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Orthopoxvirus-specific T-cell responses were analyzed in 10 patients who had recovered from Mpox including 7 people with human immunodeficiency virus (PWH). Eight participants had detectable virus-specific T-cell responses, including a PWH who was not on antiretroviral therapy and a PWH on immunosuppressive therapy. These 2 participants had robust polyfunctional CD4+ T-cell responses to peptides from the 121L vaccinia virus (VACV) protein. T-cells from 4 of 5 HLA-A2-positive participants targeted at least 1 previously described HLA-A2-restricted VACV epitope, including an epitope targeted in 2 participants. These results advance our understanding of immunity in convalescent Mpox patients., 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. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Hospital readmission trends for persons with human immunodeficiency virus (PWH) in North America in the context of policy changes, improved antiretroviral therapy (ART), and aging are not well-known. We examined readmissions during 2005-2018 among adult PWH in NA-ACCORD., Methods: Linear risk regression estimated calendar trends in 30-day readmissions, adjusted for demographics, CD4 count, AIDS history, virologic suppression (<400 copies/mL), and cohort., Results: We examined 20 189 hospitalizations among 8823 PWH (73% cisgender men, 38% White, 38% Black). PWH hospitalized in 2018 versus 2005 had higher median age (54 vs 44 years), CD4 count (469 vs 274 cells/μL), and virologic suppression (83% vs 49%). Unadjusted 30-day readmissions decreased from 20.1% (95% confidence interval [CI], 17.9%-22.3%) in 2005 to 16.3% (95% CI, 14.1%-18.5%) in 2018. Absolute annual trends were -0.34% (95% CI, -.48% to -.19%) in unadjusted and -0.19% (95% CI, -.35% to -.02%) in adjusted analyses. By index hospitalization reason, there were significant adjusted decreases only for cardiovascular and psychiatric hospitalizations. Readmission reason was most frequently in the same diagnostic category as the index hospitalization., Conclusions: Readmissions decreased over 2005-2018 but remained higher than the general population's. Significant decreases after adjusting for CD4 count and virologic suppression suggest that factors alongside improved ART contributed to lower readmissions. Efforts are needed to further prevent readmissions in PWH., Competing Interests: Potential conflicts of interest. K. N. A. reports grants to their institution from NIH; royalties or licenses from Coursera; and consulting fees from NIH and TrioHealth. R. J. B. reports grants to their institution from NIH and support for travel from NIH. J. A. C. reports grants to their institution from NIH and payment or honoraria from Prime Education and Integritas Communications. H. M. C. reports grants to their institution from AHRQ, NIH, and ViiV Healthcare; and participation in a data and safety monitoring board (DSMB) or advisory board for Gilead Sciences, NIH Office of AIDS Research, and ViiV Healthcare. J. J. E. reports grants to their institution from NIH, ViiV Healthcare, Gilead Sciences, and Janssen; consulting fees from ViiV Healthcare, Gilead Sciences, and Merck & Co; and participation on a DSMB or advisory board for TAIMED. K. A. G. reports grants to their institution from the US Department of Defense, NIH, Mental Wellness Foundation, HealthNetwork Foundation, Bloomberg Philanthropies, Defense Health Agency, the State of Maryland, Octapharma, Moriah Fund, and National Center for Advancing Translational Sciences; consulting fees from Spark HealthCare, Teach for America, and Aspen Institute; and participation on a DSMB or advisory board for Pfizer. M. J. G. reports grants to their institution from NIH; and participation on a DSMB or advisor board for Merck & Co, Gilead Sciences, and ViiV Healthcare. B. C. H. reports grants to their institution from NIH. M. A. H. reports grants to their institution from NIH. M. Y. K. reports grants to their institution from Gilead Sciences and ViiV Healthcare; payment or honoraria to their institution from Practice Point Communications CME; leadership in the AIDS Clinical Trials Group (ACTG) Underrepresented Populations Committee (Vice Chair) with payments to their institution; and uncompensated leadership on the Being Alive San Diego Board (member). M. B. K. reports grants to their institution from NIH, ViiV Healthcare, AbbVie, and Gilead Sciences; and consulting fees from ViiV Healthcare, AbbVie, and Gilead Sciences. R. L. reports support for travel from CIHR. V. D. L. reports grants to their institution from CIHR; payment or honoraria from ViiV Healthcare; support for travel from the Conference on Retroviruses and Opportunistic Infections; and participation on a DSMB or advisory board for the Providence Health Care Ethics Board. R. D. M. reports grants to their institution from NIH. S. N. reports grants to their institution from NIH. A. N. reports grants to their institution from Gilead Sciences. P. F. R. reports grants to their institution from NIH and consulting fees from Gilead Sciences and Janssen. J. E. T. reports grants to their institution from the National Eye Institute and ACTG; consulting fees from Gilead Sciences, Canfield, and UpToDate; participation on a DSMB or advisory board for NEI and Tarsier; stock or stock options in Tarsier; and fees for serving as Editor-in-Chief for Ocular Immunology and Inflammation. 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) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Coronavirus disease 2019 (COVID-19) convalescent plasma (CCP) use between October and December 2020 was characterized using the National Inpatient Sample database. CCP was administered in 18.0% of COVID-19-associated hospitalizations and was strongly associated with older age and increased disease severity. There were disparities in the receipt of CCP by race and ethnicity, geography, and insurance., Competing Interests: Potential conflicts of interest. E. M. B. reports personal fees and non-financial support from Tegus and UptoDate, outside of the submitted work. E. M. B. also reports that his time is funded in part by NHLBI through grant number 1K23HL151826 and reports consulting fees from the California Institute for Regenerative Medicine as an advisor convalescent plasma program. E. M. B. also served as an unpaid invited member for a Data Safety Monitoring Board for the following trial: “Assessment of safety and efficacy of COVID-19 Convalescent Plasma for treatment of COVID-19 in adults in Uganda: A Phase III randomized controlled trial” and is a member of the FDA Blood Products Advisory Committee. R. G. works as a consultant for NHLBI led REDS-IV-P studies and serves on the medical advisory board of Rigel pharmaceuticals. K. G. receives support from UptoDate, Teach for America and the Aspen Institute. K. G. also reports grants or contracts from Octapharma, US Department of Defense's Joint Program Executive Office for Chemical, Biological, Radiological and Nuclear Defense, Defense Health Agency (grant number W911QY2090012), National Institutes of Health (NIH) National Institute of Allergy and Infectious Diseases (grant number 3R01AI152078-01S1), State of Maryland, NIH National Center for Advancing Translational Sciences (grant numbers U24TR001609-S3 and UL1TR00309), Mental Wellness Foundation, HealthNetwork Foundation, Bloomberg Philanthropies, Moriah Fund, and NCATS grant number KL2TR0030099; consulting fees to author from Spark Healthcare; participation as unpaid advisor on Data Safety Monitoring Board or Advisory Board for Pfizer. A. A. R. T. reports personal fees from Ortho Clinical Diagnostics, Ashland Global and royalties or licenses from UptoDate, outside of the submitted work. E. M. B. is a member of the United States Food and Drug Administration (FDA) Blood Products Advisory Committee. A. C. reports a role as Chair of the COVID-19 Convalescent Plasma Project ccpp19.org. S. S. reports grants or contracts from F2G, Cidara, Ansun, Zeteo, Emergent Biosolutions; consulting fees from Celltrion, Adagio, Immunome; participation on DSMB or AB for Adamis, Karyopharm, and Intermountain Health; and stock or stock options from Immunome. D. J. S. reports grants or contracts from US Department of Defense's (DOD) Joint Program Executive Office for Chemical, Biological, Radiological and Nuclear Defense (JPEO-CBRND), in collaboration with the Defense Health Agency (DHA) (contract number W911QY2090012), US Department of Defense's (DOD) Joint Program Executive Office for Chemical, Biological, Radiological, and Nuclear Defense (contract number JPEO-CBRND), in collaboration with the Defense Health Agency (DHA) (contract number: W911QY2090012), Bloomberg Philanthropies, State of Maryland, Mental Wellness Foundation, Octapharma, Shear Family Foundation, NIH/NIAID contract number R01AI150763 Dual artemisinin action combats resistance, NIH contract number R21TR001737 Quantum model repurposing of cethromycin for liver stage malaria, NIH contract number R01AI111962 Optimized Combination Antimalarial Drug Therapy, DoD TB210115 A Pharmacokinetic and Pharmacodynamic Immunocompromised Mouse Model of the Human Tick-Borne Disease Babesia microti; royalties or licenses from Binax Inc/D/B/A Inverness Medical for plasmids for HRP aldolase for malaria diagnostic test; consulting fees for Hemozoin based malaria diagnostic Hemex Health 2018; a role as AliquantumRx Founder and Board member (macrolide for malaria), stock or stock options from AliquantumRx; and the following patents: Issued-USP 9,642,865 9 May 2017 New angiogenesis inhibitors, Issued-USP 9,568,471 14 February 2017 Malaria Diagnosis in Urine, Issued-USP 7,270,948 18 September 2007 Detection of malaria parasites by laser desorption mass spectrometry, Pending SALTS AND POLYMORPHS OF CETHROMYCIN FOR THE TREATMENT OF DISEASE Patent application (application number 20210163522), Pending- Macrolide compounds and their use in liver stage malaria and related disease application number PCT/US2015/046665. Any views or opinions that are expressed in this manuscript are those of the author's, based on his own scientific expertise and professional judgment; they do not necessarily represent the views of either the Blood Products Advisory Committee or the formal position of FDA, and do not bind or otherwise obligate or commit either Advisory Committee or the Agency to the views expressed. 