1,288 results on '"Currier, Judith S"'
Search Results
52. Dynamics of inflammatory responses after SARS-CoV-2 infection by vaccination status in the USA: a prospective cohort study
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Zhu, Xianming, Gebo, Kelly A, Abraham, Alison G, Habtehyimer, Feben, Patel, Eshan U, Laeyendecker, Oliver, Gniadek, Thomas J, Fernandez, Reinaldo E, Baker, Owen R, Ram, Malathi, Cachay, Edward R, Currier, Judith S, Fukuta, Yuriko, Gerber, Jonathan M, Heath, Sonya L, Meisenberg, Barry, Huaman, Moises A, Levine, Adam C, Shenoy, Aarthi, Anjan, Shweta, Blair, Janis E, Cruser, Daniel, Forthal, Donald N, Hammitt, Laura L, Kassaye, Seble, Mosnaim, Giselle S, Patel, Bela, Paxton, James H, Raval, Jay S, Sutcliffe, Catherine G, Abinante, Matthew, Broderick, Patrick, Cluzet, Valerie, Cordisco, Marie Elena, Greenblatt, Benjamin, Petrini, Joann, Rausch, William, Shade, David, Lane, Karen, Gawad, Amy L, Klein, Sabra L, Pekosz, Andrew, Shoham, Shmuel, Casadevall, Arturo, Bloch, Evan M, Hanley, Daniel, Sullivan, David J, and Tobian, Aaron A R
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- 2023
- Full Text
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53. Methotrexate Decreases Tenofovir Exposure in Antiretroviral-Suppressed Individuals Living With HIV.
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Gingrich, David, Deitchman, Amelia N, Kantor, Amy, Huang, Liusheng, Stein, James H, Currier, Judith S, Hsue, Priscilla Y, Ribaudo, Heather J, and Aweeka, Francesca T
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Biomedical and Clinical Sciences ,Clinical Sciences ,Clinical Trials and Supportive Activities ,Clinical Research ,Sexually Transmitted Infections ,HIV/AIDS ,Infectious Diseases ,6.1 Pharmaceuticals ,Infection ,Good Health and Well Being ,Anti-HIV Agents ,Double-Blind Method ,Drug Interactions ,Female ,HIV Infections ,Humans ,Immunosuppressive Agents ,Male ,Methotrexate ,Middle Aged ,Tenofovir ,tenofovir ,methotrexate ,pharmacokinetics ,drug interactions ,transporters ,ACTG 5314 Protocol Team ,Public Health and Health Services ,Virology ,Clinical sciences ,Epidemiology ,Public health - Abstract
BackgroundTo mitigate increased risk of premature cardiovascular disease in antiretroviral therapy (ART) suppressed adults living with HIV (PWH), low-dose methotrexate (LDMTX) was evaluated in a multicenter randomized placebo controlled clinical trial of 176 PWH taking various ART regimens (ACTG A5314). Given shared methotrexate (MTX) and tenofovir (TFV) pharmacokinetic (PK) pathways, a substudy was conducted to investigate whether LDMTX alters TFV exposure.MethodsAdults virally suppressed on ART for >24 weeks were randomized to LDMTX or placebo. The first 66 participants taking a tenofovir disoproxil fumarate-containing regimen underwent intensive PK sampling over 24 hours after the second dose of LDMTX 10 mg or placebo. TFV and MTX levels were quantified using validated mass spectrometry methods. TFV PK between LDMTX and placebo groups were compared and MTX PK was characterized.ResultsForty-eight participants completed this substudy (n = 20 on LDMTX and 28 on placebo). Baseline characteristics were balanced except for protease inhibitor (PI)-use (25% in LDMTX and 43% in placebo groups). For TFV, AUC6 (primary endpoint), and AUC24,imputed, Cmax, and Cmin (secondary endpoints) were on average 22%, and 24%, 27%, and 31% less in the LDMTX versus placebo groups, with reductions in secondary endpoints reaching statistical significance. Additional analyses suggested a greater reduction in the absence of PI although not significant.ConclusionLower TFV AUC24,imputed and Cmax indicates that LDMTX reduces TFV exposure in PWH. However, this change was modest, not warranting a change in TFV dosing at this time. Further studies of TFV PK with LDMTX, especially without PI co-administration, are warranted.
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- 2020
54. Efficacy and safety of three antiretroviral therapy regimens started in pregnancy up to 50 weeks post partum: a multicentre, open-label, randomised, controlled, phase 3 trial
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Best, Brookie M., Blanchette, Cheryl D, Browning, Renee, Jaliaah, Nagawa, Mirochnick, Mark, Murtaugh, William A., Patras, Emmanuel, Whalen, Frances, Momper, Jeremiah D., Ponatshego, Ponego L., Tirelo, Lesedi, Seme, Boitshepo J., Modise, Georginah O., Raesi, Mpho S., Budu, Marian E., Ramogodiri, Moakanyi, Oliveira, Ricardo H., Hofe, Cristina B, Fernandes de Abreu, Thalita, Pestanha, Lorena M., João, Esaú, Sidi, Leon C., Fuller, Trevon, Cruz, Maria L.S, Pinto, Jorge, Ferreira, Flãvia, Correa Jr, Mãrio, Romeiro, Juliana, Pilotto, Jose H., Fernandes, Luis E.B.C, Moreira, Luiz F., Gomes, Ivete M., Naik, Shilpa, Nevrekar, Neetal, Mave, Vidya, Kinikar, Aarti, Horne, Elizea, Soma-Kasiram, Hamisha, Violari, Avy, Mathiba, Sisinyana R., Nyati, Mandisa, Theron, Gerhard, de Jager, Jeanne, Rossouw, Magdel, Rossouw, Lindie, Hanley, Sherika, Desmond, Alicia C., Gazu, Rosemary, Govender, Vani, Chalermchockcharoenkit, Amphan, Thamkhantho, Manopchai, Werarak, Peerawong, Rungmaitree, Supattra, Achalapong, Jullapong, Sitiritkawin, Lukkana, Cressey, Tim R., Sukrakanchana, Pra-ornsuda, Aurpibul, Linda, Tongprasert, Fuanglada, Khamrong, Chintana, Kiattivej, Sopida, Wabwire, Deo, Kabugo, Enid, Maena, Joel, Nakayiwa, Frances, Ndyanabangi, Victoria, Nagaddya, Beatrice, Sekabira, Rogers, Ashaba, Justus, Mitchell, Charles D., Drada, Adriana, Alvarez, Grace A., Scott, Gwendolyn B., Rathore, Mobeen, Mahmoudi, Saniyyah, Shabbir, Adnan, Maraqa, Nizar, Mandima, Patricia F., Mutambanengwe, Mercy, Maonera, Suzen, Chareka, Gift, Nematadzira, Teacler, Chanaiwa, Vongai, Matubu, Taguma A., Tamirepi, Kevin, Maturure, Sukunena, Mhembere, Tsungai, Vhembo, Tichaona, Chidemo, Tinashe, Chinula, Lameck, Ziemba, Lauren, Brummel, Sean, McCarthy, Katie, Coletti, Anne, Krotje, Chelsea, Johnston, Benjamin, Knowles, Kevin, Moyo, Sikhulile, Stranix-Chibanda, Lynda, Hoffman, Risa, Sax, Paul E, Stringer, Jeffrey, Chakhtoura, Nahida, Jean-Philippe, Patrick, Korutaro, Violet, Cassim, Haseena, Fairlie, Lee, Masheto, Gaerolwe, Boyce, Ceejay, Frenkel, Lisa M, Amico, K Rivet, Purdue, Lynette, Shapiro, Roger, Mmbaga, Blandina Theophil, Patel, Faeezah, van Wyk, Jean, Rooney, James F, Currier, Judith S, and Lockman, Shahin
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- 2023
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55. Patterns of Antiretroviral Therapy Use and Immunologic Profiles at Enrollment in the REPRIEVE Trial
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Fichtenbaum, Carl J, Ribaudo, Heather J, Leon-Cruz, Jorge, Overton, Edgar T, Zanni, Markella V, Malvestutto, Carlos D, Aberg, Judith A, Kileel, Emma M, Fitch, Kathleen V, Van Schalkwyk, Marije, Kumarasamy, Nagalingeswaran, Martinez, Esteban, Santos, Breno Riegel, Joseph, Yvetot, Lo, Janet, Siminski, Sue, Melbourne, Kathleen, Sponseller, Craig A, Desvigne-Nickens, Patrice, Bloomfield, Gerald S, Currier, Judith S, Hoffmann, Udo, Douglas, Pamela S, Grinspoon, Steven K, Curran, Adrian, Baranauskas, Adrienne, Wilkin, Aimee, Abrams-Downey, Alexandra J, Eckard, Allison Ross, Wurcel, Alysse G, González-Cordón, Ana, Paez, Armando, Sha, Beverly E, Santos, Breno, Yoshida, Carina Beppu, Rolle, Charlotte-Paige, Somboonwit, Charurut, Funk, Connie, Gómez-Ayerbe, Cristina, Frank, Cynthia, Nixon, Daniel E, Skiest, Daniel J, Choi, David, Mushatt, David M, Rial-Crestelo, David, Perez, Deborah K, Burke, Deirdre J, dos Santos, Desirée VG, Jayaweera, Dushyantha T, Gardner, Edward M, DeJesus, Edwin, Connick, Elizabeth, Lam, Emerline G, Hecker, Emily J, Kallas, Esper G, Waters, Evan, Rhame, Frank, Sattler, Fred R, Wang, Gary P, Enrile Seedhom, Helen May, Tavares, Isabel CF, Stapleton, Jack T, Bennet, Jaclyn, Brock, James B, Scott, James, Forcht, Janet, Lama, Javier R, Valencia, Javier, Brumfield, Jennifer K, Portilla, Joaquin, Kumar, Jonathan, Navarro, Jordi, Pinto, Jorge A, Castro, Jose G, Bernardino, Jose I, Casado, Jose L, Madruga, José Valdez, Baraiaetxaburu, Josu, Berenguer, Juan, Tashima, Karen T, Ho, Ken, Costa, Laura VL, Perez Latorre, Leire, Mohapi, Lerato, López-González, L, Fantry, Lori E, Domínguez-Domínguez, Lourdes, Martín-Carbonero, Luz, Cornelissen, Lynne M, Jain, Mamta K, Masiá, Mar, Lacerda, Marcus VG, Saumoy, Maria, Villalobos-Hernández, Marina, and Mall, Mark
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Medical Microbiology ,Biomedical and Clinical Sciences ,Clinical Research ,HIV/AIDS ,Clinical Trials and Supportive Activities ,Prevention ,Infectious Diseases ,Evaluation of treatments and therapeutic interventions ,6.1 Pharmaceuticals ,Infection ,Good Health and Well Being ,Adult ,Anti-Retroviral Agents ,CD4 Lymphocyte Count ,CD4-CD8 Ratio ,Cross-Sectional Studies ,Female ,HIV Infections ,Humans ,Male ,Middle Aged ,Randomized Controlled Trials as Topic ,HIV ,statins ,pitavastatin calcium ,antiretroviral therapy ,CD4 cell count ,CD4/CD8 ratio ,REPRIEVE ,cardiovascular disease ,REPRIEVE Investigators ,Biological Sciences ,Medical and Health Sciences ,Microbiology ,Biological sciences ,Biomedical and clinical sciences ,Health sciences - Abstract
BackgroundPatterns of antiretroviral therapy (ART) use and immunologic correlates vary globally, and contemporary trends are not well described.MethodsThe REPRIEVE trial (Randomized Trial to Prevent Vascular Events in HIV) enrolled persons with human immunodeficiency virus (HIV) who were aged 40-75 years, receiving ART, and had low-to-moderate cardiovascular disease risk. ART use was summarized within Global Burden of Disease (GBD) super-regions, with adjusted linear and logistic regression analyses examining associations with immune parameters and key demographics.ResultsA total of 7770 participants were enrolled, with a median age of 50 years (interquartile range, 45-55 years); 31% were female, 43% were black or African American, 15% were Asian, 56% had a body mass index >25 (calculated as weight in kilograms divided by height in meters squared), and 49% were current or former smokers. The median CD4 T-cell count was 620/µL (interquartile range, 447-826/ µ L), and the median duration of prior ART use, 9.5 years (5.3-14.8) years. The most common ART regimens were nucleoside/nucleotide reverse-transcriptase inhibitor (NRTI) plus nonnucleoside reverse-transcriptase inhibitor (43%), NRTI plus integrase strand transfer inhibitor (25%), and NRTI plus protease inhibitor (19%). Entry ART varied by GBD region, with shifts during the trial enrollment period. In adjusted analyses, entry CD4 cell count and CD4/CD8 ratio were associated with GBD region, sex, entry regimen, duration of ART, and nadir CD4 cell count; CD4 and CD8 cell counts were also associated with body mass index and smoking status.ConclusionsThere were substantial variations in ART use by geographic region and over time, likely reflecting the local availability of specific medications, changes in treatment guidelines and provider/patient preferences. The analyses of CD4 cell counts and CD4/CD8 ratios may provide valuable insights regarding immune correlates and outcomes in people living with HIV.Clinical trials registrationNCT02344290.
