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CROI 2021
This year’s Conference on Retroviruses and Opportunistic Infections (CROI) will be taking place virtually from March 6 – 10. The ACTG is presenting 24 abstracts. See below for a short summary of those abstracts as well as presentation types and times, and HERE for the ACTG press release.
HIV CURE
NON-INVASIVE PLASMA GLYCOMIC AND METABOLIC BIOMARKERS OF POST-TREATMENT CONTROL OF HIV (NWCS 482; Oral Session: Wednesday, March 10, 11:15am – 1:15pm EST) Leila B. Giron, et al.
Non-invasive biomarkers that predict HIV remission after antiretroviral therapy interruption are urgently needed. NWCS 482 sought to identify non-invasive biomarkers with functional significance that have the potential to predict the duration and probability of viral remission after treatment interruption.
 
MATHEMATICAL MODELING IDENTIFIES PREDICTORS OF POST-TREATMENT CONTROL IN CURE TRIALS (DR 056; Science Spotlight) Gesham Magombedze, et al.
The identification of early predictors of post-treatment control could improve the efficiency of analytical treatment interruptions (ATI) in cure trials and increase participant safety by limiting time off ART in non-controllers. DR056 leveraged available data from ACTG and Gilead Sciences ATI studies to identify early predictors of viral control.
 
AUTOLOGOUS NEUTRALIZING ANTIBODIES INCREASE WITH EARLY ART AND SHAPES HIV REBOUND (NWCS 380; Science Spotlight) Elmira Esmaeilzadeh, et al.
Early initiation of ART alters viral rebound kinetics after treatment interruption and may play a role in reducing the barrier to HIV remission. NWCS 380 evaluated whether autologous neutralizing antibody responses could develop in the setting of early-ART initiation and investigated their role in treatment interruptions.
 
ASSOCIATION OF IMMUNE MARKERS TO TIME TO REBOUND DURING HIV TREATMENT INTERRUPTION (ACTG 5345; Science Spotlight) Bernard Macatangay, et al.
Understanding factors that affect viral rebound timing during ART interruption will accelerate efforts toward inducing sustained HIV remission. ACTG 5345 evaluated whether immunologic parameters prior to treatment interruption can predict time to rebound in individuals interrupting ART in a highly monitored setting.
 
RESTING AND ACTIVATED CD4+ T CELLS BOTH HAVE SILENT AND ACTIVE HIV TREATMENT INTERRUPTION (ACTG 5341; Science Spotlight) Jennifer Groebner, et al.
Despite clinically effective ART, HIV-infected T cells survive and undergo cellular proliferation. ACTG 5341 hypothesized that the minority of T cells that express unspliced HIV RNA are in an activated state, while the majority of cells with transcriptionally silent proviruses are in a resting state.
 
MONOCYTE SUBSETS AFTER LONGTERM ART AND ASSOCIATIONS WITH MEASURES OF HIV PERSISTENCE (ACTG 5321; Science Spotlight) Bernard Macatangay, et al.
Several studies have investigated the role of monocytes in HIV infection, specifically in HIV-associated chronic inflammation. Because it remains unclear how monocytes correlate with measures of HIV persistence in individuals on long-term suppressive ART, A5321 evaluated monocyte subsets among this population.
 
COVID-19
SYMPTOM OUTCOME MEASURES FOR OUTPATIENT COVID-19 PHASE 3 TREATMENT TRIALS (ACTG 5401; Science Spotlight) Kara Chew, et al.
Symptom-based outcome measures should be considered for primary efficacy assessment in outpatient phase 3 COVID-19 treatment trials. ACTG 5401 analyzed potential measures utilizing patient-reported outcomes in the ACTIV-2 (an outpatient COVID-19 treatment study) participant diary. 
 
SARS-COV-2 RNA LEVELS CORRELATE WITH SYMPTOM DURATION BUT NOT SEVERITY IN OUTPATIENTS (ACTG 5401; Science Spotlight) Kara Chew, et al.
ACTG 5401 aimed to elucidate the relationship between nasopharyngeal SARS-CoV-2 RNA, demographics, and symptom characteristics in non-hospitalized people with COVID-19.
 