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) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Coronavirus disease 2019 (COVID-19) convalescent plasma (CCP) is a safe and effective treatment for COVID-19 in immunocompromised (IC) patients. IC patients have a higher risk of persistent infection, severe disease, and death from COVID-19. Despite the continued clinical use of CCP to treat IC patients, the optimal dose, frequency/schedule, and duration of CCP treatment has yet to be determined, and related best practices guidelines are lacking. A group of individuals with expertise spanning infectious diseases, virology and transfusion medicine was assembled to render an expert opinion statement pertaining to the use of CCP for IC patients. For optimal effect, CCP should be recently and locally collected to match circulating variant. CCP should be considered for the treatment of IC patients with acute and protracted COVID-19; dosage depends on clinical setting (acute vs protracted COVID-19). CCP containing high-titer severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies, retains activity against circulating SARS-CoV-2 variants, which have otherwise rendered monoclonal antibodies ineffective., Competing Interests: Potential conflicts of interest. E. M. B. reports personal fees and non-financial support from Terumo BCT, Abbott Laboratories, Tegus and UptoDate, outside of the submitted work. K. G. receives support from UptoDate, Teach for America and the Aspen Institute. E. M. B. is a member of the US Food and Drug Administration (FDA) Blood Products Advisory Committee. Any views or opinions that are expressed in this manuscript are those of the author's, based on his own scientific expertise and professional judgment; they do not necessarily represent the views of either the Blood Products Advisory Committee or the formal position of FDA, and do not bind or otherwise obligate or commit either Advisory Committee or the Agency to the views expressed. E. M. B. also reports that his time is funded in part by NHLBI through grant number 1K23HL151826; receives royalties for an article on convalescent plasma from UpToDate; consulting fees from California Institute for Regenerative Medicine as an advisor on convalescent plasma program; and served as an unpaid, invited member for a Data Safety Monitoring Board for the following trial: “Assessment of safety and efficacy of COVID-19 Convalescent Plasma for treatment of COVID-19 in adults in Uganda: A Phase III randomized controlled trial.” A. C. reports grants or contracts with the NIH, unrelated to this work; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Pfizer, Bristo-Myers Squibb, Ortho Diagnostics; participation on a Data Safety Monitoring Board or Advisory Board for Bristo-Myers Squibb and SAB Therapeutics; a leadership or fiduciary role on COVID-19 Convalescent Plasma Project; and stock or stock options from SAB Therapeutics. R. K. A. reports study grant support paid to institution from Aicuris, Astellas, Chimerix, Merck, Oxford Immunotec, Qiagen, Regeneron, Takeda/Shire. M. J. J. reports grants or contracts from BARDA UL1TR002377, Octapharma, NBA, Millennium Pharma, United Health Group, Mayo Clinic; consulting fees from California Regenerative Medicine City of Hope. K. G. reports grants or contracts unrelated to this work made to institution (grant number NCATS KL2TR0030099); royalties or licenses as an Uptodate author; consulting fees to author from Aspen Institute, Teach for America, and Spark Healthcare; participation on a Data Safety Monitoring Board or Advisory Board as an unpaid advisor to Pfizer to increase access to Paxlovid. R. R. R. reports funds to institution from Roche, Regeneron, and Gilead; consulting fees from Roche and Merck; participation on a Data Safety Monitoring Board or Advisory Board for Novartis and Allovir; and a role as Board member of American Society of Transplantation. E. M. B. reports that his time is funded in part by NHLBI through grant number 1K23HL151826; receives royalties for an article on convalescent plasma from UpToDate; consulting fees from California Institute for Regenerative Medicine as an advisor on convalescent plasma program; and served as an unpaid, invited member for a Data Safety Monitoring Board for the following trial: “Assessment of safety and efficacy of COVID-19 Convalescent Plasma for treatment of COVID-19 in adults in Uganda: A Phase III randomized controlled trial.” S. S. reports grants or contracts made to institution from US Department of Defense (Joint Program Executive Office for Chemical, Biological, Radiological and Nuclear Defense), Defense Health Agency, Shionogi, Shire, Ansun, Cidara, Zeteo Tech Inc, F2G, Emergent Biosolutions, Bloomberg Philanthropies, the State of Maryland, NIH National Center for Advancing Translational Sciences, Mental Wellness Foundation, Moriah Fund, Octopharma, Shear Family Foundation, HealthNetwork Foundation, Mayo Clinic, University of Nebraska; consulting fees made directly to author from Immunome, Adagio Therapeutics, Celltrion Healthcare, Karius; payment or honoraria to author for lectures, presentations, speakers bureaus, manuscript writing, or educational events from Prime Inc and Peerview; travel support from Peerview for American Transplant Congress 2022, from NCCN for NCCN Guideline meeting, and from ACP for ACP board of governors meeting; paid participation on a Data Safety Monitoring Board or Advisory Board for Intermountain Health, Karyopharm, Adamis Health; a role on guideline panels for NCCN, IDSA, MSG/EORTC, on RSV vaccine workgroup for ACIP/CDC, as Governor of Washington D.C. Chapter of ACP, and as member of Board of Governors of ACP; stock or stock options from Immunome. L. R. B. reports grants to institution from NIH/Harvard Medical School, Wellcome Trust, Bill and Melinda Gates Foundation; participation on DSMB for NIH and AMDAC for FDA; and is involved in HIV and SARS-CoV-2 vaccine clinical trials conducted in collaboration with the NIH, HIV Vaccine Trials Network (HVTN), COVID Vaccine Prevention Network (CoVPN), International AIDS Vaccine Initiative (IAVI), Crucell/Janssen, Moderna, Military HIV Research Program (MHRP), the Bill and Melinda Gates Foundation, and Harvard Medical School. P. T. reports Horizon 2020 EU Grant SUPPORT-e to institution; unpaid role as President, European Blood Alliance (association of not-for-profit blood establishments in Europe); and employment by the Etablissement Français du Sang (French transfusion public service in charge of collecting, manufacturing; testing and issuing blood components in France). D. S. reports grants or contracts from US Department of Defense's (DOD) Joint Program Executive Office for Chemical, Biological, Radiological and Nuclear Defense (JPEO-CBRND), in collaboration with the Defense Health Agency (DHA) (contract number W911QY2090012), National Institutes of Health (NIH), National Institute of Allergy and Infectious Diseases (NIAID) 3R01AI152078-01S1, Bloomberg Philanthropies, NIH National Center for Advancing Translational Sciences (NCATS) U24TR001609, State of Maryland, Division of Intramural Research NIAID NIH, Mental Wellness Foundation, HealthNetwork Foundation, Octapharma, ZonMw, the Netherlands (10430062010001), Shear Family Foundation, Sanquin Blood Supply, Fight AIDS and Infectious Diseases Foundation (Badalona, Spain), Grifols Worldwide Operations (Dublin, Ireland), Crowdfunding campaign, YoMeCorono, Hospital Universitari Germans Trias i Pujol, Banc de Sang i Teixits de Catalunya, Bill and Melinda Gates Foundation, Fundación INFANT Pandemic Fund, National Heart, Lung, and Blood Institute (NHLBI) (grant numbers 1OT2HL156812-01, U24NS100659, and U24NS100655), National Institute of Neurological Disorders and Stroke of the National Institutes of Health, NIH/NIAID R01AI150763 Dual artemisinin action combats resistance, NIH R21TR001737 Quantum model repurposing of cethromycin for liver stage malaria, NIH R01AI111962 Optimized Combination Antimalarial Drug Therapy, DoD TB210115. CDMRP Tick-Borne Disease Research Program. A Pharmacokinetic and Pharmacodynamic Immunocompromised Mouse Model of the Human Tick-Borne Disease Babesia microti; royalties or licenses from Binax Inc/D/B/A Inverness Medical for plasmids for HRP aldolase for malaria diagnostic test; the following patents: Issued-USP 9,642,865 9 May 2017 New angiogenesis inhibitors, Issued-USP 9,568,471 14 February 2017 Malaria Diagnosis in Urine, Issued-USP 7,270,948 18 September 2007 Detection of malaria parasites by laser desorption mass spectrometry, Pending SALTS AND POLYMORPHS OF CETHROMYCIN FOR THE TREATMENT OF DISEASE Patent Application (Application number 20210163522), Pending- Macrolide compounds and their use in liver stage malaria and related disease Application PCT/US2015/046665, and participation on 2018 NIAID SMC/ISM Intramural; role as AliquantumRx Founder and Board member (macrolide for malaria). C. C. reports institutional payment from 1 NIH: PassItOn A trial of COVID convalescent plasma (Project Dates: 9/2020–10/2020); payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from Terumo; support for attending meetings and/or travel from Department of Lab Medicine and Pathology, University of Minnesota, Association for the Advancement of Blood and Biotherapies (AABB), and Biomedical Excellence for Safer Transfusion (BEST collaborative); participation on OrthoClinical Diagnostics Advisory Board; role as Chief Medical Officer, Association for the Advancement of Blood and Biotherapies (AABB) (salaried part time employee). V. D. reports grants or contracts to institution from AlloVir and Regeneron; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Invivyd to author. J. P. H. reports participation on Scientific Advisory Board for Immunome, Inc, regarding development of COVID-19 monoclonal antibodies, role on leadership group, unpaid, for the National Convalescent Plasma Project Advocacy Group; and stock options for Immunome, Inc, related to participation on scientific advisory board. C. S. O. reports unpaid roles as Regional Director for ISBT and Chair ISBT convalescent working group. 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) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

