Press Release

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

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

From NIAID

In September 2022, NIAID will start a clinical trial of tecovirimat in the U.S. in collaboration with the AIDS Clinical Trials Group (ACTG). People with monkeypox infection, including people living with HIV, would be eligible and encouraged to enroll. More than 500 volunteer participants will be randomly assigned to receive either tecovirimat or a placebo at a ratio of two to one. Investigators will be evaluating if those taking tecovirimat heal more quickly than those taking placebo, among other data points. There is an additional segment of the study open to pregnant and breastfeeding people and children and all will receive tecovirimat and will be closely monitored for safety. If a positive signal is seen in the study, it will provide the necessary data to make this medicine readily available for treatment of monkeypox disease.

Media Contact: Jenna Conley, AIDS Clinical Trials Group (ACTG)
jenna@conleycommunications.net
215-684-9476

Los Angeles, Calif. – Investigators from the AIDS Clinical Trials Group (ACTG), the world’s largest and longest-established HIV research network, today announced that the Journal of Clinical Investigation published new findings from the ACTG HIV Reservoirs Cohort Study (A5321). The study found that HIV DNA remained in the cerebrospinal fluid of half of participants with well-managed HIV (virologic suppression in the plasma), confirming that the central nervous system (CNS) is a major reservoir for latent HIV. Individuals who harbored HIV DNA in the cerebrospinal fluid were more likely than other study participants to experience cognitive deficits on neurocognitive testing.
“The persistence of HIV in sanctuary sites in the human body, even in the presence of long-term therapy, is a challenge to HIV remission and cure that the ACTG is actively working to address,” said ACTG Chair Judith Currier, M.D., MSc, University of California Los Angeles. “Because neurocognitive function can be compromised even in individuals whose HIV is well treated, it is very important that we understand HIV persistence in the CNS so that we can develop strategies to treat it. This study provides preliminary insights into these challenges.”
This substudy in the ACTG HIV Reservoirs Cohort Study (A5321) was led by Serena Spudich, M.D., Yale University, the late Kevin Robertson, Ph.D., University of North Carolina at Chapel Hill, and John Mellors, M.D., University of Pittsburgh. The study included 69 participants with well-treated HIV who had their cerebrospinal fluid and blood collected and underwent neurocognitive assessments, which included tests of memory, learning, motor function, and more. Participants were mostly male (97 percent) and had been on HIV treatment for a median of almost nine years, with a good response to medications (HIV viral loads in the plasma were all <100 copies/mL and median CD4 counts were in the normal range). Using highly sensitive methods to detect HIV, researchers found that almost half of these participants harbored viral DNA in cells found in the cerebrospinal fluid. Of those, 30 percent met the criteria for cognitive impairment.
While the study established an association between HIV DNA in cerebrospinal fluid with poorer performance on cognitive tests, researchers stressed that it did not establish a causal relationship, noting that there could be several explanations for the findings. Further studies will help determine strategies to reverse this persistence and improve neurological functioning in individuals with long-standing HIV.
About the AIDS Clinical Trials Group Founded in 1987, the AIDS Clinical Trials Group (ACTG) is the world’s largest and longest established HIV research network. The ACTG conducts groundbreaking studies to improve the treatment of HIV and its complications, reduce new infections and HIV-related illness, and
advance new approaches to prevent, treat, and ultimately cure HIV in adults and children. ACTG investigators and research units in 12 countries serve as major resources for HIV/AIDS research, treatment, care, and training/education in their communities. ACTG studies have helped establish current paradigms for managing HIV disease, and have informed HIV treatment guidelines, resulting in dramatic decreases in HIV-related mortality worldwide.

Media Contact: Alexis Sexton, AIDS Clinical Trials Group (ACTG)
ASexton@mednet.ucla.edu
868-603-2946 (office); 310-267-4895 (cell)

The AIDS Clinical Trials Group (ACTG), the world’s largest and longest-established HIV research network, funded by NIAID at the U.S. NIH, will make 11 oral and 19 poster presentations at CROI 2019 (Seattle, March 4-7). Several have the potential to influence clinical practice and guidelines for care.
“For more than 30 years, the ACTG has been at the forefront of research to treat HIV and its coinfections and comorbidities,“ said ACTG Chair Judith Currier, M.D., MSc of the University of California Los Angeles. “These studies represent the breadth of ACTG investigations and offer important insights into the treatment of MDR-TB, how to approach antiretroviral treatment in resource-limited settings, and strategies to address chronic complications of HIV.”