TUBERCULOSIS
ADVERSE PREGNANCY OUTCOMES AMONG HIV-INFECTED WOMEN EXPOSED TO ISONIAZID PREVENTIVE THERAPY IN THE BRIEF-TB TRIAL (ACTG 5279; Oral Session: Wednesday, March 10, 11:15am – 1:15pm EST) Amita Gupta, et al.
Isoniazid preventive therapy (IPT) is a key strategy for reducing TB and death among people living with HIV but has been associated with increased composite adverse pregnancy outcomes. ACTG 5279 assessed adverse pregnancy outcomes among women exposed to IPT in a secondary analysis of the BRIEF-TB trial, which demonstrated non-inferiority of one-month of IPT versus nine months.
 
SERUM MARKERS AND INTEGRATIVE MULTI-OMICS OF TB DIAGNOSIS IN ADVANCED HIV (NWCS 414; Science Spotlight) Sonya Krishnan, et al.
Tuberculosis (TB) accounts for a large burden of morbidity and mortality among people living with HIV and conventional diagnosis methods have lower sensitivity among that population. Because novel high-throughput diagnostics may advance our insights into subclinical and difficult to diagnose TB (especially in very advanced HIV), NWCS 414 evaluated a variety of screening mechanisms.
 
HEPATITIS C
THE KISS (KEEP IT SIMPLE AND SAFE) APPROACH TO HCV TREATMENT: PRIMARY OUTCOMES FROM THE ACTG A5360 (MINMON) STUDY (Oral Session: Tuesday, March 9, 11:15am – 1:15pm EST) Sunil Solomon, et al.
To achieve the goal of global HCV elimination by 2030, 80% of the ~71 million people with chronic HCV infection will need to be treated, requiring that treatment delivery be simplified without compromising efficacy or safety. COVID-19 has further highlighted the need for novel models of healthcare delivery that minimize in-person patient-provider contact. ACTG A5360 evaluated the safety and efficacy of a minimal monitoring (MINMON) approach to HCV therapy in treatment-naïve people with no evidence of decompensated cirrhosis.
 
CONTRACEPTION
PK OF STANDARD VS DOUBLE DOSE LEVONORGESTREL EMERGENCY CONTRACEPTION WITH EFAVIRENZ (ACTG 5375; Oral Session: Monday, March 8, 11:15am – 1:15pm EST) Kimberly Scarsi, et al.
Co-administrating levonorgestrel (LNG) emergency contraception with efavirenz (EFV) has been shown to significantly reduce concentration of LNG in healthy volunteers. While some guidelines recommend adjusting the dosage of LNG when combined with EFV, this strategy had yet not been assessed in pharmacokinetic or clinical studies. ACTG hypothesized that doubling the dose of LNG to 3mg would increase its exposure in people receiving EFV-based ART.
 
COMORBIDITIES
RISK FACTORS FOR PROGRESSION FROM PREDIABETES TO DIABETES IN PERSONS WITH HIV (ACTG 5322 (HAILO)/DACS 352; Science Spotlight) Mary Clare Masters, et al.
People living with HIV experience increased incidence and prevalence of diabetes mellitus compared to the general population. ACTG 5322 sought to identify risk factors (which have not been previously characterized) that would cause people living with HIV on ART with pre-diabetes to advance to diabetes mellitus.
 
FACTORS ASSOCIATED WITH SYSTEMIC IMMUNE ACTIVATION IN A GLOBAL HIV COHORT (ACTG 5332 (REPRIEVE); Science Spotlight) Sara Looby, et al.
Among people living with HIV who are taking ART, persistent systemic immune activation may contribute to atherogenesis, CVD events, and mortality. REPRIEVE is the first study to characterize factors associated with key indices of systemic immune activation among a global cohort of people living with HIV. The presenters report baseline data associated with markers of systemic immune activation.
 
DIET QUALITY BY GLOBAL BURDEN OF DISEASE REGION IN ADULTS WITH HIV HIV IN THE REPRIEVE TRIAL (ACTG 5332 (REPRIEVE); Science Spotlight) Kathleen Fitch, et al.
Optimizing modifiable factors, such as diet, may delay onset or improve aging-associated comorbidities, including CVD. REPRIEVE evaluated diet quality across a global cohort of people living with HIV with low-to-moderate CVD risk who were receiving ART.
 
