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UNC-authored articles published by the Public Library of Science (PLoS)

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1681. Stigma and Ebola survivorship in liberia: Results from a longitudinal cohort study

Title Tesim:: Stigma and Ebola survivorship in liberia: Results from a longitudinal cohort study
Creator:: Dube, K., Wohl, D.A., Fischer, W.A., II, Westreich, D., McMillian, D., Reeves, E., Hoover, D., Conneh, T., Johnson, H., Tozay, S., Merenbloom, C., Adjasso, D., Williams, G., Buller, A., Brown, J., Pewu, K., Overholt, L., Diggs, J., and Hawks, D.
Date of publication:: 2018
Abstract Tesim:: Background Survivors of the 2014–2016 West Africa Ebola epidemic have been reported to suffer high levels of stigmatization after return to their communities. We sought to characterize the stigma encountered by a cohort of Ebola survivors in Liberia over time. Methods Ebola-related stigma was assessed from June 2015 to August 2017 in 299 adolescent and adult Liberian Ebola Survivor Cohort participants at three month intervals using adapted HIV stigma scales scored from 0 to 10 according to the proportion of answers indicating stigmatization. Findings The median time from Ebola Virus Disease (EVD) to study entry was 393 days (IQR 336–492). Participants (43% female) had a median age of 31 (IQR 25–40) years. Mean self-reported stigma levels were greater at baseline (6.28 ± 0.15 [IQR: 4.38–8.75]) compared to the first post-baseline visit (0.60 ± 0.10 [IQR: 0–0]; p<0.0001). During follow-up, stigma levels were stable. Baseline stigma significantly increased during enrollment and following clusters of Ebola re-emergence in Liberia. Survivors encountered primarily enacted and perceived external stigma rather than internalized stigma. Conclusions Ebola-related stigma was prevalent among Liberian survivors more than a year after EVD recovery. Self-reported stigma was greater in the period before cohort enrollment; however, some degree of stigmatization persisted years after EVD. Transient rises in stigma were observed following episodic Ebola re-emergence of EVD in Liberia. During future EVD outbreaks, enhanced public health interventions designed to prevent and mitigate Ebola-related stigma that is enacted and external should be implemented to support survivor recovery and community re-integration.
Resource type:: Article
DOI:: https://doi.org/10.17615/qe80-je04
Identifier:: https://dx.doi.org/10.1371/journal.pone.0206595 and PMID 30485311
ISSN:: 1932-6203
Journal Issue:: 11
Journal Title:: PLoS ONE
Journal Volume:: 13
Keyword:: survivor, male, human, Ebola hemorrhagic fever, stigma, female, survivorship, self report, cohort analysis, controlled study, major clinical study, Liberia, adult, adolescent, and longitudinal study
Language Label:: English
License Label:: Attribution 3.0 United States
ORCID:
Other Affiliation:: , Eternal Love Winning Africa Hospital, Clinical Research Management, Inc., Abilene Christian University, and University of Michigan Medical School
Person:: Dube, K., Wohl, D.A., Fischer, W.A., II, Westreich, D., McMillian, D., Reeves, E., Hoover, D., Conneh, T., Johnson, H., Tozay, S., Merenbloom, C., Adjasso, D., Williams, G., Buller, A., Brown, J., Pewu, K., Overholt, L., Diggs, J., and Hawks, D.
Publisher:: Public Library of Science
Rights Statement Label:: In Copyright
Source:: vd66w562n and david_wohl_21

1682. Recurrent plasmodium falciparum malaria infections in kenyan children diminish t-cell immunity to epstein barr virus lytic but not latent antigens

Title Tesim:: Recurrent plasmodium falciparum malaria infections in kenyan children diminish t-cell immunity to epstein barr virus lytic but not latent antigens
Creator:: Cole, S.R., Moormann, A.M., MacDonald, P.D.M., Snider, C.J., Sumba, P.O., John, C.C., Meshnick, S.R., and Chelimo, K.
Date of publication:: 2012
Abstract Tesim:: Plasmodium falciparum malaria (Pf-malaria) and Epstein Barr Virus (EBV) infections coexist in children at risk for endemic Burkitt's lymphoma (eBL); yet studies have only glimpsed the cumulative effect of Pf-malaria on EBV-specific immunity. Using pooled EBV lytic and latent CD8+ T-cell epitope-peptides, IFN-γ ELISPOT responses were surveyed three times among children (10 months to 15 years) in Kenya from 2002–2004. Prevalence ratios (PR) and 95% confidence intervals (CI) were estimated in association with Pf-malaria exposure, defined at the district-level (Kisumu: holoendemic; Nandi: hypoendemic) and the individual-level. We observed a 46% decrease in positive EBV lytic antigen IFN-γ responses among 5–9 year olds residing in Kisumu compared to Nandi (PR: 0.54; 95% CI: 0.30–0.99). Individual-level analysis in Kisumu revealed further impairment of EBV lytic antigen responses among 5–9 year olds consistently infected with Pf-malaria compared to those never infected. There were no observed district- or individual-level differences between Pf-malaria exposure and EBV latent antigen IFN-γ response. The gradual decrease of EBV lytic antigen but not latent antigen IFN-γ responses after primary infection suggests a specific loss in immunological control over the lytic cycle in children residing in malaria holoendemic areas, further refining our understanding of eBL etiology.
Resource type:: Article
Affiliation Label Tesim:: Department of Epidemiology
DOI:: https://doi.org/10.17615/ph69-4637
Identifier:: https://dx.doi.org/10.1371/journal.pone.0031753
ISSN:: 1932-6203
Journal Issue:: 3
Journal Title:: PLoS ONE
Journal Volume:: 7
Language Label:: English
ORCID:
Other Affiliation:: , Case Western Reserve University, Kenya Medical Research Institute, and University of Minnesota Medical School
Page End:: n/a
Page Start:: n/a
Person:: Cole, S.R., Moormann, A.M., MacDonald, P.D.M., Snider, C.J., Sumba, P.O., John, C.C., Meshnick, S.R., and Chelimo, K.
Rights Statement Label:: In Copyright
Source:: rf55zf39k and stephen_cole_59