In response to the rapidly evolving coronavirus disease 2019 (COVID-19) pandemic, the All of Us Research Program longitudinal cohort study developed the COVID-19 Participant Experience (COPE) survey to better understand the pandemic experiences and health impacts of COVID-19 on diverse populations within the United States. Six survey versions were deployed between May 2020 and March 2021, covering mental health, loneliness, activity, substance use, and discrimination, as well as COVID-19 symptoms, testing, treatment, and vaccination. A total of 104,910 All of Us Research Program participants, of whom over 73% were from communities traditionally underrepresented in biomedical research, completed 275,201 surveys; 9,693 completed all 6 surveys. Response rates varied widely among demographic groups and were lower among participants from certain racial and ethnic minority populations, participants with low income or educational attainment, and participants with a Spanish language preference. Survey modifications improved participant response rates between the first and last surveys (13.9% to 16.1%, P < 0.001). This paper describes a data set with longitudinal COVID-19 survey data in a large, diverse population that will enable researchers to address important questions related to the pandemic, a data set that is of additional scientific value when combined with the program's other data sources., (© Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health 2023. This work is written by (a) US Government employee(s) and is in the public domain in the US.)

Background: Coronavirus disease 2019 (COVID-19) convalescent plasma (CCP) reduces hospitalizations among outpatients treated early after symptom onset. It is unknown whether CCP reduces time to symptom resolution among outpatients., Methods: We evaluated symptom resolution at day 14 by trial arm using an adjusted subdistribution hazard model, with hospitalization as a competing risk. We also assessed the prevalence of symptom clusters at day 14 between treatments. Clusters were defined based on biologic clustering, impact on ability to work, and an algorithm., Results: Among 1070 outpatients followed up after transfusion, 381 of 538 (70.8%) receiving CCP and 381 of 532 (71.6%) receiving control plasma were still symptomatic (P = .78) at day 14. Associations between CCP and symptom resolution by day 14 did not differ significantly from those in controls after adjustment for baseline characteristics (adjusted subdistribution hazard ratio, 0.99; P = .62). The most common cluster consisted of cough, fatigue, shortness of breath, and headache and was found in 308 (57.2%) and 325 (61.1%) of CCP and control plasma recipients, respectively (P = .16)., Conclusions: In this trial of outpatients with early COVID-19, CCP was not associated with faster resolution of symptoms compared with control. Overall, there were no differences by treatment in the prevalence of each symptom or symptom clusters at day 14., Clinical Trials Registration: NCT04373460., Competing Interests: Potential conflicts of interest. E. M. B. is a member of the Food and Drug Administration's Blood Products Advisory Committee. (All opinions in this manuscript are of the authors and do not reflect the Blood Products Advisory Committee or the position of the Food and Drug Administration; this arrangement has been reviewed and approved by Johns Hopkins University in accordance with its conflict-of-interest policies.) A. C. serves on the Scientific Advisory Board of Sabtherapeutics, which is developing cow-derived human immunoglobulins for the treatment of coronavirus disease 2019 and other infectious diseases. K. A. G. is a paid consultant for UpToDate, Teach for America, and the Aspen Institute. 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) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Background: People with human immunodeficiency virus (HIV) (PWH) may be at increased risk for severe coronavirus disease 2019 (COVID-19) outcomes. We examined HIV status and COVID-19 severity, and whether tenofovir, used by PWH for HIV treatment and people without HIV (PWoH) for HIV prevention, was associated with protection., Methods: Within 6 cohorts of PWH and PWoH in the United States, we compared the 90-day risk of any hospitalization, COVID-19 hospitalization, and mechanical ventilation or death by HIV status and by prior exposure to tenofovir, among those with severe acute respiratory syndrome coronavirus 2 infection between 1 March and 30 November 2020. Adjusted risk ratios (aRRs) were estimated by targeted maximum likelihood estimation, with adjustment for demographics, cohort, smoking, body mass index, Charlson comorbidity index, calendar period of first infection, and CD4 cell counts and HIV RNA levels (in PWH only)., Results: Among PWH (n = 1785), 15% were hospitalized for COVID-19 and 5% received mechanical ventilation or died, compared with 6% and 2%, respectively, for PWoH (n = 189 351). Outcome prevalence was lower for PWH and PWoH with prior tenofovir use. In adjusted analyses, PWH were at increased risk compared with PWoH for any hospitalization (aRR, 1.31 [95% confidence interval, 1.20-1.44]), COVID-19 hospitalizations (1.29 [1.15-1.45]), and mechanical ventilation or death (1.51 [1.19-1.92]). Prior tenofovir use was associated with reduced hospitalizations among PWH (aRR, 0.85 [95% confidence interval, .73-.99]) and PWoH (0.71 [.62-.81])., Conclusions: Before COVID-19 vaccine availability, PWH were at greater risk for severe outcomes than PWoH. Tenofovir was associated with a significant reduction in clinical events for both PWH and PWoH., Competing Interests: Potential conflicts of interest. V. C. M. has received investigator-initiated research grants (to the institution) and consultation fees, both unrelated to the current work, from Eli Lilly, Bayer, Gilead Sciences, and ViiV; research grants from the NIH, the Centers for Disease Control and Prevention, and the Department of Veterans Affairs; payment or honoraria for speaking from Medscape/WebMD/ViiV; and writing honoraria from Integritas and Lilly. V. C. M. also reports participation on a data and safety monitoring board study section for the NIH. K. N. A. has received investigator-initiated research grants from the NIH (to the institution) and consultation fees (both unrelated to the current work) from the All of Us Research Program (NIH; payment to the author), TrioHealth (payment to the author as advisory board member), and Kennedy Dundas; K. N. A. also reports royalties or licenses from Coursera as the director of a 5-course specialization (payment to the author and institution). K. A. G. has received consulting fees, unrelated to the current work, from Teach for America, the Aspen Institute, and UptoDate. K. A. G. also reports grants to the institution from Octapharma, the US Department of Defense's Joint Program Executive Office for Chemical, Biological, Radiological and Nuclear Defense, the National Institute of Allergy and Infectious Diseases, NIH (grant 3R01AI152078-01S1), the NIH National Center for Advancing Translational Sciences (grants U24TR001609-S3 and UL1TR00309), the Mental Wellness Foundation, HealthNetwork Foundation, Bloomberg Philanthropies, Moriah Fund, the Shear Family Foundation, the State of Maryland, and the Defense Health Agency (grant W911QY2090012); royalties or licenses to the author from UpToDate; consulting fees to the author from Spark Healthcare, Aspen Institute, and Teach for America; and unpaid consultation to Pfizer for Scientific Advisory Board. R. L. reports grants or contracts paid to the institution from University of Calgary. 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) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Competing Interests: Potential conflicts of interest. K. N. A. reports grants or contracts from the National Institutes of Health (NIH) and consulting fees paid to the author from TrioHealth for serving on the Scientific Advisory Board. K. A. G. initiated this work during her role as the Chief Medical and Scientific Officer of the All of Us Research Program. K. A. G. also reports grants or contracts paid to their institution from Octapharma, US Department of Defense's Joint Program Executive Office for Chemical, Biological, Radiological and Nuclear Defense; NIH National Institute of Allergy and Infectious Diseases (3R01AI152078-01S1); NIH National Center for Advancing Translational Sciences (U24TR001609-S3 and UL1TR00309); Mental Wellness Foundation; HealthNetwork Foundation; Bloomberg Philanthropies; Moriah Fund; Shear Family Foundation; and the State of Maryland Defense Health Agency (W911QY2090012). Additional royalties or licenses from UptoDate were paid directly to K. A. G., and additional consulting fees were paid directly to K. A. G. from Spark HealthCare, Teach for America, and Aspen Institute. K. A. G. serves as an uncompensated participant of Pfizer's Scientific Advisory Board. S. D. S. reports 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.

