ACTG TO PRESENT NEW HIV AND TB RESEARCH AT CROI 2020

Mar 03, 2020

Presentations Focus on Cure, Co-Morbidities, Contraception, Sex Differences,
and Predictors of Clinical Outcomes
Los Angeles, Calif. – The AIDS Clinical Trials Group (ACTG), the world’s largest and longestestablished HIV research network, will make 28 presentations at the Conference on
Retroviruses and Opportunistic Infections (CROI 2020) held in Boston, March 8-11. ACTG
investigators will present data in oral presentations and themed discussions on the impact of
chronic antiretroviral therapy (ART) on a novel metric of the HIV reservoir, predictors of
multidrug resistant tuberculosis (MDR-TB) in resource-limited settings, findings from the first
HIV cure trial that exclusively enrolled women, and interactions between contraceptives and TB
drugs and the vaginal microbiome.
“The ACTG has led research on HIV and its co-infections and comorbidities since the beginning
of the epidemic, more than 30 years ago,” said ACTG Chair Judith Currier, M.D., MSc, of the
University of California, Los Angeles. “The studies being presented at CROI this year reflect the
diversity of ACTG’s research portfolio and demonstrate our commitment to addressing the full
range of issues affecting people living with HIV. These studies provide insights into HIV cure,
TB, the interaction between contraception and HIV treatment, sex differences, and comorbidities in people living with HIV.”
The 28 ACTG presentations at CROI 2020, a premier global HIV research conference,
demonstrate ACTG’s continued impact on the understanding of HIV pathogenesis, clinical
interventions, clinical care, and the health of people living with HIV. Presentations are listed
below:
ORAL PRESENTATIONS AND THEMED DISCUSSIONS
INTACT PROVIRAL DNA LEVELS DECLINE IN PEOPLE WITH HIV ON ANTIRETROVIRAL
THERAPY (ART) (ACTG 5321; Oral Abstract Session 0-06: Targeting the Persistent HIV
Reservoir, Tuesday, March 10 10:00 am – 12:00 pm) Rajesh T. Gandhi, et al.
(rgandhi@mgh.harvard.edu) Topic: HIV Cure, the Reservoir, and Persistence
The intact proviral DNA assay is a novel metric of the HIV reservoir. This study shows that intact
proviral DNA levels decline for people on chronic ART and examines the relationship of that
decline to other metrics of HIV persistence and immune activation.
PREDICTORS OF TUBERCULOSIS INFECTION IN MDR-TB HOUSEHOLD CONTACTS ≥15
YEARS OLD (ACTG 5300/IMPAACT2003; Oral Abstract Session 0-12: Tuberculosis,
Opportunistic Infections, and HIV Testing, Wednesday, March 11 10:00 am – 12:00 pm) Soyeon
Kim, et al. (skim@sdac.harvard.edu) Topic: Tuberculosis
This presentation provides insights into predictors of active TB infection among household
contacts of individuals with MDR-TB.
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EFFECT OF TAMOXIFEN ON VORINOSTAT-INDUCED HIV RNA EXPRESSION IN WOMEN
ON ART (ACTG 5366; Themed Discussion Session TD-06: Curative Strategies: Trials and
Tribulations, Tuesday, March 10 1:30 pm – 2:30 pm) Eileen Scully, et al. (escully1@jhmi.edu)
Topic: HIV Cure, the Reservoir, and Persistence
A5366 is the first study to examine a strategy to reduce the HIV reservoir exclusively in women
using a hormone-modulating approach. Since estrogen in women blocks the expression of HIV
when researchers try to ‘turn on’ the latent reservoir in women living with HIV, A5366 examines
whether tamoxifen and vorinostat can reverse latency.
A COMBINED ESTROGEN/PROGESTIN VAGINAL RING IMPROVES VAGINAL MICROBIAL
COMMUNITIES (ACTG 5316; Themed Discussion Session TD-15: Making Sense of it All: HIV
Susceptibility in the Female Genital Tract, Wednesday, March 11, 1:30 pm – 2:30 pm) Nicole H.
Tobin, et al. (ntobin@mednet.ucla.edu) Topic: Contraception
This presentation explores the relationship between the use of hormone-base intravaginal rings
and vaginal flora.
