeek 2022, taking place in Washington D.C. from October 19-22, 2022.

“Hepatitis B is a serious liver infection that frequently affects people living with HIV,” said ACTG Chair Judith Currier, M.D., M.Sc., of the University of California, Los Angeles. “This study shows for the first time that people living with HIV with no history of hepatitis B infection or vaccination were fully protected by this vaccine. Our findings about the protection levels associated with HEPLISAV-B among people living with HIV are likely to change clinical practice and have a profound impact on people living with HIV around the world.”

The study, “High HBsAb seroprotection achieved 4 weeks after 3 doses of HepB-CpG vaccine in people living with HIV (PLWH) without prior HBV vaccination (ACTG A5379 Group B Preliminary Results)” takes place on Thursday, October 20, 2022, during the “Late-Breaking Vaccine Studies” session from 1:45-3:00 p.m. E.T., led by study chairs Kenneth Sherman M.D., University of Cincinnati College of Medicine, and Kristen Marks, M.D., Weill Cornell Medicine. ACTG 5379 is an ongoing, prospective, open-label study to evaluate the level of seroprotection provided by HEPLISAV-B for people living with HIV.

This analysis included 68 people living with HIV who had not received a hepatitis B vaccine and showed no evidence of prior hepatitis B exposure. Participants were on antiretroviral therapy with CD4>100 cells/mm3 and HIV-1 RNA<1000 copies/mL. Participants received three doses of HEPLISAV-B (at weeks 0, 4, and 24) and achieved 100 percent seroprotection. No unexpected safety issues were observed.

Participants enrolled at 13 global sites in the U.S., Thailand, and South Africa. Among them, 46 percent were male, 66 percent were Asian, 16 percent were Black, and 15 percent were white. The median age was 47.

The Food and Drug Administration (FDA) approved the HEPLISAV-B vaccine in 2017 as a two-dose regimen for adults, but until now, there has been little data around its use among people living with HIV.

Read more here.

Los Angeles, Calif. – The AIDS Clinical Trials Group (ACTG), the world’s largest HIV research network whose focus has expanded to include evaluating outpatient treatment for COVID-19, will present two oral abstracts and one poster on COVID-19 studies at IDWeek 2022, taking place in Washington D.C. from October 19-22, 2022.

“IDWeek is an important opportunity for the ACTG to present our latest findings on COVID-19,” said ACTG Chair Judith Currier, M.D., MSc, of the University of California, Los Angeles. “These presentations are all from the ACTG’s ACTIV-2 platform, which sought to rapidly identify COVID-19 treatments and better understand the pathogenesis of SARS-CoV-2. These findings expand our understanding about several key aspects of COVID-19, including the relationship between SARS-CoV-2 RNA levels in different compartments, predictors of nasopharyngeal viral clearance, and SARS-CoV-2 RNA levels as predictors for clinical outcomes.”

ACTIV-2 is a randomized controlled adaptive platform that enabled the efficient testing of a variety of promising therapeutic agents for early COVID-19 within the same trial infrastructure. ACTIV-2 is sponsored by the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health (NIH), which also funds the ACTG.

ACTG COVID-19 presentations at IDWeek 2022 include:

Nasal and plasma SARS-CoV-2 RNA levels predict timing of symptom resolution in the ACTIV-2 trial of non-hospitalized adults with COVID-19 (Friday, October 21, 11:00 a.m. E.T.); Oral session; Yijia Li, et al.

This study sought to understand the relationship between SARS-CoV-2 burden in the upper airway or plasma and the duration of COVID-19 symptoms. Among individuals with COVID-19 who did not receive treatment, participants with high anterior nasal and detectable plasma RNA at study entry were more likely to experience symptoms for a longer period of time.

Association between anterior nasal and plasma SARS-CoV-2 RNA levels and hospitalization or death for non-hospitalized adults with mild-to-moderate COVID-19 (Friday, October 21, 10:30 a.m. E.T.); Oral session; Mark J Giganti, et al.

This study sought to expand upon the limited data available regarding the performance of SARS-CoV-2 RNA levels as predictors or surrogate markers for clinical outcomes in outpatients with mild-to-moderate COVID-19. Researchers found that anterior nasal and plasma SARS-CoV-2 RNA levels were predictive of hospitalization and death among participants who received placebo, but nasal viral levels explained only a small proportion of the beneficial treatment effect of monoclonal antibodies. Differing associations of nasal viral levels between monoclonal antibody and placebo recipients raise concerns about nasal RNA as a surrogate for clinical outcomes in monoclonal antibody trials.

