ACTG Presentations at CROI 2019

The AIDS Clinical Trials Group (ACTG) is the world’s largest and longest-established HIV research network. Funded by NIAID at the U.S. NIH, the ACTG has been at the forefront of efforts to treat and reduce the global HIV epidemic for more than 30 years.

ACTG researchers made 11 oral and 19 poster presentations at CROI 2019 (Seattle, March 4-7). ACTG Chair Judith Currier, M.D., MSc of the University of California Los Angeles, states: ”These studies represent the breadth of ACTG investigations and provide 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.”

ACTG presentations at CROI 2019 included the following. Links are provided to the webcasts, posters or abstracts.

 

Tuberculosis:

84LB. QT EFFECTS OF BEDAQUILINE, DELAMANID OR BOTH IN MDR-TB PATIENTS: THE DELIBERATE TRIAL (A5343)

Kelly E. Dooley1, Susan L. Rosenkranz2, Francesca Conradie3, Laura E. Moran4, Richard Hafner5, Florian von Groote-Bidlingmaier6, Javier R. Lama7, Justin Shenje8, Kyla Comins6, Joel Morganroth9, Andreas H. Diacon6, Yoninah S. Cramer2, Kathleen M. Donahue10, Gary Maartens8

1Johns Hopkins University School of Medicine, Baltimore, MD,2Harvard T.H. Chan School of Public Health, Boston, MA, USA,3University of the Witwatersrand, Johannesburg, South Africa,4Social & Scientific Systems, Silver Spring, MD, USA,5DAIDS, NIAID, Bethesda, MD, USA,6TASK Applied Science, Cape Town, South Africa,7Barranco Clinical Research Site, Lima, Peru,8University of Cape Town, Cape Town, South Africa,9ERT, Inc, Philadelphia, PA, USA,10Frontier Science & Technology Research Foundation, Inc, Amherst, NY, USA

Study abstract

Presentation webcast

CROI press conference presentation

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 study showed that the combined effect of the two drugs on prolongation of the QT interval was modest and no more than additive, with the combination being safe and well-tolerated. By addressing this important safety concern, this work paves the way for the dual use of BDQ and DLM for MDR-TB.

82. EARLY BACTERICIDAL ACTIVITY OF HIGH-DOSE ISONIAZID AGAINST MULTI DRUG RESISTANT TB (A5312)

Kelly E. Dooley1, Sachiko Miyahara2, Florian von Groote-Bidlingmaier3, Xin Sun2, Richard Hafner4, Susan L. Rosenkranz5, Eric Nuermberger1, Laura E. Moran6, Kathleen Donahue5, Susan Swindells7, Andreas H. Diacon3

1Johns Hopkins University School of Medicine, Baltimore, MD,2Harvard University, Boston, MA, USA,3TASK Applied Science, Cape Town, South Africa,4DAIDS, NIAID, Bethesda, MD, USA,5Frontier Science & Technology Research Foundation, Inc, Amherst, NY, USA,6Social & Scientific Systems, Silver Spring, MD, USA,7University of Nebraska Medical Center, Omaha, NE, USA

Study abstract

Presentation webcast

This study showed that high-dose isoniazid (INH) had substantial early bacteriocidal activity (EBA) against Mycobacterium tuberculosis strains with inhA mutations among patients with MDR-TB, provided it was dosed at 10-15 mg/kg, supporting WHO recommendations for high-dose INH in this population. Activity at these doses was similar to the standard 5 mg/kg dose in drug-sensitive TB. Longer-term tolerability, plus efficacy of high-dose INH against strains with another key mutation (katG) require further study

78. Potential concern for timing of DMPA injection among women treated for HIV and TB (A5338)

Rosie Mngqibisa1, Susan E. Cohn2, Michelle A. Kendall3, Xingye Wu3, Kelly E. Dooley4, Helen Mcilleron5, Jennifer A. Robinson4, Cindy Firnhaber6, Jhoanna C. Roa7, Sharlaa Badal-Faesen8, Francis Angira9, Mpho S. Raesi10, James G. Hakim11, Catherine Godfrey12

1Enhancing Care Foundation, Durban, South Africa,2Northwestern University, Chicago, IL, USA,3Harvard University, Boston, MA, USA,4Johns Hopkins University School of Medicine, Baltimore, MD,5University of Cape Town, Cape Town, South Africa,6University of Colorado, Aurora, CO, USA,7Social & Scientific Systems, Silver Spring, MD, USA,8University of the Witwatersrand, Johannesburg, South Africa,9KEMRI-UCSF, Kisumu, Kenya,10Botswana Harvard AIDS Institute Partnership, Gabarone, Botswana,11University of Zimbabwe, Harare, Zimbabwe,12National Institute of Allergy and Infectious Diseases, Bethesda, MD, USA

Study abstract

Presentation webcast

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 showed that DMPA, when given with efavirenz (EFV)-based ART and rifampin (RIF)-based TB therapy, was safe and well tolerated. MPA clearance was higher than in controls, leading to sub-therapeutic concentrations of MPA in some women at 10 and 12 weeks post-dose, though progesterone levels typically associated with ovulation were not observed. It may be prudent to dose DMPA more frequently than every 12 weeks in women on EFV with HIV-associated TB taking RIF.