Highlights of ACTG presentations at CROI 2019 by topic include the following:

Tuberculosis:

* 84LB. QT EFFECTS OF BEDAQUILINE, DELAMANID OR BOTH IN MDR-TB PATIENTS: THE DELIBERATE TRIAL (ACTG 5343; CROI Oral Abstract Session 7: TB: From Contact to Cure and Beyond; Wednesday, March 6, 10:00 am – 12:00 pm) Kelly Dooley et al. (kdooley1@jhmi.edu) (presenting Gary Maartens. gary.maartens@uct.ac.za)

* FEATURED ON THE WEDNESDAY, MARCH 6 OFFICIAL CROI PRESS CONFERENCE

Bedaquiline and delaminid, the first two novel medications for MDR-TB to be developed in decades, generated extensive excitement when released. However, there is a lingering concern about overlapping toxicities with the two medications, specifically prolongation of the QT interval. This abstract resolves the debate.

82. EARLY BACTERICIDAL ACTIVITY OF HIGH-DOSE ISONIAZID AGAINST MULTI DRUG RESISTANT TB (ACTG 5312 (CROI Oral Abstract Session 7: TB: From Contact to Cure and Beyond; Wednesday, March 6, 10:00 am – 12:00 pm) Kelly Dooley et al. (kdooley1@jhmi.edu)

High-dose isoniazid (INH) 10-15 mg/kg was left off of the World Health Organization guidelines for multidrug-resistant TB recently, due to lack of data about bacteriocidal killing against TB with typical patterns of INH resistance. This abstract provides pivotal data that could impact guidelines.

78. POTENTIAL CONCERN FOR TIMING OF DMPA INJECTION AMONG WOMEN TREATED FOR HIV AND TB (ACTG 5338; CROI Oral Abstract Session 7: TB: From Contact to Cure and Beyond; Wednesday, March 6, 10:00 am – 12:00 pm) Rosie Mngqibisa et al. (mngqibisa@ecarefoundation.com)

Injectable depot medroxyprogesterone acetate (DMPA) is an important hormonal contraceptive for women in resource-limited settings, but we don’t know how it interacts with rifampin-based TB therapy. This study provides the first answers about the drug-drug interactions between DMPA and RIF based TB therapy among women on efavirenz-based ART.

ACTG at CROI 2019

Cure, Persistence, and Inflammation:

26. MULTI-DOSE IV ROMIDEPSIN: NO INCREASE HIV-1 EXPRESSION IN PERSONS ON ART, ACTG A5315 (CROI Oral Abstract Session 2: Strategies for HIV Cure; Tuesday, March 5, 10:00 am – 12:00 pm) Deborah McMahon et al. (mcmahond@pitt.edu)

* FEATURED ON THE TUESDAY, MARCH 5 OFFICIAL CROI PRESS CONFERENCE

The histone deacetylase inhibitor Romidepsin (RMD) could help in efforts to reverse HIV latency, if the drug induced HIV expression from cells. Unfortunately, this trial showed that RMD did not induce HIV expression among patients on ART as had been hoped.

37 LB. SAFETY, TOLERABILITY AND IMMUNOLOGIC ACTIVITY OF RUXOLITINIB ADDED TO SUPPRESSIVE ART (ACTG 5366 (CROI Oral Abstract Session 3: Noncommunicable Diseases in Treated HIV; Tuesday, March 5, 10:00 am – 12:00 pm) Vincent Marconi et al. (vcmarco@emory.edu)

Ruxolitinib (RUX) is a Janus kinase (Jak) inhibitor that reduces biomarkers of systemic inflammation in people without HIV and has some activity in the laboratory on reducing persistence in ex-vivo models. This abstract provides important new insights on whether RUX can safely reduce the persistent inflammation seen in people living with HIV, even when on suppressive ART.

131. SIROLIMUS REDUCES T CELL CYCLING AND IMMUNE CHECKPOINT MARKER EXPRESSION, ACTG A5337 (CROI Oral Abstract Session 12: HIV/SIV and the Immune System: An Intimate Dance; Thursday, March 7 10:00 am – 12:00 pm) Timothy Henrich et al. (Timothy.Henrich@ucsf.edu)

This abstract shows that continuous use of oral sirolimus, an mTOR inhibitor, modulates CCR5 expression and markers of cell cycling. Safety of this approach is still being evaluated, however.