CORONARY ARTERY DISEASE (CAD), TRADITIONAL RISK AND INFLAMMATION AMONG PWH IN REPRIEVE (ACTG 5332 (REPRIEVE); Science Spotlight) Steven Grinspoon, et al.
REPRIEVE is a large ongoing primary prevention trial of people living with HIV, who are at increased risk for cardiovascular disease (CVD). The REPRIEVE Mechanistic Substudy aimed to identify unique factors contributing to CVD in people living with HIV. The presenters report baseline data from REPRIEVE correlating CT angiography findings with biomarkers and other data.
 
ELEVATED PLASMA GALECTIN-9 IS ASSOCIATED WITH NON-AIDS EVENTS DURING SUPPRESSIVE ART (NWCS 411; Science Spotlight) Thomas Premeaux, et al.
Increased risk of morbidity and mortality among people living with HIV is partly driven by chronic inflammation. Soluble galectin-9 (Gal-9), a pleiotropic glycan-binding immunomodulatory protein, is an immune modulator with a variety of functions, including acting as an immune checkpoint molecule. It has been shown to be elevated in people living with HIV taking ART and associated with markers of HIV persistence, neurological complications, and indices of morbidity and mortality in HIV infection. NWCS 411 aimed to identify the relationship between Gal-9 and the occurrence of non-AIDS events in people living with HIV who are taking suppressive ART.
 
SOLUBLE IMMUNE CO-STIMULATORY MOLECULES ARE PREDICTIVE OF NON-AIDS EVENTS DURING SUPPRESSIVE ART (NWCS 411; Science Spotlight) Thomas Premeaux, et al.
Immune co-stimulatory molecules (molecules that amplify or counteract the initial activating signals provided to T cells from the T cell receptor), which exist in soluble forms in normal physiological conditions and are elevated in cancer and inflammatory diseases, may be promising early predictive biomarkers of adverse outcomes in people living with HIV. NWCS 411 aimed to identify the relationships between plasma levels of soluble immune co-stimulatory molecules and the incidence of non-AIDS events using a nested case-control study from the ACTG ALLRT cohort.
 
IMPACT OF REPRODUCTIVE AGING ON HIV PERSISTENCE IN CIS-GENDER MEN AND WOMEN WITH HIV (NWCS 443; Science Spotlight) Sara Gianella Weibel, et al.
Women represent the majority of HIV infections worldwide, yet sex differences in HIV reservoir dynamics during reproductive aging remain an under-explored area of research. NWCS sought to elucidate the intersection between aging and declining sex hormones among women and to determine the role of sex on the HIV reservoir dynamic.
 
IMPACT OF REPRODUCTIVE AGING ON IMMUNE FUNCTION IN CIS-GENDER MEN AND WOMEN WITH HIV (NWCS 443; Science Spotlight) Stephen Rawlings, et al.
NWCS 443 sought to gain better understanding of the changes in women’s immune system during reproductive aging as a crucial factor to inform treatment and cure strategies.
 
HIV TREATMENT ADHERENCE
MASS SPECTROMETRY IMAGING OF HAIR TO IDENTIFY DAILY MARAVIROC ADHERENCE IN HPTN 069/ACTG 5305 (ACTG 5305; Science Spotlight) Eli Rosen, et al.
Adherence monitoring in hair provides a long-term measure of behavior, but accurately classifying adherence by drug concentration may be less accurate for melanin-bound compounds like maraviroc because darker hair colors can absorb greater amounts of the drug. ACTG 5305 used mass spectrometry imaging to assess daily adherence to maraviroc-based PrEP regimens in HPTN 069.
 
CANNABIS USE ASSOCIATED WITH DECREASED ART ADHERENCE IN AGING PEOPLE WITH HIV (DACS 354; Science Spotlight) Jennifer Manuzak, et al.
Because cannabis use is common among people living with HIV, DACS 354 sought to longitudinally characterize the association between its use and ART adherence among older people living with HIV. The study found that among aging people living with HIV, cannabis use was associated with decreased ART adherence.
 