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- 2020
56. Correlates and Timing of Reproductive Aging Transitions in a Global Cohort of Midlife Women With Human Immunodeficiency Virus: Insights From the REPRIEVE Trial
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Zanni, Markella V, Currier, Judith S, Kantor, Amy, Smeaton, Laura, Rivard, Corinne, Taron, Jana, Burdo, Tricia H, Badal-Faesen, Sharlaa, Lalloo, Umesh G, Pinto, Jorge A, Samaneka, Wadzanai, Valencia, Javier, Klingman, Karin, Allston-Smith, Beverly, Cooper-Arnold, Katharine, Desvigne-Nickens, Patrice, Lu, Michael T, Fitch, Kathleen V, Hoffman, Udo, Grinspoon, Steven K, Douglas, Pamela S, and Looby, Sara E
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Reproductive Medicine ,Biomedical and Clinical Sciences ,Contraception/Reproduction ,Clinical Research ,Aging ,Estrogen ,Reproductive health and childbirth ,Good Health and Well Being ,Adult ,Anti-Mullerian Hormone ,Biomarkers ,Cardiometabolic Risk Factors ,Cohort Studies ,Female ,HIV Infections ,Humans ,Menopause ,Middle Aged ,Reproduction ,Residence Characteristics ,HIV ,Women ,Sex ,Reproductive Aging ,Cardiometabolic Risk ,Biological Sciences ,Medical and Health Sciences ,Microbiology ,Biological sciences ,Biomedical and clinical sciences ,Health sciences - Abstract
BackgroundReproductive aging may contribute to cardiometabolic comorbid conditions. We integrated data on gynecologic history with levels of an ovarian reserve marker (anti-müllerian hormone [AMH)] to interrogate reproductive aging patterns and associated factors among a subset of cisgender women with human immunodeficiency virus (WWH) enrolled in the REPRIEVE trial.MethodsA total of 1449 WWH were classified as premenopausal (n = 482) (menses within 12 months; AMH level ≥20 pg/mL; group 1), premenopausal with reduced ovarian reserve (n = 224) (menses within 12 months; AMH 12 months of amenorrhea). Excluding WWH with surgical menopause, age at final menstrual period was summarized for postmenopausal WWH (group 3) and estimated among all WWH (groups 1-3) using an accelerated failure-time model.ResultsCardiometabolic and demographic parameters associated with advanced reproductive age (controlling for chronologic age) included waist circumference (>88 vs ≤88 cm) (odds ratio [OR], 1.38; 95% confidence interval, 1.06-1.80; P = .02), hemoglobin (≥12 vs
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- 2020
57. Myocardial Steatosis Among Antiretroviral Therapy–Treated People With Human Immunodeficiency Virus Participating in the REPRIEVE Trial
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Neilan, Tomas G, Nguyen, Kim-Lien, Zaha, Vlad G, Chew, Kara W, Morrison, Leavitt, Ntusi, Ntobeko AB, Toribio, Mabel, Awadalla, Magid, Drobni, Zsofia D, Nelson, Michael D, Burdo, Tricia H, Van Schalkwyk, Marije, Sax, Paul E, Skiest, Daniel J, Tashima, Karen, Landovitz, Raphael J, Daar, Eric, Wurcel, Alysse G, Robbins, Gregory K, Bolan, Robert K, Fitch, Kathleen V, Currier, Judith S, Bloomfield, Gerald S, Desvigne-Nickens, Patrice, Douglas, Pamela S, Hoffmann, Udo, Grinspoon, Steven K, Ribaudo, Heather, Dawson, Rodney, Goetz, Matthew Bidwell, Jain, Mamta K, Warner, Alberta, Szczepaniak, Lidia S, and Zanni, Markella V
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Cardiovascular ,Clinical Research ,Prevention ,Clinical Trials and Supportive Activities ,Heart Disease ,6.1 Pharmaceuticals ,Evaluation of treatments and therapeutic interventions ,Good Health and Well Being ,Adipose Tissue ,Anti-Retroviral Agents ,Body Mass Index ,CD4 Lymphocyte Count ,Cardiomyopathies ,Female ,HIV Infections ,Heart Disease Risk Factors ,Humans ,Magnetic Resonance Imaging ,Magnetic Resonance Spectroscopy ,Male ,Middle Aged ,Triglycerides ,HIV ,myocardial steatosis ,intramyocardial triglyceride content ,cardiovascular magnetic resonance spectroscopy ,MRS ,cardiometabolic risk ,heart failure ,Biological Sciences ,Medical and Health Sciences ,Microbiology - Abstract
BackgroundPeople with human immunodeficiency virus (PWH) face increased risks for heart failure and adverse heart failure outcomes. Myocardial steatosis predisposes to diastolic dysfunction, a heart failure precursor. We aimed to characterize myocardial steatosis and associated potential risk factors among a subset of the Randomized Trial to Prevent Vascular Events in HIV (REPRIEVE) participants.MethodsEighty-two PWH without known heart failure successfully underwent cardiovascular magnetic resonance spectroscopy, yielding data on intramyocardial triglyceride (IMTG) content (a continuous marker for myocardial steatosis extent). Logistic regression models were applied to investigate associations between select clinical characteristics and odds of increased or markedly increased IMTG content.ResultsMedian (Q1, Q3) IMTG content was 0.59% (0.28%, 1.15%). IMTG content was increased (> 0.5%) among 52% and markedly increased (> 1.5%) among 22% of participants. Parameters associated with increased IMTG content included age (P = .013), body mass index (BMI) ≥ 25 kg/m2 (P = .055), history of intravenous drug use (IVDU) (P = .033), and nadir CD4 count
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- 2020
58. “Cure” Versus “Clinical Remission”: The Impact of a Medication Description on the Willingness of People Living with HIV to Take a Medication
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Fridman, Ilona, Ubel, Peter A, Blumenthal-Barby, Jennifer, England, Cameron V, Currier, Judith S, Eyal, Nir, Freedberg, Kenneth A, Halpern, Scott D, Kelley, Colleen F, Kuritzkes, Daniel R, Le, Catherine N, Lennox, Jeffrey L, Pollak, Kathryn I, Zikmund-Fisher, Brian J, and Scherr, Karen A
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Public Health ,Health Sciences ,Clinical Research ,Behavioral and Social Science ,Clinical Trials and Supportive Activities ,HIV/AIDS ,Evaluation of treatments and therapeutic interventions ,6.1 Pharmaceuticals ,Decision Making ,Drug Therapy ,Female ,HIV Infections ,Humans ,Intention ,Male ,Middle Aged ,Patients ,Research Personnel ,Surveys and Questionnaires ,Behavior ,Cure ,Decision-making ,HIV ,PLWHIV ,Remission ,Public Health and Health Services ,Social Work ,Public health - Abstract
Many people living with HIV (PLWHIV) state that they would be willing to take significant risks to be "cured" of the virus. However, how they interpret the word "cure" in this context is not clear. We used a randomized survey to examine whether PLWHIV had a different willingness to take a hypothetical HIV medication if it causes flu-like symptoms, but provides: (a) cure, (b) remission that was labeled "cure", or (c) remission. PLWHIV (n = 454) were more willing to take a medication that provided a "cure" versus a "remission" if the side effects lasted less than 1 year. PLWHIV were more willing to take a medication that provided a remission that was labeled "cure" versus a "remission" (p = 0.01) if the side effects lasted 2 weeks. Clinicians and researchers should be aware of the impact of the word "cure" and ensure that PLWHIV fully understand the possible outcomes of their treatment options.
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- 2020
59. Immune Biomarkers in the Prediction of Future Myocardial Infarctions in People With Human Immunodeficiency Virus
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Trevillyan, Janine M, Moser, Carlee, Currier, Judith S, and Sallam, Tamer
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Medical Microbiology ,Biomedical and Clinical Sciences ,Immunology ,HIV/AIDS ,Cardiovascular ,Clinical Research ,Infectious Diseases ,Heart Disease ,Infection ,Good Health and Well Being ,Biomarkers ,C-Reactive Protein ,HIV ,HIV Infections ,Humans ,Myocardial Infarction ,Retrospective Studies ,cardiovascular disease ,acute myocardial infarction ,inflammation ,immune activation ,Biological Sciences ,Medical and Health Sciences ,Microbiology ,Clinical sciences - Abstract
In a retrospective case control analysis, following adjustments for high-sensitivity C-reactive protein (hsCRP), traditional cardiovascular risk factors, and the CD4/CD8 T-cell ratio, higher lipopolysaccharide-binding protein (LBP) was associated with future myocardial infarctions in hsCRP human immunodeficiency virus (HIV). LBP may be a marker of cardiovascular risk with utility in HIV.
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- 2020
60. Reducing cardiovascular risk among people living with HIV: Rationale and design of the INcreasing Statin Prescribing in HIV Behavioral Economics REsearch (INSPIRE) randomized controlled trial
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Takada, Sae, Ober, Allison J, Currier, Judith S, Goldstein, Noah J, Horwich, Tamara B, Mittman, Brian S, Shu, Suzanne B, Tseng, Chi-Hong, Vijayan, Tara, Wali, Soma, Cunningham, William E, and Ladapo, Joseph A
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Biomedical and Clinical Sciences ,Cardiovascular Medicine and Haematology ,Prevention ,Dissemination and Implementation Research ,Heart Disease ,Sexually Transmitted Infections ,Behavioral and Social Science ,Health Services ,Comparative Effectiveness Research ,HIV/AIDS ,Clinical Research ,Cardiovascular ,Social Determinants of Health ,Clinical Trials and Supportive Activities ,Infectious Diseases ,Infection ,Good Health and Well Being ,Anti-HIV Agents ,Attitude of Health Personnel ,Cardiovascular Diseases ,Drug Prescriptions ,Economics ,Behavioral ,Education ,Medical ,Continuing ,HIV Infections ,HIV Long-Term Survivors ,Health Knowledge ,Attitudes ,Practice ,Health Status ,Humans ,Hydroxymethylglutaryl-CoA Reductase Inhibitors ,Implementation Science ,Inservice Training ,Los Angeles ,Medication Adherence ,Multicenter Studies as Topic ,Patient Education as Topic ,Practice Patterns ,Physicians' ,Preventive Health Services ,Protective Factors ,Randomized Controlled Trials as Topic ,Risk Assessment ,Risk Factors ,Time Factors ,Treatment Outcome ,Viral Load ,Cardiovascular disease ,HIV ,Statins ,Behavioral economics ,Implementation science ,Cardiorespiratory Medicine and Haematology ,Cardiovascular System & Hematology ,Cardiovascular medicine and haematology - Abstract
Cardiovascular disease (CVD) is a major cause of morbidity among people living with HIV (PLWH). Statins can safely and effectively reduce CVD risk in PLWH, but evidence-based statin therapy is under-prescribed in PLWH. Developed using an implementation science framework, INcreasing Statin Prescribing in HIV Behavioral Economics REsearch (INSPIRE) is a stepped-wedge cluster randomized trial that addresses organization-, clinician- and patient-level barriers to statin uptake in Los Angeles community health clinics serving racially and ethnically diverse PLWH. After assessing knowledge about statins and barriers to clinician prescribing and patient uptake, we will design, implement and measure the effectiveness of (1) educational interventions targeting leadership, clinicians, and patients, followed by (2) behavioral economics-informed clinician feedback on statin uptake. In addition, we will assess implementation outcomes, including changes in clinician acceptability of statin prescribing for PLWH, clinician acceptability of the education and feedback interventions, and cost of implementation.
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- 2020
61. Comparison of guidelines for HIV viral load monitoring among pregnant and breastfeeding women in sub-Saharan Africa.
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Lesosky, Maia, Raboud, Janet M, Glass, Tracy, Brummel, Sean S, Ciaranello, Andrea L, Currier, Judith S, Essajee, Shaffiq, Havlir, Diane V, Koss, Catherine A, Ogwu, Anthony, Shapiro, Roger L, Abrams, Elaine J, and Myer, Landon
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Infectious Diseases ,Prevention ,HIV/AIDS ,Mental Health ,Infection ,Reproductive health and childbirth ,Africa South of the Sahara ,Anti-HIV Agents ,Breast Feeding ,Female ,Fertilization ,HIV Infections ,Humans ,Infectious Disease Transmission ,Vertical ,Monte Carlo Method ,Postpartum Period ,Practice Guidelines as Topic ,Pregnancy ,Pregnancy Complications ,Infectious ,Serologic Tests ,Viral Load ,antiretroviral therapy ,HIV ,mathematical model ,pregnancy ,simulation ,viral load monitoring ,Biological Sciences ,Medical and Health Sciences ,Psychology and Cognitive Sciences ,Virology - Abstract
BackgroundIntensified viral load monitoring for pregnant and breastfeeding women has been proposed to help address concerns around antiretroviral therapy (ART) adherence, viraemia and transmission risk, but there have been no systematic evaluations of existing policies.MethodsWe used an individual Monte Carlo simulation to describe longitudinal ART adherence and viral load from conception until 2 years' postpartum. We applied national and international guidelines for viral load monitoring to the simulated data. We compared guidelines on the percentage of women receiving viral load monitoring and the percentage of women monitored at the time of elevated viral load.ResultsCoverage of viral load monitoring in pregnancy and breastfeeding varied markedly, with between 14% and 100% of women monitored antenatally and 38-98% monitored during breastfeeding. Specific recommendations for testing at either a fixed gestation or a short, fixed period after ART initiation achieved more than 95% testing in pregnancy but this was much lower (14-83%) among guidelines with no special stipulations. By the end of breastfeeding, only a small proportion of simulated episodes of elevated viral load more than 1000 copies/ml were successfully detected by monitoring (range, 20-50%).DiscussionAlthough further research is needed to understand optimal viral load frequency and timing in this population, these results suggest that current policies yield suboptimal detection of elevated viral load in pregnant and breastfeeding women.