Background: Men who have sex with men (MSM) on antiretroviral therapy (ART) are at risk for multimorbidity as life expectancy increases. Simulation models can project population sizes and age distributions to assist with health policy planning., Methods: We populated the CEPAC-US model with CDC data to project the HIV epidemic among MSM in the United States. The PEARL model was predominantly informed by NA-ACCORD data (20092017). We compared projected population sizes and age distributions of MSM receiving ART (20212031) and investigated how parameters and assumptions affected results., Results: We projected an aging and increasing population of MSM on ART: CEPAC-US, mean age 48.6 (SD 13.7) years in 2021 versus 53.9 (SD 15.0) years in 2031; PEARL, 46.7 (SD 13.2) years versus 49.2 (SD 14.6) years. We projected 548 800 MSM on ART (147 020 65 years) in 2031 (CEPAC-US) and 599 410 (113 400 65 years) (PEARL). Compared with PEARL, CEPAC-US projected a smaller population of MSM on ART by 2031 and a slower increase in population size, driven by higher estimates of disengagement in care and mortality., Conclusions: Findings from two structurally distinct microsimulation models suggest that the MSM population receiving ART in the United States will increase and age over the next decade. Subgroup-specific data regarding engagement in care and mortality can improve projections and inform health care policy planning., (The Author(s) 2022. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: The updated Veterans Aging Cohort Study (VACS) Index 2.0 combines general and human immunodeficiency virus (HIV)-specific biomarkers to generate a continuous score that accurately discriminates risk of mortality in diverse cohorts of persons with HIV (PWH), but a score alone is difficult to interpret. Using data from the North American AIDS Cohort Collaboration (NA-ACCORD), we translate VACS Index 2.0 scores into validated probability estimates of mortality., Methods: Because complete mortality ascertainment is essential for accurate calibration, we restricted analyses to cohorts with mortality from the National Death Index or equivalent sources. VACS Index 2.0 components were ascertained from October 1999 to April 2018. Mortality was observed up to March 2019. Calibration curves compared predicted (estimated by fitting a gamma model to the score) to observed mortality overall and within subgroups: cohort (VACS/NA-ACCORD subset), sex, age <50 or ≥50 years, race/ethnicity, HIV-1 RNA ≤500 or >500 copies/mL, CD4 count <350 or ≥350 cells/µL, and years 1999-2009 or 2010-2018. Because mortality rates have decreased over time, the final model was limited to 2010-2018., Results: Among 37230 PWH in VACS and 8061 PWH in the NA-ACCORD subset, median age was 53 and 44 years; 3% and 19% were women; and 48% and 39% were black. Discrimination in NA-ACCORD (C-statistic = 0.842 [95% confidence interval {CI}, .830-.854]) was better than in VACS (C-statistic = 0.813 [95% CI, .809-.817]). Predicted and observed mortality largely overlapped in VACS and the NA-ACCORD subset, overall and within subgroups., Conclusions: Based on this validation, VACS Index 2.0 can reliably estimate probability of all-cause mortality, at various follow-up times, among PWH in North America., Competing Interests: Potential conflicts of interest. K. N. A. reports receiving fees as a consultant from the All of Us Research Program (NIH) and received fees as a scientific advisory board member from Trio Health. M. K. reports grants or contracts from Gilead Sciences and ViiV Healthcare outside the submitted work; payment or honoraria for lectures, presentations, speaker’s bureaus, manuscript writing, or educational events from ViiV Healthcare for Medscape, APLA Health for DKBMed, and SAGE; and a leadership or fiduciary role for Being Alive San Diego. H. M. C. reports grants or contracts from AHRQ and ViiV paid to her institution outside the submitted work, and participation on the NIH Office of AIDS Research Advisory Board. M. J. S. reports a past grant paid to his institution from Gilead Sciences outside the submitted work. V. D. L. has received a grant from the CIHR, unrelated to this work. 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., (Published by Oxford University Press for the Infectious Diseases Society of America 2021.)

Background: With limited severe acute respiratory syndrome coronavirus (SARS-CoV-2) testing capacity in the United States at the start of the epidemic (January-March 2020), testing was focused on symptomatic patients with a travel history throughout February, obscuring the picture of SARS-CoV-2 seeding and community transmission. We sought to identify individuals with SARS-CoV-2 antibodies in the early weeks of the US epidemic., Methods: All of Us study participants in all 50 US states provided blood specimens during study visits from 2 January to 18 March 2020. Participants were considered seropositive if they tested positive for SARS-CoV-2 immunoglobulin G (IgG) antibodies with the Abbott Architect SARS-CoV-2 IgG enzyme-linked immunosorbent assay (ELISA) and the EUROIMMUN SARS-CoV-2 ELISA in a sequential testing algorithm. The sensitivity and specificity of these ELISAs and the net sensitivity and specificity of the sequential testing algorithm were estimated, along with 95% confidence intervals (CIs)., Results: The estimated sensitivities of the Abbott and EUROIMMUN assays were 100% (107 of 107 [95% CI: 96.6%-100%]) and 90.7% (97 of 107 [83.5%-95.4%]), respectively, and the estimated specificities were 99.5% (995 of 1000 [98.8%-99.8%]) and 99.7% (997 of 1000 [99.1%-99.9%]), respectively. The net sensitivity and specificity of our sequential testing algorithm were 90.7% (97 of 107 [95% CI: 83.5%-95.4%]) and 100.0% (1000 of 1000 [99.6%-100%]), respectively. Of the 24 079 study participants with blood specimens from 2 January to 18 March 2020, 9 were seropositive, 7 before the first confirmed case in the states of Illinois, Massachusetts, Wisconsin, Pennsylvania, and Mississippi., Conclusions: Our findings identified SARS-CoV-2 infections weeks before the first recognized cases in 5 US states., (Published by Oxford University Press for the Infectious Diseases Society of America 2021.)

