598 results on '"Eron JJ"'
Search Results
2. Anemia risk factors among people living with HIV across the United States in the current treatment era: a clinical cohort study
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Harding, BN, Whitney, BM, Nance, RM, Ruderman, SA, Crane, HM, Burkholder, G, Moore, RD, Mathews, WC, Eron, JJ, Hunt, PW, Volberding, P, Rodriguez, B, Mayer, KH, Saag, MS, Kitahata, MM, Heckbert, SR, and Delaney, JAC
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Public Health ,Biomedical and Clinical Sciences ,Clinical Sciences ,Health Sciences ,Hepatitis ,Digestive Diseases ,Prevention ,HIV/AIDS ,Sexually Transmitted Infections ,Infectious Diseases ,Substance Misuse ,Clinical Research ,Minority Health ,Emerging Infectious Diseases ,Liver Disease ,Hepatitis - C ,Hematology ,6.1 Pharmaceuticals ,Evaluation of treatments and therapeutic interventions ,Aetiology ,2.4 Surveillance and distribution ,Infection ,Good Health and Well Being ,Adult ,Anemia ,Anti-Retroviral Agents ,CD4 Lymphocyte Count ,Coinfection ,Female ,Follow-Up Studies ,Glomerular Filtration Rate ,HIV ,HIV Infections ,Hemoglobins ,Hepatitis C ,Humans ,Incidence ,Male ,Middle Aged ,Prospective Studies ,Retrospective Studies ,Risk Factors ,Substance-Related Disorders ,United States ,Viral Load ,Hemoglobin ,Cohort ,Microbiology ,Medical Microbiology ,Clinical sciences ,Medical microbiology ,Public health - Abstract
BackgroundAnemia is common among people living with HIV infection (PLWH) and is associated with adverse health outcomes. Information on risk factors for anemia incidence in the current antiretroviral therapy (ART) era is lacking.MethodsWithin a prospective clinical cohort of adult PLWH receiving care at eight sites across the United States between 1/2010-3/2018, Cox proportional hazards regression analyses were conducted among a) PLWH free of anemia at baseline and b) PLWH free of severe anemia at baseline to determine associations between time-updated patient characteristics and development of anemia (hemoglobin
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- 2020
3. Risk of End‐Stage Renal Disease in HIV‐Positive Potential Live Kidney Donors
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Muzaale, AD, Althoff, KN, Sperati, CJ, Abraham, AG, Kucirka, LM, Massie, AB, Kitahata, MM, Horberg, MA, Justice, AC, Fischer, MJ, Silverberg, MJ, Butt, AA, Boswell, SL, Rachlis, AR, Mayor, AM, Gill, MJ, Eron, JJ, Napravnik, S, Drozd, DR, Martin, JN, Bosch, RJ, Durand, CM, Locke, JE, Moore, RD, Lucas, GM, and Segev, DL
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Biomedical and Clinical Sciences ,Clinical Sciences ,HIV/AIDS ,Infectious Diseases ,Sexually Transmitted Infections ,Kidney Disease ,Aetiology ,2.2 Factors relating to the physical environment ,Renal and urogenital ,Infection ,Good Health and Well Being ,Adult ,Case-Control Studies ,Female ,Follow-Up Studies ,Glomerular Filtration Rate ,Graft Rejection ,Graft Survival ,HIV Infections ,HIV Seropositivity ,HIV-1 ,Humans ,Incidence ,Kidney Failure ,Chronic ,Kidney Function Tests ,Kidney Transplantation ,Living Donors ,Male ,Middle Aged ,Nephrectomy ,North America ,Prognosis ,Risk Factors ,Viral Load ,clinical research/practice ,donors and donation: living ,infection and infectious agents ,infectious disease ,kidney transplantation/nephrology ,viral: human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome ,Medical and Health Sciences ,Surgery ,Clinical sciences ,Immunology - Abstract
New federal regulations allow HIV-positive individuals to be live kidney donors; however, potential candidacy for donation is poorly understood given the increased risk of end-stage renal disease (ESRD) associated with HIV infection. To better understand this risk, we compared the incidence of ESRD among 41 968 HIV-positive participants of North America AIDS Cohort Collaboration on Research and Design followed for a median of 5 years with the incidence of ESRD among comparable HIV-negative participants of National Health and Nutrition Examination III followed for a median of 14 years. We used risk associations from multivariable Cox proportional hazards regression to derive cumulative incidence estimates for selected HIV-positive scenarios (no history of diabetes, hypertension, AIDS, or hepatitis C virus coinfection) and compared these estimates with those from similarly selected HIV-negative scenarios. For 40-year-old HIV-positive individuals with health characteristics that were similar to those of age-matched kidney donors, viral load
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- 2017
4. Estimation of the Standardized Risk Difference and Ratio in a Competing Risks Framework: Application to Injection Drug Use and Progression to AIDS After Initiation of Antiretroviral Therapy
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Cole, SR, Lau, B, Eron, JJ, Brookhart, MA, Kitahata, MM, Martin, JN, Mathews, WC, Mugavero, MJ, and for the CNICS Research Network
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Epidemiology ,Health Sciences ,HIV/AIDS ,Sexually Transmitted Infections ,Drug Abuse (NIDA only) ,Clinical Research ,Infectious Diseases ,Substance Misuse ,6.1 Pharmaceuticals ,Evaluation of treatments and therapeutic interventions ,Good Health and Well Being ,Acquired Immunodeficiency Syndrome ,Adult ,Black or African American ,Anti-HIV Agents ,Cohort Studies ,Disease Progression ,Female ,Follow-Up Studies ,Hispanic or Latino ,Humans ,Incidence ,Male ,Mathematical Computing ,Middle Aged ,Odds Ratio ,Risk Assessment ,Risk Factors ,Substance Abuse ,Intravenous ,Survival Rate ,United States ,AIDS ,cohort study ,competing risks ,HIV ,survival function ,CNICS Research Network ,Mathematical Sciences ,Medical and Health Sciences - Abstract
There are few published examples of absolute risk estimated from epidemiologic data subject to censoring and competing risks with adjustment for multiple confounders. We present an example estimating the effect of injection drug use on 6-year risk of acquired immunodeficiency syndrome (AIDS) after initiation of combination antiretroviral therapy between 1998 and 2012 in an 8-site US cohort study with death before AIDS as a competing risk. We estimate the risk standardized to the total study sample by combining inverse probability weights with the cumulative incidence function; estimates of precision are obtained by bootstrap. In 7,182 patients (83% male, 33% African American, median age of 38 years), we observed 6-year standardized AIDS risks of 16.75% among 1,143 injection drug users and 12.08% among 6,039 nonusers, yielding a standardized risk difference of 4.68 (95% confidence interval: 1.27, 8.08) and a standardized risk ratio of 1.39 (95% confidence interval: 1.12, 1.72). Results may be sensitive to the assumptions of exposure-version irrelevance, no measurement bias, and no unmeasured confounding. These limitations suggest that results be replicated with refined measurements of injection drug use. Nevertheless, estimating the standardized risk difference and ratio is straightforward, and injection drug use appears to increase the risk of AIDS.
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- 2015
5. Lessons Learned From the Design and Implementation of Myocardial Infarction Adjudication Tailored for HIV Clinical Cohorts
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Crane, HM, Heckbert, SR, Drozd, DR, Budoff, MJ, Delaney, JAC, Rodriguez, C, Paramsothy, P, Lober, WB, Burkholder, G, Willig, JH, Mugavero, MJ, Mathews, WC, Crane, PK, Moore, RD, Napravnik, S, Eron, JJ, Hunt, P, Geng, E, Hsue, P, Barnes, GS, McReynolds, J, Peter, I, Grunfeld, C, Saag, MS, Kitahata, MM, and Investigators, for the Centers for AIDS Research Network of Integrated Clinical Systems Cohort
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Epidemiology ,Health Sciences ,HIV/AIDS ,Cardiovascular ,Heart Disease ,Sexually Transmitted Infections ,Infectious Diseases ,Heart Disease - Coronary Heart Disease ,Infection ,Adult ,Aged ,Aged ,80 and over ,Cohort Studies ,Decision Support Techniques ,Epidemiologic Research Design ,False Positive Reactions ,Female ,HIV Infections ,Humans ,Male ,Middle Aged ,Myocardial Infarction ,Predictive Value of Tests ,Sensitivity and Specificity ,Single-Blind Method ,HIV ,myocardial infarction ,validation ,Centers for AIDS Research Network of Integrated Clinical Systems Cohort Investigators ,Mathematical Sciences ,Medical and Health Sciences - Abstract
We developed, implemented, and evaluated a myocardial infarction (MI) adjudication protocol for cohort research of human immunodeficiency virus. Potential events were identified through the centralized Centers for AIDS Research Network of Integrated Clinical Systems data repository using MI diagnoses and/or cardiac enzyme laboratory results (1995-2012). Sites assembled de-identified packets, including physician notes and results from electrocardiograms, procedures, and laboratory tests. Information pertaining to the specific antiretroviral medications used was redacted for blinded review. Two experts reviewed each packet, and a third review was conducted if discrepancies occurred. Reviewers categorized probable/definite MIs as primary or secondary and identified secondary causes of MIs. The positive predictive value and sensitivity for each identification/ascertainment method were calculated. Of the 1,119 potential events that were adjudicated, 294 (26%) were definite/probable MIs. Almost as many secondary (48%) as primary (52%) MIs occurred, often as the result of sepsis or cocaine use. Of the patients with adjudicated definite/probable MIs, 78% had elevated troponin concentrations (positive predictive value = 57%, 95% confidence interval: 52, 62); however, only 44% had clinical diagnoses of MI (positive predictive value = 45%, 95% confidence interval: 39, 51). We found that central adjudication is crucial and that clinical diagnoses alone are insufficient for ascertainment of MI. Over half of the events ultimately determined to be MIs were not identified by clinical diagnoses. Adjudication protocols used in traditional cardiovascular disease cohorts facilitate cross-cohort comparisons but do not address issues such as identifying secondary MIs that may be common in persons with human immunodeficiency virus.