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- 2020
62. Cabotegravir Is Not Associated With Weight Gain in Human Immunodeficiency Virus–uninfected Individuals in HPTN 077
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Landovitz, Raphael J, Zangeneh, Sahar Z, Chau, Gordon, Grinsztejn, Beatriz, Eron, Joseph J, Dawood, Halima, Magnus, Manya, Liu, Albert Y, Panchia, Ravindre, Hosseinipour, Mina C, Kofron, Ryan, Margolis, David A, Rinehart, Alex, Adeyeye, Adeola, Burns, David, McCauley, Marybeth, Cohen, Myron S, and Currier, Judith S
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Medical Microbiology ,Biomedical and Clinical Sciences ,Immunology ,HIV/AIDS ,Clinical Trials and Supportive Activities ,Clinical Research ,Nutrition ,Prevention ,Obesity ,Evaluation of treatments and therapeutic interventions ,6.1 Pharmaceuticals ,Metabolic and endocrine ,Infection ,Good Health and Well Being ,Anti-HIV Agents ,HIV ,HIV Infections ,Humans ,Pyridones ,Weight Gain ,cabotegravir ,CAB ,weight gain ,HIV uninfected ,Biological Sciences ,Medical and Health Sciences ,Microbiology ,Clinical sciences - Abstract
Studies in human immunodeficiency virus (HIV)-infected individuals suggest excess weight gain with integrase inhibitor-based antiretroviral therapy. The HIV Prevention Trials Network Study 077 evaluated changes in weight and fasting metabolic parameters in HIV-uninfected individuals randomized to cabotegravir or a placebo. No differences between arms were found for change in weight or fasting metabolic parameters overall or for subgroups.
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- 2020
63. The impact of short term Antiretroviral Therapy (ART) interruptions on longer term maternal health outcomes—A randomized clinical trial
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Atuhaire, Patience, S. Brummel, Sean, Mmbaga, Blandina Theophil, Angelidou, Konstantia, Fairlie, Lee, Violari, Avy, Theron, Gerhard, Mukuzunga, Cornelius, Mawlana, Sajeeda, Mubiana-Mbewe, Mwangelwa, Naidoo, Megeshinee, Makanani, Bonus, Mandima, Patricia, Nematadzira, Teacler, Suryavanshi, Nishi, Mbengeranwa, Tapiwa, Loftis, Amy, Basar, Michael, McCarthy, Katie, Currier, Judith S, and Fowler, Mary Glenn
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Reproductive Medicine ,Biomedical and Clinical Sciences ,Public Health ,Health Sciences ,Prevention ,Pregnancy ,HIV/AIDS ,Clinical Research ,Infectious Diseases ,Women's Health ,Clinical Trials and Supportive Activities ,Sexually Transmitted Infections ,Maternal Health ,6.1 Pharmaceuticals ,3.1 Primary prevention interventions to modify behaviours or promote wellbeing ,Infection ,Reproductive health and childbirth ,Good Health and Well Being ,Aged ,Algorithms ,Antiretroviral Therapy ,Highly Active ,Area Under Curve ,Female ,Humans ,Magnetic Resonance Imaging ,Male ,Middle Aged ,Models ,Biological ,Outcome Assessment ,Health Care ,ROC Curve ,Reproducibility of Results ,Time Factors ,1077BF/1077FF PROMISE Team ,General Science & Technology - Abstract
BackgroundGiven well documented challenges faced by pregnant women living with HIV taking lifetime ART, it is critical to understand the impact of short-term ART exposure followed by treatment interruption on maternal health outcomes.MethodsHIV+ breastfeeding (BF) and Formula Feeding (FF) women with CD4 counts > 350 cells/mm3, enrolled in the 1077BF/1077FF PROMISE trial were followed to assess the effect of ART during pregnancy and breastfeeding respectively. The first analysis compared ART use limited to the antepartum period (AP-only) relative to women randomized to Zidovudine. The second analysis included women with no pregnancy combination ART exposure; and compared women randomized to either ART or no ART during postpartum (PP-only). Both analyses included follow-up time beyond breastfeeding period. The primary outcome was progression to AIDS and/or death. Secondary outcomes included adverse events and HIV-related events.Results3490 and 1137 HIV+ women were enrolled from 14 sites in Africa and India from April 2011 through September 2014 in cohort AP-only and PP-only, respectively. Most were Black African (96%); median age was 27 years; 97% were WHO Clinical Stage I; and most had a screening CD4 count ≥500 cells/mm3 (78%). The rate of progression to AIDS and/or death was similar and low across all comparison arms (AP comparison, HR = 1.14, 95%CI (0.44, 2.96), p-value = 0.79). In the PP-only cohort, the rate of WHO stage 2-3 events was lower for women randomized to ART(HR = 0.65, 95% CI 0.42, 1.01, p-value = 0.05).ConclusionThe incidence of AIDS and/or death was low in pregnant/postpartum HIV+ women with highCD4 cell counts for all comparison arms. This provides some reassurance that there were limited consequences for short term ART interruption in this group of asymptomatic HIV+ women during up to 4 years of follow up; and underscores that even short term ART exposure postpartum may reduce the risk of WHO grade 2-3 disease progression.
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- 2020
64. Predictors of Viremia in Postpartum Women on Antiretroviral Therapy
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Hoffman, Risa M, Warshaw, Meredith G, Amico, K Rivet, Pilotto, Jose, Masheto, Gaerolwe, Achalapong, Jullapong, Machado, Elizabeth, Chokephaibulkit, Kulkanya, Duarte, Geraldo, João, Esau, Graham, Kathleen K, Knapp, Katherine M, Stek, Alice M, Scott, Gwendolyn B, Coletti, Anne, Loftis, Amy J, Chakhtoura, Nahida, and Currier, Judith S
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Infectious Diseases ,HIV/AIDS ,Clinical Research ,Evaluation of treatments and therapeutic interventions ,6.1 Pharmaceuticals ,Infection ,Reproductive health and childbirth ,Adult ,Anti-HIV Agents ,Female ,HIV Infections ,Humans ,Postpartum Period ,Pregnancy ,Pregnancy Complications ,Infectious ,Viremia ,Young Adult ,HIV ,AIDS ,ART ,postpartum ,adherence ,viremia ,PROMISE 1077HS Team ,Clinical Sciences ,Public Health and Health Services ,Virology - Abstract
BackgroundHIV-infected, postpartum women on antiretroviral therapy (ART) have high rates of viremia. We examined predictors of postpartum viremia in the PROMISE study.MethodsWomen with pre-ART CD4 T-cell counts ≥400 cells/mm who started ART during pregnancy were randomized postpartum to continue ART (CTART) or discontinue ART (DCART). Viral load and self-reported adherence were collected every 12 weeks, up to 144 weeks. Women in DCART reinitiated therapy when clinically indicated. Viremia was defined as 2 consecutive viral loads >1000 copies/mL after 24 weeks on ART. Adherence was dichotomized as missing versus not missing ART doses in the past 4 weeks. Predictors of viremia were examined using Cox proportional hazards regression with adherence as a time-varying covariate.ResultsAmong 802 women in the CTART arm, median age at entry was 27 years and median CD4 T-cell count 696 cells/mm. Of 175 women in CTART with viremia (22%), 141 had resistance data, and 12% had resistance to their current regimen. There was an estimated 0.12 probability of viremia by week 48 and 0.25 by week 144. Predictors of viremia included missed ART doses within the past 4 weeks, younger age, shorter duration of pre-entry ART, and being from the South American/Caribbean region. Of 137 women in DCART who reinitiated therapy, probability of viremia was similar to CTART (0.24 by week 96; 0.27 by week 144).ConclusionsRates of postpartum viremia are high and viremia is more likely in younger postpartum women who start ART later in pregnancy. Interventions should target these higher-risk women.
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- 2020
65. Time to viral rebound and safety after antiretroviral treatment interruption in postpartum women compared with men.
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Le, Catherine N, Britto, Paula, Brummel, Sean S, Hoffman, Risa M, Li, Jonathan Z, Flynn, Patricia M, Taha, Taha E, Coletti, Anne, Fowler, Mary Glenn, Bosch, Ronald J, Gandhi, Rajesh T, Klingman, Karin L, McIntyre, James A, and Currier, Judith S
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Infectious Diseases ,Clinical Research ,HIV/AIDS ,Clinical Trials and Supportive Activities ,6.1 Pharmaceuticals ,Evaluation of treatments and therapeutic interventions ,Infection ,Reproductive health and childbirth ,Adolescent ,Adult ,Aged ,Anti-HIV Agents ,Antiretroviral Therapy ,Highly Active ,CD4 Lymphocyte Count ,Disease Progression ,Drug Administration Schedule ,Female ,HIV Infections ,HIV-1 ,Humans ,Male ,Middle Aged ,Postpartum Period ,Prospective Studies ,RNA ,Viral ,Viral Load ,Virus Replication ,Young Adult ,cure ,postpartum period ,reservoir ,sex differences ,viral latency ,women ,Biological Sciences ,Medical and Health Sciences ,Psychology and Cognitive Sciences ,Virology - Abstract
Objective(s)The short-term safety of treatment interruptions, a necessary part of cure studies, is not well established, particularly in women. We explored viral rebound kinetics and safety in a group of postpartum women discontinuing ART and compared results to men in historical interruption trials.DesignProspective evaluation of time to virologic rebound.MethodsOne thousand and seventy-six asymptomatic, virally suppressed, postpartum women living with HIV enrolled in the PROMISE trial with baseline CD4 cell counts at least 350 cells/μl underwent antiretroviral treatment (ART) discontinuation. Proportion with virologic suppression at weeks 4 and 12 were compared with participants in ACTG treatment interruption trials (91% male population).ResultsIn PROMISE, using interval censored methods, the estimated median time to HIV viral rebound was 2 weeks. An estimated 6% of women would remain virally suppressed at 30 weeks. Of those who had viral rebound by 30 weeks (N = 993), less than 4% experienced grade 3 or higher laboratory events, and 1% experienced WHO stage 2 or higher clinical events. Overall, less than 1% of participants progressed from WHO Stage 1 to Stage 2 or higher after discontinuation of ART, and 3.9% experienced a decline in CD4 cell count to less than 350 cells/μl or local treatment guidelines. A significantly higher proportion of women in PROMISE (25.4%) were virologically suppressed (
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- 2019
66. Linked dual-class HIV resistance mutations are associated with treatment failure
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Boltz, Valerie F, Shao, Wei, Bale, Michael J, Halvas, Elias K, Luke, Brian, McIntyre, James A, Schooley, Robert T, Lockman, Shahin, Currier, Judith S, Sawe, Fred, Hogg, Evelyn, Hughes, Michael D, Kearney, Mary F, Coffin, John M, and Mellors, John W
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Clinical Trials and Supportive Activities ,Infectious Diseases ,Human Genome ,Genetics ,HIV/AIDS ,Clinical Research ,Evaluation of treatments and therapeutic interventions ,6.1 Pharmaceuticals ,Infection ,Good Health and Well Being ,Anti-HIV Agents ,Antineoplastic Combined Chemotherapy Protocols ,Drug Resistance ,Viral ,Emtricitabine ,Female ,Genome ,Viral ,HIV Infections ,HIV-1 ,Humans ,Mutation ,Nevirapine ,Tenofovir ,Treatment Failure ,Whole Genome Sequencing ,AIDS/HIV ,Drug therapy - Abstract
We hypothesized that HIV-1 with dual-class but not single-class drug resistance mutations linked on the same viral genome, present in the virus population before initiation of antiretroviral therapy (ART), would be associated with failure of ART to suppress viremia. To test this hypothesis, we utilized an ultrasensitive single-genome sequencing assay that detects rare HIV-1 variants with linked drug resistance mutations (DRMs). A case (ART failure) control (nonfailure) study was designed to assess whether linkage of DRMs in pre-ART plasma samples was associated with treatment outcome in the nevirapine/tenofovir/emtricitabine arm of the AIDS Clinical Trials Group A5208/Optimal Combined Therapy After Nevirapine Exposure (OCTANE) Trial 1 among women who had received prior single-dose nevirapine. Ultrasensitive single-genome sequencing revealed a significant association between pre-ART HIV variants with DRMs to 2 drug classes linked on the same genome (dual class) and failure of combination ART with 3 drugs to suppress viremia. In contrast, linked, single-class DRMs were not associated with ART failure. We conclude that linked dual-class DRMs present before the initiation of ART are associated with ART failure, whereas linked single-class DRMs are not.