1683. Sensitivity analyses for effect modifiers not observed in the target population when generalizing treatment effects from a randomized controlled trial: Assumptions, models, effect scales, data scenarios, and implementation details

Title Tesim:: Sensitivity analyses for effect modifiers not observed in the target population when generalizing treatment effects from a randomized controlled trial: Assumptions, models, effect scales, data scenarios, and implementation details
Creator:: Edwards, J.K., Kitahata, M., Cole, S.R., Eron, J.J., Moore, R.D., and Mathews, W.C.
Date of publication:: 2018
Abstract Tesim:: Background inform policy and practice for broad populations. The average treatment effect (ATE) for a target population, however, may be different from the ATE observed in a trial if there are effect modifiers whose distribution in the target population is different that from that in the trial. Methods exist to use trial data to estimate the target population ATE, provided the distributions of treatment effect modifiers are observed in both the trial and target population—an assumption that may not hold in practice. Methods The proposed sensitivity analyses address the situation where a treatment effect modifier is observed in the trial but not the target population. These methods are based on an outcome model or the combination of such a model and weighting adjustment for observed differences between the trial sample and target population. They accommodate several types of outcome models: linear models (including single time outcome and pre- and post-treatment outcomes) for additive effects, and models with log or logit link for multiplicative effects. We clarify the methods’ assumptions and provide detailed implementation instructions. Illustration We illustrate the methods using an example generalizing the effects of an HIV treatment regimen from a randomized trial to a relevant target population. Conclusion These methods allow researchers and decision-makers to have more appropriate confidence when drawing conclusions about target population effects.
Resource type:: Article
Affiliation Label Tesim:: Department of Epidemiology and School of Medicine
DOI:: https://doi.org/10.17615/sfes-6r13
Identifier:: https://dx.doi.org/10.1371/journal.pone.0208795
ISSN:: 1932-6203
Journal Issue:: 12
Journal Title:: PLoS ONE
Journal Volume:: 13
Language Label:: English
ORCID:
Other Affiliation:: , University of Washington, Johns Hopkins University, and University of California San Diego
Page End:: 17
Page Start:: 1
Person:: Edwards, J.K., Kitahata, M., Cole, S.R., Eron, J.J., Moore, R.D., and Mathews, W.C.
Rights Statement Label:: In Copyright
Source:: stephen_cole_27 and j6731937s

1684. Efficacy and Safety of Three Antiretroviral Regimens for Initial Treatment of HIV-1: A Randomized Clinical Trial in Diverse Multinational Settings