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- 2014
6. Vaporized Nicotine (E-cigarette) and Tobacco Smoking Among People with HIV: Use Patterns and Associations with Depression and Panic Symptoms
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Hahn, AW, primary, Ruderman, SA, additional, Nance, RM, additional, Whitney, BW, additional, Eltonsy, S, additional, Haidar, L, additional, Delaney, JAC, additional, Drumright, LN, additional, Ma, J, additional, Mayer, KH, additional, O’Cleirigh, C, additional, Napravnik, S, additional, Eron, JJ, additional, Christopoulos, K, additional, Bamford, L, additional, Cachay, E, additional, Jacobson, JM, additional, Willig, A, additional, Cropsey, K, additional, Chander, G, additional, Crane, HM, additional, and Fredericksen, RJ, additional
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- 2022
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7. Weight gain following antiretroviral therapy (ART) initiation in ART-naïve people living with HIV in the current treatment era
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Ruderman, SA, Crane, HM, Nance, RM, Whitney, BM, Harding, BN, Mayer, KH, Moore, RD, Eron, JJ, Geng, E, Mathews, WC, Willig, AL, Burkholder, GA, Lindström, S, Wood, BR, Collier, AC, Vannappagari, V, Henegar, C, Van Wyk, J, Curtis, L, Saag, MS, Kitahata, MM, and Delaney, JAC
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Adult ,Cyclopropanes ,Male ,Alanine ,Anti-HIV Agents ,Pyridones ,HIV Infections ,Middle Aged ,Weight Gain ,Article ,Dideoxynucleosides ,Piperazines ,Benzoxazines ,Anti-Retroviral Agents ,Alkynes ,Oxazines ,Humans ,Female ,HIV Integrase Inhibitors ,Tenofovir ,Heterocyclic Compounds, 3-Ring - Abstract
Evaluate differences in weight change by regimen among people living with HIV (PLWH) initiating antiretroviral therapy (ART) in the current era.Between 2012 and 2019, 3232 ART-naïve PLWH initiated ≥3-drug ART regimens in 8 Centers for AIDS Research Network of Integrated Clinical Systems sites. We estimated weight change by regimen for 11 regimens in the immediate (first 6 months) and extended (all follow-up on initial regimen) periods using linear mixed models adjusted for time on regimen, interaction between time and regimen, age, sex, race/ethnicity, hepatitis B/C coinfection, nadir CD4, smoking, diabetes, antipsychotic medication, and site. We included more recently approved regimens [eg, with tenofovir alafenamide fumarate (TAF)] only in the immediate period analyses to ensure comparable follow-up time.Mean follow-up was 1.9 years on initial ART regimen. In comparison to efavirenz/tenofovir disoproxil fumarate (TDF)/emtricitabine (FTC), initiating bictegravir/TAF/FTC {3.9 kg [95% confidence interval (CI): 2.2 to 5.5]} and dolutegravir/TAF/FTC [4.4 kg (95% CI: 2.1 to 6.6)] were associated with the greatest weight gain in the immediate period, followed by darunavir/TDF/FTC [3.7 kg (95% CI: 2.1 to 5.2)] and dolutegravir/TDF/FTC [2.6 kg (95% CI: 1.3 to 3.9)]. In the extended period, compared with efavirenz/TDF/FTC, initiating darunavir/TDF/FTC was associated with a 1.0 kg (95% CI: 0.5 to 1.5) per 6-months greater weight gain, whereas dolutegravir/abacavir/FTC was associated with a 0.6-kg (95% CI: 0.3 to 0.9) and dolutegravir/TDF/FTC was associated with a 0.6-kg (95% CI: 0.1 to 1.1) per 6-months greater gain. Weight gain on dolutegravir/abacavir/FTC and darunavir/TDF/FTC was significantly greater than that for several integrase inhibitor-based regimens.There is heterogeneity between regimens in weight gain following ART initiation among previously ART-naïve PLWH; we observed greater gain among PLWH taking newer integrase strand transfer inhibitors (DTG, BIC) and DRV-based regimens.
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- 2021
8. Second-line treatment in the Malawi antiretroviral programme: high early mortality, but good outcomes in survivors, despite extensive drug resistance at baseline*
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Hosseinipour, MC, Kumwenda, JJ, Weigel, R, Brown, LB, Mzinganjira, D, Mhango, B, Eron, JJ, Phiri, S, and van Oosterhout, JJ
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- 2010
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9. Efficacy and safety of switching from boosted protease inhibitors plus emtricitabine and tenofovir disoproxil fumarate regimens to single-tablet darunavir, cobicistat, emtricitabine, and tenofovir alafenamide at 48 weeks in adults with virologically suppressed HIV-1 (EMERALD): a phase 3, randomised, non-inferiority trial
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Orkin, C, Molina, JM, Negredo, E, Arribas, JR, Gathe, J, Eron, JJ, Van Landuyt, E, Lathouwers, E, Hufkens, V, Petrovic, R, Vanveggel, S, and Opsomer, M
- Abstract
Background Simplified regimens with reduced pill burden and fewer side-effects are desirable for people living with HIV. We investigated the efficacy and safety of switching to a single-tablet regimen of darunavir, cobicistat, emtricitabine, and tenofovir alafenamide versus continuing a regimen of boosted protease inhibitor, emtricitabine, and tenofovir disoproxil fumarate. Methods EMERALD was a phase-3, randomised, active-controlled, open-label, international, multicentre trial, done at 106 sites across nine countries in North America and Europe. HIV-1-infected adults were eligible to participate if they were treatment-experienced and virologically suppressed (viral load = 2 months; one viral load of 50-200 copies per mL was allowed within 12 months before screening), and patients with a history of virological failure on non-darunavir regimens were allowed. Randomisation was by computer-generated interactive web-response system and stratified by boosted protease inhibitor use at baseline. Patients were randomly assigned (2: 1) to switch to the open-label study regimen or continue the control regimen. The study regimen consisted of a fixed-dose tablet containing darunavir 800 mg, cobicistat 150 mg, emtricitabine 200 mg, and tenofovir alafenamide 10 mg, which was taken once per day for 48 weeks. The primary outcome was the proportion of participants with virological rebound (confirmed viral load >= 50 copies per mL or premature discontinuations, with last viral load >= 50 copies per mL) cumulative through week 48; we tested non-inferiority (4% margin) of the study regimen versus the control regimen in the intention-to-treat population. This study is registered with ClinicalTrials.gov, number NCT02269917. Findings The study began on April 1, 2015, and the cutoff date for the week 48 primary analysis was Feb 24, 2017. Of 1141 patients (763 in the study group and 378 in the control group), 664 (58%) had previously received five or more antiretrovirals, including screening antiretrovirals, and 169 (15%) had previous virological failure on a non-darunavir regimen. The study regimen was non-inferior to the control for virological rebound cumulative through week 48 (19 [2. 5%] of 763 patients in the study group vs eight (2 .1%) of 378 patients in the control group; difference 0.4%, 95% CI - 1.5 to 2 . 2; p< 0.0001). No resistance to any study drug was observed. Numbers of discontinuations related to adverse events (11 [1%] of 763 patients in the study group vs four [1%] of 378 patients in the control group) and grade 3-4 adverse events (52 [7%] patients vs 31 [8%] patients) were similar between the two groups. There was a small non-clinically relevant but statistically significant (0 . 2 [SD 1.1] vs 0.1 [1.1], p=0.010) difference between the two groups in change from baseline in total cholesterol to HDL-cholesterol ratio. Only one serious adverse event (pancreatitis in the study group) was deemed as possibly related to the study regimen. Interpretation Our findings show the safety and efficacy of single-tablet darunavir, cobicistat, emtricitabine, and tenofovir alafenamide as a potential switch option for the treatment of HIV-1 infection in adults with viral suppression.
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- 2018
10. Efficacy and safety of switching from boosted protease inhibitors plus emtricitabine and tenofovir disoproxil fumarate regimens to single-tablet darunavir, cobicistat, emtricitabine, and tenofovir alafenamide at 48 weeks in adults with virologically suppressed HIV-1 (EMERALD): a phase 3, randomised, non-inferiority trial
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Orkin C, Molina JM, Negredo E, Arribas JR, Gathe J, Eron JJ, Van Landuyt E, Lathouwers E, Hufkens V, Petrovic R, Vanveggel S, Opsomer M, and EMERALD study group
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- 2018
11. Types of Myocardial Infarction Among Human Immunodeficiency Virus-Infected Individuals in the United States
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Crane, HM, Paramsothy, P, Drozd, DR, Nance, RM, Delaney, JAC, Heckbert, SR, Budoff, MJ, Burkholder, GA, Willig, JH, Mugavero, MJ, Mathews, WC, Crane, PK, Moore, RD, Eron, JJ, Napravnik, S, Hunt, PW, Geng, E, Hsue, P, Rodriguez, C, Peter, I, Barnes, GS, McReynolds, J, Lober, WB, Crothers, K, Feinstein, MJ, Grunfeld, C, Saag, MS, Kitahata, MM, and Cl, CAIDSRNI
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Adult ,Male ,Time Factors ,Myocardial Infarction ,HIV Infections ,Coronary Angiography ,Cardiovascular ,Risk Assessment ,Centers for AIDS Research Network of Integrated Clinical Systems (CNICS) Cohort ,Electrocardiography ,Risk Factors ,Clinical Research ,Humans ,Heart Disease - Coronary Heart Disease ,Retrospective Studies ,Incidence ,HIV ,Hematology ,Middle Aged ,United States ,Survival Rate ,Good Health and Well Being ,Infectious Diseases ,Heart Disease ,Female ,Infection ,Follow-Up Studies - Abstract
ImportanceThe Second Universal Definition of Myocardial Infarction (MI) divides MIs into different types. Type 1 MIs result spontaneously from instability of atherosclerotic plaque, whereas type 2 MIs occur in the setting of a mismatch between oxygen demand and supply, as with severe hypotension. Type 2 MIs are uncommon in the general population, but their frequency in human immunodeficiency virus (HIV)-infected individuals is unknown.ObjectivesTo characterize MIs, including type; identify causes of type 2 MIs; and compare demographic and clinical characteristics among HIV-infected individuals with type 1 vs type 2 MIs.Design, setting, and participantsThis longitudinal study identified potential MIs among patients with HIV receiving clinical care at 6 US sites from January 1, 1996, to March 1, 2014, using diagnoses and cardiac biomarkers recorded in the centralized data repository. Sites assembled deidentified packets, including physician notes and electrocardiograms, procedures, and clinical laboratory tests. Two physician experts adjudicated each event, categorizing each definite or probable MI as type 1 or type 2 and identifying the causes of type 2 MI.Main outcomes and measuresThe number and proportion of type 1 vs type 2 MIs, demographic and clinical characteristics among those with type 1 vs type 2 MIs, and the causes of type 2 MIs.ResultsAmong 571 patients (median age, 49 years [interquartile range, 43-55 years]; 430 men and 141 women) with definite or probable MIs, 288 MIs (50.4%) were type 2 and 283 (49.6%) were type 1. In analyses of type 1 MIs, 79 patients who underwent cardiac interventions, such as coronary artery bypass graft surgery, were also included, totaling 362 patients. Sepsis or bacteremia (100 [34.7%]) and recent use of cocaine or other illicit drugs (39 [13.5%]) were the most common causes of type 2 MIs. A higher proportion of patients with type 2 MIs were younger than 40 years (47 of 288 [16.3%] vs 32 of 362 [8.8%]) and had lower current CD4 cell counts (median, 230 vs 383 cells/µL), lipid levels (mean [SD] total cholesterol level, 167 [63] vs 190 [54] mg/dL, and mean (SD) Framingham risk scores (8% [7%] vs 10% [8%]) than those with type 1 MIs or who underwent cardiac interventions.Conclusions and relevanceApproximately half of all MIs among HIV-infected individuals were type 2 MIs caused by heterogeneous clinical conditions, including sepsis or bacteremia and recent use of cocaine or other illicit drugs. Demographic characteristics and cardiovascular risk factors among those with type 1 and type 2 MIs differed, suggesting the need to specifically consider type among HIV-infected individuals to further understand MI outcomes and to guide prevention and treatment.