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- 2019
67. Tenofovir concentrations in hair strongly predict virologic suppression in breastfeeding women.
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Murnane, Pamela M, Bacchetti, Peter, Currier, Judith S, Brummel, Sean, Okochi, Hideaki, Phung, Nhi, Louie, Alexander, Kuncze, Karen, Hoffman, Risa M, Nematadzira, Teacler, Soko, Dean K, Owor, Maxensia, Saidi, Friday, Flynn, Patricia M, Fowler, Mary G, and Gandhi, Monica
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Reproductive Medicine ,Biomedical and Clinical Sciences ,Clinical Research ,Infectious Diseases ,Maternal Health ,Women's Health ,Reproductive health and childbirth ,Good Health and Well Being ,Adult ,Africa South of the Sahara ,Anti-HIV Agents ,Breast Feeding ,Female ,HIV Infections ,Hair ,Humans ,Longitudinal Studies ,Medication Adherence ,Postpartum Period ,Pregnancy ,Sustained Virologic Response ,Tenofovir ,Treatment Outcome ,Viral Load ,Young Adult ,adherence ,breastfeeding ,hair ,HIV ,pregnancy ,viral load ,Biological Sciences ,Medical and Health Sciences ,Psychology and Cognitive Sciences ,Virology ,Biomedical and clinical sciences ,Health sciences - Abstract
BackgroundAntiretroviral treatment (ART) adherence is often suboptimal in the perinatal period. We measured hair tenofovir (TFV) concentrations as a metric of adherence in postpartum women to understand patterns and predictors of adherence throughout this critical period. In addition, we examined the association between hair TFV concentrations and virologic outcomes.MethodsBetween 12/2012 and 09/2016, hair samples were collected longitudinally from delivery through breastfeeding from women on ART in the Promoting Maternal and Infant Survival Everywhere study (NCT01061151) in sub-Saharan Africa. Hair TFV levels were measured using validated methods. Using generalized estimating equations, we estimated the association between hair TFV levels and virologic suppression (
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- 2019
68. Characteristics, Prevention, and Management of Cardiovascular Disease in People Living With HIV: A Scientific Statement From the American Heart Association
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Feinstein, Matthew J, Hsue, Priscilla Y, Benjamin, Laura A, Bloomfield, Gerald S, Currier, Judith S, Freiberg, Matthew S, Grinspoon, Steven K, Levin, Jules, Longenecker, Chris T, Post, Wendy S, and Council, On behalf of the American Heart Association Prevention Science Committee of the Council on Epidemiology and Prevention and Council on Cardiovascular and Stroke Nursing Council on Clinical Cardiology and Stroke
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Cardiovascular ,Infectious Diseases ,Heart Disease - Coronary Heart Disease ,Prevention ,Clinical Research ,Heart Disease ,Clinical Trials and Supportive Activities ,HIV/AIDS ,Evaluation of treatments and therapeutic interventions ,6.1 Pharmaceuticals ,Good Health and Well Being ,American Heart Association ,Anti-Retroviral Agents ,Cardiovascular Diseases ,Comorbidity ,Disease Management ,HIV Infections ,Humans ,Risk Factors ,Risk Reduction Behavior ,United States ,AHA Scientific Statements ,cardiovascular diseases ,HIV ,preventive medicine ,Cardiorespiratory Medicine and Haematology ,Clinical Sciences ,Public Health and Health Services ,Cardiovascular System & Hematology - Abstract
As early and effective antiretroviral therapy has become more widespread, HIV has transitioned from a progressive, fatal disease to a chronic, manageable disease marked by elevated risk of chronic comorbid diseases, including cardiovascular diseases (CVDs). Rates of myocardial infarction, heart failure, stroke, and other CVD manifestations, including pulmonary hypertension and sudden cardiac death, are significantly higher for people living with HIV than for uninfected control subjects, even in the setting of HIV viral suppression with effective antiretroviral therapy. These elevated risks generally persist after demographic and clinical risk factors are accounted for and may be partly attributed to chronic inflammation and immune dysregulation. Data on long-term CVD outcomes in HIV are limited by the relatively recent epidemiological transition of HIV to a chronic disease. Therefore, our understanding of CVD pathogenesis, prevention, and treatment in HIV relies on large observational studies, randomized controlled trials of HIV therapies that are underpowered to detect CVD end points, and small interventional studies examining surrogate CVD end points. The purpose of this document is to provide a thorough review of the existing evidence on HIV-associated CVD, in particular atherosclerotic CVD (including myocardial infarction and stroke) and heart failure, as well as pragmatic recommendations on how to approach CVD prevention and treatment in HIV in the absence of large-scale randomized controlled trial data. This statement is intended for clinicians caring for people with HIV, individuals living with HIV, and clinical and translational researchers interested in HIV-associated CVD.
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- 2019
69. Rationale and design of the Randomized Trial to Prevent Vascular Events in HIV (REPRIEVE)
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Grinspoon, Steven K, Fitch, Kathleen V, Overton, Edgar Turner, Fichtenbaum, Carl J, Zanni, Markella V, Aberg, Judith A, Malvestutto, Carlos, Lu, Michael T, Currier, Judith S, Sponseller, Craig A, Waclawiw, Myron, Alston-Smith, Beverly, Cooper-Arnold, Katharine, Klingman, Karin L, Desvigne-Nickens, Patrice, Hoffmann, Udo, Ribaudo, Heather J, Douglas, Pamela S, and Investigators, on behalf of the REPRIEVE
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Biomedical and Clinical Sciences ,Cardiovascular Medicine and Haematology ,Clinical Trials and Supportive Activities ,Patient Safety ,Heart Disease ,Infectious Diseases ,HIV/AIDS ,Prevention ,Clinical Research ,Cardiovascular ,Atherosclerosis ,6.1 Pharmaceuticals ,Evaluation of treatments and therapeutic interventions ,Good Health and Well Being ,Adult ,Aged ,Anti-HIV Agents ,Cardiovascular Diseases ,Cholesterol ,LDL ,Double-Blind Method ,Female ,HIV Infections ,Humans ,Hydroxymethylglutaryl-CoA Reductase Inhibitors ,Male ,Middle Aged ,Primary Prevention ,Prospective Studies ,Quinolines ,Risk Factors ,REPRIEVE Investigators ,Cardiorespiratory Medicine and Haematology ,Public Health and Health Services ,Cardiovascular System & Hematology ,Cardiovascular medicine and haematology - Abstract
BackgroundCardiovascular disease (CVD) is more frequent among people with HIV (PWH) and may relate to traditional and nontraditional factors, including inflammation and immune activation. A critical need exists to develop effective strategies to prevent CVD in this population.MethodsThe Randomized Trial to Prevent Vascular Events in HIV (REPRIEVE) (A5332) is a prospective, randomized, placebo-controlled trial of a statin strategy for the primary prevention of major adverse cardiovascular events (MACE) in PWH with low to moderate traditional risk. At least 7,500 PWH, 40-75 years of age, on stable antiretroviral therapy, will be randomized to pitavastatin calcium (4 mg/d) or identical placebo and followed for up to 8 years. Participants are enrolled based on the 2013 American College of Cardiology (ACC)/American Heart Association (AHA) atherosclerotic cardiovascular disease (ASCVD) risk score and low-density lipoprotein cholesterol (LDL-C) level with a goal to identify a low- to moderate-risk population who might benefit from a pharmacologic CVD prevention strategy. Potential participants with a risk score ≤ 15% were eligible based on decreasing LDL-C thresholds for increasing risk score >7.5% (LDL-C 7,500 participants at approximately 120 sites across 11 countries, generating a diverse and representative population of PWH to investigate the primary objective of the trial.ConclusionsREPRIEVE is the first trial investigating a primary CVD prevention strategy in PWH. REPRIEVE will inform the field of the efficacy and safety of a statin strategy among HIV-infected participants on antiretroviral therapy and provide critical information on CVD mechanisms and non-CVD events in PWH.
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- 2019
70. Safety and Impact of Low-dose Methotrexate on Endothelial Function and Inflammation in Individuals With Treated Human Immunodeficiency Virus: AIDS Clinical Trials Group Study A5314
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Hsue, Priscilla Y, Ribaudo, Heather J, Deeks, Steven G, Bell, Tanvir, Ridker, Paul M, Fichtenbaum, Carl, Daar, Eric S, Havlir, Diane, Yeh, Eunice, Tawakol, Ahmed, Lederman, Michael, Currier, Judith S, and Stein, James H
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Biomedical and Clinical Sciences ,Clinical Sciences ,Immunology ,Prevention ,Infectious Diseases ,HIV/AIDS ,Cardiovascular ,Clinical Research ,Clinical Trials and Supportive Activities ,Complementary and Integrative Health ,Evaluation of treatments and therapeutic interventions ,6.1 Pharmaceuticals ,Inflammatory and immune system ,Infection ,Good Health and Well Being ,Anti-Inflammatory Agents ,Antiretroviral Therapy ,Highly Active ,Atherosclerosis ,CD4 Lymphocyte Count ,Dose-Response Relationship ,Drug ,Double-Blind Method ,Endothelium ,Female ,HIV Infections ,HIV-1 ,Humans ,Inflammation ,Male ,Methotrexate ,Middle Aged ,endothelial function ,human immunodeficiency virus ,inflammation ,Biological Sciences ,Medical and Health Sciences ,Microbiology ,Clinical sciences - Abstract
BackgroundChronic inflammation in treated HIV infection is associated with mortality and atherosclerotic cardiovascular disease (ASCVD). We evaluated the safety and potential efficacy of low-dose methotrexate (LDMTX) in treated HIV.MethodsThis was a phase 2 randomized, double-blind, multicenter trial in adults ≥40 years old with treated HIV, with CD4+ T-cell count ≥400 cells/μL and with/at increased risk for ASCVD. Participants received LDMTX (5-15 mg/week) or placebo (plus folic acid) for 24 weeks and were followed for an additional 12 weeks. Primary endpoints were safety and brachial artery flow-mediated dilation (FMD).ResultsThe 176 participants (90% male) had a median (Q1, Q3) age of 54 (49, 59) years. LDMTX was associated with decreases in CD4+ T cells at week 24 and CD8+ T cells at weeks 8, 12, and 24. Eleven participants (12.8%) experienced safety events in the LDMTX group vs 5 (5.6%) in placebo (Δ = 7.2%, upper 1-sided 90% CI, 13.4%; Pnoninferiority = .037). Week 24 change in FMD was 0.47% with LDMTX and 0.09% with placebo (P = .55). No inflammatory markers changed differentially with LDMTX compared to placebo.ConclusionsAdults with HIV and increased ASCVD risk treated with LDMTX had more safety events than with placebo, but the prespecified noninferiority margin of 15% was not exceeded. LDMTX had no significant effect on endothelial function or inflammatory biomarkers but was associated with a significant decrease in CD8+ T cells. The balance of risks and potential benefits of LDMTX in this population will require additional investigation.Clinical trials registrationNCT01949116.
- Published
- 2019
71. Lower Pretreatment Gut Integrity Is Independently Associated With Fat Gain on Antiretroviral Therapy
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Kamari, Vanessa El, Moser, Carlee, Hileman, Corrilynn O, Currier, Judith S, Brown, Todd T, Johnston, Liz, Hunt, Peter W, and McComsey, Grace A
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Biomedical and Clinical Sciences ,Clinical Sciences ,Infectious Diseases ,HIV/AIDS ,Clinical Research ,Prevention ,6.1 Pharmaceuticals ,Evaluation of treatments and therapeutic interventions ,Infection ,Oral and gastrointestinal ,Good Health and Well Being ,Adult ,Anti-HIV Agents ,Biomarkers ,Body Composition ,Female ,Gastrointestinal Microbiome ,HIV Infections ,Humans ,Male ,Middle Aged ,gut integrity ,microbial translocation ,body composition ,Biological Sciences ,Medical and Health Sciences ,Microbiology ,Clinical sciences - Abstract
BackgroundFat accumulation and insulin resistance remain a threat to the success of antiretroviral therapy (ART). The role of gut dysfunction in metabolic complications associated with ART initiation is unclear.MethodsHuman immunodeficiency virus (HIV)-infected ART-naive participants were randomized to tenofovir disoproxil fumarate/emtricitabine plus atazanavir/ritonavir, darunavir/ritonavir, or raltegravir (RAL). Changes in the gut integrity markers zonulin, lipopolysaccharide-binding protein (LBP), and intestinal fatty acid and ileal bile acid binding proteins (I-FABP and I-BABP) were assessed over 96 weeks. Wilcoxon rank-sum tests were used to compare changes between groups and linear regression models to quantify associations between gut markers, insulin resistance, body mass index (BMI), and visceral, subcutaneous, and total adipose tissue (VAT, SAT, and TAT).Results: 90% were male and 48% were White non-Hispanic. The median age was 36 years, HIV-1 ribonucleic acid was 4.56 log10 copies/mL, and CD4 count was 338 cells/µL. An overall 1.7-fold increase in I-FABP was observed throughout 96 weeks, with no difference between arms. Zonulin levels increased with RAL compared to protease inhibitor-based regimens (week 96, P = .02); minimal changes in I-BABP or LBP levels were observed. Higher baseline I-FABP levels were associated with increases in VAT, TAT, and BMI (16%, 9%, and 2.5%, respectively; P < .04) over 96 weeks.ConclusionsWhile ART induces changes in the markers of gut barrier dysfunction, the extent to which they improve or worsen the gut barrier function remains unclear. Nevertheless, markers of gut barrier dysfunction in ART-naive individuals predict increases in total and visceral abdominal fat with treatment initiation.
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- 2019
72. CROI 2019: complications and coinfections in HIV infection.
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Currier, Judith S and Havlir, Diane V
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Humans ,Tuberculosis ,AIDS-Related Opportunistic Infections ,Mycoses ,HIV Infections ,Neoplasms ,Metabolic Diseases ,Coinfection ,Infectious Diseases ,HIV/AIDS ,Infection ,Good Health and Well Being - Abstract
The 2019 Conference on Retroviruses and Opportunistic Infections provided a considerable amount of new information on the progress in implementation of strategies to reduce morbidity and mortality from complications and coinfections that occur in people with HIV infection, and on the clinical management of these important problems. This review will address new insights into the prevention and treatment of tuberculosis, fungal infections, sexually transmitted infections, malignancies, and a range of metabolic complications and noncommunicable diseases.
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- 2019
73. Antiretroviral Concentrations in Hair Strongly Predict Virologic Response in a Large Human Immunodeficiency Virus Treatment-naive Clinical Trial
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Gandhi, Monica, Bacchetti, Peter, Ofokotun, Igho, Jin, Chengshi, Ribaudo, Heather J, Haas, David W, Sheth, Anandi N, Horng, Howard, Phung, Nhi, Kuncze, Karen, Okochi, Hideaki, Landovitz, Raphael J, Lennox, Jeffrey, Currier, Judith S, and Team, AIDS Clinical Trials Group 5257 Study
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Medical Microbiology ,Biomedical and Clinical Sciences ,Immunology ,Clinical Research ,Infectious Diseases ,Clinical Trials and Supportive Activities ,HIV/AIDS ,Sexually Transmitted Infections ,6.1 Pharmaceuticals ,Evaluation of treatments and therapeutic interventions ,Infection ,Good Health and Well Being ,Adolescent ,Adult ,Aged ,Anti-HIV Agents ,Antiretroviral Therapy ,Highly Active ,Female ,HIV Infections ,HIV-1 ,Hair ,Humans ,Male ,Middle Aged ,Randomized Controlled Trials as Topic ,Tissue Distribution ,Treatment Failure ,Treatment Outcome ,Viral Load ,Young Adult ,HIV ,A5257 study ,AIDS Clinical Trials Group ,hair concentrations ,non-NNRTI regimens ,AIDS Clinical Trials Group (ACTG) 5257 Study Team ,Biological Sciences ,Medical and Health Sciences ,Microbiology ,Clinical sciences - Abstract
Concentrations of antiretrovirals in hair are associated with virologic outcomes in cohorts of human immunodeficiency virus (HIV)-positive individuals but have never been examined in a clinical trial. We show for the first time the predictive utility of hair antiretroviral concentrations in a large HIV treatment-naive trial (AIDS Clinical Trials Group protocol A5257).