Background: Persons with human immunodeficiency virus (PWH) with persistently low CD4 counts despite efficacious antiretroviral therapy could have higher hospitalization risk., Methods: In 6 US and Canadian clinical cohorts, PWH with virologic suppression for ≥1 year in 2005-2015 were followed until virologic failure, loss to follow-up, death, or study end. Stratified by early (years 2-5) and long-term (years 6-11) suppression and lowest presuppression CD4 count <200 and ≥200 cells/µL, Poisson regression models estimated hospitalization incidence rate ratios (aIRRs) comparing patients by time-updated CD4 count category, adjusted for cohort, age, gender, calendar year, suppression duration, and lowest presuppression CD4 count., Results: The 6997 included patients (19 980 person-years) were 81% cisgender men and 40% white. Among patients with lowest presuppression CD4 count <200 cells/μL (44%), patients with current CD4 count 200-350 vs >500 cells/μL had aIRRs of 1.44 during early suppression (95% confidence interval [CI], 1.01-2.06), and 1.67 (95% CI, 1.03-2.72) during long-term suppression. Among patients with lowest presuppression CD4 count ≥200 (56%), patients with current CD4 351-500 vs >500 cells/μL had an aIRR of 1.22 (95% CI, .93-1.60) during early suppression and 2.09 (95% CI, 1.18-3.70) during long-term suppression., Conclusions: Virologically suppressed patients with lower CD4 counts experienced higher hospitalization rates and could potentially benefit from targeted clinical management strategies., (© The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Background: To assess the possible impact of antiretroviral therapy improvements, aging, and comorbidities, we examined trends in all-cause and cause-specific hospitalization rates among persons with HIV (PWH) from 2005 to 2015., Methods: In 6 clinical cohorts, we followed PWH in care (≥1 outpatient CD4 count or HIV load [VL] every 12 months) and categorized ICD codes of primary discharge diagnoses using modified Clinical Classifications Software. Poisson regression estimated hospitalization rate ratios for calendar time trends, adjusted for demographics, HIV risk factor, and annually updated age, CD4, and VL., Results: Among 28 057 patients (125 724 person-years), from 2005 to 2015, the median CD4 increased from 389 to 580 cells/µL and virologic suppression from 55% to 85% of patients. Unadjusted all-cause hospitalization rates decreased from 22.3 per 100 person-years in 2005 (95% confidence interval [CI], 20.6-24.1) to 13.0 in 2015 (95% CI, 12.2-14.0). Unadjusted rates decreased for almost all diagnostic categories. Adjusted rates decreased for all-cause, cardiovascular, and AIDS-defining conditions, increased for non-AIDS-defining infection, and were stable for most other categories., Conclusions: Among PWH with increasing CD4 counts and viral suppression, unadjusted hospitalization rates decreased for all-cause and most cause-specific hospitalizations, despite the potential effects of aging, comorbidities, and cumulative exposure to HIV and antiretrovirals., (Published by Oxford University Press for the Infectious Diseases Society of America 2020.)

Background: Persons who inject drugs (PWID) are at a disproportionately high risk of HIV infection. We aimed to determine the highest-valued combination implementation strategies to reduce the burden of HIV among PWID in 6 US cities., Methods: Using a dynamic HIV transmission model calibrated for Atlanta, Baltimore, Los Angeles, Miami, New York City, and Seattle, we assessed the value of implementing combinations of evidence-based interventions at optimistic (drawn from best available evidence) or ideal (90% coverage) scale-up. We estimated reduction in HIV incidence among PWID, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratios (ICERs) for each city (10-year implementation; 20-year horizon; 2018 $ US)., Results: Combinations that maximized health benefits contained between 6 (Atlanta and Seattle) and 12 (Miami) interventions with ICER values ranging from $94 069/QALY in Los Angeles to $146 256/QALY in Miami. These strategies reduced HIV incidence by 8.1% (credible interval [CI], 2.8%-13.2%) in Seattle and 54.4% (CI, 37.6%-73.9%) in Miami. Incidence reduction reached 16.1%-75.5% at ideal scale., Conclusions: Evidence-based interventions targeted to PWID can deliver considerable value; however, ending the HIV epidemic among PWID will require innovative implementation strategies and supporting programs to reduce social and structural barriers to care., (© The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Among 1942 persons with human immunodeficiency virus (HIV) without healthcare coverage in 2012-2015, transitioning to Medicaid (adjusted prevalence ratio, 0.95 [0.87, 1.04]) or to private health insurance (1.04 [0.95, 1.13]) was not associated with a change in consistent HIV viral suppression compared to continued reliance on the Ryan White HIV/AIDS Program., (© The Author(s) 2018. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Background: Age-associated conditions are increasingly common among persons living with human immunodeficiency virus (HIV) (PLWH). A longitudinal investigation of their accrual is needed given their implications on clinical care complexity. We examined trends in the co-occurrence of age-associated conditions among PLWH receiving clinical care, and differences in their prevalence by demographic subgroup., Methods: This cohort study was nested within the North American AIDS Cohort Collaboration on Research and Design. Participants from HIV outpatient clinics were antiretroviral therapy-exposed PLWH receiving clinical care (ie, ≥1 CD4 count) in the United States during 2000-2009. Multimorbidity was irreversible, defined as having ≥2: hypertension, diabetes mellitus, chronic kidney disease, hypercholesterolemia, end-stage liver disease, or non-AIDS-related cancer. Adjusted prevalence ratios (aPR) and 95% confidence intervals (CIs) comparing demographic subgroups were obtained by Poisson regression with robust error variance, using generalized estimating equations for repeated measures., Results: Among 22969 adults, 79% were male, 36% were black, and the median baseline age was 40 years (interquartile range, 34-46 years). Between 2000 and 2009, multimorbidity prevalence increased from 8.2% to 22.4% (Ptrend < .001). Adjusting for age, this trend was still significant (P < .001). There was no difference by sex, but blacks were less likely than whites to have multimorbidity (aPR, 0.87; 95% CI, .77-.99). Multimorbidity was the highest among heterosexuals, relative to men who have sex with men (aPR, 1.16; 95% CI, 1.01-1.34). Hypertension and hypercholesterolemia most commonly co-occurred., Conclusions: Multimorbidity prevalence has increased among PLWH. Comorbidity prevention and multisubspecialty management of increasingly complex healthcare needs will be vital to ensuring that they receive needed care.

Background: Before implementation of the Patient Protection and Affordable Care Act (ACA) in 2014, 100 000 persons living with human immunodeficiency virus (HIV) (PLWH) lacked healthcare coverage and relied on a safety net of Ryan White HIV/AIDS Program support, local charities, or uncompensated care (RWHAP/Uncomp) to cover visits to HIV providers. We compared HIV provider coverage before (2011-2013) versus after (first half of 2014) ACA implementation among a total of 28 374 PLWH followed up in 4 sites in Medicaid expansion states (California, Oregon, and Maryland), 4 in a state (New York) that expanded Medicaid in 2001, and 2 in nonexpansion states (Texas and Florida)., Methods: Multivariate multinomial logistic models were used to assess changes in RWHAP/Uncomp, Medicaid, and private insurance coverage, using Medicare as a referent., Results: In expansion state sites, RWHAP/Uncomp coverage decreased (unadjusted, 28% before and 13% after ACA; adjusted relative risk ratio [ARRR], 0.44; 95% confidence interval [CI], .40-.48). Medicaid coverage increased (23% and 38%; ARRR, 1.82; 95% CI, 1.70-1.94), and private coverage was unchanged (21% and 19%; 0.96; .89-1.03). In New York sites, both RWHAP/Uncomp (20% and 19%) and Medicaid (50% and 50%) coverage were unchanged, while private coverage decreased (13% and 12%; ARRR, 0.86; 95% CI, .80-.92). In nonexpansion state sites, RWHAP/Uncomp (57% and 52%) and Medicaid (18% and 18%) coverage were unchanged, while private coverage increased (4% and 7%; ARRR, 1.79; 95% CI, 1.62-1.99)., Conclusions: In expansion state sites, half of PLWH relying on RWHAP/Uncomp coverage shifted to Medicaid, while in New York and nonexpansion state sites, reliance on RWHAP/Uncomp remained constant. In the first half of 2014, the ACA did not eliminate the need for RWHAP safety net provider visit coverage., (© The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.)