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- 2017
12. Efficacy and safety of raltegravir for treatment of HIV for 5 years in the BENCHMRK studies:final results of two randomised, placebo-controlled trials
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Eron, Jj, Cooper, Da, Steigbigel, Rt, Clotet, B, Gatell, Jm, Kumar, Pn, Rockstroh, Jk, Schechter, M, Markowitz, M, Yeni, P, Loutfy, Mr, Lazzarin, A, Lennox, Jl, Strohmaier, Km, Wan, H, Barnard, Rj, Nguyen, By, Teppler, H, Vullo, Vincenzo, and BENCHMRK Study Teams
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Adult ,Male ,medicine.medical_specialty ,Drug-Related Side Effects and Adverse Reactions ,Anti-HIV Agents ,Nausea ,Salvage therapy ,HIV Infections ,Placebo ,Article ,law.invention ,Raltegravir Potassium ,Placebos ,Double-Blind Method ,Randomized controlled trial ,law ,Internal medicine ,medicine ,Humans ,Adverse effect ,Salvage Therapy ,business.industry ,Middle Aged ,Viral Load ,Raltegravir ,Pyrrolidinones ,CD4 Lymphocyte Count ,Surgery ,Treatment Outcome ,Infectious Diseases ,HIV-1 ,Female ,medicine.symptom ,business ,Viral load ,medicine.drug - Abstract
Summary Background Two randomised, placebo-controlled trials—BENCHMRK-1 and BENCHMRK-2—investigated the efficacy and safety of raltegravir, an HIV-1 integrase strand-transfer inhibitor. We report final results of BENCHMRK-1 and BENCHMRK-2 combined at 3 years (the end of the double-blind phase) and 5 years (the end of the study). Methods Integrase-inhibitor-naive patients with HIV resistant to three classes of drug and who were failing antiretroviral therapy were enrolled. Patients were randomly assigned (2:1) to raltegravir 400 mg twice daily or placebo, both with optimised background treatment. Patients and investigators were masked to treatment allocation until week 156, after which all patients were offered open-label raltegravir until week 240. The primary endpoint was previously assessed at 16 weeks. We assessed long-term efficacy with endpoints of the proportion of patients with an HIV viral load of less than 50 copies per mL and less than 400 copies per mL, and mean change in CD4 cell count, at weeks 156 and 240. Findings 1012 patients were screened for inclusion. 462 were treated with raltegravir and 237 with placebo. At week 156, 51% in the raltegravir group versus 22% in the placebo group (non-completer classed as failure) had viral loads of less than 50 copies per mL, and 54% versus 23% had viral loads of less than 400 copies per mL. Mean CD4 cell count increase (analysed by an observed failure approach) was 164 cells per μL versus 63 cells per μL. After week 156, 251 patients (54%) from the raltegravir group and 47 (20%) from the placebo group entered the open-label raltergravir phase; 221 (47%) versus 44 (19%) completed the entire study. At week 240, viral load was less than 50 copies per mL in 193 (42%) of all patients initially assigned to raltegravir and less than 400 copies per mL in 210 (45%); mean CD4 cell count increased by 183 cells per μL. Virological failure occurred in 166 raltegravir recipients (36%) during the double-blind phase and in 17 of all patients (6%) during the open-label phase. The most common drug-related adverse events at 5 years in both groups were nausea, headache, and diarrhoea, and occurred in similar proportions in each group. Laboratory test results were similar in both treatment groups and showed little change after year 2. Interpretation Raltegravir has a favourable long-term efficacy and safety profile in integrase-inhibitor-naive patients with triple-class resistant HIV in whom antiretroviral therapy is failing. Raltegravir is an alternative for treatment-experienced patients, particularly those with few treatment options. Funding Merck Sharp & Dohme.
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- 2013
13. Second-line treatment in the Malawi antiretroviral programme: high early mortality, but good outcomes in survivors, despite extensive drug resistance at baseline
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Mhango, B, Kumwenda, JJ, Weigel, R, Brown, LB, Eron, JJ, Phiri, S, Hosseinipour, MC, Mzinganjira, D, and van Oosterhout, JJ
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parasitic diseases - Abstract
The Malawi antiretroviral therapy (ART) programme uses the public health approach to identify ART failure. Advanced disease progression may occur before switching to second-line ART. We report outcomes for patients evaluated and initiated on second-line treatment in Malawi.
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- 2010
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14. Long-term efficacy and safety of Raltegravir combined with optimized background therapy in treatment-experienced patients with drug-resistant HIV infection: week 96 results of the BENCHMRK 1 and 2 Phase III trials
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Steigbigel, Rt, Cooper, Da, Teppler, H, Eron, Jj, Gatell, Jm, Kumar, Pn, Rockstroh, Jk, Schechter, M, Katlama, C, Markowitz, M, Yeni, P, Loutfy, Mr, Lazzarin, A, Vullo, Vincenzo, Lennox, Jl, Clotet, B, Zhao, J, Wan, H, Rhodes, Rr, Strohmaier, Km, Barnard, Rj, Isaacs, Rd, Nguyen, By, and BENCHMRK STUDY TEAMSA
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Microbiology (medical) ,Male ,medicine.medical_specialty ,Anti-HIV Agents ,Integrase inhibitor ,HIV Infections ,Article ,Raltegravir Potassium ,law.invention ,Pharmacotherapy ,Acquired immunodeficiency syndrome (AIDS) ,Randomized controlled trial ,Double-Blind Method ,law ,Internal medicine ,Drug Resistance, Viral ,medicine ,Humans ,business.industry ,Middle Aged ,Viral Load ,Raltegravir ,medicine.disease ,Pyrrolidinones ,Surgery ,CD4 Lymphocyte Count ,Clinical trial ,Infectious Diseases ,HIV-1 ,RNA, Viral ,Drug Therapy, Combination ,Female ,business ,Viral load ,medicine.drug - Abstract
BENCHMRK-1 and -2 are ongoing double-blind phase III studies of raltegravir in patients experiencing failure of antiretroviral therapy with triple-class drug-resistant human immunodeficiency virus infection. At week 96 (combined data), raltegravir (400 mg twice daily) plus optimized background therapy was generally well tolerated, with superior and durable antiretroviral and immunological efficacy, compared with optimized background therapy alone.
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- 2010
15. Recruitment of HIV/AIDS treatment-naïve patients to clinical trials in the highly active antiretroviral therapy era: influence of gender, sexual orientation and race
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Menezes, P, primary, Eron, JJ, additional, Leone, PA, additional, Adimora, AA, additional, Wohl, DA, additional, and Miller, WC, additional
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- 2010
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16. Amplified HIV Transmission: The Missing Link in the HIV Pandemic?
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Cohen, MS, primary, Pilcher, C, additional, Eron, JJ, additional, Leone, PA, additional, Fiscus, SA, additional, and Swanstrom, R, additional
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- 2005
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17. Safety and efficacy of dolutegravir in treatment-experienced subjects with raltegravir-resistant HIV type 1 infection: 24-week results of the VIKING Study.
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Eron JJ, Clotet B, Durant J, Katlama C, Kumar P, Lazzarin A, Poizot-Martin I, Richmond G, Soriano V, Ait-Khaled M, Fujiwara T, Huang J, Min S, Vavro C, Yeo J, VIKING Study Group, Eron, Joseph J, Clotet, Bonaventura, Durant, Jacques, and Katlama, Christine
- Abstract
Background: Dolutegravir (DTG; S/GSK1349572), a human immunodeficiency virus type 1 (HIV-1) integrase inhibitor, has limited cross-resistance to raltegravir (RAL) and elvitegravir in vitro. This phase IIb study assessed the activity of DTG in HIV-1-infected subjects with genotypic evidence of RAL resistance.Methods: Subjects received DTG 50 mg once daily (cohort I) or 50 mg twice daily (cohort II) while continuing a failing regimen (without RAL) through day 10, after which the background regimen was optimized, when feasible, for cohort I, and at least 1 fully active drug was mandated for cohort II. The primary efficacy end point was the proportion of subjects on day 11 in whom the plasma HIV-1 RNA load decreased by ≥0.7 log(10) copies/mL from baseline or was <400 copies/mL.Results: A rapid antiviral response was observed. More subjects achieved the primary end point in cohort II (23 of 24 [96%]), compared with cohort I (21 of 27 [78%]) at day 11. At week 24, 41% and 75% of subjects had an HIV-1 RNA load of <50 copies/mL in cohorts I and II, respectively. Further integrase genotypic evolution was uncommon. Dolutegravir had a good, similar safety profile with each dosing regimen.Conclusion: Dolutegravir 50 mg twice daily with an optimized background provided greater and more durable benefit than the once-daily regimen. These data are the first clinical demonstration of the activity of any integrase inhibitor in subjects with HIV-1 resistant to RAL. [ABSTRACT FROM AUTHOR]- Published
- 2013
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18. Raltegravir once daily or twice daily in previously untreated patients with HIV-1: a randomised, active-controlled, phase 3 non-inferiority trial.