HIV DRUG RESISTANCE
DRUG RESISTANCE MUTATIONS IN HIV PROVIRUS ARE ASSOCIATED WITH HYPERMUTATIONS (NWCS 371; Science Spotlight) Yijia Li, et al.
While HIV drug resistance mutations tests are crucial to clinical care, current methods require the plasma RNA copy number to be ­­>500-1000 copies/ml and can only detect major viral quasispecies in peripheral blood. NWCS 371 evaluated the clinical relevance of HIV proviral sequencing, which overcomes the limit of plasma viral load requirement by detecting all the "archive mutations."
 
MUTATIONS IN GP41 IN PRIMARY HIV-1 ISOLATES CONFER RESISTANCE TO ANTIRETROVIRALS (ACTG 5273; Science Spotlight) Yuta Hikichi, et al.
Recent research demonstrated that the lab-adapted HIV-1 NL4-3 strain can develop resistance to dolutegravir. ACTG 5273 examined whether Env-mediated drug resistance arises in clinically relevant isolates, whether Env mutations can confer resistance to other classes of ARVs, and the possibility that Env mutations contribute to drug resistance in vivo.
PRESS RELEASE
             
This month the ACTG announced the addition of four new therapies to the ACTIV-2/A5401, Outpatient Monoclonal Antibodies and Other Therapies Trial. The new agents, which will be evaluated in phase 2 studies among non-hospitalized adults with COVID-19 are:
  • AZD7442 (AstraZeneca): a combination of two monoclonal antibodies (AZD8895 and AZD1061) being studied as both an infusion administered over 15 minutes and an intramuscular injection
  • SNG001 (Synairgen): a nebulized formulation of beta interferon being studied as an inhalant
  • Camostat (Sagent Pharmaceuticals): an orally administered serine protease inhibitor that inhibits viral entry by blocking a host cell protease 
Read the full press release HERE.
 
Additionally, ACTIV-2/A5401 has completed enrollment of Phase 2 of the Brii monoclonal antibodies and has started enrolling into Phase 3! Thank you to everyone for their hard work and helping us reach this milestone.
IN MEMORIAM
John. G. Gerber, MD
-Courtney Fletcher, PharmD; Elizabeth Connick, MD; Edward Acosta, PharmD; Jennifer Kiser, PharmD, PhD; Peter Anderson, PharmD; Angela Kashuba, PharmD; Jane Oppenheim, MPH; Robert “Chip” Schooley, MD; Constance Benson, MD

Photo courtesy of Ed Acosta
We share sad news with the ACTG family that John G. Gerber, M.D., passed away on February 6, 2021.

John was born in Budapest, Hungary. He attended Queens College in Flushing, New York. He received a Doctor of Medicine degree from the Medical College of Virginia in Richmond, VA, where he also completed his residency in internal medicine. He trained in two postdoctoral NIH fellowships at the Division of Clinical Pharmacology at Vanderbilt University, and at the University of Colorado School of Medicine in Denver. He joined the faculty in the Division of Clinical Pharmacology at the University of Colorado School of Medicine as an Assistant Professor of Medicine and Pharmacology in 1978 and was promoted rapidly to Associate Professor and then full Professor. In 1993, John turned his focus to infectious diseases and HIV, following his passion to complete a clinical fellowship in infectious diseases he became board certified in Infectious Diseases and received an appointment in the Division of Infectious Diseases at the University of Colorado School of Medicine. 
 
John was an outstanding physician, scientist and educator. His research was focused on pharmacology at both the basic science and clinical level. Broadly, John was interested in drug metabolism and aging. His early work focused on cardiovascular pharmacology, including work with prostaglandins, histamine analogs and beta-adrenergic blockers. He pursued questions of the influence of age and gender on drug effects, and stereoselective drug metabolism, which he subsequently carried over to his work in HIV. John led clinical pharmacologic studies of pharmacokinetic interactions between HIV protease inhibitors and statins, the role of protein binding, stereoselective metabolism of methadone, and antiretroviral drug pharmacokinetics in persons with hepatic dysfunction. He authored more than 160 papers in scientific journals. He used his research program, in his career as a scientist and physician, to learn and to teach other health professionals how to make drugs better and safer in humans. In particular, John was an excellent mentor. He was always encouraging of young scientists in pharmacology, helping them navigate their career path, and providing them with many scientific ideas and opportunities.
 