Title Tesim:: Efficacy and Safety of Three Antiretroviral Regimens for Initial Treatment of HIV-1: A Randomized Clinical Trial in Diverse Multinational Settings
Creator:: Martinez, A.I., Webb, N., Infante, R., Steele, J., Chen, Y., Jaffe, H., Hoffman, I., Poongulali, S., Cu-Uvin, S., Santos, B., Shugarts, D.L., van der Horst, C., Stroberg, T., Riviere, C., Tashima, K.T., Gallant, J.E., Swann, E., Kanyama, C., Lalloo, U., Brizz, B., Amod, F., Faria, D.L., Hurley, C., Cheng, A., Fiscus, S.A., Marcus, C.J., Gangakhedkar, R.R., Said, F., Firnhaber, C., Chariyalertsak, S., Jain, M., Cespedes, M., Currin, D., Lira, R.A., Ramratnam, B., Chisada, A., Walawander, A., Mitsuyasu, R.T., Mildvan, D., Pendame, R.B., Sanchez, J., Eshleman, S., Cardoso, S.W., Severe, P., Maponga, C., Asmuth, D., Putnam, B., Flanigan, T., Descallar, R.S., Barnett, R.L., Snowden, W., Corales, R., Sha, B.E., Hammer, S.M., Feinberg, J., Haas, D.W., Tripathy, S., Palmer, M., Kumwenda, N., Frarey, L., Safren, S., Sanne, I., Para, M.F., Solomon, S., Dhayarkar, S., Klingman, K.L., Samaneka, W.P., Taha, T., Noel-Connor, J., Watson, K.J., Smeaton, L.M., Nair, A., Zifchak, L., Lawrence, J., Geiseler, P.J., Berendes, S., Cohen, M., Kumwenda, J., Pollard, R.B., Bailey, V.L., Lopez, R., Loeliger, E., Hakim, J.G., Tebas, P., Klebert, M.K., Rooney, J.F., Adams, M., Kazembe, P., Forcht, J., Andrade, A., Silberman, M., Faesen, S., McGregor, D., Martinson, F., Bollinger, R.C., Baer, J., Gormley, J., Hosseinipour, M.C., Gulick, R.M., Petersen, T., Ntshele, S., Uy, J., Eron, J., Cox, G.M., Delph, Y., Chilongozi, D., Winters, M.A., Daar, E.S., Tabet, S., la Rosa, A., Moran, L., Fritsche, J.M., Sharma, J., Melo, M., Kayoyo, V., Celentano, D., Berthaud, V., Martin, J.C., Godbole, S., Mogridge, C., Grinsztejn, B., Mullan, B., Basler, C., Taiwo, B., Bischofberger, N., Mngqibisa, R., Campbell, T.B., Mayer, K., Kumarasamy, N., Joglekar, A.A., Luque, A., Torres, M., Patterson, H., Wulfsohn, M., Gettinger, N., Gaikwad, A., Bryson, Y., Haas, D.H., Supparatpinyo, K., Sirisanthana, T., Flexner, C., de Gruttola, V., Kim, G.-Y., Ray, M.G., Schooley, R.T., Burke, K., Nielsen, K., Currier, J.S., Pappa, K.A., Lama, J.R., Collier, A.C., OBrien, W.A., Lopez-Detres, L., Wanke, C., Balfour, H.H., and Revuelta, M.
Date of publication:: 2012
Abstract Tesim:: Background:Antiretroviral regimens with simplified dosing and better safety are needed to maximize the efficiency of antiretroviral delivery in resource-limited settings. We investigated the efficacy and safety of antiretroviral regimens with once-daily compared to twice-daily dosing in diverse areas of the world.Methods and Findings:1,571 HIV-1-infected persons (47% women) from nine countries in four continents were assigned with equal probability to open-label antiretroviral therapy with efavirenz plus lamivudine-zidovudine (EFV+3TC-ZDV), atazanavir plus didanosine-EC plus emtricitabine (ATV+DDI+FTC), or efavirenz plus emtricitabine-tenofovir-disoproxil fumarate (DF) (EFV+FTC-TDF). ATV+DDI+FTC and EFV+FTC-TDF were hypothesized to be non-inferior to EFV+3TC-ZDV if the upper one-sided 95% confidence bound for the hazard ratio (HR) was â‰¤1.35 when 30% of participants had treatment failure.An independent monitoring board recommended stopping study follow-up prior to accumulation of 472 treatment failures. Comparing EFV+FTC-TDF to EFV+3TC-ZDV, during a median 184 wk of follow-up there were 95 treatment failures (18%) among 526 participants versus 98 failures among 519 participants (19%; HR 0.95, 95% CI 0.72-1.27; p = 0.74). Safety endpoints occurred in 243 (46%) participants assigned to EFV+FTC-TDF versus 313 (60%) assigned to EFV+3TC-ZDV (HR 0.64, CI 0.54-0.76; p<0.001) and there was a significant interaction between sex and regimen safety (HR 0.50, CI 0.39-0.64 for women; HR 0.79, CI 0.62-1.00 for men; p = 0.01). Comparing ATV+DDI+FTC to EFV+3TC-ZDV, during a median follow-up of 81 wk there were 108 failures (21%) among 526 participants assigned to ATV+DDI+FTC and 76 (15%) among 519 participants assigned to EFV+3TC-ZDV (HR 1.51, CI 1.12-2.04; p = 0.007).Conclusion: EFV+FTC-TDF had similar high efficacy compared to EFV+3TC-ZDV in this trial population, recruited in diverse multinational settings. Superior safety, especially in HIV-1-infected women, and once-daily dosing of EFV+FTC-TDF are advantageous for use of this regimen for initial treatment of HIV-1 infection in resource-limited countries. ATV+DDI+FTC had inferior efficacy and is not recommended as an initial antiretroviral regimen.Trial Registration:http://www.ClinicalTrials.gov NCT00084136.
Resource type:: Article
Affiliation Label Tesim:: University of North Carolina at Chapel Hill, Department of Medicine, and Division of Infectious Diseases
DOI:: https://doi.org/10.17615/6qek-p039
Identifier:: PMID 22936892 and https://dx.doi.org/10.1371/journal.pmed.1001290
ISSN:: 1549-1277
Journal Issue:: 8
Journal Title:: PLoS Medicine
Journal Volume:: 9
Keyword:: antiretrovirus agent, efavirenz plus lamivudine plus zidovudine, atazanavir, didanosine, efavirenz plus emtricitabine plus tenofovir disoproxil, virus RNA, and emtricitabine
Language Label:: English
ORCID:
Other Affiliation:: National Institutes of Health, Frontier Science and Technology Research Foundation, Inc., Investigaciones Medicas en Salud - INMENSA, Gilead Sciences, , YRG Centre for AIDS Research and Education, The Miriam Hospital, Brown University, University of Southern California, University of Colorado Health Sciences, Cornell University, Institut Nacional de laboratoire et de Recherches, The Miriam Hospital, Johns Hopkins University School of Medicine, NIH, Kamuzu Central Hospital, Nelson R. Mandela School of Medicine, Social and Scientific Systems, Inc, Nelson R Mandela School of Medicine, Instituto de Pesquisa Clinica Evandro Chagas-Fiocruz, Georgetown University, Department of Microbiology and Immunology, NARI Clinic at Gadikhana Dr. Kotnis Municipal Dispensary, University of the Witwatersrand, Chiang Mai University, UT Southwestern Medical Center at Dallas, New York University/NYC HHC at Bellevue Hospital Center, Hospital Conceicao, Brown University Medical School, University of Zimbabwe College of Health Sciences, Frontier Science and Technology Research Foundation, UCLA CARE Center, Beth Israel Medical Center, Asociacion Civil Impacta Salud y Educacion, Johns Hopkins University, Institute de Laboratories et de Recherches, Medical University of Zimbabwe, UC Davis School of Medicine, Brown Medical School, GlaxoSmithKline, Rush University Medical Center, Columbia Presbyterian Medical Centre, University of Cincinnati, Vanderbilt University, National AIDS Research Institute, Johns Hopkins Project, Malawi, Harvard Medical School, University of Witwatersrand, The Ohio State University, NARI Clinic at NIV, Harvard School of Public Health, Johns Hopkins University, School of Hygiene and Public Health, Columbia University, Hospital of the University of Pennsylvania, University of California, San Francisco, College of Medicine, Blantyre, Malawi, College of Medicine, Harbor-UCLA, Clinical Development and Medical Affairs, Washington University, Gilead Sciences, Inc., University of Rochester, Baylor College of Medicine-Abbott Fund Childrens Clinical Centre of Excellence, John Hopkins University, Duke University Medical Center, Northwestern University, The Miriam Hospital, Immunology Centre, The Cornell Clinical Trials Unit, Bristol-Myers Squibb Company, Stanford University Medical Center, University of Washington, Harborview Medical Centre, Asociacion Civil Impacta Salud y Educacion - Miraflores, Hospital Nossa Senhora da Conceicao-GHC, Johns Hopkins School of Hygiene and Public Health, Vanderbilt University Medical Centre, The University of Texas Medical Branch, Evandro Chagas Clinical Research Institute, University of Minnesota, Minneapolis, University of Colorado Hospital, Nelson Mandela School of Medicine, University of Colorado School of Medicine, Brown University School of Medicine, Social and Scientific Systems Inc, UCLA School of Medicine, Johns Hopkins University Hospital, University of California San Diego, University of California, Los Angeles, Investigaciones Medicas en Salud (INMENSA), University of Washington, Cornell University, and Tufts University School of Medicine
Person:: Martinez, A.I., Webb, N., Infante, R., Steele, J., Chen, Y., Jaffe, H., Hoffman, I., Poongulali, S., Cu-Uvin, S., Santos, B., Shugarts, D.L., van der Horst, C., Stroberg, T., Riviere, C., Tashima, K.T., Gallant, J.E., Swann, E., Kanyama, C., Lalloo, U., Brizz, B., Amod, F., Faria, D.L., Hurley, C., Cheng, A., Fiscus, S.A., Marcus, C.J., Gangakhedkar, R.R., Said, F., Firnhaber, C., Chariyalertsak, S., Jain, M., Cespedes, M., Currin, D., Lira, R.A., Ramratnam, B., Chisada, A., Walawander, A., Mitsuyasu, R.T., Mildvan, D., Pendame, R.B., Sanchez, J., Eshleman, S., Cardoso, S.W., Severe, P., Maponga, C., Asmuth, D., Putnam, B., Flanigan, T., Descallar, R.S., Barnett, R.L., Snowden, W., Corales, R., Sha, B.E., Hammer, S.M., Feinberg, J., Haas, D.W., Tripathy, S., Palmer, M., Kumwenda, N., Frarey, L., Safren, S., Sanne, I., Para, M.F., Solomon, S., Dhayarkar, S., Klingman, K.L., Samaneka, W.P., Taha, T., Noel-Connor, J., Watson, K.J., Smeaton, L.M., Nair, A., Zifchak, L., Lawrence, J., Geiseler, P.J., Berendes, S., Cohen, M., Kumwenda, J., Pollard, R.B., Bailey, V.L., Lopez, R., Loeliger, E., Hakim, J.G., Tebas, P., Klebert, M.K., Rooney, J.F., Adams, M., Kazembe, P., Forcht, J., Andrade, A., Silberman, M., Faesen, S., McGregor, D., Martinson, F., Bollinger, R.C., Baer, J., Gormley, J., Hosseinipour, M.C., Gulick, R.M., Petersen, T., Ntshele, S., Uy, J., Eron, J., Cox, G.M., Delph, Y., Chilongozi, D., Winters, M.A., Daar, E.S., Tabet, S., la Rosa, A., Moran, L., Fritsche, J.M., Sharma, J., Melo, M., Kayoyo, V., Celentano, D., Berthaud, V., Martin, J.C., Godbole, S., Mogridge, C., Grinsztejn, B., Mullan, B., Basler, C., Taiwo, B., Bischofberger, N., Mngqibisa, R., Campbell, T.B., Mayer, K., Kumarasamy, N., Joglekar, A.A., Luque, A., Torres, M., Patterson, H., Wulfsohn, M., Gettinger, N., Gaikwad, A., Bryson, Y., Haas, D.H., Supparatpinyo, K., Sirisanthana, T., Flexner, C., de Gruttola, V., Kim, G.-Y., Ray, M.G., Schooley, R.T., Burke, K., Nielsen, K., Currier, J.S., Pappa, K.A., Lama, J.R., Collier, A.C., OBrien, W.A., Lopez-Detres, L., Wanke, C., Balfour, H.H., and Revuelta, M.
Publisher:: Public Library of Science
Rights Statement Label:: In Copyright
Source:: fq9780935 and joseph_eron_92