Female sex and SARS-CoV-2 serostatus predict nasopharyngeal RNA clearance during early COVID-19 (Friday October 21, 12:15 p.m. E.T.); Poster session; Carlee Moser, et al.

This study sought to better characterize predictors of SARS-CoV-2 RNA levels and changes over time during early COVID-19. It found that shorter symptom duration, older age, white race, lower BMI and a lack of anti-SARS CoV-2 antibodies were associated with higher RNA in early COVID-19 infection. Female sex and the presence of antibodies were associated with faster viral clearance.

To read more here.

ACTG Announces Results from Investigational Inhaled COVID-19 Treatment in ACTIV-2 Phase 2 Study

Los Angeles, Calif. – The AIDS Clinical Trials Group (ACTG), the largest global HIV research   network, which recently expanded its focus to include evaluating outpatient treatment for COVID-19, today announced results from a trial comparing SNG001, an inhaled formulation of interferon beta, with placebo in the ACTIV-2 Outpatient Monoclonal Antibodies and Other Therapies Trial (ACTG A5401). For more information about the trial, please visit the study website.

ACTIV-2 is the first U.S. study to evaluate SNG001 (developed by Synairgen) among non-hospitalized people with COVID-19. SNG001 is self-administered as a nebulized dose (15.6 MIU) that participants inhale once daily for 14 days. Participants are trained to use the nebulizer device by study staff and take all doses at home.

The SNG001 arm of the phase 2 ACTIV-2 platform trial enrolled 221 adults with mild-to-moderate COVID-19. Inhaled SNG001 was generally safe and well tolerated with fewer adverse events (AEs), including new Grade 3 or higher AEs, in participants who received SNG001 compared with those who received placebo.

There were no statistically significant differences between the SNG001 and placebo arms in the proportion of individuals without detectable nasopharyngeal RNA at days 3, 7, and 14 post-treatment, or the duration of COVID-19 associated symptoms, the two primary measurements of efficacy in the study. However, as a secondary outcome, individuals who received SNG001 had a lower risk of hospitalization compared with individuals who received placebo (1/110 vs. 7/110, P=0.07). While the results were not statistically significant, the study was not designed to detect differences in hospitalization.

“These results, including a decrease in hospitalizations and AEs among participants who received SNG001, are promising and warrant further investigation in a larger phase 3 clinical trial,” said William Fischer, M.D., University of North Carolina (UNC), a lead investigator of SNG001. “SNG001 is the first nebulized inhaled therapeutic to demonstrate promising results and, if confirmed in larger studies, could represent a potential treatment option for people who have COVID-19 but are not hospitalized.”

ACTIV-2 is a randomized, blinded, controlled adaptive platform that allows promising therapies to be added and removed over the course of the study to efficiently test a variety of new agents within the same trial infrastructure. The SNG001 study is being led by Dr. Fischer and Upinder Singh, M.D., and Prasanna Jagannathan, M.D., both of Stanford University. ACTIV-2 is led by Kara W. Chew, M.D., M.S., University of California, Los Angeles (UCLA) and Davey Smith, M.D., University of California, San Diego (protocol chairs) and David Alain Wohl, M.D., UNC and Eric S. Daar, M.D., Lundquist Institute at Harbor-UCLA Medical Center (vice-chairs) and supported by ACTG Chair Judith Currier, M.D., M.Sc., UCLA and ACTG Co-Chair Joseph J. Eron, M.D., UNC.

ACTIV-2 is sponsored by the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health (NIH), which also funds the ACTG. ACTIV-2 is part of NIH’s Accelerating COVID-19 Therapeutic Interventions and Vaccines (ACTIV), a public-private partnership program to create a coordinated research strategy that prioritizes and speeds development of the most promising treatments and vaccines. It also receives support from the Federal COVID Response-Therapeutics, the U.S. government’s multi-agency effort to accelerate the development, manufacturing, and distribution of COVID-19 vaccines, therapeutics, and diagnostics.

For more information about ACTIV-2, please visit www.riseabovecovid.org, www.actgnetwork.org, or clinicaltrials.gov.

Read more here. 

The leader of ACTG’s STOMP monkeypox treatment study Dr. Timothy Wilkin joined Dr. Carl Dieffenbach, Director of the NIH’s Division of AIDS and Dr. Demetre Daskalakis, White House National Monkeypox Response Deputy Coordinator, for an IDSA media briefing monkeypox treatment trials. Please check it out here!