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Eron JJ Jr, Rockstroh JK, Reynes J, Andrade-Villanueva J, Ramalho-Madruga JV, Bekker LG, Young B, Katlama C, Gatell-Artigas JM, Arribas JR, Nelson M, Campbell H, Zhao J, Rodgers AJ, Rizk ML, Wenning L, Miller MD, Hazuda D, DiNubile MJ, and Leavitt R
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- 2011
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19. Antiretroviral drug resistance in HIV-1-infected patients experiencing persistent low-level viremia during first-line therapy.
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Taiwo B, Gallien S, Aga E, Ribaudo H, Haubrich R, Kuritzkes DR, Eron JJ Jr, Taiwo, Babafemi, Gallien, Sebastien, Aga, Evgenia, Ribaudo, Heather, Haubrich, Richard, Kuritzkes, Daniel R, and Eron, Joseph J Jr
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Population sequencing was performed for persons identified with persistent low-level viremia in 2 clinical trials. Persistent low-level viremia (defined as plasma HIV-1 RNA level >50 and <1000 copies/mL in at least 2 determinations over a 24-week period, after at least 24 weeks of antiretroviral therapy) was observed in 65 (5.6%) of 1158 patients at risk. New resistance mutations were detected during persistent low-level viremia in 37% of the 54 evaluable cases. The most common mutations were M184I/V (14 cases), K103N (9), and M230L (3). Detection of new mutations was associated with higher HIV-1 RNA levels during persistent low-level viremia. [ABSTRACT FROM AUTHOR]
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- 2011
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20. Switch to a raltegravir-based regimen versus continuation of a lopinavir-ritonavir-based regimen in stable HIV-infected patients with suppressed viraemia (SWITCHMRK 1 and 2): two multicentre, double-blind, randomised controlled trials.
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Eron JJ, Young B, Cooper DA, Youle M, Dejesus E, Andrade-Villanueva J, Workman C, Zajdenverg R, Fätkenheuer G, Berger DS, Kumar PN, Rodgers AJ, Shaughnessy MA, Walker ML, Barnard RJ, Miller MD, Dinubile MJ, Nguyen BY, Leavitt R, and Xu X
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- 2010
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21. Antiretroviral treatment of adult HIV infection: 2008 recommendations of the International AIDS Society-USA panel.
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Hammer SM, Eron JJ Jr, Reiss P, Schooley RT, Thompson MA, Walmsley S, Cahn P, Fischl MA, Gatell JM, Hirsch MS, Jacobsen DM, Montaner JS, Richman DD, Yeni PG, Volberding PA, International AIDS Society-USA, Hammer, Scott M, Eron, Joseph J Jr, Reiss, Peter, and Schooley, Robert T
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Context: The availability of new antiretroviral drugs and formulations, including drugs in new classes, and recent data on treatment choices for antiretroviral-naive and -experienced patients warrant an update of the International AIDS Society-USA guidelines for the use of antiretroviral therapy in adult human immunodeficiency virus (HIV) infection.Objectives: To summarize new data in the field and to provide current recommendations for the antiretroviral management and laboratory monitoring of HIV infection. This report provides guidelines in key areas of antiretroviral management: when to initiate therapy, choice of initial regimens, patient monitoring, when to change therapy, and how best to approach treatment options, including optimal use of recently approved drugs (maraviroc, raltegravir, and etravirine) in treatment-experienced patients.Data Sources and Study Selection: A 14-member panel with expertise in HIV research and clinical care was appointed. Data published or presented at selected scientific conferences since the last panel report (August 2006) through June 2008 were identified.Data Extraction and Synthesis: Data that changed the previous guidelines were reviewed by the panel (according to section). Guidelines were drafted by section writing committees and were then reviewed and edited by the entire panel. Recommendations were made by panel consensus.Conclusions: New data and considerations support initiating therapy before CD4 cell count declines to less than 350/microL. In patients with 350 CD4 cells/microL or more, the decision to begin therapy should be individualized based on the presence of comorbidities, risk factors for progression to AIDS and non-AIDS diseases, and patient readiness for treatment. In addition to the prior recommendation that a high plasma viral load (eg, >100,000 copies/mL) and rapidly declining CD4 cell count (>100/microL per year) should prompt treatment initiation, active hepatitis B or C virus coinfection, cardiovascular disease risk, and HIV-associated nephropathy increasingly prompt earlier therapy. The initial regimen must be individualized, particularly in the presence of comorbid conditions, but usually will include efavirenz or a ritonavir-boosted protease inhibitor plus 2 nucleoside reverse transcriptase inhibitors (tenofovir/emtricitabine or abacavir/lamivudine). Treatment failure should be identified and managed promptly, with the goal of therapy, even in heavily pretreated patients, being an HIV-1 RNA level below assay detection limits. [ABSTRACT FROM AUTHOR]- Published
- 2008
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22. Prevalence and comorbidity of psychiatric diagnoses based on reference standard in an HIV+ patient population.
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Gaynes BN, Pence BW, Eron JJ Jr., Miller WC, Gaynes, Bradley N, Pence, Brian Wells, Eron, Joseph J Jr, and Miller, William C
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- 2008
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23. Emotional distress in African American women with HIV.
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Miles MS, Holditch-Davis D, Pedersen C, Eron JJ Jr., and Schwartz T
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This study identified factors associated with emotional distress in 109 African American women with HIV. The relationship of personal factors (demographic, social conflict, social support, and spirituality), health-related factors (perception of health, physical and mental health problems, and years diagnosed), and cognitive/coping responses (stigma, worry, and emotion focused coping) on depressive symptoms and mood state was examined. Younger age, more social conflict, less social support, lower perception of health, and more HIV worry were associated with higher depressive symptom scores. Variables most often affecting various mood states included personal factors (public housing, unemployment, and social conflict) and worry about having HIV worry. [ABSTRACT FROM AUTHOR]
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- 2007
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24. Evidence that intermittent structured treatment interruption, but not immunization with ALVAC-HIV vCP1452, promotes post control of HIV replication: the results of AIDS Clinical Trials Group 5068.
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Jacobson JM, Bucy RP, Spritzler J, Saag MS, Eron JJ Jr., Coombs RW, Wang R, Fox L, Johnson VA, Cu-Uvin S, Cohn SE, Mildvan D, O'Neill D, Janik J, Purdue L, O'Connor DK, Vita CD, Frank I, and National Institute of Allergy and Infectious Diseases. AIDS Clinical Trials Group 5068 Protocol Team
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Background. The ability to control human immunodeficiency virus (HIV) replication in vivo in the absence of antiretroviral therapy (ART) is a measure of the efficiency of antiviral immunity. In a study of patients with chronic, ART-suppressed HIV infection, AIDS Clinical Trials Group 5068 investigated the effects of immunization with an exogenous HIV vaccine and pulse exposure to the subject's unique viral epitopes, by means of structured treatment interruptions (STIs), on the dynamics of viral rebound during a subsequent analytical treatment interruption (ATI). Methods. Ninety-seven subjects receiving stable ART with an HIV-1 RNA load <50 copies/mL and CD4(+) T lymphocyte count >400 cells/mm(3) were randomized to undergo continued ART, STIs, ALVAC-HIV vCP1452 immunization, or STIs and ALVAC-HIV vCP1452 immunization. Results. Subjects in the 2 STI arms had a significantly longer median doubling time in the period of the initial rise of viral load, a significantly lower median peak viral load, a significantly lower median end-of-ATI viral load set point, and a greater proportion of subjects with an end-of-ATI viral load set point <1000 copies/mL, compared with the subjects in the 2 arms without STIs. With an immunization schedule of 3 sets of 3 weekly injections, ALVAC-HIV vCP1452 did not affect viral load measures. Conclusions. In this randomized, controlled study of intermittent STI as a therapeutic autoimmunization strategy, evidence of enhanced immunologic control of HIV replication was demonstrated. Copyright © 2006 Infectious Diseases Society of America [ABSTRACT FROM AUTHOR]
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- 2006
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25. Clinical observation. Infrequent diagnosis of primary human immunodeficiency virus infection: missed opportunities in acute care settings.
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Weintrob AC, Giner J, Menezes P, Patrick E, Benjamin DK Jr., Lennox J, Pilcher CD, Eron JJ, and Hicks CB
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- 2003
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26. A randomized trial of 2 different 4-drug antiretroviral regimens versus a 3-drug regimen, in advanced human immunodeficiency virus disease.
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Fischl MA, Ribaudo HJ, Collier AC, Erice A, Giuliano M, Dehlinger M, Eron JJ Jr., Saag MS, Hammer SM, Vella S, Morse GD, Feinberg JE, and Adult AIDS Clinical Trials Group 388 Study Team
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To compare long-term virologic benefits of antiretroviral regimens in persons with advanced human immunodeficiency virus (HIV) disease, a randomized, open-label study was conducted of 517 subjects with no or limited previous experience with antiretroviral therapy. Subjects received lamivudine plus zidovudine and indinavir (indinavir group), efavirenz plus indinavir (efavirenz + indinavir group), or nelfinavir plus indinavir (nelfinavir + indinavir group) and were monitored for 2.1 years. Virologic failure was lower in the efavirenz + indinavir group (P=.04) and higher in the nelfinavir + indinavir group (P=.006), compared with that in the indinavir group. No difference in grade 3 or 4 adverse event rates in the efavirenz + indinavir group (P=.97) and a trend toward an increased rate in the nelfinavir + indinavir group (P=.07), compared with the indinavir group, were noted. A 4-drug regimen containing efavirenz plus indinavir resulted in a superior virologic response, whereas one containing nelfinavir plus indinavir resulted in an inferior response and a greater likelihood of toxicity. Copyright © 2003 The University of Chicago [ABSTRACT FROM AUTHOR]
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- 2003
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27. Mechanisms of disease: novel therapies based on mechanisms of HIV-1 cell entry.
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Kilby JM and Eron JJ
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- 2003
28. Oral manifestations of HIV in a southeast USA population.
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Patton LL, McKaig RG, Strauss RP, and Eron JJ Jr.