John’s work in HIV pharmacology and pharmacotherapy made an important difference in improving treatment and the lives of persons living with HIV infection. He was actively involved in the clinical trials of the ACTG, serving as both protocol chair and clinical pharmacologist. He was a highly valued member of the AIDS Clinical Trials Group’s Pharmacology Committee and served as Vice Chair and then Chair of the Committee; he also served as a member of the SASC. His pharmacology expertise was recognized and put to good use when he was invited to serve as a member of the Antiviral Drug Advisory Committee for the FDA.
 
John was a loyal and kind friend to many and a devoted godfather to Sam Keene. He especially enjoyed socializing with his colleagues and friends. He loved a good dinner with wine (always red!), with the conversation flowing about his three passions of poker, horse racing and tennis. He enthusiastically enjoyed his retirement in Palm Springs where he expanded his friendships and played tennis frequently. We will all cherish the time we had with John.
SPOTLIGHTS
INVESTIGATOR SPOTLIGHT
Sara Gianella Weibel, MD
 
Sara Gianella Weibel, M.D. directs the San Diego Center for AIDS Research (SD CFAR) Translational Virology Core, a position she has held since 2017. She graduated from the University of Zurich (Switzerland) and, after her residency in Internal Medicine and Infectious Disease in Switzerland, she began her fellowship in the Department of Infectious Disease and Hospital Epidemiology of the University Hospital of Zurich in 2007. She moved to UC San Diego in 2009 to work as a postdoctoral fellow with Drs. Douglas Richman and Davey Smith. In 2013 she joined the faculty of the Department of Medicine (Division of Infectious Diseases and Global Public Health) and currently works both at the UC San Diego Antiviral Research Center and in her laboratory on the UC San Diego Campus, where she performs bench research. 
 
Her research is focused on delineating virus and host interactions to answer fundamental open questions in the fields of inflammation, end organ damage, and HIV persistence. Her laboratory’s current research efforts include: (1) understanding the interactions between HIV and co-infecting viruses (CMV in particular) and investigating clinical complications related to persistent inflammation during effective ART, (2) characterizing the immunologic and viral milieu in anatomic compartments and tissues (e.g. genital tract and central nervous system), (3) understanding sex and gender-based differences in HIV pathogenesis and viral persistence.
 
For her productivity and scientific leadership, she has been awarded multiple prestigious awards, including the California HIV Research Program IDEA award, Creative and Novel Ideas in HIV Research Award, CFAR Emerging Investigator Award, UCSD Integrity Champion Award, and NIDA Avenir Award for excellent HIV/AIDS Research.
 
She has been an active member of the AIDS Clinical Trials Group since 2013, where she serves on the Women's Health Inter-Network Scientific Committee, the Comorbidity Transformative Science Group, and the Underrepresented Populations Scientific Committee. She is currently serving as the chair of A5355 anti-CMV vaccine clinical trial, and co-chair of A5383 letermovir clinical trial and A5400 letermovir sub-studies protocol. She is also the protocol virologist for A5403, The GET IT RIgHT Study, in development for transgender women only.
 
Above everything, Dr. Gianella Weibel enjoys spending time with her husband (Nadir) and her three wonderful kids, Emma (age 13), Noah (age 10) and Rebecca (Age 7).
COMMUNITY MEMBER SPOTLIGHT 
David "Jax" Kelly

David “Jax” Kelly has been involved in HIV/AIDS advocacy since 1991 when he served on the board of the Upper Room AIDS Ministry in Harlem, New York. As a Black, gay man living with HIV, he has served on the UCLA CARE Community Advisory Board (CAB), and, for the past three years, has been a member of the Case Western Reserve/University Hospital’s CAB in Cleveland. In late 2019 he was appointed to the Community Scientific Subcommittee (CSS) and is a representative on A5402 (COPE) and A5368 (CHECK HBV). Jax also attends meetings of the HIV and Aging Working Group and the Ethics Working Group. He looks forward to being active with the newly formed Behavioral and Social Sciences Working Group.
 