 

Cure, Persistence, and Inflammation:

26. Multi-dose IV Romidepsin: no increase HIV-1 expression in persons on ART, ACTG A5315

Deborah McMahon1, Lu Zheng2, Joshua C. Cyktor1, Evgenia Aga2, Bernard J. Macatangay1, Catherine Godfrey3, Michael Para4, Ronald T. Mitsuyasu5, Joseph Hesselgesser6, Curtis Dobrowolski7, Jonathan Karn7, Edward P. Acosta8, Rajesh T. Gandhi9, John W. Mellors1

1University of Pittsburgh, Pittsburgh, PA, USA,2Harvard University, Boston, MA, USA,3NIH, Bethesda, MD, USA,4The Ohio State University, Columbus, OH, USA,5University of California Los Angeles, Los Angeles, CA, USA,6Gilead Sciences, Inc, Foster City, CA, USA,7Case Western Reserve University, Cleveland, OH, USA,8University of Alabama at Birmingham, Birmingham, AL, USA,9Massachusetts General Hospital, Boston, MA, USA

Study abstract

Presentation webcast

CROI press conference presentation

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. This finding is important, however, as we continue to seek out strategies to reduce HIV persistence and induce remission.

37 LB. SAFETY, TOLERABILITY AND IMMUNOLOGIC ACTIVITY OF RUXOLITINIB ADDED TO SUPPRESSIVE ART (A5336)

Vincent C. Marconi1, Carlee Moser2, Christina Gavegnano1, Athe Tsibris3, Amy Kantor2, Edgar T. Overton4, Charles W. Flexner5, Peter W. Hunt6, Rafick-Pierre Sekaly7, Carlos del Rio1, Michael M. Lederman7, Randall Tressler8, Steven G. Deeks6, Jeffrey J. Lennox1, Raymond F. Schinazi1

1Emory University, Atlanta, GA, USA,2Harvard T.H. Chan School of Public Health, Boston, MA, USA,3Harvard Medical School, Boston, MA, USA,4University of Alabama at Birmingham, Birmingham, AL, USA,5Johns Hopkins University School of Medicine, Baltimore, MD,6University of California San Francisco, San Francisco, CA, USA,7Case Western Reserve University, Cleveland, OH, USA,8NIH, Bethesda, MD, USA

Study abstract

Presentation webcast

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. The study found that ruxolitinib was safe and well tolerated, but did not significantly reduce IL6 levels. RUX treatment led to a modest decrease in sCD14 with an increase in circulating T cells through mechanisms undefined. This proof-of-concept trial provides a rationale for future studies of Jak inhibitors in PLWH who have residual inflammation or immune dysfunction despite long-term suppressive ART.

131. SIROLIMUS REDUCES T CELL CYCLING AND IMMUNE CHECKPOINT MARKER EXPRESSION, ACTG A5337

Timothy J. Henrich1, Ronald Bosch2, Catherine Godfrey3, Hanna Mar2, Apsara Nair4, Elizabeth Hawkins5, Carl Fichtenbaum6, Michael Keefer7, Jonathan Z. Li8, Daniel R. Kuritzkes8, Michael M. Lederman9, Priscilla Hsue1, Steven G. Deeks1

1University of California San Francisco, San Francisco, CA, USA,2Harvard University, Boston, MA, USA,3National Institute of Allergy and Infectious Diseases, Bethesda, MD, USA,4Frontier Science & Technology Research Foundation, Inc, Amherst, NY, USA,5Social & Scientific Systems, Silver Spring, MD, USA,6University of Cincinnati, Cincinnati, OH, USA,7University of Rochester, Rochester, NY, USA,8Brigham and Women's Hospital, Boston, MA, USA,9Case Western Reserve University, Cleveland, OH, USA

Study abstract

Presentation webcast

Use of the mTOR inhibitor Sirolimus was associated with significant reductions in CCR5 expression and T-cell markers of cell cycling and immune exhaustion in this study. There was a relatively high rate of treatment discontinuation, in part because of protocol-defined stopping criteria, and further safety and efficacy studies are ongoing.