Background: The transmission of human immunodeficiency virus (HIV) among youth through high-risk behaviors continues to increase. Retention in Care is associated with positive clinical outcomes and a decrease in HIV transmission risk behaviors. We evaluated the clinical and demographic characteristics of non-perinatally HIV (nPHIV)-infected youth associated with retention 1 year after initiating care and in the 2 years thereafter. We also assessed the impact retention in year 1 had on retention in years 2 and 3., Methods: This was a retrospective analysis of treatment-naive nPHIV-infected 12- to 24-year-old youth presenting for care in 16 US HIV clinical sites within the HIV Research Network between 2002 and 2008. Multivariate logistic regression identified factors associated with retention., Results: Of 1160 nPHIV-infected youth, 44.6% were retained in care during the first year, and 22.4% were retained in all 3 years. Retention in the first year was associated with starting antiretroviral therapy in the first year (adjusted odds ratio [AOR], 3.47 [95% confidence interval (CI), 2.57-4.67]), Hispanic ethnicity (AOR, 1.66 [95% CI, 1.08-2.56]), men who have sex with men (AOR, 1.59 [95% CI, 1.07-2.36]), and receiving care at a pediatric site (AOR, 5.37 [95% CI, 3.20-9.01]). Retention in years 2 and 3 was associated with being retained 1 year after initiating care (AOR, 7.44 [95% CI, 5.11-10.83])., Conclusion: A high proportion of newly enrolled nPHIV-infected youth were not retained for 1 year, and only 1 in 4 were retained for 3 years. Patients who were Hispanic, were men who have sex with men, or were seen at pediatric clinics were more likely to be retained in care. Interventions that target those at risk of being lost to follow up are essential for this high-risk population., (© The Author 2014. Published by Oxford University Press on behalf of the Pediatric Infectious Diseases Society. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)

Because of limitations in the availability of data on primary care encounters, patient retention in human immunodeficiency virus (HIV) care is often estimated using laboratory measurement dates as proxies for clinical encounters, leading to possible outcome misclassification. This study included 83,041 HIV-infected adults from 14 clinical cohorts in the North American AIDS Cohort Collaboration on Research and Design (NA-ACCORD) who had ≥1 HIV primary care encounters during 2000-2010, contributing 468,816 person-years of follow-up. Encounter-based retention (REB) was defined as ≥2 encounters in a calendar year, ≥90 days apart. Laboratory-based retention (RLB) was defined similarly, using the dates of CD4-positive cell counts or HIV-1 RNA measurements. Percentage of agreement and the κ statistic were used to characterize agreement between RLB and REB. Logistic regression with generalized estimating equations and stabilized inverse-probability-of-selection weights was used to elucidate temporal trends and the discriminatory power of RLB as a predictor of REB, accounting for age, sex, race/ethnicity, primary HIV risk factor, and cohort site as potential confounders. Both REB and RLB increased from 2000 to 2010 (from 67% to 78% and from 65% to 77%, respectively), though REB was higher than RLB throughout (P < 0.01). RLB agreed well with REB (80%-86% agreement; κ = 0.55-0.62, P < 0.01) and had a strong, imperfect ability to discriminate between persons retained and not retained in care by REB (C statistic: C = 0.81, P < 0.05). As a proxy for REB, RLB had a sensitivity and specificity of 84% and 77%, respectively, with misclassification error of 18%., (© The Author 2015. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Elite controllers spontaneously suppress human immunodeficiency virus (HIV) viremia but also demonstrate chronic inflammation that may increase risk of comorbid conditions. We compared hospitalization rates and causes among elite controllers to those of immunologically intact persons with medically controlled HIV., Methods: For adults in care at 11 sites from 2005 to 2011, person-years with CD4 T-cell counts ≥350 cells/mm(2) were categorized as medical control, elite control, low viremia, or high viremia. All-cause and diagnostic category-specific hospitalization rates were compared between groups using negative binomial regression., Results: We identified 149 elite controllers (0.4%) among 34 354 persons in care. Unadjusted hospitalization rates among the medical control, elite control, low-viremia, and high-viremia groups were 10.5, 23.3, 12.6, and 16.9 per 100 person-years, respectively. After adjustment for demographic and clinical factors, elite control was associated with higher rates of all-cause (adjusted incidence rate ratio, 1.77 [95% confidence interval, 1.21-2.60]), cardiovascular (3.19 [1.50-6.79]) and psychiatric (3.98 [1.54-10.28]) hospitalization than was medical control. Non-AIDS-defining infections were the most common reason for admission overall (24.1% of hospitalizations) but were rare among elite controllers (2.7%), in whom cardiovascular hospitalizations were most common (31.1%)., Conclusions: Elite controllers are hospitalized more frequently than persons with medically controlled HIV and cardiovascular hospitalizations are an important contributor., (© The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)

Background: Although it has been shown that human immunodeficiency virus (HIV)-infected adults are at greater risk for aging-associated events, it remains unclear as to whether these events happen at similar, or younger ages, in HIV-infected compared with uninfected adults. The objective of this study was to compare the median age at, and risk of, incident diagnosis of 3 age-associated diseases in HIV-infected and demographically similar uninfected adults., Methods: The study was nested in the clinical prospective Veterans Aging Cohort Study of HIV-infected and demographically matched uninfected veterans, from 1 April 2003 to 31 December 2010. The outcomes were validated diagnoses of myocardial infarction (MI), end-stage renal disease (ESRD), and non-AIDS-defining cancer (NADC). Differences in mean age at, and risk of, diagnosis by HIV status were estimated using multivariate linear regression models and Cox proportional hazards models, respectively., Results: A total of 98 687 (31% HIV-infected and 69% uninfected) adults contributed >450 000 person-years and 689 MI, 1135 ESRD, and 4179 NADC incident diagnoses. Mean age at MI (adjusted mean difference, -0.11; 95% confidence interval [CI], -.59 to .37 years) and NADC (adjusted mean difference, -0.10 [95% CI, -.30 to .10] years) did not differ by HIV status. HIV-infected adults were diagnosed with ESRD at an average age of 5.5 months younger than uninfected adults (adjusted mean difference, -0.46 [95% CI, -.86 to -.07] years). HIV-infected adults had a greater risk of all 3 outcomes compared with uninfected adults after accounting for important confounders., Conclusions: HIV-infected adults had a higher risk of these age-associated events, but they occurred at similar ages than those without HIV., (© The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)

Background:  The role of active hepatitis C virus (HCV) replication in chronic kidney disease (CKD) risk has not been clarified., Methods:  We compared CKD incidence in a large cohort of HIV-infected subjects who were HCV seronegative, HCV viremic (detectable HCV RNA), or HCV aviremic (HCV seropositive, undetectable HCV RNA). Stages 3 and 5 CKD were defined according to standard criteria. Progressive CKD was defined as a sustained 25% glomerular filtration rate (GFR) decrease from baseline to a GFR < 60 mL/min/1.73 m2. We used Cox models to calculate adjusted hazard ratios (HRs) and 95% confidence intervals (CIs)., Results:  A total of 52 602 HCV seronegative, 9508 HCV viremic, and 913 HCV aviremic subjects were included. Compared with HCV seronegative subjects, HCV viremic subjects were at increased risk for stage 3 CKD (adjusted HR 1.36 [95% CI, 1.26, 1.46]), stage 5 CKD (1.95 [1.64, 2.31]), and progressive CKD (1.31 [1.19, 1.44]), while HCV aviremic subjects were also at increased risk for stage 3 CKD (1.19 [0.98, 1.45]), stage 5 CKD (1.69 [1.07, 2.65]), and progressive CKD (1.31 [1.02, 1.68])., Conclusions:  Compared with HIV-infected subjects who were HCV seronegative, both HCV viremic and HCV aviremic individuals were at increased risk for moderate and advanced CKD.