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- 2019
74. Outcomes of a Career Development Program for Underrepresented Minority Investigators in the AIDS Clinical Trials Group
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Velásquez, Gustavo E, Huaman, Moises A, Powell, Kimberly R, Cohn, Susan E, Swaminathan, Shobha, Outlaw, Martine, Schulte, Gail, McNeil, Quinteka, Currier, Judith S, Del Rio, Carlos, and Castillo-Mancilla, Jose
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Medical Microbiology ,Biomedical and Clinical Sciences ,Clinical Sciences ,Clinical Trials and Supportive Activities ,Prevention ,Clinical Research ,HIV/AIDS ,Genetics ,Infectious Diseases ,Infection ,Good Health and Well Being ,career development ,infectious diseases ,mentorship ,minority investigators ,training ,Clinical sciences ,Medical microbiology - Abstract
We surveyed awardees of the Minority HIV Investigator Mentoring Program (MHIMP) of the AIDS Clinical Trials Group. Most reported clinical specialization in infectious diseases or HIV medicine (86%), and all but 1 (95%) are engaged in medical/health sciences research. The MHIMP helped retain early-career minority investigators in HIV/AIDS-related research.
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- 2019
75. Racial Disparities in Virologic Failure and Tolerability During Firstline HIV Antiretroviral Therapy
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Bhagwat, Priya, Kapadia, Shashi N, Ribaudo, Heather J, Gulick, Roy M, and Currier, Judith S
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Medical Microbiology ,Biomedical and Clinical Sciences ,Clinical Sciences ,Clinical Trials and Supportive Activities ,Infectious Diseases ,HIV/AIDS ,Clinical Research ,Prevention ,Evaluation of treatments and therapeutic interventions ,6.1 Pharmaceuticals ,Infection ,adverse drug events ,antiretroviral therapy ,health care disparities ,HIV ,social determinants of health ,adverse drug events ,Clinical sciences ,Medical microbiology - Abstract
BackgroundRacial/ethnic disparities in HIV outcomes have persisted despite effective antiretroviral therapy. In a study of initial regimens, we found viral suppression varied by race/ethnicity. In this exploratory analysis, we use clinical and socioeconomic data to assess factors associated with virologic failure and adverse events within racial/ethnic groups.MethodsData were from AIDS Clinical Trial Group A5257, a randomized trial of initial regimens with either atazanavir/ritonavir, darunavir/ritonavir, or raltegravir (each combined with tenofovir DF and emtricitabine). We grouped participants by race/ethnicity and then used Cox-proportional hazards regression to examine the impact of demographic, clinical, and socioeconomic factors on the time to virologic suppression and time to adverse event reporting within each racial/ethnic group.ResultsWe analyzed data from 1762 participants: 757 self-reported as non-Hispanic black (NHB), 615 as non-Hispanic white (NHW), and 390 as Hispanic. The proportion with virologic failure was higher for NHB (22%) and Hispanic (17%) participants compared with NHWs (9%). Factors associated with virologic failure were poor adherence and higher baseline HIV RNA level. Prior clinical AIDS diagnosis was associated with virologic failure for NHBs only, and unstable housing and illicit drug use for NHWs only. Factors associated with adverse events were female sex in all groups and concurrent use of medications for comorbidities in NHB and Hispanic participants only.ConclusionsClinical and socioeconomic factors that are associated with virologic failure and tolerability of antiretroviral therapy vary between and within racial and ethnic groups. Further research may shed light into mechanisms leading to disparities and targeted strategies to eliminate those disparities.
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- 2019
76. Adverse Pregnancy Outcomes Among Women Who Conceive on Antiretroviral Therapy
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Hoffman, Risa M, Brummel, Sean S, Britto, Paula, Pilotto, Jose H, Masheto, Gaerolwe, Aurpibul, Linda, Joao, Esau, Purswani, Murli U, Buschur, Shelley, Pierre, Marie Flore, Coletti, Anne, Chakhtoura, Nahida, Klingman, Karin L, Currier, Judith S, Losso, M, Machado, E, de Menezes, J, Duarte, G, Sperhacke, R, Pinto, J, Kreitchman, R, Santos, B, Wei, L, Pape, JW, Sanchez, J, Sandoval, E, Chokephaibulkit, K, Achalapong, J, Halue, G, Yuthavisuthi, P, Prommas, S, Bowonwatanuwong, C, Sirisanthana, V, Riddler, S, Kumar, P, Shearer, W, Yogev, R, Scott, G, Spector, S, Cunningham, C, Bamji, M, Cooper, E, Wiznia, A, Hitti, J, Emmanuel, P, Scott, R, Acevedo, M, Nachman, S, Jones, T, Rana, S, Keller, M, Stek, A, Rathore, M, McFarland, E, Puga, A, Agwu, A, Chen, T, Van Dyke, R, Deville, J, Purswani, M, Tebas, P, Flynn, P, and Fischl, M
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Reproductive Medicine ,Biomedical and Clinical Sciences ,Contraception/Reproduction ,Infectious Diseases ,Reproductive health and childbirth ,Abortion ,Spontaneous ,Adult ,Anti-Retroviral Agents ,Female ,HIV Infections ,Humans ,Pregnancy ,Stillbirth ,Young Adult ,HIV/AIDS ,antiretroviral therapy ,pregnancy ,conception ,pregnancy outcomes ,PROMISE (Promoting Maternal and Infant Safety Everywhere) 1077HS Team ,Biological Sciences ,Medical and Health Sciences ,Microbiology ,Clinical sciences - Abstract
BackgroundAdverse pregnancy outcomes for women who conceive on antiretroviral therapy (ART) may be increased, but data are conflicting.MethodsHuman immunodeficiency virus-infected, nonbreastfeeding women with pre-ART CD4 counts ≥400 cells/μL who started ART during pregnancy were randomized after delivery to continue ART (CTART) or discontinue ART (DCART). Women randomized to DCART were recommended to restart if a subsequent pregnancy occurred or for clinical indications. Using both intent-to-treat and as-treated approaches, we performed Fisher exact tests to compare subsequent pregnancy outcomes by randomized arm.ResultsSubsequent pregnancies occurred in 277 of 1652 (17%) women (CTART: 144/827; DCART: 133/825). A pregnancy outcome was recorded for 266 (96%) women with a median age of 27 years (interquartile range [IQR], 24-31 years) and median CD4+ T-cell count 638 cells/μL (IQR, 492-833 cells/μL). When spontaneous abortions and stillbirths were combined, there was a significant difference in events, with 33 of 140 (23.6%) in the CTART arm and 15 of 126 (11.9%) in the DCART arm (relative risk [RR], 2.0 [95% confidence interval {CI}, 1.1-3.5]; P = .02). In the as-treated analysis, the RR was reduced and no longer statistically significant (RR, 1.4 [95% CI, .8-2.4]).ConclusionsWomen randomized to continue ART who subsequently conceived were more likely to have spontaneous abortion or stillbirth, compared with women randomized to stop ART; however, the findings did not remain significant in the as-treated analysis. More data are needed on pregnancy outcomes among women conceiving on ART, particularly with newer regimens.
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- 2019
77. Brachial Artery Echogenicity and Grayscale Texture Changes in HIV-Infected Individuals Receiving Low-Dose Methotrexate
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Stein, James H, Yeh, Eunice, Weber, Joanne M, Korcarz, Claudia, Ridker, Paul M, Tawakol, Ahmed, Hsue, Priscilla Y, Currier, Judith S, Ribaudo, Heather, and Mitchell, Carol KC
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Biomedical and Clinical Sciences ,Clinical Sciences ,Clinical Research ,Cardiovascular ,Clinical Trials and Supportive Activities ,Evaluation of treatments and therapeutic interventions ,6.1 Pharmaceuticals ,Good Health and Well Being ,Adult ,Atherosclerosis ,Biomarkers ,Brachial Artery ,CD4 Lymphocyte Count ,Double-Blind Method ,Female ,Fibrin Fibrinogen Degradation Products ,HIV Infections ,Humans ,Immunosuppressive Agents ,Male ,Methotrexate ,Middle Aged ,Predictive Value of Tests ,Risk Factors ,Time Factors ,Treatment Outcome ,Ultrasonography ,Doppler ,United States ,arteries ,brachial artery ,cardiovascular disease ,HIV infection ,methotrexate ,ultrasound ,Cardiorespiratory Medicine and Haematology ,Cardiovascular System & Hematology ,Cardiovascular medicine and haematology ,Clinical sciences - Abstract
Objective- We evaluated the biological effects of low-dose methotrexate on 3 novel brachial artery grayscale ultrasound measures that may indicate subclinical arterial injury. Approach and Results- Exploratory analysis from a clinical trial of people with HIV infection at increased cardiovascular disease risk who were randomly assigned to low-dose methotrexate (target dose 15 mg/wk) or placebo. Brachial artery ultrasound grayscale median, gray level difference statistic texture-contrast (GLDS-CON), and gray level texture entropy were measured at baseline and after 24 weeks of intervention. Findings from the intention-to-treat (N=148) and adequately-dosed (N=118) populations were consistent, so the adequately-dosed population results are presented. Participants were a median (Q1, Q3) age of 54 (50, 60) years. After 24 weeks, the low-dose methotrexate intervention was associated with a 25.4% (-18.1, 58.6; P=0.007) increase in GLDS-CON compared with 1.3% (-29.1, 44.7; P=0.97) with placebo ( P=0.05) and a 0.10 u (-0.06, 0.23; P=0.026) increase in entropy compared with 0.02 u (-0.11, 0.14; P=0.54) with placebo ( P=0.14). At week 24, changes in CD4+ T cells correlated inversely with changes in GLDS-CON (ρ=-0.20; P=0.031), and entropy (ρ=-0.21; P=0.023). Changes in D-dimer levels, but no other inflammatory biomarkers, also correlated inversely with changes in GLDS-CON (ρ=-0.23; P=0.014) and entropy (ρ=-0.26; P=0.005). Conclusions- Brachial artery GLDS-CON and entropy increased after 24 weeks of low-dose methotrexate, though the latter was not significantly different from placebo. Grayscale changes were associated with decreases in CD4+ T-cell and D-dimer concentrations and may indicate favorable arterial structure changes.
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- 2018
78. Maternal health outcomes among HIV-infected breastfeeding women with high CD4 counts: results of a treatment strategy trial
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Hoffman, Risa M, Angelidou, Konstantia Nadia, Brummel, Sean S, Saidi, Friday, Violari, Avy, Dula, Dingase, Mave, Vidya, Fairlie, Lee, Theron, Gerhard, Kamateeka, Moreen, Chipato, Tsungai, Chi, Benjamin H, Stranix-Chibanda, Lynda, Nematadzira, Teacler, Moodley, Dhayendre, Bhattacharya, Debika, Gupta, Amita, Coletti, Anne, McIntyre, James A, Klingman, Karin L, Chakhtoura, Nahida, Shapiro, David E, Fowler, Mary Glenn, Currier, Judith S, and team, for the IMPAACT PROMISE 1077BF FF
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Reproductive Medicine ,Biomedical and Clinical Sciences ,HIV/AIDS ,Clinical Trials and Supportive Activities ,Prevention ,Infectious Diseases ,Rare Diseases ,Clinical Research ,Pediatric ,6.1 Pharmaceuticals ,Evaluation of treatments and therapeutic interventions ,Reproductive health and childbirth ,Infection ,Good Health and Well Being ,Adult ,Anti-HIV Agents ,Antiretroviral Therapy ,Highly Active ,Breast Feeding ,CD4 Lymphocyte Count ,Disease Progression ,Female ,HIV Infections ,Humans ,Maternal Health ,Postpartum Period ,Pregnancy ,Treatment Outcome ,Young Adult ,antiretroviral therapy ,postpartum maternal health ,HIV and breastfeeding ,IMPAACT PROMISE 1077BF/FF team - Abstract
BackgroundIMPAACT PROMISE 1077BF/FF was a randomized study of antiretroviral therapy (ART) strategies for pregnant and postpartum women with high CD4+ T-cell counts. We describe postpartum outcomes for women in the study who were randomized to continue or discontinue ART after delivery.MethodsWomen with pre-ART CD4+ cell counts ≥350 cells/mm3 who started ART during pregnancy were randomized postpartum to continue or discontinue treatment. Women were enrolled from India, Malawi, South Africa, Tanzania, Uganda, Zambia, and Zimbabwe. The primary outcome was a composite of progression to AIDS-defining illness or death. Log-rank tests and Cox regression models assessed treatment effects. Incidence rates were calculated per 100 person-years. A post hoc analysis evaluated WHO Stage 2/3 events. All analyses were intent-to-treat.Findings1611 women were enrolled (June 2011-October 2014) and 95% were breastfeeding. Median age at entry was 27 years, CD4+ count 728 cells/mm3 and the majority of women were Black African (97%). After a median follow-up of 1.6 years, progression to AIDS-defining illness or death was rare and there was no significant difference between arms (HR: 0·55; 95%CI 0·14, 2·08, p = 0.37). WHO Stage 2/3 events were reduced with continued ART (HR: 0·60; 95%CI 0·39, 0·90, p = 0.01). The arms did not differ with respect to the rate of grade 2, 3, or 4 safety events (p = 0.61).InterpretationSerious clinical events were rare among predominately breastfeeding women with high CD4+ cell counts over 18 months after delivery. ART had significant benefit in reducing WHO 2/3 events in this population.