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- 1998
29. Aciclovir treatment for human immunodeficiency virus-1: is the “juice worth the squeeze?”.
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Cohen MS, Eron JJ Jr, Cohen, Myron S, and Eron, Joseph J Jr
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- 2011
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30. A controlled trial of two nucleoside analogues plus indinavir in persons with human immunodeficiency virus infection and CD4 cell counts of 200 per cubic millimeter or less. AIDS Clinical Trials Group 320 Study Team
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Hammer, SM, Squires, KE, Hughes, MD, Grimes, JM, Demeter, LM, Currier, JS, Eron, JJ RR, Feinberg, JE, Balfour, HH JR, Deyton, LR, Chodakewitz, JA, Fischl, MA, Phair, JP, Pedneault, L, Nguyen, BY, and Cook, JC
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BACKGROUND: The efficacy and safety of adding a protease inhibitor to two nucleoside analogues to treat human immunodeficiency virus type 1 (HIV-1) infection are not clear. We compared treatment with the protease inhibitor indinavir in addition to zidovudine and lamivudine with treatment with the two nucleosides alone in HIV-infected adults previously treated with zidovudine.\ud \ud METHODS: A total of 1156 patients not previously treated with lamivudine or protease inhibitors were stratified according to CD4 cell count (50 or fewer vs. 51 to 200 cells per cubic millimeter) and randomly assigned to one of two daily regimens: 600 mg of zidovudine (or stavudine) and 300 mg of lamivudine, or that regimen with 2400 mg of indinavir. The primary end point was the time to the development of the acquired immunodeficiency syndrome (AIDS) or death.\ud \ud RESULTS: The proportion of patients whose disease progressed to AIDS or death was lower with indinavir, zidovudine, and lamivudine (6 percent) than with zidovudine and lamivudine alone (11 percent; estimated hazard ratio, 0.50; 95 percent confidence interval, 0.33 to 0.76; P=0.001). Mortality in the two groups was 1.4 percent and 3.1 percent, respectively (estimated hazard ratio, 0.43; 95 percent confidence interval, 0.19 to 0.99; P=0.04). The effects of treatment were similar in both CD4 cell strata. The responses of CD4 cells and plasma HIV-1 RNA paralleled the clinical results.\ud \ud CONCLUSIONS: Treatment with indinavir, zidovudine, and lamivudine as compared with zidovudine and lamivudine alone significantly slows the progression of HIV-1 disease in patients with 200 CD4 cells or fewer per cubic millimeter and prior exposure to zidovudine.
31. How clean was the KLEAN trial?
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Bellman P, Eron JJ Jr., and Shaefer MS
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- 2006
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32. Factors associated with fewer visits for HIV primary care at a tertiary care center in the Southeastern U.S.
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Napravnik S, Eron JJ Jr., McKaig RG, Heine AD, Menezes P, and Quinlivan EB
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In this study we sought to evaluate sociodemographic and clinical characteristics associated with decreased access to HIV outpatient care in a University-based clinic in the Southeastern U.S. The number of HIV outpatient clinic visits per person-year was estimated among 1,404 HIV-infected individuals participating in a large observational clinical cohort study. On average, participants attended 3.38 visits per person-year (95% CI = 3.32, 3.44), with 71% attending fewer than 4 visits per year. Younger persons, of Black race/ethnicity, with less advanced HIV disease, and a shorter time from entry to HIV care, had poorer access to care, as did participants without health insurance and residing a greater distance from care. Vulnerable subgroups of HIV-infected patients in the South have decreased access to ongoing HIV health care. Interventions including more intensive counseling and active outreach for newly HIV diagnosed individuals and support with obtaining health insurance and transportation may lead to improved outcomes. [ABSTRACT FROM AUTHOR]
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- 2006
33. Detection of acute infections during HIV testing in North Carolina.
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Pilcher CD, Fiscus SA, Nguyen TQ, Foust E, Wolf L, Williams D, Ashby R, O'Dowd JO, McPherson JT, Stalzer B, Hightow L, Miller WC, Eron JJ Jr., Cohen MS, Leone PA, Pilcher, Christopher D, Fiscus, Susan A, Nguyen, Trang Q, Foust, Evelyn, and Wolf, Leslie
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Background: North Carolina has added nucleic acid amplification testing for the human immunodeficiency virus (HIV) to standard HIV antibody tests to detect persons with acute HIV infection who are viremic but antibody-negative.Methods: To determine the effect of nucleic acid amplification testing on the yield and accuracy of HIV detection in public health practice, we conducted a 12-month observational study of methods for state-funded HIV testing. We compared the diagnostic performance of standard HIV antibody tests (i.e., enzyme immunoassay and Western blot analysis) with an algorithm whereby serum samples that yielded negative results on standard antibody tests were tested again with the use of nucleic acid amplification. A surveillance algorithm with repeated sensitive-less-sensitive enzyme immunoassay tests was also evaluated. HIV infection was defined as a confirmed positive result on a nucleic acid amplification test or as HIV antibody seroconversion.Results: Between November 1, 2002, and October 31, 2003, 109,250 persons at risk for HIV infection who had consented to HIV testing presented at state-funded sites. There were 606 HIV-positive results. Established infection, as identified by standard enzyme immunoassay or Western blot analysis, appeared in 583 participants; of these, 107 were identified, with the use of sensitive-less-sensitive enzyme immunoassay tests, as recent infections. A total of 23 acutely infected persons were identified only with the use of the nucleic acid amplification algorithm. With all detectable infections taken into account, the sensitivity of standard antibody testing was 0.962 (95 percent confidence interval, 0.944 to 0.976). There were two false positive results on nucleic acid amplification tests. The specificity and positive predictive value of the algorithm that included nucleic acid amplification testing were greater than 0.999 (95 percent confidence interval, 0.999 to >0.999) and 0.997 (95 percent confidence interval, 0.988 to >0.999), respectively. Of the 23 acute HIV infections, 16 were detected at sexually transmitted disease clinics. Emergency measures for HIV prevention protected 48 sex partners and one fetus from high-risk exposure to HIV.Conclusions: The addition of nucleic acid amplification testing to an HIV testing algorithm significantly increases the identification of cases of infection without impairing the performance of diagnostic testing. The detection of highly contagious, acutely infected persons creates new opportunities for HIV surveillance and prevention. [ABSTRACT FROM AUTHOR]- Published
- 2005
34. Enfuvirtide, an HIV-1 fusion inhibitor, for drug-resistant HIV infection in North and South America.
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Lalezari JP, Henry K, O'Hearn M, Montaner JSG, Piliero PJ, Trottier B, Walmsley S, Cohen C, Kuritzkes DR, Eron JJ Jr., Chung J, DeMasi R, Donatacci L, Drobnes C, Delehanty J, Salgo M, and TORO 1 (T-20 vs. Optimized Regimen Only Study 1) Study Group
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- 2003
35. Treatment with indinavir, zidovudine, and lamivudine in adults with human immunodeficiency virus infection and prior antiretroviral therapy.
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Gulick RM, Mellors JW, Havlir D, Eron JJ, Gonzalez C, McMahon D, Richman DD, Valentine FT, Jonas L, Meibohm A, Emini EA, and Chodakewitz JA
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- 1997
36. A controlled trial of two nucleoside analogues plus indinavir in persons with human immunodeficiency virus infection and CD4 cell counts of 200 per cubic millimeter or less. AIDS Clinical Trials Group 320 Study Team.
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Hammer SM, Squires KE, Hughes MD, Grimes JM, Demeter LM, Currier JS, Eron JJ Jr, Feinberg JE, Balfour HH Jr, Deyton LR, Chodakewitz JA, and Fischl MA
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- 1997
37. Correlates of Intimate Partner Violence, Including Psychological Partner Violence, in a Multisite U.S. Cohort of People in HIV Care.
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Fredericksen RJ, Mixson LS, Drumright LN, Nance RM, Delaney JAC, Ruderman SA, Whitney BM, Hahn A, Ma J, Mayer KH, Christopoulos KA, Willig AL, Napravnik S, Bamford L, Cachay E, Eron JJ, Saag M, Jacobson J, Kitahata MM, and Crane HM
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- Humans, Female, Male, Middle Aged, United States epidemiology, Adult, Sexual Partners psychology, Risk Factors, Cohort Studies, Viral Load, Depression epidemiology, Depression psychology, Intimate Partner Violence psychology, Intimate Partner Violence statistics & numerical data, HIV Infections psychology, HIV Infections epidemiology, HIV Infections drug therapy
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We examined past-year intimate partner violence (IPV), including psychological violence without physical/sexual violence, and health outcomes among people with HIV (PWH) in care in a multi-site U.S. cohort. Between 2016 and 2022, PWH reported 12-month psychological, physical, and sexual IPV in a routine assessment. We used linear and logistic regression models adjusted for age, race/ethnicity, and site to examine relationships with health outcomes. Among 9748 PWH (median age 50 years, 81% cisgender male/16% cisgender female/1% transgender female; 44% non-Hispanic white/36% non-Hispanic Black/15% Hispanic), 9.3% (n = 905) reported any IPV in the past 12 months; half reported psychological IPV without physical/sexual IPV (n = 453). PWH reporting any type of IPV were on average younger than those who did not experience IPV. In adjusted models, any IPV was associated with increased likelihood of unstable housing, HIV viral load detection (HIV viral load ≥ 75 copies/mL), moderate-to-severe depressive symptoms, anxiety with panic symptoms, substance use (methamphetamines, cocaine/crack, illicit opioids, marijuana, heavy episodic/hazardous drinking), and concern about exposure to sexually transmitted infection. PWH reporting any IPV in the past 12 months had 4.2% lower adherence to antiretroviral therapy, 2.4 more HIV-related symptoms, a 1.9 point higher HIV stigma score, and a 9.5% lower quality of life score than those without IPV. We found similar associations among PWH reporting only psychological IPV, without physical/sexual IPV. IPV was common among PWH. Half reporting IPV reported only psychological IPV and had similarly poor outcomes as those reporting physical/sexual IPV, demonstrating the need to assess psychological as well as physical and sexual IPV., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)
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- 2024
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38. Sex Differences in the Risk of Stroke Associated With Traditional and Non-Traditional Factors in a US Cohort of People With HIV Infection.