Background: Our objective was to determine the impact of combination antiretroviral therapy (cART) and the degree of immunosuppression on biologic false-positive (BFP) rapid plasma reagin (RPR) tests among persons infected with human immunodeficiency virus (HIV)., Methods: This was a nested retrospective study of HIV-infected patients enrolled in the Johns Hopkins HIV Clinical Cohort. BFP RPR was defined as a reactive RPR and a nonreactive fluorescent treponemal antibody-absorption (FTA-ABS) test. Patients with BFP tests were compared to 2 control groups: HIV-infected patients (1) with active syphilis (reactive RPR and FTA-ABS) and (2) without current syphilis (nonreactive RPR). A persistent BFP test was defined by having at least 2 visits with consistent BFP at all visits., Results: Of 711 patients with HIV, 96 (13.5%) had BFP tests and 342 (48.1%) had syphilis. Twenty-two of 96 (23%) had persistent BFP tests. cART use was associated with decreased odds of BFP tests compared to having syphilis (adjusted odds ratio [AOR], 0.31; 95% CI, .15-.63) and those with nonreactive RPR (AOR, 0.42; 95% CI, .22-.81). cART use was also associated with decreased odds of BFP persistence (AOR, 0.07; 95% CI, .01-.33). Neither CD4 count nor HIV RNA was significantly associated with BFP test results. Lower RPR titers, younger age, and injection drug use were associated with increased odds of BFP., Conclusions: The use of cART appears to decrease the odds of BFP RPR tests. This finding suggests that nontreponemal titer fluctuations in persons with HIV may reflect the influence of factors unrelated to syphilis disease activity.

Background: Since the mid-1990s, effective antiretroviral therapy (ART) regimens have improved in potency, tolerability, ease of use, and class diversity. We sought to examine trends in treatment initiation and resulting human immunodeficiency virus (HIV) virologic suppression in North America between 2001 and 2009, and demographic and geographic disparities in these outcomes., Methods: We analyzed data on HIV-infected individuals newly clinically eligible for ART (ie, first reported CD4+ count<350 cells/µL or AIDS-defining illness, based on treatment guidelines during the study period) from 17 North American AIDS Cohort Collaboration on Research and Design cohorts. Outcomes included timely ART initiation (within 6 months of eligibility) and virologic suppression (≤500 copies/mL, within 1 year). We examined time trends and considered differences by geographic location, age, sex, transmission risk, race/ethnicity, CD4+ count, and viral load, and documented psychosocial barriers to ART initiation, including non-injection drug abuse, alcohol abuse, and mental illness., Results: Among 10,692 HIV-infected individuals, the cumulative incidence of 6-month ART initiation increased from 51% in 2001 to 72% in 2009 (Ptrend<.001). The cumulative incidence of 1-year virologic suppression increased from 55% to 81%, and among ART initiators, from 84% to 93% (both Ptrend<.001). A greater number of psychosocial barriers were associated with decreased ART initiation, but not virologic suppression once ART was initiated. We found significant heterogeneity by state or province of residence (P<.001)., Conclusions: In the last decade, timely ART initiation and virologic suppression have greatly improved in North America concurrent with the development of better-tolerated and more potent regimens, but significant barriers to treatment uptake remain, both at the individual level and systemwide.

Background: Antiretroviral therapy (ART) medication errors can lead to drug resistance, treatment failure, and death. Prior research suggests that ART medication errors are on the rise in US hospitals. This analysis provides a current estimate of inpatient antiretroviral prescribing errors., Methods: Retrospective review of medication orders during the first 48 hours of hospitalization for patients with human immunodeficiency virus (HIV) infection admitted to the Johns Hopkins Hospital between 1 January and 31 December 2009. Errors were classified as (1) incomplete regimen, (2) incorrect dosage, (3) incorrect schedule, and (4) nonrecommended drug-drug combinations. Multivariable regression was used to identify factors associated with errors., Results: A total of 702 admissions occurred in 2009. Of these, 380 had ART medications prescribed on the first day and 308 on the second day of hospitalization. A total of 145 ART medication errors in 110 admissions were identified on the first day (29%), and 22 errors were identified in 21 admissions on the second day (7%). The most common errors were incomplete regimen and incorrect dosage or schedule. Protease inhibitors accounted for the majority of dosing and scheduling errors (71%-73%). Compared with patients admitted to the HIV/AIDS service, those admitted to surgical services were at increased risk of errors (adjusted odds ratio, 3.10; 95% confidence interval, 1.18-8.18)., Conclusions: ART medication errors are common among hospitalized HIV-infected patients on the first day of admission, but most are corrected within 48 hours. Interventions are needed to safeguard patients and prevent serious complications of ART medication errors especially during the first 24 hours of hospitalization.

Background: Anal cancer is one of the most common cancers affecting individuals infected with human immunodeficiency virus (HIV), although few have evaluated rates separately for men who have sex with men (MSM), other men, and women. There are also conflicting data regarding calendar trends., Methods: In a study involving 13 cohorts from North America with follow-up between 1996 and 2007, we compared anal cancer incidence rates among 34 189 HIV-infected (55% MSM, 19% other men, 26% women) and 114 260 HIV-uninfected individuals (90% men)., Results: Among men, the unadjusted anal cancer incidence rates per 100 000 person-years were 131 for HIV-infected MSM, 46 for other HIV-infected men, and 2 for HIV-uninfected men, corresponding to demographically adjusted rate ratios (RRs) of 80.3 (95% confidence interval [CI], 42.7-151.1) for HIV-infected MSM and 26.7 (95% CI, 11.5-61.7) for other HIV-infected men compared with HIV-uninfected men. HIV-infected women had an anal cancer rate of 30/100 000 person-years, and no cases were observed for HIV-uninfected women. In a multivariable Poisson regression model, among HIV-infected individuals, the risk was higher for MSM compared with other men (RR, 3.3; 95% CI, 1.8-6.0), but no difference was observed comparing women with other men (RR, 1.0; 95% CI, 0.5-2.2). In comparison with the period 2000-2003, HIV-infected individuals had an adjusted RR of 0.5 (95% CI, .3-.9) in 1996-1999 and 0.9 (95% CI, .6-1.2) in 2004-2007., Conclusions: Anal cancer rates were substantially higher for HIV-infected MSM, other men, and women compared with HIV-uninfected individuals, suggesting a need for universal prevention efforts. Rates increased after the early antiretroviral therapy era and then plateaued.

Background: Screening for tuberculosis prior to highly active antiretroviral therapy (HAART) initiation is not routinely performed in low-incidence settings. Identifying factors associated with developing tuberculosis after HAART initiation could focus screening efforts., Methods: Sixteen cohorts in the United States and Canada contributed data on persons infected with human immunodeficiency virus (HIV) who initiated HAART December 1995-August 2009. Parametric survival models identified factors associated with tuberculosis occurrence., Results: Of 37845 persons in the study, 145 were diagnosed with tuberculosis after HAART initiation. Tuberculosis risk was highest in the first 3 months of HAART (20 cases; 215 cases per 100000 person-years; 95% confidence interval [CI]: 131-333 per 100000 person-years). In a multivariate Weibull proportional hazards model, baseline CD4+ lymphocyte count <200, black race, other nonwhite race, Hispanic ethnicity, and history of injection drug use were independently associated with tuberculosis risk. In addition, in a piece-wise Weibull model, increased baseline HIV-1 RNA was associated with increased tuberculosis risk in the first 3 months; male sex tended to be associated with increased risk., Conclusions: Screening for active tuberculosis prior to HAART initiation should be targeted to persons with baseline CD4 <200 lymphocytes/mm³ or increased HIV-1 RNA, persons of nonwhite race or Hispanic ethnicity, history of injection drug use, and possibly male sex.