ANTIRETROVIRAL AND RIFAMPICIN CO-TREATMENT AFFECTS DMPA EXPOSURE:
DOSING IMPLICATIONS (ACTG 5338; Themed Discussion Session TD-13: The Long and
Short of it: What’s Next for Long-Acting Drugs, Wednesday, March 11, 1:30 pm – 2:30 pm) Jose
Francis, et al. (jose.francis@uct.ac.za) Topic: Contraception
Because TB coinfection among pregnant women living with HIV is associated with poor
outcomes, effective contraception to prevent unintended pregnancy is important. This study
examines the impact of HIV and rifampicin-based TB therapy on depot medroxyprogesterone
acetate (DMPA) levels when used as an injectable contraceptive.
POSTER PRESENTATIONS
HIV Cure, the Reservoir, and Persistence
RISK AND PREVALENCE OF RESIDUAL VIREMIA AFTER cART IN RESOURCE-LIMITED
COUNTRIES (NWCS 425; Poster Session P-E02: Measuring the HIV Reservoir, Monday,
March 9, 2:30 pm – 4:00 pm) Sivaporn Gatechompol, et al. (sivaporn.k@hivnat.org)
This study compares factors associated with residual single copy viremia in people living with
HIV who are virally suppressed on ART between the United States and resource-limited
settings.
TELMISARTAN DECREASES MONOCYTE CX3CR1 EXPRESSION IN TREATED HIV
INFECTION (ACTG 5317; Poster Session P-M02: Adipose Tissue and Obesity, Tuesday, March
10, 2:30 pm – 4:00 pm) Jordan E. Lake, et al. (jordan.e.lake@uth.tmc.edu)
Telmisartan is an angiotensin receptor blocker with anti-inflammatory properties, especially in
adipose tissue. This presentation evaluates whether telmisartan improves inflammatory and
obesity markers in patients on ART.
AMINOBISPHOSPHONATES REVERSE LATENCY IN HIV-SEROPOSITIVE INDIVIDUALS
(NWCS 464; Poster Session P-E07: HIV Curative Strategies: In Vitro Studies, Tuesday, March
10, 2:30 pm – 4:00 pm) Natalia Soriano-Sarabia, et al. (nataliasorsar@email.gwu.edu)
Aminobisphosphonates, which are used to treat osteoporosis, may reverse latency in chronic
HIV infection due to disruptions in cell signaling. This study examines that association for the
first time.
TH2 CYTOKINES ARE ASSOCIATED WITH HIGHER LEVELS OF INTACT PROVIRUSES
ON ART (ACTG 5321; Poster Session P-E10: Immune Pressure on the HIV Reservoir,
Wednesday, March 11, 2:30 pm – 4:00 pm) Joshua C. Cyktor, et al. (jcc114@pitt.edu)
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This study examines the relationship between levels of various cytokines among people on ART
and different metrics of the HIV-1 reservoir.
MODELING HIV RESERVOIR DECLINE AFTER ART INITIATION AS A FUNCTION OF NK
CELL FEATURES (NWCS 441; Poster Session P-E10: Immune Pressure on the HIV Reservoir,
Wednesday, March 11, 2:30 pm – 4:00 pm) Elena Vendrame, et al. (elenaven@stanford.edu)
HIV DNA levels decline after ART initiation, and this study examines factors associated with that
decline, including natural killer cells.
Viral Control with or without Structured Treatment Interruptions
FACTORS ASSOCIATED WITH VIRAL CONTROL AFTER STRUCTURED TREATMENT
INTERRUPTION (NWCS 470; Poster Session P-E04: Insights from Analytical Treatment
Interruptions, Monday, March 9, 2:30 pm – 4:00 pm) Nikolaus Jilg, et al. (njilg@partners.org)
Structured treatment interruptions (STIs) will be a critical strategy to determine if HIV remission
or cure efforts are successful. This study examines the factors immediately following STIs that
predict longer periods of virologic control.
HIV POST-TREATMENT CONTROL DESPITE PLASMA VIRAL EVOLUTION AND DUAL
INFECTION (NWCS 470; Poster Session P-E04: Insights from Analytical Treatment Interruptions,
Monday, March 9, 2:30 pm – 4:00 pm) Behzad Etemad, et al. (betemad@bwh.harvard.edu)
HIV post-treatment controllers (PTCs) serve as models for sustained HIV remission and may
provide clues for HIV remission or cure studies. This study examines plasma virus composition
and diversification within HIV PTCs.
FREQUENCY OF POST-TREATMENT CONTROL VARIES BY ART RESTART AND VIRAL
LOAD CRITERIA (NWCS 380; Poster Session P-E04: Insights from Analytical Treatment
Interruptions, Monday, March 9, 2:30 pm – 4:00 pm) Jesse M. Fajnzylber, et al.
(jesse_fajnzylber@dfci.harvard.edu)
Analytic treatment interruptions (ATI) are critical strategies to examine the efficacy of HIV
remission or cure strategies. This study examines an interactive tool for estimating viral rebound
timing in the setting of an ATI.