1685. HIV cure strategies: How good must they be to improve on current antiretroviral therapy?

Title Tesim:: HIV cure strategies: How good must they be to improve on current antiretroviral therapy?
Creator:: Paltiel, A.D., Sypek, A., Morris, B.L., Berkowitz, B.K., Kelly, K.A., Sax, P.E., Seage, G.R., III, Weinstein, M.C., Walensky, R.P., Freedberg, K.A., Losina, E., and Eron, J.
Date of publication:: 2014
Abstract Tesim:: Background: We examined efficacy, toxicity, relapse, cost, and quality-of-life thresholds of hypothetical HIV cure interventions that would make them cost-effective compared to life-long antiretroviral therapy (ART). Copyright:Methods: We used a computer simulation model to assess three HIV cure strategies: Gene Therapy, Chemotherapy, and Stem Cell Transplantation (SCT), each compared to ART. Efficacy and cost parameters were varied widely in sensitivity analysis. Outcomes included quality-adjusted life expectancy, lifetime cost, and cost-effectiveness in dollars/quality-adjusted life year ($/QALY) gained. Strategies were deemed cost-effective with incremental cost-effectiveness ratios <$100,000/ QALY.Results: For patients on ART, discounted quality-adjusted life expectancy was 16.4 years and lifetime costs were $591,400. Gene Therapy was cost-effective with efficacy of 10%, relapse rate 0.5%/month, and cost $54,000. Chemotherapy was costeffective with efficacy of 88%, relapse rate 0.5%/month, and cost $12,400/month for 24 months. At $150,000/procedure, SCT was cost-effective with efficacy of 79% and relapse rate 0.5%/month. Moderate efficacy increases and cost reductions made Gene Therapy cost-saving, but substantial efficacy/cost changes were needed to make Chemotherapy or SCT cost-saving.Conclusions: Depending on efficacy, relapse rate, and cost, cure strategies could be cost-effective compared to current ART and potentially cost-saving. These results may help provide performance targets for developing cure strategies for HIV.
Resource type:: Article
Affiliation Label Tesim:: Division of Infectious Diseases
DOI:: https://doi.org/10.17615/77tz-zc77
Identifier:: PMID 25397616 and https://dx.doi.org/10.1371/journal.pone.0113031
ISSN:: 1932-6203
Journal Issue:: 11
Journal Title:: PLoS ONE
Journal Volume:: 9
Keyword:: antiretrovirus agent, tenofovir, emtricitabine, and efavirenz
Language Label:: English
ORCID:
Other Affiliation:: Yale School of Public Health, Massachusetts General Hospital, Brigham and Womens Hospital, Harvard University, and
Person:: Paltiel, A.D., Sypek, A., Morris, B.L., Berkowitz, B.K., Kelly, K.A., Sax, P.E., Seage, G.R., III, Weinstein, M.C., Walensky, R.P., Freedberg, K.A., Losina, E., and Eron, J.
Publisher:: Public Library of Science
Rights Statement Label:: In Copyright
Source:: joseph_eron_89 and 7d279090z

1686. Real-world efficacy of direct acting antiviral therapies in patients with HIV/HCV

Title Tesim:: Real-world efficacy of direct acting antiviral therapies in patients with HIV/HCV
Creator:: Eron, J.J., Moyle, G., Patel, S.V., Althoff, K.N., Sax, P.E., Mounzer, K., Mills, A., Huhn, G.D., Santiago, S., Gillman, J., Radtchenko, J., Elion, R.A., and Jayaweera, D.T.
Date of publication:: 2020
Abstract Tesim:: The advent of direct-acting antiviral (DAA) therapies has dramatically transformed HCV treatment, with most recent trials demonstrating high efficacy rates (>90%) across all genotypes and special populations, including patients with HIV/HCV coinfection. The efficacy rates of HCV treatment are nearly identical between patients with HCV monofection and patients with HIV/HCV coinfection; however, there are limited studies to compare real-world efficacy with efficacy observed in clinical trials. Using a database from HIV clinics across the United States (US), we identified 432 patients with HIV/HCV coinfection who completed DAA therapy from January 1, 2014 to March 31, 2017 and were assessed for efficacy. Efficacy was evaluated as sustained virologic response (SVR) 12 weeks after DAA completion; furthermore, factors associated with achieving SVR12 were identified. In this analysis, we found DAA therapies to be effective, with 94% of the patients achieving SVR12 and 6% experiencing virologic failure. Baseline variables, including older age, HCV viral load <800K IU/ML, FIB-4 score <1.45, absence of depression, diabetes, substance abuse, and use of DAA regimens without ribavirin were significant predictors of achieving SVR12. Patients with fewer comorbidities, better liver health, and lower HCV viral loads at baseline were more likely to achieve treatment success. Our results were consistent with other real-world studies, supporting the use of HCV therapy in HIV/HCV coinfected patients.
Resource type:: Article
Affiliation Label Tesim:: Division of Infectious Diseases
DOI:: https://doi.org/10.17615/5qhn-ad14
Identifier:: PMID 32053682 and https://dx.doi.org/10.1371/journal.pone.0228847
ISSN:: 1932-6203
Journal Issue:: 2
Journal Title:: PLoS ONE
Journal Volume:: 15
Keyword:: ledipasvir plus sofosbuvir, elbasvir plus grazoprevir, alanine aminotransferase, aspartate aminotransferase, sofosbuvir, ribavirin, sofosbuvir plus velpatasvir, daclatasvir, peginterferon, dasabuvir plus ombitasvir plus paritaprevir plus ritonavir, and simeprevir
Language Label:: English
License Label:: Attribution 3.0 United States
ORCID:
Other Affiliation:: , Chelsea and Westminster Hospital, Cook County Health, Johns Hopkins University, Harvard Medical School, University of Pennsylvania and Philadelphia Fight Community Health Centers, Southern California Mens Medical Group, Rush University Medical Center, Care Resource, Prism Health North Texas, Trio Health Analytics, George Washington University School of Medicine, and University of Miami
Person:: Eron, J.J., Moyle, G., Patel, S.V., Althoff, K.N., Sax, P.E., Mounzer, K., Mills, A., Huhn, G.D., Santiago, S., Gillman, J., Radtchenko, J., Elion, R.A., and Jayaweera, D.T.
Publisher:: Public Library of Science
Rights Statement Label:: In Copyright
Source:: joseph_eron_13 and m326m7436