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- 2018
79. Changes in Waist Circumference in HIV-Infected Individuals Initiating a Raltegravir or Protease Inhibitor Regimen: Effects of Sex and Race
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Bhagwat, Priya, Ofotokun, Ighovwerha, McComsey, Grace A, Brown, Todd T, Moser, Carlee, Sugar, Catherine A, and Currier, Judith S
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Medical Microbiology ,Biomedical and Clinical Sciences ,Clinical Sciences ,Clinical Research ,Infectious Diseases ,HIV/AIDS ,6.1 Pharmaceuticals ,Evaluation of treatments and therapeutic interventions ,abdominal fat ,central adiposity ,lipodystrophy ,metabolic complications ,waist circumference ,Clinical sciences ,Medical microbiology - Abstract
BackgroundThis study investigates the association of clinical and demographic predictors with abdominal fat gain, measured using waist circumference (WC) and self-reported abdominal size.MethodsWe analyzed data from ACTG A5257, a clinical trial that randomized treatment-naïve HIV-infected participants to 1 of 3 antiretroviral regimens: raltegravir (RAL) or the protease inhibitors (PIs) atazanavir/ritonavir (ATV/r) or darunavir/ritonavir (DRV/r), each in combination with tenofovir disoproxil fumarate/emtricitabine. Associations of treatment and baseline/demographic characteristics with 96-week WC change were assessed using repeated-measures models. Ordinal logistic regression was used to examine the associations of predictors with week 96 self-reported abdominal changes.ResultsThe study population (n = 1809) was 76.0% male and predominantly black non-Hispanic (41.9%) and white non-Hispanic (34.1%). Mean baseline WC was 90.6 cm, with an average 96-week increase of 3.4 cm. WC increases were higher in the RAL arm compared with DRV/r (P = .0130). Females experienced greater increases in WC on RAL vs ATV/r than males (P = .0065). Similarly, a larger difference in WC change was found for RAL vs DRV/r for black vs nonblack individuals (P = .0043). A separate multivariable model found that in addition to the treatment regimen, higher baseline viral load and lower CD4+ were also associated with WC increases.ConclusionsWith antiretroviral therapy initiation, higher WC increases in the RAL arm compared with PIs were more pronounced in female and black participants, and a more advanced baseline HIV disease state was a strong predictor of larger abdominal increases. Understanding factors predisposing individuals to abdominal fat gain could inform health management after therapy initiation.
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- 2018
80. Characterization of Treatment Resistance and Viral Kinetics in the Setting of Single-Active Versus Dual-Active Monoclonal Antibodies Against Severe Acute Respiratory Syndrome Coronavirus 2.
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Choudhary, Manish C, Deo, Rinki, Evering, Teresa H, Chew, Kara W, Giganti, Mark J, Moser, Carlee, Ritz, Justin, Regan, James, Flynn, James P, Crain, Charles R, Wohl, David Alain, Currier, Judith S, Eron, Joseph J, Margolis, David, Zhu, Qing, Zhon, Lijie, Ya, Li, Greninger, Alexander L, Hughes, Michael D, and Smith, Davey
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SARS-CoV-2 ,VIRAL load ,NUCLEOTIDE sequencing ,TREATMENT effectiveness ,DISEASE progression - Abstract
Background Monoclonal antibodies (mAbs) represent a crucial antiviral strategy for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, but it is unclear whether combination mAbs offer a benefit over single-active mAb treatment. Amubarvimab and romlusevimab significantly reduced the risk of hospitalizations or death in the ACTIV-2/A5401 trial. Certain SARS-CoV-2 variants are intrinsically resistant against romlusevimab, leading to only single-active mAb therapy with amubarvimab in these variants. We evaluated virologic outcomes in individuals treated with single- versus dual-active mAbs. Methods Participants were nonhospitalized adults at higher risk of clinical progression randomized to amubarvimab plus romlusevimab or placebo. Quantitative SARS-CoV-2 RNA levels and targeted S-gene next-generation sequencing was performed on anterior nasal samples. We compared viral load kinetics and resistance emergence between individuals treated with effective single- versus dual-active mAbs depending on the infecting variant. Results Study participants receiving single- or dual-active mAbs had similar demographics, baseline nasal viral load, symptom score, and symptom duration. Compared with single-active mAb treatment, treatment with dual-active mAbs led to faster viral load decline at study days 3 (P <.001) and 7 (P <.01). Treatment-emergent resistance mutations were more likely to be detected after amubarvimab plus romlusevimab treatment than with placebo (2.6% vs 0%; P <.001) and were more frequently detected in the setting of single-active compared with dual-active mAb treatment (7.3% vs 1.1%; P <.01). Single-active and dual-active mAb treatment resulted in similar decrease in rates of hospitalizations or death. Conclusions Compared with single-active mAb therapy, dual-active mAbs led to similar clinical outcomes but significantly faster viral load decline and a lower risk of emergent resistance. [ABSTRACT FROM AUTHOR]
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- 2024
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81. Low-Dose Methotrexate Does Not Affect Measures of HIV-1 Persistence in Individuals With Chronically Treated HIV-1 Infection.
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Cyktor, Joshua C., Yeh, Eunice, Ribaudo, Heather, Hoeth, Dianna, Naqvi, Asma, Bell, Tanvir, Ridker, Paul M., Fichtenbaum, Carl, Daar, Eric S., Havlir, Diane, Tawakol, Ahmed, Lederman, Michael M., Stein, James H., Deeks, Steven G., Currier, Judith S., Hsue, Priscilla Y., and Mellors, John W.
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- 2024
82. Brief Report
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Kelesidis, Theodoros, Moser, Carlee B, Johnston, Elizabeth, Stein, James H, Dube, Michael P, Yang, Otto O, McComsey, Grace A, Currier, Judith S, and Brown, Todd T
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Medical Microbiology ,Biomedical and Clinical Sciences ,Clinical Sciences ,Prevention ,Infectious Diseases ,HIV/AIDS ,Clinical Research ,Clinical Trials and Supportive Activities ,Osteoporosis ,6.1 Pharmaceuticals ,Evaluation of treatments and therapeutic interventions ,Musculoskeletal ,Infection ,Good Health and Well Being ,Adult ,Female ,HIV Infections ,Humans ,Male ,Middle Aged ,Osteoprotegerin ,Prospective Studies ,RANK Ligand ,HIV ,RANKL ,OPG ,CVD ,bone disease ,Public Health and Health Services ,Virology ,Clinical sciences ,Epidemiology ,Public health - Abstract
BackgroundThe contributions of the receptor activator of nuclear factor kappa-B ligand (RANKL)/osteoprotegerin (OPG) axis to cardiovascular and bone disease in treated HIV-1 infection are not well defined.SettingProspective, observational, longitudinal study.MethodsIn a subset analysis of a prospective randomized clinical trial, 234 HIV-1-infected antiretroviral therapy-naive participants received tenofovir-emtricitabine plus either atazanavir/ritonavir, darunavir/ritonavir, or raltegravir and achieved plasma HIV-1 RNA
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- 2018
83. Soluble levels of receptor for advanced glycation endproducts and dysfunctional high-density lipoprotein in persons infected with human immunodeficiency virus
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Kelesidis, Theodoros, Kendall, Michelle A, Danoff, Ann, Aberg, Judith A, Currier, Judith S, and Schmidt, Ann Marie
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Biomedical and Clinical Sciences ,Clinical Sciences ,Immunology ,Clinical Research ,Atherosclerosis ,HIV/AIDS ,Cardiovascular ,2.1 Biological and endogenous factors ,Aetiology ,Adult ,Biomarkers ,Cohort Studies ,Disease Progression ,Female ,HIV Infections ,Humans ,Lipoproteins ,HDL ,Male ,Middle Aged ,Prospective Studies ,Receptor for Advanced Glycation End Products ,Retrospective Studies ,Risk Factors ,cardiovascular disease ,glycation ,HDL ,HDL function ,HIV ,inflammation ,oxidation - Abstract
The role of high-density lipoprotein (HDL) function and advanced glycation end products (AGEs) in HIV-related atherosclerotic cardiovascular disease (CVD) is unclear. Both glycation and oxidation (HDLox) are major modifications of HDL that can alter its composition and function. Therefore, we explored the longitudinal association of HDLox with progression of glycation, as evaluated by measurement of circulating forms of receptor for AGE that predict morbidity (soluble Receptors for Advanced Glycation Endproducts [sRAGE], endogenous secretory Receptors for Advanced Glycation Endproducts [esRAGE]), in people with HIV-1 (PWH; HIV-1) and uninfected (HIV-1) individuals.We retrospectively assessed if levels of plasma sRAGE and esRAGE and HDL function (reduced antioxidant function is associated with increased HDL lipid hydroperoxide content; HDLox) in a subset of participants (n = 80) from a prospective 3-year study (AIDS Clinical Trials Group A5078). Primary outcomes were baseline and yearly rates of change over 96 of 144 weeks (Δ) in HDLox in HIV-1 versus uninfected HIV-1 controls (noted as HIV-1).Higher baseline levels of sRAGE in PWH on effective anti-retroviral therapy and with low CVD risk, but not in HIV-1 persons, were independently associated with higher HDLox. EsRAGE, but not sRAGE, had consistent inverse relationships with ΔHDLox in both HIV-1 and HIV-1 persons at baseline. In HIV-1 but not in HIV-1 persons, ΔHDLox had positive and inverse relationships with ΔRAGE and ΔesRAGE, respectively.Glycation and oxidation of HDL may contribute to impaired HDL function present in PWH.
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- 2018
84. Telmisartan Therapy Does Not Improve Lymph Node or Adipose Tissue Fibrosis More Than Continued Antiretroviral Therapy Alone
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Utay, Netanya S, Kitch, Douglas W, Yeh, Eunice, Fichtenbaum, Carl J, Lederman, Michael M, Estes, Jacob D, Deleage, Claire, Magyar, Clara, Nelson, Scott D, Klingman, Karen L, Bastow, Barbara, Luque, Amneris E, McComsey, Grace A, Douek, Daniel C, Currier, Judith S, Lake, Jordan E, Aweeka, Francesca, Baer, Jenifer, Benns, Alex, Dragavon, Joan, Hensel, Christopher, Hsue, Priscilla, Kaytes, Andy, Ribaudo, Heather, Rusin, David, Shin, Katherine, Simmons, Antoine, and Zhan, Xinyan
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Medical Microbiology ,Biomedical and Clinical Sciences ,Immunology ,Infectious Diseases ,Sexually Transmitted Infections ,HIV/AIDS ,Clinical Research ,Clinical Trials and Supportive Activities ,6.1 Pharmaceuticals ,Evaluation of treatments and therapeutic interventions ,Infection ,Adipose Tissue ,Adult ,Antihypertensive Agents ,Antiretroviral Therapy ,Highly Active ,Female ,Fibrosis ,HIV Infections ,Humans ,Inflammation ,Lymph Nodes ,Male ,Middle Aged ,PPAR gamma ,Telmisartan ,HIV ,ART ,lymph node fibrosis ,adipose tissue fibrosis ,TGF-beta ,A5317 AIDS Clinical Trials Group Team ,Biological Sciences ,Medical and Health Sciences ,Microbiology ,Biological sciences ,Biomedical and clinical sciences ,Health sciences - Abstract
BackgroundFibrosis in lymph nodes may limit CD4+ T-cell recovery, and lymph node and adipose tissue fibrosis may contribute to inflammation and comorbidities despite antiretroviral therapy (ART). We hypothesized that the angiotensin receptor blocker and peroxisome proliferator-activated receptor γ agonist telmisartan would decrease lymph node or adipose tissue fibrosis in treated human immunodeficiency virus type 1 (HIV) infection.MethodsIn this 48-week, randomized, controlled trial, adults continued HIV-suppressive ART and received telmisartan or no drug. Collagen I, fibronectin, and phosphorylated SMAD3 (pSMAD3) deposition in lymph nodes, as well as collagen I, collagen VI, and fibronectin deposition in adipose tissue, were quantified by immunohistochemical analysis at weeks 0 and 48. Two-sided rank sum and signed rank tests compared changes over 48 weeks.ResultsForty-four participants enrolled; 35 had paired adipose tissue specimens, and 29 had paired lymph node specimens. The median change overall in the percentage of the area throughout which collagen I was deposited was -2.6 percentage points (P = 0.08) in lymph node specimens and -1.3 percentage points (P = .001) in adipose tissue specimens, with no between-arm differences. In lymph node specimens, pSMAD3 deposition changed by -0.5 percentage points overall (P = .04), with no between-arm differences. Telmisartan attenuated increases in fibronectin deposition (P = .06). In adipose tissue, changes in collagen VI deposition (-1.0 percentage point; P = .001) and fibronectin deposition (-2.4 percentage points; P < .001) were observed, with no between-arm differences.ConclusionsIn adults with treated HIV infection, lymph node and adipose tissue fibrosis decreased with continued ART alone, with no additional fibrosis reduction with telmisartan therapy.