Cognitive Function, Obesity and Long-Term HIV Infection:

128. CARDIOVASCULAR RISK SCORES PREDICT LONGITUDINAL COGNITIVE FUNCTION IN OLDER PLHIV (ACTG 5322; CROI Oral Abstract Session 11: Suppressive ART and the CNS: Switches, Outcomes, and Biomarkers; Thursday, March 7 10:00 am – 12:00 pm) Felicia Chow et al. (felicia.chow@ucsf.edu)

Addressing neurocognitive decline in people living with HIV requires targets for intervention. This study shows that the established baseline 10-year cardiovascular risk score predicts longitudinal cognitive function in people living with HIV – – and may provide clinicians with new insights into opportunities to optimize both heart health and brain health.

129. OBESITY IS INDEPENDENTLY ASSOCIATED WITH COGNITIVE DECLINE IN HIV (ACTG 5322; CROI Oral Abstract Session 11: Suppressive ART and the CNS: Switches, Outcomes, and Biomarkers; Thursday, March 7 10:00 am – 12:00 pm) Jeremiah Perez et al. (perez@sdac.harvard.edu)

Much remains to be learned about what contributes to neurocognitive decline in persons living with HIV, and how to prevent or reverse it. In the ACTG 5322 (HALIO) study, both greater age and obesity were independently associated with neurocognitive decline.
This is just one of the many important ACTG abstracts at CROI 2019 highlighting the impact of obesity in HIV disease, including:

ACTG at CROI 2019

• 669. RISK FACTORS FOR EXCESS WEIGHT GAIN FOLLOWING SWITCH TO INTEGRASE INHIBITOR-BASED ART (ACTG 5322, ACTG 5001; Themed Discussion Session 08, Weight Gain During ART, Wednesday, March 6, 1:30 pm) Jordan Lake et al. (Jordan.E.Lake@uth.tmc.edu)
• 673. THE IMPACT OF WEIGHT GAIN AND SEX ON IMMUNE ACTIVATION FOLLOWING INITIATION OF ART (NWCS 407; Themed Discussion Session 08, Weight Gain During ART, Wednesday, March 6, 1:30 pm) Sarah Bares et al. (sara.bares@unmc.edu)
• 384. SEX AND OBESITY ARE ASSOCIATED WITH RESIDUAL VIREMIA IN ARTSUPPRESSED INDIVIDUALS (ACTG 5321; Poster Session P-E09; Mechanisms of Persistence; Thursday, March 7, 2:30 pm) Joshua Cyktor. et al. (jcc114@pitt.edu)
• 681. CHANGES IN FAT DENSITY AFTER ART INITIATION (NWCS 450; Poster Session P-N3: Adipose Tissue Density and Biology; Thursday, March 7, 2:30 pm) Jordan Lake et al. (Jordan.E.Lake@uth.tmc.edu)

Antiretroviral therapy:

52. PHARMACOGENETICS WORSENS AN ADVERSE ANTIRETROVIRAL-HORMONAL CONTRACEPTIVE INTERACTION (ACTG 5316; CROI Oral Abstract Session O-05: Strange Bedfellows: STIs, Contraception, and Trials of HIV Testing, Tuesday, March 5 10:00 am – 12:00 pm) David Haas et al. (david.haas@vanderbilt.edu)

We already know that efavirenz influences the levels of the birth control products etonogestrol and ethinyl estradiol in injectable implants. This important study looks at whether there are genetic traits we can screen for that influence that interaction.

518. IMPORTANT SEX DIFFERENCES IN OUTCOMES FOR INDIVIDUALS PRESENTING FOR THIRD LINE ART (ACTG 5288; Themed Discussion Session TD-04: Women with HIV: Are Outcomes Different? Tuesday, March 5, 1:30 pm) Catherine Godfrey et al. (cgodfrey@niaid.nih.gov)

This study looked at how to treat people living with HIV on failing 2nd-line ART in low- and middle- income countries. This abstract explores the very important topic of sex differences in safety and outcomes for men and women in that large study.

496. QUALITY OF LIFE AND ADHERENCE AS PREDICTORS OF SECOND-LINE ART VIROLOGICAL FAILURE (ACTG 5373; CROI Poster Session P-H3, Virologic Failures: To Second Line and Beyond, Wednesday, March 6, 2:30 pm). Thiago Torres et al. (thiago.torres@ini.fiocruz.br)

Can quality of life influence adherence when switching to a new regimen? If so, providers can help patients with adherence by focusing more on their overall quality of life.

499. PREDICTORS OF VIROLOGIC OUTCOME WHILE CONTINUING A PI-BASED ART REGIMEN IN ACTG A5288. (CROI Poster Session P-H3, Virologic Failures: To Second Line and Beyond, Wednesday, March 6, 2:30 pm). Robert Salata et al. (ras7@case.edu)

This important presentation provides further evidence of the factors that lead to better or worse outcomes for people failing 2nd line therapy in low- and middle-income countries.