1687. Selective k Opioid Antagonists nor-BNI, GNTI and JDTic Have Low Affinities for Non-Opioid Receptors and Transporters

Title Tesim:: Selective k Opioid Antagonists nor-BNI, GNTI and JDTic Have Low Affinities for Non-Opioid Receptors and Transporters
Creator:: Huang, X.-P., Inglese, C., Munro, T.A., Perrone, M.G., Beguin, C., Van't Veer, A., Roth, B.L., Carroll, F.I., Carlezon Jr., W.A., Colabufo, N.A., and Cohen, B.M.
Date of publication:: 2013
Abstract Tesim:: Background:Nor-BNI, GNTI and JDTic induce selective Îº opioid antagonism that is delayed and extremely prolonged, but some other effects are of rapid onset and brief duration. The transient effects of these compounds differ, suggesting that some of them may be mediated by other targets.Results:In binding assays, the three antagonists showed no detectable affinity (Kiâ‰¥10 Î¼M) for most non-opioid receptors and transporters (26 of 43 tested). There was no non-opioid target for which all three compounds shared detectable affinity, or for which any two shared sub-micromolar affinity. All three compounds showed low nanomolar affinity for Îº opioid receptors, with moderate selectivity over Î¼ and Î´ (3 to 44-fold). Nor-BNI bound weakly to the Î±2C-adrenoceptor (Ki = 630 nM). GNTI enhanced calcium mobilization by noradrenaline at the Î±1A-adrenoceptor (EC50 = 41 nM), but did not activate the receptor, displace radioligands, or enhance PI hydrolysis. This suggests that it is a functionally-selective allosteric enhancer. GNTI was also a weak M1 receptor antagonist (KB = 3.7 Î¼M). JDTic bound to the noradrenaline transporter (Ki = 54 nM), but only weakly inhibited transport (IC50 = 1.1 Î¼M). JDTic also bound to the opioid-like receptor NOP (Ki = 12 nM), but gave little antagonism even at 30 Î¼M. All three compounds exhibited rapid permeation and active efflux across Caco-2 cell monolayers.Conclusions:Across 43 non-opioid CNS targets, only GNTI exhibited a potent functional effect (allosteric enhancement of Î±1A-adrenoceptors). This may contribute to GNTI's severe transient effects. Plasma concentrations of nor-BNI and GNTI may be high enough to affect some peripheral non-opioid targets. Nonetheless, Îº opioid antagonism persists for weeks or months after these transient effects dissipate. With an adequate pre-administration interval, our results therefore strengthen the evidence that nor-BNI, GNTI and JDTic are highly selective Îº opioid antagonists. Â© 2013 Munro et al.
Resource type:: Article
Affiliation Label Tesim:: Department of Pharmacology
DOI:: https://doi.org/10.17615/xnpg-9245
Identifier:: https://dx.doi.org/10.1371/journal.pone.0070701, PMID 23976952
ISSN:: 1932-6203
Journal Issue:: 8
Journal Title:: PLoS ONE
Journal Volume:: 8
Language Label:: English
License Label:: Attribution 3.0 United States
ORCID:
Other Affiliation:: , Universita degli Studi di Bari, McLean Hospital, Universita degli Studi di Bari, and Research Triangle Institute
Person:: Huang, X.-P., Inglese, C., Munro, T.A., Perrone, M.G., Beguin, C., Van't Veer, A., Roth, B.L., Carroll, F.I., Carlezon Jr., W.A., Colabufo, N.A., and Cohen, B.M.
Publisher:: Public Library of Science
Rights Statement Label:: In Copyright
Source:: v979v851w and bryan_roth_56

1688. Attrition among human immunodeficiency virus (HIV)- infected patients initiating antiretroviral therapy in China, 2003-2010

Title Tesim:: Attrition among human immunodeficiency virus (HIV)- infected patients initiating antiretroviral therapy in China, 2003-2010
Creator:: Zhu, H., Eron, J., Dou, Z., Ma, Y., Liu, Z., Napravnik, S., Zhao, D., Wohl, D., Cole, S., Zhang, F., Cohen, M., and Zhang, Y.
Date of publication:: 2012
Abstract Tesim:: Background: Mortality and morbidity from HIV have dramatically decreased in both high- and low-income countries. However, some patients may not benefit from combination antiretroviral therapy (cART) because of inadequate access to HIV care, including attrition after care initiation. Methodology/Principal Findings: The study population included all HIV-infected patients receiving cART through the Chinese National Free Antiretroviral Treatment Program from 1 January 2003 to 31 December 2010 (n = 106,542). We evaluated retention in HIV care and used multivariable Cox proportional hazard models to identify independent factors predictive of attrition. The cumulative probability of attrition from cART initiation was 9% at 12 months, 13% at 18 months, 16% at 24 months and 24% at 60 months. A number of factors were associated with attrition, including younger age, male gender, and being single or divorced. Patients with higher CD4 cell counts at cART initiation were more likely to drop out of HIV care. The proportion of patients remaining in HIV care increased in more recent calendar years and among patients who initiated modern cART regimens. Conclusions/Significance: Retention in HIV care is essential for optimizing individual and public health outcomes. Attrition, even the degree observed in our study, can lead to premature morbidity and mortality, and possibly affect further transmission of HIV and HIV resistant drug variants. Effective strategies to promote retention in HIV care programs are needed. In China these strategies may include focusing particularly on younger male patients and those with higher CD4 cell counts at therapy initiation.
Resource type:: Article
Affiliation Label Tesim:: Department of Epidemiology and Division of Infectious Diseases
DOI:: https://doi.org/10.17615/2jyc-3c11
Identifier:: https://dx.doi.org/10.1371/journal.pone.0039414 and PMID 22761787
ISSN:: 1932-6203
Journal Issue:: 6
Journal Title:: PLoS ONE
Journal Volume:: 7
Keyword:: antiretrovirus agent, unclassified drug, lamivudine plus nevirapine, efavirenz plus nevirapine, nevirapine plus zidovudine, nevirapine plus stavudine, efavirenz plus lamivudine, efavirenz plus didanosine, efavirenz plus stavudine, and efavirenz plus zidovudine
Language Label:: English
ORCID:
Other Affiliation:
Person:: Zhu, H., Eron, J., Dou, Z., Ma, Y., Liu, Z., Napravnik, S., Zhao, D., Wohl, D., Cole, S., Zhang, F., Cohen, M., and Zhang, Y.
Publisher:: Public Library of Science
Rights Statement Label:: In Copyright
Source:: 736669917 and joseph_eron_93