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- 2018
85. CROI 2018: Complications of HIV Infection and Antiretroviral Therapy.
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Currier, Judith S and Havlir, Diane V
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Humans ,Tuberculosis ,Cryptococcosis ,HIV Infections ,Anti-Retroviral Agents ,Congresses as Topic ,Rare Diseases ,Prevention ,HIV/AIDS ,Infectious Diseases ,Evaluation of treatments and therapeutic interventions ,6.1 Pharmaceuticals ,Infection ,Good Health and Well Being - Abstract
This year marked the 25th Conference on Retroviruses and Opportunistic Infections (CROI), and although there is much progress to celebrate in terms of treatment of HIV infection and expanding ART globally, many challenges remain. Tuberculosis is still the leading cause of death among people with HIV infection globally. This year, the results of investments in research to improve the prevention and treatment of tuberculosis were a highlight of the meeting. Noninfectious causes remain an important source of morbidity. Progress in identifying risk factors for non-AIDS complications and improvements in screening and monitoring for such conditions continue to be reported, but to date, despite the efforts of many investigators around the globe, interventions to effectively reduce HIV-related inflammation beyond effective and safer antiretroviral therapy (ART) remain elusive. This section will review highlights of the meeting on tuberculosis and cryptococcal infection as well as complications of long-term ART.
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- 2018
86. Birth Outcomes for Pregnant Women with HIV Using Tenofovir–Emtricitabine
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Rough, Kathryn, Seage, George R, Williams, Paige L, Hernandez-Diaz, Sonia, Huo, Yanling, Chadwick, Ellen G, Currier, Judith S, Hoffman, Risa M, Barr, Emily, Shapiro, David E, and Patel, Kunjal
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Paediatrics ,Reproductive Medicine ,Biomedical and Clinical Sciences ,HIV/AIDS ,Pediatric ,Infant Mortality ,Infectious Diseases ,Perinatal Period - Conditions Originating in Perinatal Period ,Clinical Research ,Preterm ,Low Birth Weight and Health of the Newborn ,Prevention ,Clinical Trials and Supportive Activities ,Reproductive health and childbirth ,Infection ,Good Health and Well Being ,Adult ,Anti-HIV Agents ,Cohort Studies ,Disease Transmission ,Infectious ,Drug Administration Schedule ,Drug Therapy ,Combination ,Emtricitabine ,Female ,HIV Infections ,Humans ,Infant ,Low Birth Weight ,Infant ,Newborn ,Lamivudine ,Lopinavir ,Pregnancy ,Pregnancy Complications ,Infectious ,Pregnancy Outcome ,Premature Birth ,Risk ,Ritonavir ,Tenofovir ,Zidovudine ,PHACS and the IMPAACT P1025 Study Teams ,Medical and Health Sciences ,General & Internal Medicine ,Biomedical and clinical sciences ,Health sciences - Abstract
BackgroundIn a previous trial of antiretroviral therapy (ART) involving pregnant women with human immunodeficiency virus (HIV) infection, those randomly assigned to receive tenofovir, emtricitabine, and ritonavir-boosted lopinavir (TDF-FTC-LPV/r) had infants at greater risk for very premature birth and death within 14 days after delivery than those assigned to receive zidovudine, lamivudine, and ritonavir-boosted lopinavir (ZDV-3TC-LPV/r).MethodsUsing data from two U.S.-based cohort studies, we compared the risk of adverse birth outcomes among infants with in utero exposure to ZDV-3TC-LPV/r, TDF-FTC-LPV/r, or TDF-FTC with ritonavir-boosted atazanavir (ATV/r). We evaluated the risk of preterm birth (
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- 2018
87. Management of Long-Term Complications of HIV Disease: Focus on Cardiovascular Disease.
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Currier, Judith S
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Humans ,HIV Infections ,Cardiovascular Diseases ,Inflammation ,Anti-HIV Agents ,CD4 Lymphocyte Count ,Risk Factors ,Risk Reduction Behavior ,Cardiovascular ,Heart Disease ,Clinical Research ,Prevention ,HIV/AIDS ,Infectious Diseases ,6.1 Pharmaceuticals ,Evaluation of treatments and therapeutic interventions ,Infection ,Good Health and Well Being - Abstract
HIV-infected individuals on effective antiretroviral therapy experience a number of non-AIDS noncommunicable diseases, such as cardiovascular disease, more frequently than uninfected individuals. Common pathways for such diseases are chronic immune activation and inflammation, including the prolonged inflammation associated with lower nadir CD4+ cell count. Prevention and treatment of non-AIDS conditions include treatment of traditional risk factors, lifestyle interventions, earlier initiation of antiretroviral therapy, and potentially therapies specifically targeting inflammation and immune activation (eg, statins). This article summarizes a presentation by Judith S. Currier, MD, at the IAS-USA continuing education program, Improving the Management of HIV Disease, held in New York, New York, in February 2017.
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- 2018
88. Development and validation of an assay to analyze atazanavir in human hair via liquid chromatography/tandem mass spectrometry
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Phung, Nhi, Kuncze, Karen, Okochi, Hideaki, Louie, Alexander, Benet, Leslie Z, Ofokotun, Igho, Haas, David W, Currier, Judith S, Chawana, Tariro D, Sheth, Anandi N, Bacchetti, Peter, Gandhi, Monica, and Horng, Howard
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Analytical Chemistry ,Chemical Sciences ,Infectious Diseases ,Sexually Transmitted Infections ,HIV/AIDS ,Clinical Research ,Development of treatments and therapeutic interventions ,5.1 Pharmaceuticals ,Good Health and Well Being ,Anti-HIV Agents ,Atazanavir Sulfate ,Chromatography ,High Pressure Liquid ,HIV Infections ,Hair ,Humans ,Spectrometry ,Mass ,Electrospray Ionization ,Earth Sciences ,Biological Sciences ,Biological sciences ,Chemical sciences ,Earth sciences - Abstract
RationaleAssays to quantify antiretrovirals in hair samples are increasingly used to monitor adherence and exposure in both HIV prevention and treatment studies. Atazanavir (ATV) is a protease inhibitor used in combination antiretroviral therapy (ART). We developed and validated a liquid chromatography/tandem mass spectrometry (LC/MS/MS)-based method to quantify ATV in human hair, per the NIH Division of AIDS Clinical Pharmacology Quality Assurance (CPQA) program and the FDA bioanalytical method validation guidelines.MethodsATV was extracted from hair using optimized methods and the extracts were injected onto a BDS C-18 column (5 μm, 4.6 × 100 mm), followed by isocratic elution via a mobile phase composed of 55% acetonitrile, 45% water, 0.15% acetic acid, and 4 mM ammonium acetate, at a flow rate of 0.8 mL/min prior to analysis by MS/MS. Levels were quantified using positive electrospray ionization by multiple reaction monitoring (MRM) for the transitions MH+ m/z 705.3 to m/z 168.0 and MH+ m/z 710.2 to m/z 168.0 for ATV and ATV-d5 (internal standard), respectively.ResultsOur assay demonstrated a linear standard curve (r = 0.99) over the concentration range of 0.0500 ng ATV/mg hair to 20.0 ng/mg hair. The inter- and intraday accuracy of ATV quality control (QC) samples was -1.33 to 4.00% and precision (% coefficient of variation (%CV)) was 1.75 to 6.31%. The %CV for ATV levels in hair samples from highly adherent patients (incurred samples) was less than 10%. No significant endogenous peaks or crosstalk were observed in the specificity test with other HIV drugs. The overall extraction efficiency of ATV from incurred hair samples was greater than 95%.ConclusionsThis highly sensitive, highly specific and validated assay can be considered for therapeutic drug monitoring for HIV-infected patients on ATV-based ART.
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- 2018
89. Low Levels of Endothelial Progenitor Cells and Their Association with Systemic Inflammation and Monocyte Activation in Older HIV-Infected Men
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Seang, Sophie, Kelesidis, Theodoros, Huynh, Diana, Park, Sangeun, Moe, Ardis A, Currier, Judith S, and Lake, Jordan E
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Biomedical and Clinical Sciences ,Clinical Sciences ,Immunology ,Infectious Diseases ,Stem Cell Research ,Clinical Research ,Cardiovascular ,Prevention ,Heart Disease ,Aging ,Stem Cell Research - Nonembryonic - Human ,2.1 Biological and endogenous factors ,Aetiology ,Good Health and Well Being ,Age Factors ,Atherosclerosis ,Endothelial Progenitor Cells ,Endothelium ,Vascular ,Flow Cytometry ,HIV ,HIV Infections ,Humans ,Inflammation ,Leukocytes ,Mononuclear ,Macrophage Activation ,Male ,Middle Aged ,Pilot Projects ,Risk Factors ,endothelial progenitor cells ,inflammation ,Virology ,Clinical sciences - Abstract
Endothelial progenitor cells (EPCs) repair damaged vascular endothelium, and low circulating EPC levels have been associated with cardiovascular disease (CVD). CD34+/KDR+ EPCs are commonly reported in the literature and CD34+/CD133+/KDR+ EPCs are rare in circulation but highly specific for endothelial lineage. HIV-infected (HIV+) adults have chronic inflammation and increased CVD risk, but the relationship between CVD, vascular inflammation, and EPCs in HIV remains unclear. In a pilot study, EPCs were measured in 57 HIV+ men [≥50 years old, HIV-1 RNA
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- 2018
90. Pregnancy outcomes among HIV-infected women who conceived on antiretroviral therapy
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Stringer, Elizabeth M, Kendall, Michelle A, Lockman, Shahin, Campbell, Thomas B, Nielsen-Saines, Karin, Sawe, Fred, Cu-uvin, Susan, Wu, Xingye, and Currier, Judith S
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Reproductive Medicine ,Biomedical and Clinical Sciences ,Preterm ,Low Birth Weight and Health of the Newborn ,Perinatal Period - Conditions Originating in Perinatal Period ,Contraception/Reproduction ,Pediatric ,Clinical Research ,Mental Health ,Infectious Diseases ,Infant Mortality ,Conditions Affecting the Embryonic and Fetal Periods ,Reproductive health and childbirth ,Good Health and Well Being ,Adult ,Anti-HIV Agents ,Antiretroviral Therapy ,Highly Active ,Female ,HIV Infections ,Humans ,Pregnancy ,Pregnancy Complications ,Infectious ,Pregnancy Outcome ,Premature Birth ,Proportional Hazards Models ,Stillbirth ,United States ,General Science & Technology - Abstract
As antiretroviral therapy (ART) expands in resource-limited settings, understanding the impact of ART on pregnancy outcomes is critical. We analyzed women who became pregnant on ART while enrolled in a clinical trial (HPTN 052, ACTG A5208, and ACTG A5175); the majority of women were from Africa, with a median age of 29 years. Eligible women were on ART at conception and had a documented date of a last menstrual period and a pregnancy outcome. The primary outcome was non-live birth (stillbirth; spontaneous abortion; elective termination; or ectopic pregnancy) versus live birth. Preterm birth (
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- 2018
91. Subclinical myocardial disease by cardiac magnetic resonance imaging and spectroscopy in healthy HIV/Hepatitis C virus-coinfected persons
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Chew, Kara W, Liu, Chia-Ying, Ambale-Venkatesh, Bharath, Liao, Diana, Horwich, Tamara B, Lima, João AC, Bluemke, David A, Finn, J Paul, Butt, Adeel A, and Currier, Judith S
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Medical Microbiology ,Biomedical and Clinical Sciences ,Clinical Sciences ,Clinical Research ,Hepatitis - C ,Liver Disease ,Hepatitis ,HIV/AIDS ,Cardiovascular ,Chronic Liver Disease and Cirrhosis ,Emerging Infectious Diseases ,Heart Disease ,Sexually Transmitted Infections ,Digestive Diseases ,Infectious Diseases ,Biomedical Imaging ,Women's Health ,Evaluation of treatments and therapeutic interventions ,6.1 Pharmaceuticals ,Infection ,Good Health and Well Being ,Adult ,Coinfection ,HIV Infections ,Hepacivirus ,Hepatitis C ,Chronic ,Humans ,Linear Models ,Magnetic Resonance Imaging ,Male ,Middle Aged ,Myocardium ,Proton Magnetic Resonance Spectroscopy ,Spectrum Analysis ,HIV ,hepatitis C ,cardiac magnetic resonance imaging ,magnetic resonance spectroscopy ,heart disease ,myocardial fibrosis ,myocardial steatosis ,Medical and Health Sciences ,General & Internal Medicine ,Biomedical and clinical sciences ,Health sciences - Abstract
Objective The contribution of hepatitis C virus (HCV) infection to the risk of heart failure in human immunodeficiency virus (HIV)-coinfected persons is unknown. The objective was to characterize cardiac function and morphology in HIV-treated coinfected persons. Methods In a cross-sectional study, HIV-infected patients virologically suppressed on antiretroviral therapy without known cardiovascular disease or diabetes mellitus underwent cardiac magnetic resonance imaging and spectroscopy for measures of cardiac function, myocardial fibrosis, and steatosis. Results The study included 18 male patients with a median age of 44 years. Of these, 10 had untreated HCV coinfection and eight had HIV monoinfection. Global systolic and diastolic function in the cohort were normal, and median myocardial fat content was 0.48% (interquartile range 0.35-1.54). Left ventricular (LV) mass index and LV mass/volume ratio were significantly greater in the HIV/HCV-coinfected group compared with the HIV-monoinfected group. In the HIV-monoinfected group, there was more myocardial fibrosis as measured by extracellular volume fraction. Conclusions There were differences between HIV/HCV-coinfected and HIV-monoinfected patients in cardiac structure and morphology. Larger studies are needed to examine whether HIV and HCV independently contribute to mechanisms of heart failure.