208. PD-1HI CD4+T Cells are Associated with Reduced HIV-Specific Responses (A5321)

Bernard J. Macatangay1, Rajesh T. Gandhi2, R. Brad Jones3, Deborah McMahon1, Allison S. Thomas4, Christina Lalama5, Ronald Bosch5, Luann Borowski1, Evelyn Hogg6, Joseph J. Eron7, John W. Mellors1, Charles Rinaldo1

1University of Pittsburgh, Pittsburgh, PA, USA,2Harvard Medical School, Boston, MA, USA,3New York Presbyterian Hospital, New York, NY, USA,4Boston University, Boston, MA, USA,5Harvard University, Boston, MA, USA,6Social & Scientific Systems, Silver Spring, MD, USA,7University of North Carolina at Chapel Hill, Chapel Hill, NC, USA

Study abstract

Peripheral blood frequencies of PD-1HI CD4+ T cells of people with HIV on ART in A5321 were negatively associated with HIV-specific interferon gamma (IFNγ) responses, but not with CMV or EBV responses. These findings suggest that the PD-1HI CD4+ T cell subset contains HIV-specific cells that have decreased helper function and should be targeted to reverse immune dysfunction and improve immune control of HIV.

213. Oral Cytokine Expression is Linked to Oral HIV-1 Levels in ACTG A5254

Joseph Rocco1, Zachary York2, Janet McLaughlin1, Luann Borowski1, Jennifer Webster-Cyriaque3, Caroline H. Shiboski4, Judith Aberg5, Charles Rinaldo1, Bernard J. Macatangay1

1University of Pittsburgh, Pittsburgh, PA, USA,2University of Wisconsin–Madison, Madison, WI, USA,3University of North Carolina at Chapel Hill, Chapel Hill, NC, USA,4University of California San Francisco, San Francisco, CA, USA,5Icahn School of Medicine at Mt Sinai, New York, NY, USA

Study abstract

e-poster

This study suggests that high levels of oral HIV rather than low CD4 counts or plasma HIV are more linked to production of oral immune mediators. Despite severe immunosuppression, participants with AIDS demonstrated elevated levels of cytokines corresponding to both Th1 and Th2 T cell responses. The interplay of HIV and these immune mediators could be an important factor in the oral health of people living with HIV.

305. Susceptibility to bnAbs is Concordant in pre-ART Plasma and on-ART PBMCs Samples (NWCS 413)

Jacqueline Reeves1, Yu Zheng2, Maxine Olefsky3, Yolanda Lie1, Leah Burke4, Babafemi Taiwo5, Christos Petropoulos1, Pablo Tebas6, Marina Caskey7, Katharine J. Bar6

1Monogram BioSciences, San Francisco, CA, USA,2Harvard University, Cambridge, MA, USA,3Harvard University, Boston, MA, USA,4Yale University, New Haven, CT, USA,5Northwestern University, Chicago, IL, USA,6University of Pennsylvania, Philadelphia, PA, USA,7The Rockefeller University, New York, NY, USA

Study abstract

e-poster

ACTG NWCS 413 found a wide range in baseline neutralization susceptibilities to clinically relevant bnAbs with highly correlated values across plasma and PBMC-derived samples over 3 years of ART. In A5340, PhenoSense nAb susceptibilities from Monogram on entry PBMCs were similar to published pre-ART values and IC50<0.5 µg/mL was associated with delayed rebound after acute treatment interruption. These results support the utility of screening for neutralization susceptibility prior to therapeutic bnAb use.

395. Telmisartan Decreases HIV-1 RNA in Lymph Nodes in Treated HIV Infection (A5317)

Netanya S. Utay1, Jordan E. Lake1, Claire Deleage2, Douglas W. Kitch3, Eunice Yeh3, Karin L. Klingman4, Michael M. Lederman5, Carl Fichtenbaum6, Daniel Douek7, Judith S. Currier8, Jacob D. Estes2

1University of Texas at Houston, Houston, TX, USA,2Leidos Biomedical Research, Inc, Frederick, MD, USA,3Harvard University, Boston, MA, USA,4DAIDS, NIAID, Bethesda, MD, USA,5Case Western Reserve University, Cleveland, OH, USA,6University of Cincinnati, Cincinnati, OH, USA,7National Institute of Allergy and Infectious Diseases, Bethesda, MD, USA,8University of California Los Angeles, Los Angeles, CA, USA

Study abstract

e-poster

In A5317, the number of lymph noden(LN) HIV-1 RNA+ cells declined 45% with telmisartan added to suppressive ART. At Week 0, people with less LN fibrosis and fewer vRNA+ cells had more LN CD4+ T cells. Decreases in macrophages were accompanied by better LN CD4+ T cell recovery. Further characterization of these macrophages and the reservoir will clarify the interactions between HIV-1, LN immune cells, and their effects on fibrosis and the HIV reservoir.