1689. Cancer risk in HIV patients with incomplete viral suppression after initiation of antiretroviral therapy

Title Tesim:: Cancer risk in HIV patients with incomplete viral suppression after initiation of antiretroviral therapy
Creator:: AIDS Research (CFAR) Network of Integrated Clinical Systems (CNICS), Althoff, K.N., Richardson, D.B., Mathews, C., Eron, J.J., Jr., Cole, S.R., Moore, R.D., Lee, J.S., Achenbach, C.J., Miller, W.C., and Dittmer, D.P.
Date of publication:: 2018
Abstract Tesim:: Background Cancer causes significant morbidity and mortality among HIV patients in the US due to extended life expectancy with access to effective antiretroviral therapy. Low, detectable HIV RNA has been studied as a risk factor for adverse health outcomes, but its clinical impact on cancer risk remains unclear. The objective of this study was to determine whether HIV RNA <1,000 copies/mL six months after starting therapy was associated with 10-year first cancer risk. Methods We followed 7,515 HIV therapy initiators from a US-based multicenter clinical cohort from 1998 to 2014. We used nonparametric multiple imputation to account for viral loads that fell below assay detection limits, and categorized viral loads six months after therapy initiation into four groups: <20, 20–199, 200–999, and >999 copies/mL. We calculated estimates of the cumulative incidence of cancer diagnosis, accounting for death as a competing event. Inverse probability of exposure and censoring weights were used to control for confounding and differential loss to follow up, respectively. Results Crude 10-year first cancer risk in the study sample was 7.03% (95% CI: 6.08%, 7.98%), with the highest risk observed among patients with viral loads between 200 and 999 copies/mL six months after ART initiation (10.7%). After controlling for baseline confounders, 10-year first cancer risk was 6.90% (95% CI: 5.69%, 8.12%), and was similar across viral load categories. Conclusion Overall risk of first cancer was not associated with incomplete viral suppression; however, cancer remains a significant threat to HIV patients after treatment initiation. As more HIV patients gain access to treatment in the current “treat all” era, occurrences of incomplete viral suppression will be observed more frequently in clinical practice, which supports continued study of the role of low-level HIV RNA on cancer development.
Resource type:: Article
Affiliation Label Tesim:: Department of Epidemiology and Center for AIDS Research
DOI:: https://doi.org/10.17615/9hbp-jb62
Identifier:: https://dx.doi.org/10.1371/journal.pone.0197665 and PMID 29870537
ISSN:: 1932-6203
Journal Issue:: 6
Journal Title:: PLoS ONE
Journal Volume:: 13
Keyword:: follow up, female, clinical practice, nonhuman, limit of detection, death, human, cancer diagnosis, antiretroviral therapy, cohort analysis, incidence, multicenter study, body weight, virus load, cancer risk, adult, risk assessment, disease course, Human immunodeficiency virus, controlled study, male, and probability
Language Label:: English
License Label:: Attribution 3.0 United States
ORCID:
Other Affiliation:: , Johns Hopkins University, University of California, San Diego, Northwestern University, and Ohio State University
Person:: AIDS Research (CFAR) Network of Integrated Clinical Systems (CNICS), Althoff, K.N., Richardson, D.B., Mathews, C., Eron, J.J., Jr., Cole, S.R., Moore, R.D., Lee, J.S., Achenbach, C.J., Miller, W.C., and Dittmer, D.P.
Publisher:: Public Library of Science
Rights Statement Label:: In Copyright
Source:: br86b875z and joseph_eron_61

1690. Safety, tolerability, and pharmacokinetics of long-acting injectable cabotegravir in low-risk HIV-uninfected individuals: HPTN 077, a phase 2a randomized controlled trial