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Chow FC, Nance RM, Becker K, Ho EL, Huffer A, Kalani R, Marra CM, Zunt JR, Bamford L, Burkholder GA, Cachay E, Eron JJ, Keruly J, Kitahata MM, Napravnik S, Saag MS, Willig AL, Moore RD, Tirschwell DL, Delaney JA, and Crane HM
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- Humans, Female, Male, Adult, Middle Aged, Cohort Studies, United States epidemiology, Risk Factors, Sex Factors, Sex Characteristics, HIV Infections epidemiology, HIV Infections complications, Stroke epidemiology
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Background and Objectives: Although stroke risk associated with HIV may be greater for women than men, little is known about whether the impact of different factors on cerebrovascular risk varies by sex in people with HIV (PWH) and contributes to stroke risk disparities in this population. The primary objective of this study was to examine whether sex modifies the effect of demographics, cardiometabolic factors, health-related behaviors, and HIV-specific variables on stroke risk in PWH from the Centers for AIDS Research Network of Integrated Clinical Systems (CNICS) cohort., Methods: In this observational cohort study, we analyzed data from clinical encounters for PWH followed at 5 CNICS sites from approximately 2005 to 2020. All potential stroke events were adjudicated by neurologists. Patient-reported outcomes collected at clinic visits, including substance use and depression, were also available. We used Cox proportional hazards models to determine whether sex modified the association of predictors of interest with incident stroke., Results: Among 13,573 PWH (19% female sex at birth, mean age 44 years, mean follow-up 5.6 years), female sex was associated with a higher risk of stroke only among individuals aged 50 years or younger (hazard ratio [HR] 2.01 at age 40 [1.25-3.21] vs HR 0.60 at age 60 [0.34-1.06]; p = 0.001 for the interaction). Younger female participants who developed a stroke were more likely to have treated hypertension, a higher cardiovascular risk score, and detectable HIV than younger male participants whereas these factors were comparable by sex among older participants who developed a stroke. Sex modified the effect of detectable HIV (HR 4.66 for female participants [2.48-8.74] vs HR 1.30 for male participants [0.83-2.03]; p = 0.001 for the interaction), methamphetamine use (HR 4.78 for female participants [1.47-15.56] vs HR 1.19 for male participants [0.62-2.29]; p = 0.04 for the interaction), and treated hypertension (HR 3.44 for female participants [1.74-6.81] vs HR 1.66 for male participants [1.14-2.41]; p = 0.06 for the interaction) on stroke risk., Discussion: Younger female participants with HIV were at elevated cerebrovascular risk compared with younger male participants. Several risk factors had a greater adverse effect on stroke risk in female participants than in male participants, including HIV viremia, methamphetamine use, and treated hypertension. These findings underscore the importance of a personalized approach to predict and prevent cerebrovascular risk among PWH.
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- 2024
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39. Impact of SARS-CoV-2 Resistance to Antiviral Monoclonal Antibody Therapy on Neutralizing Antibody Response.
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Paul MK, Choudhary MC, Heaps AL, Deo R, Moisi D, Gordon KC, Mellors JW, Moser C, Klekotka P, Landay A, Currier JS, Eron JJ, Chew KW, Smith DM, Sieg SF, Parikh UM, and Li JZ
- Abstract
Background: Anti-SARS-CoV-2 monoclonal antibodies (mAbs) have played a key role as an anti-viral against SARS-CoV-2, but there is a potential for resistance to develop. The interplay between host antibody responses and the development of monoclonal antibody (mAb) resistance is a critical area of investigation. In this study, we assessed host neutralizing antibody (nAb) responses against both ancestral virus and those with treatment-emergent E484K bamlanivimab resistance mutations., Methods: Study participants were enrolled in the ACTIV-2/Advancing Clinical Therapeutics Globally (ACTG) A5401 phase 2 randomized, placebo-controlled trial of bamlanivimab 700 mg mAb therapy (NCT04518410). Anterior nasal and nasopharyngeal swabs were collected for SARS-CoV-2 RNA testing and S gene next-generation sequencing to identify the E484K bamlanivimab resistance mutation. Serum nAb titers were assessed by pseudovirus neutralization assays., Results: Higher baseline (pre-treatment) nAb titers against either ancestral or E484K virus was associated with lower baseline viral load. Participants with emerging resistance had low levels of nAb titers against either ancestral or E484K nAb at the time of study entry. Participants with emergent E484K resistance developed significantly higher levels of E484K-specific nAb titers compared to mAb-treated individuals who did not develop resistance. All participants who developed the E484K mAb resistance mutation were eventually able to clear the virus., Conclusion: Emerging drug resistance after SARS-CoV-2-specific mAb therapy led to a heightened host neutralizing antibody response to the mAb-resistant variant that was associated with eventual viral clearance. This demonstrates the interplay between the antiviral treatment-directed viral evolution and subsequent host immune response in viral clearance., Competing Interests: UMP has consulted for Merck unrelated to the current work. JWM is a consultant for and receives grant support from Gilead Sciences, unrelated to the current work. JZL has consulted for Abbvie and received research support from Merck unrelated to the current work. KWC has consulted for Pardes Biosciences. DMS has consulted for Bayer Pharmaceuticals, Linear Therapies, Model Medicines, FluxErgy, and Vx Biosciences. ALL has consulted for Gilead and Abbott., (Copyright © 2024 Pathogens and Immunity.)
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- 2024
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40. Early antiviral CD4 and CD8 T cell responses and antibodies are associated with upper respiratory tract clearance of SARS-CoV-2.
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Ramirez SI, Lopez PG, Faraji F, Parikh UM, Heaps A, Ritz J, Moser C, Eron JJ, Wohl DA, Currier JS, Daar ES, Greninger AL, Klekotka P, Grifoni A, Weiskopf D, Sette A, Peters B, Hughes MD, Chew KW, Smith DM, and Crotty S
- Abstract
T cells are involved in protective immunity against numerous viral infections. Data regarding functional roles of human T cells in SARS-CoV-2 (SARS2) viral clearance in primary COVID-19 are limited. To address this knowledge gap, samples were assessed for associations between SARS2 upper respiratory tract viral RNA levels and early virus-specific adaptive immune responses for 95 unvaccinated clinical trial participants with acute primary COVID-19 aged 18-86 years old, approximately half of whom were considered high risk for progression to severe COVID-19. Functionality and magnitude of acute SARS2-specific CD4 and CD8 T cell responses were evaluated, in addition to antibody responses. Most individuals with acute COVID-19 developed SARS2-specific T cell responses within 6 days of COVID-19 symptom onset. Early CD4 T cell and CD8 T cell responses were polyfunctional, and both strongly associated with reduced upper respiratory tract SARS2 viral RNA, independent of neutralizing antibody titers. Overall, these findings provide evidence for protective roles for circulating SARS2-specific CD4 and CD8 T cells during acute COVID-19.
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- 2024
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41. Post-acute COVID-19 outcomes including participant-reported long COVID: amubarvimab/romlusevimab versus placebo in the ACTIV-2 trial.
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Evering TH, Moser C, Jilg N, Ritz J, Wohl DA, Li JZ, Margolis D, Javan AC, Eron JJ, Currier JS, Daar ES, Smith DM, Hughes MD, and Chew KW
- Abstract
Background: It is unknown if early COVID-19 monoclonal antibody (mAb) therapy can reduce risk of Long COVID. The mAbs amubarvimab/romlusevimab were previously demonstrated to reduce risk of hospitalization/death by 79%. This study assessed the impact of amubarvimab/romlusevimab on late outcomes, including Long COVID., Methods: Non-hospitalized high-risk adults within 10 days of COVID-19 symptom onset enrolled in a randomized, double-blind, placebo-controlled phase 2/3 trial of amubarvimab/romlusevimab for COVID-19 treatment. Late symptoms, assessed using a participant-completed symptom diary, were a pre-specified exploratory endpoint. The primary outcome for this analysis was the composite of Long COVID by participant self-report (presence of COVID-19 symptoms as recorded in the diary at week 36) or hospitalization or death by week 36. Inverse probability weighting (IPW) was used to address incomplete outcome ascertainment, giving weighted risk ratios (wRR) comparing amubarvimab/romlusevimab to placebo., Findings: Participants received amubarvimab/romlusevimab (n = 390) or placebo (n = 390) between January and July 2021. Median age was 49 years, 52% were female, 18% Black/African American, 49% Hispanic/Latino, and 9% COVID-19-vaccinated at entry. At week 36, 103 (13%) had incomplete outcome ascertainment, and 66 (17%) on amubarvimab/romlusevimab and 92 (24%) on placebo met the primary outcome (wRR = 0.70, 95% confidence interval (CI) 0.53-0.93). The difference was driven by fewer hospitalizations/deaths with amubarvimab/romlusevimab (4%) than placebo (13%). Among 652 participants with available diary responses, 53 (16%) on amubarvimab/romlusevimab and 44 (14%) on placebo reported presence of Long COVID., Interpretation: Amubarvimab/romlusevimab treatment, while highly effective in preventing hospitalizations/deaths, did not reduce risk of Long COVID. Additional interventions are needed to prevent Long COVID., Funding: National Institute of Allergy and Infectious Diseases of the National Institutes of Health. Amubarvimab and romlusevimab supplied by Brii Biosciences., Competing Interests: Dr. Evering reports other from AIDS Clinical Trials Group (ACTG), during the conduct of the study; personal fees from Tonix Pharmaceuticals, outside the submitted work. Dr. Moser reports grants from NIH/NIAID, grants from NIH/NIAID, during the conduct of the study. Dr. Jilg reports other from AIDS Clinical Trials Group (ACTG), during the conduct of the study; grants from National Institutes of Health (NIH), grants from Harvard University Center for AIDS Research (HU-CFAR), other from Sagent Pharmaceuticals, outside the submitted work. Mr. Ritz reports grants from NIH/NIAID, grants from NIH/NIAID, during the conduct of the study. Dr. Wohl reports grants and personal fees from Gilead Sciences, grants and personal fees from ViiV Healthcare, grants and personal fees from Merck & Co, personal fees from Janssen Pharmaceuticals, personal fees from BMS, personal fees from Theratechnologies, personal fees from EMD Serono, personal fees from Regeneron, outside the submitted work. Dr. Margolis reports other from BRII Biosciences, outside the submitted work. Dr. Eron reports grants from National Institutes of Health, during the conduct of the study; personal fees from Merck & Co, grants and personal fees from Gilead Sciences, other from Invivyd, outside the submitted work. Dr. Currier reports personal fees from Merck, outside the submitted work. Dr. Daar reports grants from NIH, during the conduct of the study; grants and personal fees from Gilead, grants and personal fees from ViiV, personal fees from Theratechnologies, outside the submitted work. Dr. Smith reports grants from NIH, during the conduct of the study; personal fees from Model Medicines, personal fees from Bayer, personal fees from Gilead, personal fees from Lucira, personal fees from VXBiosciences, personal fees from Linear Therapies, personal fees from Red Queen Therapeutics, other from A2 Bio, personal fees from Pharma Holdings, personal fees from Evidera, personal fees from Hyundai, outside the submitted work. Dr. Hughes reports grants from United States National Institutes of Health, during the conduct of the study. Dr. Chew reports grants from NIH/NIAID, grants from NIH/NCATS, during the conduct of the study; personal fees from Pardes Biosciences, outside the submitted work. The remaining authors have no competing interests to disclose., (© 2024 Published by Elsevier Ltd.)