557. HIV-1 RNA Detection by Abbott M2000 Correlates with Integrase Single Copy Assay (A5001)

Melissa A. Tosiano1, Hanna Mar2, Joshua C. Cyktor1, Dianna L. Koontz1, Joseph J. Eron3, Rajesh T. Gandhi4, Deborah McMahon1, Ronald Bosch2, John W. Mellors1

1University of Pittsburgh, Pittsburgh, PA, USA,2Harvard University, Boston, MA, USA,3University of North Carolina at Chapel Hill, Chapel Hill, NC, USA,4Massachusetts General Hospital, Boston, MA, USA

Study abstract

e-poster

Using data from A5321, 73% of plasma samples with an Abbott HIV-1 RNA result of <40 cp/mL target detected also had HIV-1 RNA detected by integrase single copy assy (iSCA), whereas 43% of samples that were target non-detected (TND) by Abbott had HIV-1 RNA detected by iSCA. The difference presents meaningful information that can be used to estimate the likelihood of HIV-1 RNA detectability by iSCA. The strong association between the results of both assays indicates that a high-throughput automated assay such as Abbott M2000 could be used in epidemiologic investigations of low-level viremia and to screen for changes in low-level viremia following therapeutic interventions, thereby reducing the need for more labor-intensive research single copy assays.

 

Cognitive Function, Obesity, Co-Morbidities, and Long-Term HIV Infection:

128. Cardiovascular risk scores predict longitudinal cognitive function in older PLHIV (ACTG 5322)

Felicia C. Chow1, Asya Lyass2, Joseph Massaro2, Virginia Triant3, Kunling Wu4, Baiba Berzins5, Kevin Robertson6, Ronald J. Ellis7, Katherine Tassiopoulos4, Babafemi Taiwo5, Ralph D'Agostino2

1University of California San Francisco, San Francisco, CA, USA,2Boston University, Boston, MA, USA,3Massachusetts General Hospital, Boston, MA, USA,4Harvard University, Boston, MA, USA,5Northwestern University, Chicago, IL, USA,6University of North Carolina at Chapel Hill, Chapel Hill, NC, USA,7University of California San Diego, San Diego, CA, USA

Study abstract

Presentation webcast

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 worse cognitive function at Year 4 in PLHIV, though this association was attenuated in men (not women) after adjusting for covariates. A higher CV risk score may help to identify PLHIV at risk for worse cognitive function over time, and 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)

Jeremiah Perez1, Adriana Andrade2, Ronald J. Ellis3, Mary Clare Masters4, Karl Goodkin5, Susan L. Koletar6, Frank J. Palella4, Kevin Robertson7, Ned Sacktor8, Katherine Tassiopoulos1, Kristine M. Erlandson9

1Harvard University, Boston, MA, USA,2DAIDS, NIAID, Rockville, MD, USA,3University of California San Diego, San Diego, CA, USA,4Northwestern University, Chicago, IL, USA,5East Tennessee State University, Johnson City, TN, USA,6The Ohio State University, Columbus, OH, USA,7University of North Carolina at Chapel Hill, Chapel Hill, NC, USA,8Johns Hopkins Hospital, Baltimore, MD, USA,9University of Colorado, Aurora, CO, USA

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 worsening cognitive function. These results extend previous work demonstrating a higher risk of neurocognitive impairment among obese PLWH by showing that obese individuals are also at greater risk of subsequently transitioning from unimpaired to impaired neurocognition.

Study abstract

Presentation webcast

669. Risk factors for excess weight gain following switch to integrase inhibitor-based ART (ACTG 5322, ACTG 5001)

Jeremiah Perez1, Adriana Andrade2, Ronald J. Ellis3, Mary Clare Masters4, Karl Goodkin5, Susan L. Koletar6, Frank J. Palella4, Kevin Robertson7, Ned Sacktor8, Katherine Tassiopoulos1, Kristine M. Erlandson9

1Harvard University, Boston, MA, USA,2DAIDS, NIAID, Rockville, MD, USA,3University of California San Diego, San Diego, CA, USA,4Northwestern University, Chicago, IL, USA,5East Tennessee State University, Johnson City, TN, USA,6The Ohio State University, Columbus, OH, USA,7University of North Carolina at Chapel Hill, Chapel Hill, NC, USA,8Johns Hopkins Hospital, Baltimore, MD, USA,9University of Colorado, Aurora, CO, USA

Study abstract

Presentation webcast

Yearly weight gain increased following switch to an integrase inhibitor (INSTI) in the A5322 and A5001 studies. These increases were particularly significant for women, blacks and persons age ≥60. When compared to pre-switch weight changes on stable suppressive ART, and given concomitant increases in waist circumference, these data suggest increases in weight/fat mass greater than expected for age. The cardiometabolic implications of increased weight gain following switch to INSTI need to be established.