Tuberculosis
GEOGRAPHIC AND INDIVIDUAL RISK FACTORS FOR TB OR DEATH IN THE BRIEF-TB
TRIAL (ACTG 5279; Poster Session P-N02: Latent TB Infection: Risk Factors, Treatment, and
Prevention, Monday, March 9, 2:30 pm – 4:00 pm) Cynthia Riviere, et al. (criviere@ghesiko.org)
The original A5279 trial compared one month of isoniazid and rifapentine to nine months of
isoniazid for TB prevention in resource-limited settings. This follow-up presentation explores
clinical, demographic, and geographic factors associated with TB acquisition, TB-related death,
and death in each group.
Comorbidities
ADVANCED GLYCATION END PRODUCTS ASSOCIATED WITH CARDIOMETABOLIC RISK
ON ART (ACTG 5260; Poster Session P-L01: Inflammatory Biomarkers and Cardiovascular
Outcomes, Monday, March 9, 2:30 pm – 4:00 pm) Vanessa El Kamari, et al.
(Vanessa.ElKamari@UHhospitals.org)
This study evaluates changes in serum advanced glycation end products (AGEs), usually
associated with aging, in the ACTG 5257 trial after ART initiation with one of three NNRTIbased regimens.
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TRICARBOXYLIC ACID METABOLITES PREDICT METABOLIC COMORBIDITIES AND
DEATH IN AGING PWH (NWCS 447; Poster Session P-M03: Metabolic Complications,
Monday, March 9, 2:30 pm – 4:00 pm) Corrilynn O. Hileman, et al. (chileman@metrohealth.org)
Monocyte activation may contribute to inflammatory and metabolic changes among people
aging with HIV. This study analyzes associations between concentrations of monocyte
activation markers and comorbidities in the HIV Infection, Aging, and Immune Function LongTerm Observational (HAILO) study.
PREDICTIVE VALUE OF THE CD8 COUNTS AND CD4/CD8 RATIO AT TWO YEARS OF
SUCCESSFUL ART (DACS 322.1; Poster Session P-Q05: T Cell Patterns, Monday, March 9,
2:30 pm – 4:00 pm) Sergio Serrano-Villar, et al. (sergio.serrano@salud.madrid.org)
Although CD4 cell counts predict clinical events, there is variability in the predictive power of
CD8+ T cell counts and CD4/CD8 ratios on clinical outcomes in HIV. This study examines these
factors in relation to clinical events on suppressive ART.
GUT INTEGRITY MARKERS AND ASSOCIATIONS WITH ADIPOSITY IN PEOPLE WITH
AND WITHOUT HIV (ACTG 5260s; Poster Session P-M02: Adipose Tissue and Obesity,
Tuesday, March 10, 2:30 pm – 4:00 pm) Allison Ross Eckard, et al. (eckarda@musc.edu)
Fat accumulation after ART initiation remains a serious problem among people living with HIV,
but little is known about the pathophysiology of this process, especially with Integrase Strand
Transfer Inhibitors. This presentation assesses the relationship between gut integrity markers
and body composition for the first time.
A CROSS-SECTIONAL ANALYSIS OF ANTIRETROVIRAL REGIMEN ACTIVITY IN
CEREBROSPINAL FLUID (ACTG 5321; Poster Session P-G03: Pharmacokinetics and
Pharmacodynamics in Special Populations and Body Sites, Tuesday, March 10, 2:30 pm – 4:00
pm) Courtney V. Fletcher, et al. (cfletcher@unmc.edu)
This study analyzes the distribution of different antiretrovirals (ARVs) in cerebrospinal fluid and
the relationship between that distribution and biomarkers of HIV persistence and inflammation in
the cerebrospinal fluid.
T-CELL AND MONOCYTE ACTIVATION CORRELATE AND DECLINE DURING HCV
THERAPY FOR HCV-HIV (ACTG 5329; Poster Session P-J06: HCV After the SVR: Gone but
Not Forgotten, Tuesday, March 10, 2:30 pm – 4:00 pm) Ann Auma, et al. (awa28@case.edu)
Successful hepatitis C (HCV) therapy has been associated with partial or complete
normalization of immune activation during mono-HCV infection. This presentation shows that
successful therapy for HCV among patients with HIV-HCV co-infection similarly leads to a
decline in markers of immune activation, despite the ongoing HIV.