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- 2024
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42. 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 MC, Deo R, Evering TH, Chew KW, Giganti MJ, Moser C, Ritz J, Regan J, Flynn JP, Crain CR, Wohl DA, Currier JS, Eron JJ, Margolis D, Zhu Q, Zhon L, Ya L, Greninger AL, Hughes MD, Smith D, Daar ES, and Li JZ
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- Humans, Female, Male, Middle Aged, Drug Resistance, Viral, Antiviral Agents therapeutic use, Antiviral Agents pharmacology, COVID-19 immunology, COVID-19 virology, Antibodies, Monoclonal therapeutic use, Antibodies, Monoclonal immunology, Aged, Adult, Drug Therapy, Combination, SARS-CoV-2 immunology, SARS-CoV-2 drug effects, Viral Load drug effects, Antibodies, Monoclonal, Humanized therapeutic use, Antibodies, Monoclonal, Humanized pharmacology, COVID-19 Drug Treatment
- 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., Competing Interests: Potential conflicts of interest. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)
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- 2024
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43. Comparison Study of the Bio-Plex and Meso Scale Multiplexed SARS-CoV-2 Serology Assays Reveals Evidence of Diminished Host Antibody Responses to SARS-CoV-2 after Monoclonal Antibody Treatment.
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Parikh UM, Heaps AL, Moisi D, Gordon KC, Mellors JW, Choudhary MC, Deo R, Moser C, Klekotka P, Landay AL, Currier JS, Eron JJ, Chew KW, Smith DM, Li JZ, and Sieg SF
- Abstract
Background: Assessing the breadth and duration of antigen-specific binding antibodies provides valuable information for evaluating interventions to treat or prevent SARS-CoV-2 infection. Multiplex immunoassays are a convenient method for rapid measurement of antibody responses but can sometimes provide discordant results, and antibody positive percent agreement for COVID-19 diagnosis can vary depending on assay type, disease severity, and population sampled. Therefore, we compared two assays marked for research applications, MSD and Bio-Plex Pro, to evaluate qualitative interpretation of serostatus and quantitative detection of antibodies of varying isotypes (IgG, IgM, and IgA) against receptor binding domain (RBD) and nucleocapsid (N) antigens., Methods: Specimens from ACTIV-2/A5401, a placebo-controlled clinical trial of the SARSCoV-2 monoclonal antibody (mAb) bamlanivimab to prevent COVID-19 disease progression, were used to evaluate the concordance of the Bio-Rad Bio-Plex Pro Human SARS-CoV-2 Serology Assay and the Meso Scale Discovery (MSD) V-PLEX COVID-19 Panel 1 serology assay in detecting and quantifying IgG, IgA, and IgM binding anti-SARS-CoV-2 antibody responses against the RBD and N antigens. Data were disaggregated by study arm, bamlanivimab dose, days post-enrollment, and presence of emerging resistance., Results: We observed 90.5% (412 of 455 tests) concordance for anti-RBD IgG and 87% (396 of 455) concordance for anti-N IgG in classifying samples as negative or positive based on assay-defined cutoffs. Antibody levels converted to the WHO standard BAU/mL were significantly correlated for all isotypes (IgG, IgM, and IgA) and SARS-CoV-2 antigen targets (RBD and N) tested that were common between the two assays (Spearman r 0.65 to 0.92, P < 0.0001). Both assays uncovered evidence of diminished host-derived IgG immune responses in participants treated with bamlanivimab compared to placebo. Assessment of immune responses in the four individuals treated with the 700 mg of bamlanivimab with emerging mAb resistance demonstrated a stronger anti-N IgG response (MSD) at day 28 (median 2.18 log BAU/mL) compared to participants treated with bamlanivimab who did not develop resistance (median 1.55 log BAU/mL)., Conclusions: These data demonstrate the utility in using multiplex immunoassays for characterizing the immune responses with and without treatment in a study population and provide evidence that monoclonal antibody treatment in acute COVID-19 may have a modest negative impact on development of host IgG responses., Competing Interests: U.M.P. has consulted for Merck unrelated to the current work. J.W.M. is a consultant to Gilead Sciences, Inc. and has received grant funding from Gilead Sciences, Inc. to the University of Pittsburgh (unrelated to the current work); receives compensation from Galapagos NV (unrelated to the current work); and holds share options in Galapagos NV, Infectious Disease Connect, Inc., and MingMed Biotechnology Co., Ltd. (unrelated to the current work). A.L.L. has consulted for Gilead and Abbott. J.S.C. has served on a Merck Advisory Board. J.J.E. is a consultant to Merck and Gilead and has received research funding to his institution from Gilead; he is also on a Data Safety Monitoring Committee for Invivyd. K.W.C. has received research funding to the institution from Merck Sharp & Dohme and has consulted for Pardes Biosciences. D.M.S. has consulted for Bayer Pharmaceuticals, Linear Therapies, Model Medicines, Fluxergy, and Vx Biosciences. J.Z.L. has consulted for Abbvie., (Copyright © 2024 Pathogens and Immunity.)
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- 2024
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44. SARS-CoV-2 monoclonal antibody treatment followed by vaccination shifts human memory B cell epitope recognition suggesting antibody feedback.
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Bloom N, Ramirez SI, Cohn H, Parikh UM, Heaps A, Sieg SF, Greninger A, Ritz J, Moser C, Eron JJ, Bajic G, Currier JS, Klekotka P, Wohl DA, Daar ES, Li J, Hughes MD, Chew KW, Smith DM, Crotty S, and Coelho CH
- Abstract
Therapeutic monoclonal antibodies (mAbs) have been studied in humans, but the impact on immune memory of mAb treatment during an ongoing infection has remained unclear. We evaluated the effect of infusion of the anti-SARS-CoV-2 spike receptor binding domain (RBD) mAb bamlanivimab on memory B cells (MBCs) in SARS-CoV-2-infected individuals. Bamlanivimab treatment skewed the repertoire of memory B cells targeting Spike towards non-RBD epitopes. Furthermore, the relative affinity of RBD memory B cells was weaker in mAb-treated individuals compared to placebo-treated individuals over time. Subsequently, after mRNA COVID-19 vaccination, memory B cell differences persisted and mapped to a specific reduction in recognition of the class II RBD site, the same RBD epitope recognized by bamlanivimab. These findings indicate a substantial role of antibody feedback in regulating memory B cell responses to infection, and single mAb administration can continue to impact memory B cell responses to additional antigen exposures months later., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)
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- 2024
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45. Safety and Efficacy of SAB-185 for Non-hospitalized Adults with COVID-19: A Randomized Clinical Trial.
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Chew KW, Taiwo BO, Moser C, Daar ES, Wohl DA, Ritz J, Javan AC, Li JZ, Fischer W, Greninger AL, Bausch C, Luke T, Call R, Neytman G, Giganti MJ, Fletcher CV, Hughes MD, Eron JJ, Currier JS, and Smith DM
- Abstract
Background: To address the need for novel COVID-19 therapies, we evaluated the fully-human polyclonal antibody product SAB-185 in a phase 3 clinical trial., Methods: Non-hospitalized high-risk adults within 7 days of COVID-19 symptom onset were randomized 1:1 to open-label SAB-185 3,840 units/kg or casirivimab/imdevimab 1200 mg. Non-inferiority comparison was undertaken for the pre-Omicron population (casirivimab/imdevimab expected to be fully active) and superiority comparison for the Omicron population (casirivimab/imdevimab not expected to be active). Primary outcomes were the composite of all-cause hospitalizations/deaths and grade ≥3 treatment-emergent adverse events (TEAEs) through day 28. Secondary outcomes included time to sustained symptom improvement and resolution., Results: Enrollment was terminated early due to low hospitalization/death rates upon Omicron emergence. 733 adults were randomized, 255 included in pre-Omicron and 392 in Omicron analysis populations. Hospitalizations/deaths occurred in 6 (5.0%) and 3 (2.2%) of pre-Omicron SAB-185 and casirivimab/imdevimab arms, respectively (absolute difference [95% CI] 2.7% [-2.3%, 8.6%]), inconclusive for non-inferiority; and 5 (2.5%) versus 3 (1.5%) (absolute difference 1.0% [-2.3%, 4.5%]) for Omicron. Risk ratios for grade ≥3 TEAEs were 0.94 [0.52, 1.71] (pre-Omicron) and 1.71 [0.96, 3.07] (Omicron). Time to symptom improvement and resolution were shorter for SAB-185, median 11 vs 14 (pre-Omicron) and 11 vs 13 days (Omicron) (symptom improvement), and 16 vs 24 days and 18 vs >25 days (symptom resolution), p<0.05 for symptom resolution for Omicron only., Conclusions: SAB-185 had an acceptable safety profile with faster symptom resolution in the Omicron population. Additional studies are needed to characterize its efficacy for COVID-19., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)
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- 2024
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46. Severe Acute Respiratory Syndrome Coronavirus 2 Plasma Antibody and Nucleocapsid Antigen Status Predict Outcomes in Outpatients With Coronavirus Disease 2019.