673. THE IMPACT OF WEIGHT GAIN AND SEX ON IMMUNE ACTIVATION FOLLOWING INITIATION OF ART (NWCS 407)

Sara H. Bares1, Laura M. Smeaton2, Vincent Vu2, Beth A. Zavoda-Smith3, Sarah E. Scott3, Catherine Godfrey4, Grace A. McComsey3

1University of Nebraska Medical Center, Omaha, NE, USA,2Harvard T.H. Chan School of Public Health, Boston, MA, USA,3Case Western Reserve University, Cleveland, OH, USA,4DAIDS, NIAID, Bethesda, MD, USA

Study abstract

e-poster

Presentation webcast

Higher pre-treatment immune activation markers are significantly associated with weight gain following ART initiation, even after controlling for pre-ART CD4 counts in A5202 and A5257. Weight gain attenuates the decline in several immune activation markers following ART initiation among women; thus, women may be at increased risk for complications of weight gain. Identifying individuals at risk of weight gain may allow for targeted investigation of preventive interventions.

384. Sex and obesity are associated with residual viremia in ART-suppressed individuals (ACTG 5321)

Joshua C. Cyktor1, Hanna Mar2, Ann Collier3, Evelyn Hogg4, Catherine Godfrey5, Joseph J. Eron6, Ronald Bosch2, Deborah McMahon1, John W. Mellors1, Rajesh T. Gandhi7

1University of Pittsburgh, Pittsburgh, PA, USA,2Harvard University, Boston, MA, USA,3University of Washington, Seattle, WA, USA,4Social & Scientific Systems, Silver Spring, MD, USA,5DAIDS, NIAID, Bethesda, MD, USA,6University of North Carolina at Chapel Hill, Chapel Hill, NC, USA,7Massachusetts General Hospital, Boston, MA, USA

Study abstract

e-poster

In the A5321 study, higher BMI and obesity are associated with higher levels of residual viremia in persons on long-term ART. Adipose tissue may be an important site of HIV production due to its proinflammatory milieu or altered ARV penetration. The finding that females have lower residual viremia than males may reflect the effects of estrogen on HIV expression or other biologic and immunologic differences. Studies of the mechanism by which obesity and sex affect HIV persistence are needed to inform cure strategies

681. Changes in Fat Density After ART Initiation (NWCS 450)

Jordan E. Lake1, Carlee Moser2, Maxine Olefsky2, Kristine M. Erlandson3, Ann Scherzinger3, James H. Stein4, Judith S. Currier5, Todd T. Brown6, Grace A. McComsey7

1University of Texas at Houston, Houston, TX, USA,2Harvard University, Cambridge, MA, USA,3University of Colorado Anschutz Medical Campus, Aurora, CO, USA,4University of Wisconsin–Madison, Madison, WI, USA,5University of California Los Angeles, Los Angeles, CA, USA,6Johns Hopkins University School of Medicine, Baltimore, MD,7Case Western Reserve University, Cleveland, OH, USA

Study abstract

e-poster

In A5257, visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) density decreased following ART initiation. Women and PLWH with higher HIV-1 RNA had greater decreases. Following virologic suppression, lower AT density was associated with greater systemic inflammation, lipid parameter disruption and insulin resistance independent of adipose tissue area. These findings suggest that changes in fat tissue during ART may have adverse health consequences

253. EBV and CMV Levels in Blood are Associated with Non-AIDS Events During ART (NWCS 411)

Sara Gianella1, Carlee Moser2, Andrej Vitomirov1, Ashley McKhann2, Laura Layman1, Brianna Scott1, Steven Lada1, Ronald Bosch2, Martin Hoenigl1, Nell Lurain3, Alan Landay3, Michael M. Lederman4, Peter W. Hunt5, Davey M. Smith1

1University of California San Diego, La Jolla, CA, USA,2Harvard University, Boston, MA, USA,3Rush University, Chicago, IL, USA,4Case Western Reserve University, Cleveland, OH, USA,5University of California San Francisco, San Francisco, CA, USA

Study abstract

e-poster

In the ACTG ALLRT cohort, subclinical replication of EBV and (to lesser extent) CMV in blood was associated with increased inflammation and was predictive of non-AIDS events (myocardial infarction/stroke, malignancy, serious bacterial infection) and mortality among patients on ARTwith virologic suppression.

508. HIV Controllers Maintain Viral Suppression Despite Waning T-Cell Responses on ART (A5308)

Nikolaus Jilg1, Pilar Garcia-Broncano2, Michael Peluso3, Florencia Pereyra4, Ronald Bosch5, Carla Roberts-Toler5, Cornelius N. Van Dam6, Michael Keefer7, Daniel R. Kuritzkes4, Alan Landay8, Steven G. Deeks3, Xu G. Yu2, Paul E. Sax4, Jonathan Z. Li4

1Massachusetts General Hospital, Boston, MA, USA,2Ragon Institute of MGH, MIT and Harvard, Cambridge, MA, USA,3University of California San Francisco, San Francisco, CA, USA,4Brigham and Women's Hospital, Boston, MA, USA,5Harvard University, Boston, MA, USA,6University of North Carolina at Chapel Hill, Chapel Hill, NC, USA,7University of Rochester, Rochester, NY, USA,8Rush University, Chicago, IL, USA

In A5308, ART significantly reduced both HIV-specific CD4+ and CD8+ T cell responses in HIV controllers. ART did not adversely affect controller status, as HIV controllers maintained a low viral load after ART discontinuation.