Title Tesim:: Safety, tolerability, and pharmacokinetics of long-acting injectable cabotegravir in low-risk HIV-uninfected individuals: HPTN 077, a phase 2a randomized controlled trial
Creator:: Burns, D., Tolley, E., Panchia, R., Li, S., Richardson, P., Cohen, M.S., Rinehart, A.R., Grinsztejn, B., Spreen, W.R., Hendrix, C.W., Eshleman, S.H., Landovitz, R.J., Hosseinipour, M.C., Kofron, R., Zhang, Y., Adeyeye, A., Sugarman, J., Marzinke, M.A., Liu, A.Y., Cottle, L., Dawood, H., McCauley, M., Margolis, D., Eron, J.J., Chau, G., and Magnus, M.
Date of publication:: 2018
Abstract Tesim:: Background: Cabotegravir (CAB) is a novel strand-transfer integrase inhibitor being developed for HIV treatment and prevention. CAB is formulated both as an immediate-release oral tablet for daily administration and as a long-acting injectable suspension (long-acting CAB [CAB LA]) for intramuscular (IM) administration, which delivers prolonged plasma exposure to the drug after IM injection. HIV Prevention Trials Network study 077 (HPTN 077) evaluated the safety, tolerability, and pharmacokinetics of CAB LA in HIV-uninfected males and females at 8 sites in Brazil, Malawi, South Africa, and the United States. Methods and findings: HPTN 077 was a double-blind, placebo-controlled phase 2a trial. Healthy individuals age 18–65 years at low HIV risk were randomized (3:1) to receive CAB or placebo (PBO). In the initial oral phase, participants received 1 daily oral tablet (CAB or PBO) for 4 weeks. Those without safety concerns in the oral phase continued and received injections in the injection phase (Cohort 1: 3 injections of CAB LA 800 mg or 0.9% saline as PBO IM every 12 weeks for 3 injection cycles; Cohort 2: CAB LA 600 mg or PBO IM for 5 injection cycles; the first 2 injections in Cohort 2 were separated by 4 weeks, the rest by 8 weeks). The primary analysis included weeks 5 to 41 of study participation, encompassing the injection phase. The cohorts were enrolled sequentially. Primary outcomes were safety and tolerability. Secondary outcomes included pharmacokinetics and events occurring during the oral and injection phases. Between February 9, 2015, and May 27, 2016, the study screened 443 individuals and enrolled 110 participants in Cohort 1 and 89 eligible participants in Cohort 2. Participant population characteristics were as follows: 66% female at birth; median age 31 years; 27% non-Hispanic white, 41% non-Hispanic black, 24% Hispanic/Latino, 3% Asian, and 6% mixed/other; and 6 transgender men and 1 transgender woman. Twenty-two (11%) participants discontinued the oral study product; 6 of these were for clinical or laboratory adverse events (AEs). Of those who received at least 1 CAB LA injection, 80% of Cohort 1 and 92% of Cohort 2 participants completed all injections; injection course completion rates were not different from those in the PBO arm. Injection site reactions (ISRs) were common (92% of Cohort 1 and 88% of Cohort 2 participants who received CAB LA reported any ISR). ISRs were mostly Grade 1 (mild) to Grade 2 (moderate), and 1 ISR event (Cohort 1) led to product discontinuation. Grade 2 or higher ISRs were the only AEs reported more commonly among CAB LA recipients than PBO recipients. Two Grade 3 (severe) ISRs occurred in CAB recipients, 1 in each cohort, but did not lead to product discontinuation in either case. Seven incident sexually transmitted infections were diagnosed in 6 participants. One HIV infection occurred in a participant 48 weeks after last injection of CAB LA: CAB was not detectable in plasma both at the time of first reactive HIV test and at the study visit 12 weeks prior to the first reactive test. Participants in Cohort 2 (unlike Cohort 1) consistently met prespecified pharmacokinetic targets of at least 95% of participants maintaining CAB trough concentrations above PA-IC90, and 80% maintaining trough concentrations above 4× PA-IC90. Study limitations include a modest sample size, a short course of injections, and a low-risk study population. Conclusions: In this study, CAB LA was well tolerated at the doses and dosing intervals used. ISRs were common, but infrequently led to product discontinuation. CAB LA 600 mg every 8 weeks met pharmacokinetic targets for both male and female study participants. The safety and pharmacokinetic results observed support the further development of CAB LA, and efficacy studies of CAB LA for HIV treatment and prevention are in progress. Trial registration: ClinicalTrials.gov Registry: ClinicalTrials.gov Trial number: NCT02178800.
Resource type:: Article
Affiliation Label Tesim:: University of North Carolina at Chapel Hill
DOI:: https://doi.org/10.17615/mnq7-rm09
Identifier:: PMID 30408115 and https://dx.doi.org/10.1371/journal.pmed.1002690
ISSN:: 1549-1277
Journal Issue:: 11
Journal Title:: PLoS Medicine
Journal Volume:: 15
Keyword:: placebo, hemoglobin, cabotegravir, alanine aminotransferase, creatine kinase, aspartate aminotransferase, and creatinine
Language Label:: English
License Label:: CC0 1.0 Universal
ORCID:
Other Affiliation:: National Institutes of Health, FHI360, Chris Hani Baragwanath Hospital, Fred Hutchinson Cancer Research Center, Johns Hopkins University, , ViiV Healthcare, Oswaldo Cruz Foundation, UCLA Center for Clinical AIDS Research and Education, San Francisco Department of Health, University of KwaZulu Natal, and George Washington University
Person:: Burns, D., Tolley, E., Panchia, R., Li, S., Richardson, P., Cohen, M.S., Rinehart, A.R., Grinsztejn, B., Spreen, W.R., Hendrix, C.W., Eshleman, S.H., Landovitz, R.J., Hosseinipour, M.C., Kofron, R., Zhang, Y., Adeyeye, A., Sugarman, J., Marzinke, M.A., Liu, A.Y., Cottle, L., Dawood, H., McCauley, M., Margolis, D., Eron, J.J., Chau, G., and Magnus, M.
Publisher:: Public Library of Science
Rights Statement Label:: In Copyright
Source:: joseph_eron_59 and x920g316p