Jax splits his time between Cleveland, OH and Palm Springs, CA, which he considers home. In California he is the president of Let’s Kick ASS (AIDS Survivor Syndrome) Palm Springs (LKAPS.org), a non-profit serving HIV long-term survivors and witnesses to the plague years providing social connection, HIV and aging education, and advocacy. He leads the HIV and Aging Committee on the California Planning Group, a community advisory board to the California Department of Health’s Office of AIDS. Jax is treasurer and a member of the Steering Committee for The Reunion Project, a national group representing HIV long-term survivors. This spring, Jax will begin his pursuit of an MPH in Health Services and Policy at the Keck School of Medicine of the University of Southern California.
 
Jax is inspired by grass-roots organizers and members of the scientific community who can speak to their needs. He hopes to see the creation of standards of care for people aging with HIV and better integration of people aging with HIV in senior-living, nursing homes, and senior community centers.
SITE SPOTLIGHT
This year the ACTG Network added five new core ACTG Clinical research sites. Over the next few months, we will spotlight each one so the network can get to know more about them.

Yen Hoa Health Clinic CRS, Hanoi, Vietnam
 
The Yen Hoa Health Clinic CRS, located in Hanoi, Vietnam, is led by the University of North Carolina in Vietnam (UNC Vietnam). It recently became an ACTG CRS of the University of North Carolina Global HIV Prevention and Treatment Clinical Trials Unit. It is also an HPTN site and the Vietnam site for HPTN 083. Under the leadership of Drs. Vivian Go and Tran Viet Ha, UNC Vietnam has been conducting NIH-sponsored HIV research in Vietnam since 2001, with more than 20 studies among people living with HIV, people who inject drugs, MSM, and transgender women, including two studies of the HPTN network (HPTN 074 & HPTN 083) and four R01 randomized controlled trials. Currently, UNC Vietnam is implementing four studies: an R01 implementation science trial to scale up the HPTN 074 intervention among people living with HIV who inject drugs in 10 provinces across Vietnam; HPTN 083, which is evaluating long-acting injectable vs. daily oral PrEP to prevent HIV among HIV-uninfected MSM and transgender women; an R34 pilot grant to improve mental health and HIV outcomes among people living with HIV who inject drugs; and a qualitative study to understand the feasibility and acceptability of long-acting injectable ART among people living with HIV who inject drugs in Vietnam.
 
Yen Hoa CRS is operated by a team of 30 highly qualified, trained staff including pharmacists, nurses, doctors, laboratory technicians, receptionists, research assistants, and participant recruiters. With 20 years of experience conducting research studies in Vietnam, our site is highly knowledgeable about the epidemiology of infectious diseases and the healthcare system in Vietnam. We have established strong partnerships with the leading healthcare system organizations in Vietnam, including the Ministry of Health, Vietnam Authority of HIV/AIDS Control, Bach Mai Hospital, the National Institute of Hygiene and Epidemiology, provincial Departments of Health and Centers of Disease Control, Hanoi Medical University, Hanoi University of Public Health, and NGOs that support our study populations. The Yen Hoa CRS is supported by the advisory board comprising Drs. Irving Hoffman, Joe Eron and Bill Miller.
 
TheYen Hoa Health Clinic CRS is thrilled to be joining the ACTG and is excited to have the opportunity to participate in studies on HIV, tuberculosis, hepatitis, and other infectious diseases that affect the Vietnamese population. They hope that the study outcomes will be helpful for people living with HIV and other patients with infectious diseases in the world and especially in Vietnam, where the burden of HIV remains severe for many people.
CORRECTION
Last month’s newsletter featured a tribute to Dr. David Katzenstein. Unfortunately we were mistaken in publishing that he was the co-chair of ACTG 384. Apologies for any confusion.
SOCIAL MEDIA
Follow the ACTG on all of our social media accounts! Follow us throughout CROI for updates on ACTG presentations. Additionally, March 10 is National Women and Girls HIV/AIDS Awareness Day (#NWGHAAD)! Check out our social media pages to hear from our network about the importance of highlighting the experiences of women and girls living with HIV. 

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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 Leadership & Operations Center Communications Specialist Karen Hoffman.
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