Study abstract

e-poster

258. Telomere Length, Telomerase Activity and Age-related Disease: ACTG NWCS 422.

Chad J. Achenbach1, Drew Nannini1, Isabelle Clerc1, Hannah Hudson1, Brian Joyce1, Kunling Wu2, Katherine Tassiopoulos2, Peter W. Hunt3, Babafemi Taiwo1, Richard D'Aquila1, Sudhir Penugonda1, Lifang Hou1, Frank J. Palella1

1Northwestern University, Chicago, IL, USA,2Harvard University, Boston, MA, USA,3University of California San Francisco, San Francisco, CA, USA

Study abstract

e-poster

In the ACTG ALLRT cohort, pre-ART telomeres were significantly shorter among PWH with higher VL levels; however, pre-ART telomere length and telomerase activity were not associated with age-related disease. Longitudinal data of changes in telomere length and telomerase activity during ART and associations with disease events are forthcoming.

616. Liver Inflammation is Common and Linked to Metabolic Derangements in Treated HIV (A5322)

Kara W. Chew1, Katherine Tassiopoulos2, Frank J. Palella3, Kunling Wu2, Susanna Naggie4, Netanya S. Utay5, Edgar T. Overton6, Mark Sulkowski7

1University of California Los Angeles, Los Angeles, CA, USA,2Harvard University, Boston, MA, USA,3Northwestern University, Chicago, IL, USA,4Duke University, Durham, NC, USA,5University of Texas at Houston, Houston, TX, USA,6University of Alabama at Birmingham, Birmingham, AL, USA,7Johns Hopkins University, Baltimore, MD, USA

Study abstract

e-poster

In the ACTG HALIO cohort, after exclusion of HCV, HBV and alcohol, liver enzyme elevation was remarkably common and independently associated with metabolic disease, presence of hepatic steatosis, Hispanic ethnicity, and lower CD4 at entry. These findings suggest that NAFLD may be a common cause of liver inflammation in PWH receiving suppressive ART. Further research is needed to understand the contribution of NAFLD and other mechanisms of liver injury in PWH on suppressive ART.

648. HDL Cholesterol Efflux Capacity and Incident Cardiovascular Disease in HIV: Impact of HAART (NWCS 398)

Roger Bedimo1, Colby Ayers2, Jason Gillman3, Amneris Luque2, Ayea El-Ghazali2, Constance A. Benson4, Edgar T. Overton5, Pablo Tebas6, Anand Rohatgi2

1VA North Texas Health Care Center, Dallas, TX, USA,2University of Texas Southwestern, Dallas, TX, USA,3Prism Health North Texas, Dallas, TX, USA,4University of California San Diego, San Diego, CA, USA,5University of Alabama at Birmingham, Birmingham, AL, USA,6University of Pennsylvania, Philadelphia, PA, USA

Study abstract

e-poster

In the ACTG ALLRT study, unlike data from the general population, researchers did not observe an inverse association of HDL cholesterol efflux capacity (CEC) with risk of atherosclerotic cardiovascular disease (ASCVD) among HIV-infected participants on ART. ATV use was associated with less impaired CEC than DRV, EFV and RAL, but not with lower risk of incident ASCVD events. There was a trend for lower CEC with ABC vs. TDF exposure. Larger studies will be required to fully evaluate whether certain ARVs alter CEC and its role in ASCVD progression.

702. Weak Grip and Frailty are Associated with mtDNA Haplogroup in Adults with HIV (NWCS 275)

Kristine M. Erlandson1, Yuki Bradford2, David C. Samuels3, Todd T. Brown4, Jing Sun4, Kunling Wu5, Katherine Tassiopoulos5, Marylyn D. Ritchie2, David Haas3, Todd Hulgan3

1University of Colorado Anschutz Medical Campus, Aurora, CO, USA,2University of Pennsylvania, Philadelphia, PA, USA,3Vanderbilt University, Nashville, TN, USA,4Johns Hopkins University, Baltimore, MD, USA,5Harvard University, Boston, MA, USA

Study abstract

e-poster

In this analysis of ART-treated PLWH, European mtDNA haplogroup H was independently associated with weak grip and frailty versus with non-H European haplogroups. Mechanisms may include primary effects on mitochondrial function in skeletal muscle or indirectly through neurologic pathways, and warrants further study. This association, which has not been reported among people without HIV, could represent a unique contribution of HIV to weakness and frailty.