PLASMA CITRATE AND SUCCINATE PREDICT NEUROCOGNITIVE IMPAIRMENT IN
OLDER PWH (NWCS 447; Poster Session P-F02: Neurocognition: Biomarkers, Therapies, and
Outcomes, Tuesday, March 10, 2:30 pm – 4:00 pm) Corrilynn O. Hileman, et al.
(chileman@metrohealth.org)
This study evaluates the effect of specific neuroinflammatory markers on neurocognitive
impairment among older people living with HIV.
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PREVALENCE OF PHYSICAL FUNCTION IMPAIRMENT AND FRAILTY IN MIDDLE-AGED
PWH (ACTG 5361; Poster Session P-M08: Functional Status and Frailty, Wednesday, March
11, 2:30 pm – 4:00 pm) Triin Umbleja, et al. (tumbleja@sdac.harvard.edu)
People living with HIV have an increased risk of falls, hospitalizations, and mortality due to
frailty. This study evaluates the risk factors for physical function impairment among patients with
HIV at low to moderate cardiovascular risk.
PRINCIPAL COMPONENTS ANALYSIS TO IDENTIFY BIOMARKERS PREDICTIVE OF
NON-AIDS EVENTS (NWCS 411; Poster Session P-B08: Non-AIDS Consequences of HIV
Infection, Wednesday, March 11, 2:30 pm – 4:00 pm) Carlee Moser, et al.
(cmoser@sdac.harvard.edu)
In this presentation, biomarkers of monocyte and macrophage activation are examined in
relationship to non-AIDS events among individuals living with HIV.
TOTAL HIV DNA LEVELS DO NOT PREDICT NON-AIDS-DEFINING EVENTS (NWCS 411;
Poster Session P-B08: Non-AIDS Consequences of HIV Infection, Wednesday, March 11, 2:30
pm – 4:00 pm) Colline Wong, et al. (cwong22@bwh.harvard.edu)
While total HIV DNA levels predict the size of the HIV reservoir, this study shows that this
biomarker is not associated with non-AIDS defining events among people living with HIV.
Sex Differences
SEX-SPECIFIC ANALYSES IN ORAL ABSTRACTS FROM CROI 2019 (A5001; Poster
Session P-Q02: HIV in Key Populations, Monday, March 9, 2:30 pm – 4:00 pm) William R.
Short, et al. (wshort@pennmedicine.upenn.edu)
Globally, women account for more than half of all people living with HIV yet remain
underrepresented in research. CROI guidelines (starting in 2018) specifically recommend
reporting sex distribution and sex-adjusted analyses, but adherence to these guidelines has
been relatively poor. This updated analysis examines adherence to these guidelines among oral
abstracts from CROI 2019.
DYNAMICS OF HIV-SPECIFIC T-CELLS ON DURABLE ART DIFFER BY ANTIGEN
RECOGNIZED & BY SEX (ACTG 5321; Poster Session P-D08: Impact of Antiretrovirals on the
Immune Response, Wednesday, March 11, 2:30 pm – 4:00 pm) Eva M. Stevenson, et al.
(ems2200@med.cornell.edu)
In order to advance understanding toward HIV cure, sex differences must be examined to
determine whether cure strategies will differ by sex. This study examines differences in HIVspecific T cell responses by sex among chronically treated patients on ART.
HIV Diagnosis/Predictors of Clinical Outcomes
INFLAMMATION AND MITOCHONDRIAL DYSFUNCTION NOT NRTIS DRIVE EVENTS IN
ACTG A5241 (NWCS 423; Poster Session P-M10: Epigenetic and Mitochondrial Toxicities,
Tuesday, March 10, 2:30 pm – 4:00 pm) Carl J. Fichtenbaum, et al. (fichtecj@ucmail.uc.edu)
A recent ACTG study found that among people living with HIV experiencing treatment failure,
the treatment arm that added an NRTI to a regimen of two or more ARVs had more deaths and
clinical events than the arm that did not. However, inflammation and mitochondrial dysfunction
seem to drive these events (not the NRTIs) in this study.
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NOVEL CRITERIA FOR DIAGNOSING ACUTE HIV IN A MULTI-NATIONAL ART INITIATION
STUDY (ACTG 5354; Poster Session P-R06: Diagnosing Early HIV Infection, Wednesday,
March 11, 2:30 pm – 4:00 pm) Trevor A. Crowell, et al. (tcrowell@hivresearch.org)
ART initiation during acute HIV infection (AHI) limits the size of the HIV reservoir, but identifying
patients with AHI can be logistically challenging. This presentation evaluates a novel way to
diagnose AHI incorporating modern diagnostic algorithms to facilitate early treatment.

 

ACTG CROI press release 3.2