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Jilg N, Giganti MJ, Chew KW, Shaw-Saliba K, Ritz J, Moser C, Evering TH, Daar ES, Eron JJ, Currier JS, Hughes MD, Lane HC, Dewar R, Smith DM, and Li JZ
- Abstract
Background: Reliable biomarkers of coronavirus disease 2019 (COVID-19) outcomes are critically needed. We evaluated associations of spike antibody (Ab) and plasma nucleocapsid antigen (N Ag) with clinical outcomes in nonhospitalized persons with mild-to-moderate COVID-19., Methods: Participants were nonhospitalized adults with mild-to-moderate COVID-19 enrolled in ACTIV-2 between January and July 2021 and randomized to placebo. We used quantitative assays for severe acute respiratory syndrome coronavirus 2 spike Ab and N Ag in blood and determined numbers of hospitalization/death events within 28 days and time to symptom improvement., Results: Of 209 participants, 77 (37%) had quantifiable spike Ab and 139 (67%) quantifiable N Ag. Median age was 50 years; 111 (53%) were female, 182 (87%) White, and 105 (50%) Hispanic/Latino. Higher risk of hospitalization/death was seen with unquantifiable (22/132 [16.7%]) versus quantifiable (1/77 [1.3%]) spike Ab (risk ratio [RR], 12.83 [95% confidence interval {CI}, 1.76-93.34]) and quantifiable (22/139 [15.8%]) vs unquantifiable (1/70 [1.4%]) N Ag (RR, 11.08 [95% CI, 1.52-80.51]). Increasing risk of hospitalizations/deaths was seen with increasing N Ag levels. Time to symptom improvement was longer with unquantifiable versus quantifiable spike Ab (median, 14 [interquartile range {IQR}, 8 to >27] vs 8 [IQR, 4-22] days; adjusted hazard ratio [aHR], 0.66 [95% CI, .45-.96]) and with quantifiable versus unquantifiable N Ag (median, 12 [7 to >27] vs 10 [5-22] days; aHR, 0.79 [95% CI, .52-1.21])., Conclusions: Absence of spike Ab and presence of plasma N Ag predicted hospitalization/death and delayed symptom improvement in COVID-19 outpatients., Competing Interests: Potential conflicts of interest. N. J. received salary support to the institution from Sagent Pharmaceuticals. D. A. W. has received funding to his institution to support research and honoraria for advisory boards and consulting from Gilead Sciences. T. H. E. serves as a consultant for Tonix Pharmaceuticals. E. S. D. receives consulting fees from Gilead Sciences, Merck, and GSK/ViiV and research support through his institution from Gilead Sciences and GSK/ViiV. J. Z. L. has received research funding from Merck. J. J. E. is an ad hoc consultant to GSK/VIR, data monitoring committee chair for Adagio Phase 3 studies. J. S. C. has consulted for Merck and Company. D. M. S. has consulted for Fluxergy, Kiadis, Linear Therapies, Matrix BioMed, Arena Pharmaceuticals, VxBiosciences, Model Medicines, Bayer Pharmaceuticals, Signant Health, and Brio Clinical. K. W. C. received research funding to the institution from Merck Sharp & Dohme and is a consultant for Pardes Biosciences. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)
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- 2024
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47. Impact of antiretroviral therapy during acute or early HIV infection on virologic and immunologic outcomes: results from a multinational clinical trial.
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Crowell TA, Ritz J, Zheng L, Naqvi A, Cyktor JC, Puleo J, Clagett B, Lama JR, Kanyama C, Little SJ, Cohn SE, Riddler SA, Collier AC, Heath SL, Tantivitayakul P, Grinsztejn B, Arduino RC, Rooney JF, van Zyl GU, Coombs RW, Fox L, Ananworanich J, Eron JJ, Sieg SF, Mellors JW, and Daar ES
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- Humans, Female, Adult, Male, Young Adult, Anti-Retroviral Agents therapeutic use, Viral Load, CD4-Positive T-Lymphocytes immunology, DNA, Viral analysis, DNA, Viral blood, Treatment Outcome, Asia, Africa, HIV Infections drug therapy, HIV Infections immunology
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Objective: To assess how antiretroviral therapy (ART) initiation during acute or early HIV infection (AEHI) affects the viral reservoir and host immune responses., Design: Single-arm trial of ART initiation during AEHI at 30 sites in the Americas, Africa, and Asia., Methods: HIV DNA was measured at week 48 of ART in 5 million CD4 + T cells by sensitive qPCR assays targeting HIV gag and pol . Peripheral blood mononuclear cells were stimulated with potential HIV T cell epitope peptide pools consisting of env , gag , nef, and pol peptides and stained for expression of CD3, CD4, CD8, and intracellular cytokines/chemokines., Results: From 2017 to 2019, 188 participants initiated ART during Fiebig stages I ( n = 6), II ( n = 43), III ( n = 56), IV ( n = 23), and V ( n = 60). Median age was 27 years (interquartile range 23-38), 27 (14%) participants were female, and 180 (97%) cisgender. Among 154 virally suppressed participants at week 48, 100% had detectable HIV gag or pol DNA. Participants treated during Fiebig I had the lowest HIV DNA levels ( P < 0.001). Week 48 HIV DNA mostly did not correlate with concurrent CD4 + or CD8 + T cell HIV-specific immune responses (rho range -0.11 to +0.19, all P > 0.025). At week 48, the magnitude, but not polyfunctionality, of HIV-specific T cell responses was moderately reduced among participants who initiated ART earliest., Conclusion: Earlier ART initiation during AEHI reduced but did not eliminate the persistence of HIV-infected cells in blood. These findings explain the rapid viral rebound observed after ART cessation in early-treated individuals with undetectable HIV DNA by less sensitive methods., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)
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- 2024
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48. Differences in internalized HIV stigma across subpopulations of people with HIV in care across the United States.
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Drumright LN, Johnson MO, Mayer KH, Christopoulos K, Cachay E, Crawford TN, Whitney BM, Dai M, Ruderman SA, Mixson LS, Keruly JC, Chander G, Saag MS, Kitahata MM, Moore RD, Willig AL, Eron JJ, Napravnik S, Nance RM, Hahn A, Ma J, Bamford L, Fredericksen RJ, Delaney JAC, and Crane HM
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- Humans, Male, Female, Middle Aged, United States epidemiology, Adult, Longitudinal Studies, Young Adult, Aged, Adolescent, HIV Infections psychology, Social Stigma
- Abstract
Background: Few studies have examined which subgroups of people with HIV (PWH) carry the greatest burden of internalized HIV stigma (IHS), which may be important to care provision and interventions., Methods: PWH in the CFAR Network of Integrated Clinical Systems (CNICS) longitudinal, US-based, multisite, clinical care cohort completed tablet-based assessments during clinic visits including a four-item, Likert scale (low 1-5 high), IHS instrument. Associations between sociodemographic characteristics and IHS scores were assessed in adjusted linear regression models., Results: Twelve thousand six hundred and fifty-six PWH completed the IHS assessment at least once from February 2016 to November 2022, providing 28 559 IHS assessments. At baseline IHS assessment, the mean age was 49 years, 41% reported White, 38% Black/African American, and 16% Latine race/ethnicity, and 80% were cisgender men. The mean IHS score was 2.04, with all subgroups represented among those endorsing IHS. In regression analyses, younger PWH and those in care fewer years had higher IHS scores. In addition, cisgender women vs. cisgender men, PWH residing in the West vs. the Southeast, and those with sexual identities other than gay/lesbian had higher IHS scores. Compared with White-identifying PWH, those who identified with Black/African American or Latine race/ethnicity had lower IHS scores. Age stratification revealed patterns related to age category, including specific age-related differences by gender, geographic region and race/ethnicity., Discussion: IHS is prevalent among PWH, with differential burden by subgroups of PWH. These findings highlight the benefits of routine screening for IHS and suggest the need for targeting/tailoring interventions to reduce IHS among PWH., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)
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- 2024
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49. Response to Drs de Grooth and Parienti.
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Giganti MJ, Chew KW, Eron JJ, Smith DM, Currier JS, and Hughes MD
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Competing Interests: Potential conflicts of interest. All authors: No reported conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest.
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- 2024
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50. Persistence of a Skewed Repertoire of NK Cells in People with HIV-1 on Long-Term Antiretroviral Therapy.
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Anderko RR, DePuyt AE, Bronson R, Bullotta AC, Aga E, Bosch RJ, Jones RB, Eron JJ, Mellors JW, Gandhi RT, McMahon DK, Macatangay BJ, Rinaldo CR, and Mailliard RB
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- Humans, Male, Female, Adult, Middle Aged, Immunologic Memory immunology, Lectins, C-Type immunology, Receptors, Immunologic, Viremia immunology, Viremia drug therapy, Cytomegalovirus Infections immunology, Cytomegalovirus Infections drug therapy, Receptors, IgG immunology, Longitudinal Studies, Anti-Retroviral Agents therapeutic use, Killer Cells, Natural immunology, HIV Infections immunology, HIV Infections drug therapy, HIV Infections virology, HIV-1 immunology, CD57 Antigens immunology
- Abstract
HIV-1 infection greatly alters the NK cell phenotypic and functional repertoire. This is highlighted by the expansion of a rare population of FcRγ- NK cells exhibiting characteristics of traditional immunologic memory in people with HIV (PWH). Although current antiretroviral therapy (ART) effectively controls HIV-1 viremia and disease progression, its impact on HIV-1-associated NK cell abnormalities remains unclear. To address this, we performed a longitudinal analysis detailing conventional and memory-like NK cell characteristics in n = 60 PWH during the first 4 y of ART. Throughout this regimen, a skewed repertoire of cytokine unresponsive FcRγ- memory-like NK cells persisted and accompanied an overall increase in NK surface expression of CD57 and KLRG1, suggestive of progression toward immune senescence. These traits were linked to elevated serum inflammatory biomarkers and increasing Ab titers to human CMV, with human CMV viremia detected in approximately one-third of PWH at years 1-4 of ART. Interestingly, 40% of PWH displayed atypical NK cell subsets, representing intermediate stages of NK-poiesis based on single-cell multiomic trajectory analysis. Our findings indicate that NK cell irregularities persist in PWH despite long-term ART, underscoring the need to better understand the causative mechanisms that prevent full restoration of immune health in PWH., (Copyright © 2024 by The American Association of Immunologists, Inc.)
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- 2024
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