703. Glycemic Control and Cognition are Independently Associated with Gait Speed Decline (A5322)

Mary Clare Masters1, Jeremiah Perez2, Katherine Tassiopoulos2, Adriana Andrade3, Ronald J. Ellis4, Jingyan Yang5, Todd T. Brown6, Frank J. Palella1, Kristine M. Erlandson7

1Northwestern University, Chicago, IL, USA,2Harvard University, Boston, MA, USA,3DAIDS, NIAID, Rockville, MD, USA,4University of California San Diego, San Diego, CA, USA,5Columbia University, New York, NY, USA,6Johns Hopkins University, Baltimore, MD, USA,7University of Colorado, Aurora, CO, USA

Study abstract

e-poster

In A5322, the association between baseline hemoglobin A1C and development of slow gait speed highlights an intervenable target to prevent progression of physical function limitations. Additionally, the presence of neurocognitive impairment (NCI) among PLWH should prompt screening for and early intervention to avert declines in physical function.

 

Antiretroviral therapy:

52. Pharmacogenetics worsens an adverse antiretroviral-hormonal contraceptive interaction (ACTG 5316)

David Haas1, Yoninah S. Cramer2, Catherine Godfrey3, Susan L. Rosenkranz2, Francesca Aweeka4, Baiba Berzins5, Robert Coombs6, Kristine Coughlin2, Laura E. Moran7, David Gingrich4, Carmen D. Zorrilla8, Paxton Baker1, Susan E. Cohn5, Kimberly K. Scarsi9

1Vanderbilt University, Nashville, TN, USA,2Frontier Science & Technology Research Foundation, Inc, Amherst, NY, USA,3NIAID, Bethesda, MD, USA,4University of California San Francisco, San Francisco, CA, USA,5Northwestern University, Chicago, IL, USA,6University of Washington, Seattle, WA, USA,7Social & Scientific Systems, Silver Spring, MD, USA,8University of Puerto Rico, San Juan, Puerto Rico,9University of Nebraska Medical Center, Omaha, NE, USA

Study abstract

Presentation webcast

In ACTG A5316, women receiving efavirenz (EFV)-containing ART had 79% and 59% lower etonogestrel (ENG) and ethinyl estradiol (EE) concentrations, respectively, after 21 days of ENG/EE given as a vaginal ring (VR). Women receiving atazanavir/ritonavir (ATV/RTV)-containing ART had 71% higher ENG and 38% lower EE. These results are likely related to ART modulation of pathways responsible for hormone metabolism. This study examined whether genetics influenced these associations. CYP2B6 slow metabolizer genotype worsens the adverse PK interaction of EFV with ENG and EE administered by VR, likely due to enhanced cytochrome P450 induction by higher EFV concentrations. The study thus concludes that lower EFV dosing based on CYP2B6 genotype may reduce, but likely not eliminate, the impact of EFV on ENG and EE PK.

518. Important sex differences in outcomes for individuals presenting for third line ART (ACTG 5288)

Catherine Godfrey1, Michael D. Hughes2, Justin Ritz2, Robert Gross3, Robert A. Salata4, Rosie Mngqibisa5, Carole Wallis6, Mumbi Makanga7, Marije Van Schalkwyk8, Mitch Matoga9, Courtney V. Fletcher10, Beatriz Grinsztejn11, Ann Collier12

1National Institute of Allergy and Infectious Diseases, Bethesda, MD, USA,2Harvard University, Boston, MA, USA,3University of Pennsylvania, Philadelphia, PA, USA,4Case Western Reserve University, Cleveland, OH, USA,5Enhancing Care Foundation, Durban, South Africa,6Lancet Labs and BARC SA, Johannesburg, South Africa,7Kenya Medical Research Institute, Kisumu, Kenya,8Stellenbosch University, Cape Town, South Africa,9KEMRI–Centre for Global Health Research, Kisumu, Kenya,10University of Nebraska, Omaha, NE, USA,11Instituto Nacional de Infectologia Evandro Chagas, Rio de Janeiro. Brazil,12University of Washington, Seattle, WA, USA

Study abstract

e-poster

Presentation webcast

ACTG 5288 looked at how to treat people living with HIV on failing 2nd-line ART in low- and middle- income countries. Participants were assigned to cohorts based on resistance profiles and ART history: Cohort A had no LPV/r resistance, susceptibility to at least one NRTI, and stayed on their LPV/r- or ATV/r-based 2nd-line regimen; others with increasing resistance were assigned to Cohorts B, C or D and changed to 2nd line regimens. More women than men entered the study in cohort A, with a resistance profile suggesting they could be suppressed on their current regimen and therefore stayed on that regimen in the study. Women had a more frequent occurrence of Grade 3 signs and symptoms than men, suggesting that tolerability issues were under-recognized in women on 2nd-line therapy with demonstrated clinical consequences. More work is needed to identify determinants of drug exposure and tolerability in women in LMIC.