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- 2017
92. A Conversation Among the IAS-USA Board of Directors: Hot Topics and Emerging Data in HIV Research and Care.
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Benson, Constance A, Currier, Judith S, Del Rio, Carlos, Gallant, Joel E, Gulick, Roy M, Marrazzo, Jeanne M, Richman, Douglas D, Saag, Michael S, Schooley, Robert T, and Volberding, Paul A
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Humans ,HIV Infections ,Anti-HIV Agents ,Antiretroviral Therapy ,Highly Active ,Biomedical Research ,Societies ,Scientific ,United States ,Drug Discovery - Abstract
The IAS-USA volunteer Board of Directors met in October 2016 for its annual meeting. For the second year, the Board conducted a live, hour-long, interactive, roundtable webinar covering current questions and issues in HIV research, prevention, and care. Important highlights from the Board's discussion, which was moderated by Paul A. Volberding, MD, are included below. Members of the IAS-USA volunteer Board of Directors are Constance A. Benson, MD; Judith S. Currier, MD; Carlos del Rio, MD; Joel E. Gallant, MD, MPH; Roy M. Gulick, MD, MPH; Jeanne M. Marrazzo, MD, MPH; Douglas D. Richman, MD; Michael S. Saag, MD; Robert T. Schooley, MD; and Paul A. Volberding, MD.
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- 2017
93. Changes in Abdominal Fat following Antiretroviral Therapy Initiation in HIV-Infected Individuals Correlate with Waist Circumference and Self-Reported Changes
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Bhagwat, Priya, Ofotokun, Ighovwerha, McComsey, Grace A, Brown, Todd T, Moser, Carlee, Sugar, Catherine A, and Currier, Judith S
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Medical Microbiology ,Biomedical and Clinical Sciences ,Infectious Diseases ,Obesity ,HIV/AIDS ,Adiposity ,Adult ,Analysis of Variance ,Antiretroviral Therapy ,Highly Active ,Body Mass Index ,Female ,HIV Infections ,Humans ,Intra-Abdominal Fat ,Male ,Middle Aged ,Retrospective Studies ,Self Report ,Tomography ,X-Ray Computed ,Waist Circumference ,Young Adult ,Microbiology ,Clinical Sciences ,Virology ,Clinical sciences ,Medical microbiology - Abstract
BackgroundWe examined whether waist circumference (WC) and self-reported abdominal size changes can estimate visceral adipose tissue (VAT) changes for those initiating antiretroviral therapy (ART).MethodsProspectively collected data from ACTG A5257 and its metabolic substudy, A5260s, were used for this analysis. ART-naive HIV-infected participants were randomized to one of three contemporary ART regimens. Changes in abdominal CT-measured VAT and total adipose tissue (TAT) and DXA-measured trunk fat were tested for association with WC changes (by Pearson correlation) and categories of self-reported abdominal size changes (by ANOVA) between entry and week 96. Linear models compared WC and self-reported changes.ResultsThe study population (n=328) was predominantly male (90%) and White non-Hispanic (44%) with a baseline median age of 36 years and body mass index of 25 kg/m2. At week 96, median WC change was +2.8 cm. Of those reporting at week 96, 53% indicated 'no change/lost', 39% 'gained some/somewhat larger' and 8% 'gained a lot/much larger' as their self-reported changes. Trunk fat, VAT and TAT changes differed across self-reported groups (ANOVA P
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- 2017
94. Transgender Women Living with HIV Frequently Take Antiretroviral Therapy and/or Feminizing Hormone Therapy Differently Than Prescribed Due to Drug–Drug Interaction Concerns
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Braun, Hannan M, Candelario, Jury, Hanlon, Courtney L, Segura, Eddy R, Clark, Jesse L, Currier, Judith S, and Lake, Jordan E
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Health Services and Systems ,Policy and Administration ,Health Sciences ,Human Society ,Infectious Diseases ,Clinical Research ,HIV/AIDS ,Evaluation of treatments and therapeutic interventions ,6.1 Pharmaceuticals ,Infection ,Anti-HIV Agents ,Cross-Sectional Studies ,Drug Interactions ,Female ,HIV Infections ,Hormone Replacement Therapy ,Humans ,Los Angeles ,Male ,Medication Adherence ,Middle Aged ,Pilot Projects ,Transgender Persons ,antiretroviral therapy ,health disparities ,HIV ,medication adherence ,transgender ,Health services and systems ,Policy and administration - Abstract
PurposeBoth hormone therapy (HT) and antiretroviral therapy (ART) can be lifesaving for transgender women (TW) living with HIV, but each has side effects and potential drug-drug interactions (DDI). We assessed how concerns about HT-ART interactions affect treatment adherence.MethodsThis study used a cross-sectional survey of TW (n = 87) in Los Angeles, CA.ResultsFifty-four percent were living with HIV; 64% used HT. Only 49% of TW living with HIV discussed ART-HT DDI with their provider; 40% reported not taking ART (12%), HT (12%), or both (16%) as directed due to DDI concerns.ConclusionImperfect HT/ART use and limited provider communication suggests a need for improved HT-ART integration.
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- 2017
95. Outpatient COVID-19 convalescent plasma recipient antibody thresholds correlated to reduced hospitalizations within a randomized trial
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Park, Han-Sol, primary, Yin, Anna, additional, Barranta, Caelan, additional, Lee, John S., additional, Caputo, Christopher A., additional, Sachithanandham, Jaiprasath, additional, Li, Maggie, additional, Yoon, Steve, additional, Sitaras, Ioannis, additional, Jedlicka, Anne, additional, Eby, Yolanda, additional, Ram, Malathi, additional, Fernandez, Reinaldo E., additional, Baker, Owen R., additional, Shenoy, Aarthi G., additional, Mosnaim, Giselle S., additional, Fukuta, Yuriko, additional, Patel, Bela, additional, Heath, Sonya L., additional, Levine, Adam C., additional, Meisenberg, Barry R., additional, Spivak, Emily S., additional, Anjan, Shweta, additional, Huaman, Moises A., additional, Blair, Janis E., additional, Currier, Judith S., additional, Paxton, James H., additional, Gerber, Jonathan M., additional, Petrini, Joann R., additional, Broderick, Patrick B., additional, Rausch, William, additional, Cordisco, Marie Elena, additional, Hammel, Jean, additional, Greenblatt, Benjamin, additional, Cluzet, Valerie C., additional, Cruser, Daniel, additional, Oei, Kevin, additional, Abinante, Matthew, additional, Hammitt, Laura L., additional, Sutcliffe, Catherine G., additional, Forthal, Donald N., additional, Zand, Martin S., additional, Cachay, Edward R., additional, Raval, Jay S., additional, Kassaye, Seble G., additional, Marshall, Christi E., additional, Yarava, Anusha, additional, Lane, Karen, additional, McBee, Nichol A., additional, Gawad, Amy L., additional, Karlen, Nicky, additional, Singh, Atika, additional, Ford, Daniel E., additional, Jabs, Douglas A., additional, Appel, Lawrence J., additional, Shade, David M., additional, Lau, Bryan, additional, Ehrhardt, Stephan, additional, Baksh, Sheriza N., additional, Shapiro, Janna R., additional, Ou, Jiangda, additional, Na, Yu Bin, additional, Knoll, Maria D., additional, Ornelas-Gatdula, Elysse, additional, Arroyo-Curras, Netzahualcoyotl, additional, Gniadek, Thomas J., additional, Caturegli, Patrizio, additional, Wu, Jinke, additional, Ndahiro, Nelson, additional, Betenbaugh, Michael J., additional, Ziman, Alyssa, additional, Hanley, Daniel F., additional, Casadevall, Arturo, additional, Shoham, Shmuel, additional, Bloch, Evan M., additional, Gebo, Kelly A., additional, Tobian, Aaron A.R., additional, Laeyendecker, Oliver, additional, Pekosz, Andrew, additional, Klein, Sabra L., additional, and Sullivan, David J., additional
- Published
- 2024
- Full Text
- View/download PDF
96. Response to Drs de Grooth and Parienti
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Giganti, Mark J, primary, Chew, Kara W, additional, Eron, Joseph J, additional, Smith, Davey M, additional, Currier, Judith S, additional, and Hughes, Michael D, additional
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- 2024
- Full Text
- View/download PDF
97. Antiretroviral initiation is associated with increased skeletal muscle area and fat content
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Erlandson, Kristine M, Fiorillo, Suzanne, Masawi, Fadzai, Scherzinger, Ann, McComsey, Grace A, Lake, Jordan E, Stein, James H, Currier, Judith S, and Brown, Todd T
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Biomedical and Clinical Sciences ,Clinical Sciences ,Health Sciences ,Infectious Diseases ,HIV/AIDS ,Clinical Research ,Evaluation of treatments and therapeutic interventions ,6.1 Pharmaceuticals ,Adipose Tissue ,Adult ,Anthropometry ,Anti-Retroviral Agents ,Female ,HIV Infections ,Humans ,Male ,Middle Aged ,Muscle ,Skeletal ,Radiography ,Abdominal ,Tomography ,X-Ray Computed ,aging ,frailty ,HIV ,muscle density ,skeletal muscle ,Biological Sciences ,Medical and Health Sciences ,Psychology and Cognitive Sciences ,Virology ,Biomedical and clinical sciences ,Health sciences - Abstract
ObjectiveA greater burden of physical function impairment occurs in HIV-infected adults; the impact of antiretroviral therapy (ART) initiation on muscle density (less dense = more fat), a measure of muscle quality, is unknown.DesignAIDS Clinical Trials Group Study A5260s, a cardiometabolic substudy of A5257, randomized HIV-infected, ART-naive adults to ritonavir-boosted atazanavir, darunavir, or raltegravir with tenofovir/emtricitabine backbone. Single-slice abdominal computed tomography scans from baseline and week 96 were reanalyzed for total and lean muscle area and density.MethodsTwo-sample t-tests described the differences between baseline and week 96 variables. Linear regression analysis was used to explore the role of a priori identified variables and potential confounders.ResultsParticipants (n = 235) were mostly men (90%); 31% were Black non-Hispanic; 21% were Hispanic. Over 96 weeks, small but significant increases were seen in oblique/transverse abdominal, rectus, and psoas muscle total area (range 0.21-0.83 cm; P
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- 2017
98. Predictors of Impaired HDL Function in HIV-1 Infected Compared to Uninfected Individuals
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Kelesidis, Theodoros, Oda, Michael N, Borja, Mark S, Yee, Yumin, Ng, Kit F, Huynh, Diana, Elashoff, David, and Currier, Judith S
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HDL function ,human immunodeficiency virus ,cardiovascular disease ,HDL-apoA-I exchange ,HDL remodeling ,oxidized HDL ,Virology ,Clinical Sciences ,Public Health and Health Services - Published
- 2017
99. Practical Review of Recognition and Management of Obesity and Lipohypertrophy in Human Immunodeficiency Virus Infection
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Lake, Jordan E, Stanley, Takara L, Apovian, Caroline M, Bhasin, Shalendar, Brown, Todd T, Capeau, Jaqueline, Currier, Judith S, Dube, Michael P, Falutz, Julian, Grinspoon, Steven K, Guaraldi, Giovanni, Martinez, Esteban, McComsey, Grace A, Sattler, Fred R, and Erlandson, Kristine M
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Medical Microbiology ,Biomedical and Clinical Sciences ,Clinical Sciences ,Immunology ,Infectious Diseases ,Prevention ,Obesity ,Clinical Research ,Nutrition ,HIV/AIDS ,Aetiology ,2.2 Factors relating to the physical environment ,2.1 Biological and endogenous factors ,Infection ,Metabolic and endocrine ,Good Health and Well Being ,Adiposity ,Anti-HIV Agents ,Antiretroviral Therapy ,Highly Active ,CD4 Lymphocyte Count ,Disease Management ,Female ,HIV Infections ,HIV-Associated Lipodystrophy Syndrome ,Humans ,Male ,Risk Factors ,human immunodeficiency virus ,obesity ,lipohypertrophy ,antiretroviral therapy ,antiretroviral therapy. ,Biological Sciences ,Medical and Health Sciences ,Microbiology ,Clinical sciences - Abstract
BackgroundObesity and lipohypertrophy are common in treated human immunodeficiency virus (HIV) infection and contribute to morbidity and mortality among HIV-infected adults on antiretroviral therapy (ART).MethodsWe present a consensus opinion on the diagnosis, clinical consequences, and treatment of excess adiposity in adults with treated HIV infection.ResultsObesity and lipohypertrophy commonly occur among HIV-infected adults on ART and may have overlapping pathophysiologies and/or synergistic metabolic consequences. Traditional, HIV-specific, and ART-specific risk factors all contribute. The metabolic and inflammatory consequences of excess adiposity are critical drivers of non-AIDS events in this population. Although promising treatment strategies exist, further research is needed to better understand the pathophysiology and optimal treatment of obesity and lipohypertrophy in the modern ART era.ConclusionsBoth generalized obesity and lipohypertrophy are prevalent among HIV-infected persons on ART. Aggressive diagnosis and management are key to the prevention and treatment of end-organ disease in this population and critical to the present and future health of HIV-infected persons.
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- 2017
100. CROI 2017: Complications and Comorbidities of HIV Disease and Its Treatment.
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Currier, Judith S and Havlir, Diane V
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Humans ,HIV Infections ,Bone Diseases ,Cardiovascular Diseases ,Comorbidity ,HIV/AIDS ,Tuberculosis ,Rare Diseases ,Infectious Diseases ,Prevention ,Obesity ,Aetiology ,2.1 Biological and endogenous factors ,Infection ,Good Health and Well Being - Abstract
Complications of HIV disease remained a major focus at the 2017 Conference on Retroviruses and Opportunistic Infections (CROI), and included studies focused on noncommunicable chronic diseases (eg, cardiovascular disease, obesity, bone disease, and malignancies) and opportunistic infections (Mycobacterium tuberculosis and cryptococcosis). Progress in identifying predictors of specific complications as well as interventions for the prevention and treatment of these comorbidities are summarized below.
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- 2017
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