496. Quality of life and adherence as predictors of second-line ART virological failure (ACTG 5373)

Thiago S. Torres1, Linda J. Harrison2, Alberto M. La Rosa3, Lu Zheng2, Ann Collier4, Michael D. Hughes2

1Instituto Nacional de Infectologia Evandro Chagas, Rio de Janeiro. Brazil,2Harvard University, Boston, MA, USA,3Asociacion Civil Impacta Salud y Educacion, Lima, Peru,4University of Washington, Seattle, WA, USA

Study abstract

e-poster

In A5273, poor quality of life, particularly cognitive function (self-report) and low energy and fatigue, adds to self-reported incomplete adherence after 4 weeks of 2nd-line ART in predicting VF at week 24. Evaluation is needed to assess whether patients with poorer quality of life might be targeted for greater support to reduce risk of VF.

499. PREDICTORS OF VIROLOGIC OUTCOME WHILE CONTINUING A PI-BASED ART REGIMEN IN ACTG A5288

Robert A. Salata1, Beatriz Grinsztejn2, Justin Ritz3, Ann Collier4, Peter Mugyenyi5, Evelyn Hogg6, Linda Wieclaw7, Robert Gross8, Catherine Godfrey9, Nagalingeswaran Kumarasamy10, Cecilia Kanyama11, John W. Mellors12, Carole Wallis13, Michael D. Hughes3

1Case Western Reserve University, Cleveland, OH, USA,2Instituto Nacional de Infectologia Evandro Chagas, Rio de Janeiro. Brazil,3Harvard University, Boston, MA, USA,4University of Washington, Seattle, WA, USA,5Joint Clinical Research Centre, Kampala, Uganda,6Social & Scientific Systems, Silver Spring, MD, USA,7Frontier Science & Technology Research Foundation, Inc, Amherst, NY, USA,8University of Pennsylvania, Philadelphia, PA, USA,9DAIDS, NIAID, Bethesda, MD, USA,10YR Gaitonde Center for AIDS Research and Education, Chennai, India,11University of North Carolina Project–Malawi, Lilongwe, Malawi,12University of Pittsburgh, Pittsburgh, PA, USA,13Lancet Labs and BARC SA, Johannesburg, South Africa

Study abstract

e-poster

In this 3rd-line ART trial (A5288) in resource-limited settings, fewer than 50% of participants with no lopinavir resistance at entry who continued their 2nd-line ART had VL suppression at 48 weeks. Participants with more advanced disease or any resistance mutations had worse rates of suppression. This group likely represents individuals with continued poor ARV adherence.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.

509. Restricted Mean Survival Time as a Treatment Measure in HIV/AIDS Clinical Trials (ACTG A5257)

Xian Abulizi1, Philippe Flandre1, Heather Ribaudo2

1INSERM, Paris, France,2Harvard T.H. Chan School of Public Health, Boston, MA, USA

Study abstract

e-poster

Via a methodologic reworking of the A5257 treatment trial, the authors of this study found that the restricted mean survival time (RMST) measure analysis could be a promising alternative measure of efficacy in HIV/AIDS clinical trials, although further discussion to define non-inferiority bounds is needed.

916. Low rate of sex-specific analyses in CROI presentations in 2018: Room to improve (A5001).

Monica Gandhi1, Laura M. Smeaton2, Christina Vernon3, Eileen P. Scully4, Sara Gianella5, Selvamuthu Poongulali6, Anandi N. Sheth7, Marije Van Schalkwyk8, Karin L. Klingman9, William R. Short10, Valarie S. Opollo11, Susan E. Cohn12, Kimberly K. Scarsi13, Rosie Mngqibisa14, Elizabeth Connick15

1University of California San Francisco, San Francisco, CA, USA,2Harvard T.H. Chan School of Public Health, Boston, MA, USA,3Social & Scientific Systems, Silver Spring, MD, USA,4Johns Hopkins University, Baltimore, MD, USA,5University of California San Diego, La Jolla, CA, USA,6YR Gaitonde Center for AIDS Research and Education, Chennai, India,7Emory University, Atlanta, GA, USA,8Stellenbosch University, Cape Town, South Africa,9NIH, Bethesda, MD, USA,10University of Pennsylvania, Philadelphia, PA, USA,11Kenya Medical Research Institute, Kisumu, Kenya,12Northwestern University, Chicago, IL, USA,13University of Nebraska, Omaha, NE, USA,14Enhancing Care Initiative, Durban, South Africa,15University of Arizona, Tucson, AZ, USA

Study abstract

e-poster

Despite CROI 2018 providing guidelines for presentations consistent with US federal mandates on reporting by sex, more than a third of oral presentations failed to report sex demographics and only a quarter included sex-stratified analyses. Further education of researchers on guidelines requiring reporting of sex as a biological variable is essential to maximize knowledge about sex differences and similarities in HIV and its associated conditions.

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