BACKGROUND. Initiatives to improve early detection and access to human immunodeficiency virus (HIV) services have increased over time. We assessed the immune status of patients at initial presentation for HIV care from 1997 to 2007 in 13 US and Canadian clinical cohorts. METHODS. We analyzed data from 44,491 HIV-infected patients enrolled in the North American-AIDS Cohort Collaboration on Research and Design. We identified first presentation for HIV care as the time of first CD4(+) T lymphocyte (CD4) count and excluded patients who prior to this date had HIV RNA measurements, evidence of antiretroviral exposure, or a history of AIDS-defining illness. Trends in mean CD4 count (measured as cells/mm(3)) and 95% confidence intervals were determined using linear regression adjusted for age, sex, race/ethnicity, HIV transmission risk, and cohort. RESULTS. Median age at first presentation for HIV care increased over time (range, 40-43 years; P < .01), whereas the percentage of patients with injection drug use HIV transmission risk decreased (from 26% to 14%; P < .01) and heterosexual transmission risk increased (from 16% to 23%; P < .01). Median CD4 count at presentation increased from 256 cells/mm(3) (interquartile range, 96-455 cells/mm(3)) to 317 cells/mm(3) (interquartile range, 135-517 cells/mm(3)) from 1997 to 2007 (P < .01). The percentage of patients with a CD4 count > or = 350 cells/mm(3) at first presentation also increased from 1997 to 2007 (from 38% to 46%; P < .01). The estimated adjusted mean CD4 count increased at a rate of 6 cells/mm(3) per year (95% confidence interval, 5-7 cells/mm(3) per year). CONCLUSION. CD4 count at first presentation for HIV care has increased annually over the past 11 years but has remained <350 cells/mm(3), which suggests the urgent need for earlier HIV diagnosis and treatment.

Background: Although combination antiretroviral therapy continues to evolve, with potentially more effective options emerging each year, the ability of therapy to prevent multiple regimen failure and mortality in clinical practice remains poorly defined., Methods: Sixteen cohorts representing over 60 sites contributed data on all individuals who initiated combination antiretroviral therapy. We identified those individuals who experienced virologic failure (defined as a human immunodeficiency virus [HIV] RNA level >1000 copies/mL), received modified therapy, and subsequently had a second episode of virologic failure. Multivariate Cox regression was used to assess factors associated with time to second regimen failure and the time to death after the onset of second regimen failure., Results: Of the 42,790 individuals who received therapy, 7159 experienced a second virologic failure. The risk of second virologic failure decreased from 1996 (56 cases per 100 person-years) through 2005 (16 cases per 100 person-years; P < .001). The cumulative mortality after onset of second virologic failure was 26% at 5 years and decreased over time. A history of AIDS, a lower CD4(+) T cell count, and a higher plasma HIV RNA level were each independently associated with mortality. Similar trends were observed when analysis was limited to the subset of previously treatment-naive patients, Conclusions: Although the rates of multiple regimen failure have decreased dramatically over the past decade, mortality rates for those who have experienced failure of at least 2 regimens have remained high. Plasma HIV RNA levels, CD4(+) T cell counts at time of treatment failure, and a history of AIDS remain independent risk factors for death, which emphasizes that these factors remain important targets for those in need of more-aggressive therapeutic interventions.

Background: Most persons with human immunodeficiency virus (HIV) infection in the United States present to care with advanced disease, and many patients discontinue therapy prematurely. We sought to evaluate sex and racial/ethnic disparities in life-years lost as a result of risk behavior, late presentation, and early discontinuation of HIV care, and we compared these survival losses for HIV-infected persons with losses attributable to high-risk behavior and HIV disease itself., Methods: With use of a state-transition model of HIV disease, we simulated cohorts of HIV-infected persons and compared them with uninfected individuals who had similar demographic characteristics. We estimated non-HIV-related mortality with use of risk-adjusted standardized mortality ratios, as well as years of life lost because of late presentation and early discontinuation of antiretroviral therapy (ART) for HIV infection. Data from the national HIV Research Network, stratified by sex and race/ethnicity, were used for estimating CD4+ cell counts at ART initiation., Results: For HIV-uninfected persons in the United States who have risk profiles similar to those of individuals with HIV infection, the projected life expectancy, starting at 33 years of age, was 34.58 years, compared with 42.91 years for the general US population. Those with HIV infection lost an additional 11.92 years of life if they received HIV care concordant with guidelines; late treatment initiation resulted in 2.60 additional years of life lost, whereas premature ART discontinuation led to 0.70 more years of life lost. Losses from late initiation and early discontinuation were greatest for Hispanic individuals (3.90 years)., Conclusions: The high-risk profile of HIV-infected persons, HIV infection itself, as well as late initiation and early discontinuation of care, all lead to substantial decreases in life expectancy. Survival disparities resulting from late initiation and early discontinuation of therapy are most pronounced for Hispanic HIV-infected men and women. Interventions focused on risk behaviors, as well as on earlier linkage to and better retention in care, will lead to improved survival for HIV-infected persons in the United States.

Background: The decision to perform lumbar puncture in patients with asymptomatic human immunodeficiency virus (HIV) infection and syphilis is controversial. The Centers for Disease Control and Prevention recommend certain criteria that warrant lumbar puncture. Here, we assess the performance of these criteria for detecting asymptomatic neurosyphilis (ANS)., Methods: Eligible subjects consisted of all patients with concurrent HIV infection and syphilis in a prospective clinical cohort who had no neurologic symptoms at the time of lumbar puncture. We retrospectively applied different stratification criteria to calculate the performance of lumbar puncture in detecting ANS: (1) lumbar puncture in patients with late latent syphilis or syphilis of an unknown duration, regardless of the CD4 cell count or rapid plasma reagin titer; (2) lumbar puncture if the CD4 cell count was 350 cells/mL and/or the rapid plasma reagin titer was 1:32, regardless of the syphilis stage; and (3) lumbar puncture in the context of serologic nonresponse to syphilis therapy., Results: Two hundred two of 231 patients with syphilis did not have neurologic symptoms. Immediate lumbar puncture was performed for 46 patients, and 10 cases (22%) of ANS were detected. With use of the first criterion, 2 (14%) of 10 cases of ANS in patients with early-stage syphilis would have been missed (sensitivity, 80% [95% confidence interval [CI], 44%-97%]; specificity, 23% (95% confidence interval [CI], 11.4%-40.2%) [corrected] Criterion 2 would not have missed any cases of ANS (sensitivity, 100% [95% CI, 70%-100%]; specificity, 13.2% (95% CI, 4.4%-29.1%) [corrected] but would have required that a lumbar puncture be performed for 88% of patients. Performance of lumbar puncture performed in 13 cases based on serologic nonresponse to syphilis therapy yielded 4 cases (31%) of ANS., Conclusions: In patients with concurrent HIV infection and syphilis, the use of criteria based on rapid plasma reagin titer and CD4 cell count, instead of stage-based criteria, improved the ability to identify ANS.

The rate of comorbidities not related to human immunodeficiency virus (HIV) infection or acquired immunodeficiency syndrome (AIDS) among HIV-infected patients may be higher than expected. We assessed the incidence of comorbidities not related to HIV infection or AIDS by CD4 cell count and highly active antiretroviral therapy (HAART) use status in an HIV clinical practice. A total of 2824 patients contributed 9172 person-years of longitudinal data during the period 1997-2006. Among patients with a CD4 cell count <350 cells/mm(3), receipt of HAART was associated with a significantly decreased incidence of comorbidities not related to HIV infection or AIDS.

Background: Syphilis and human immunodeficiency virus (HIV) frequently coexist in patients, but the effects of immunosuppression on the course of syphilis are unknown. Our goal was to determine whether the degree of HIV-mediated immunosuppression and the use of highly active antiretroviral therapy impact syphilis serologic responses., Methods: We assessed all cases of syphilis with positive serologic test results from 1990 through 2006 in a prospective, observational clinical cohort of HIV-infected patients. We defined seroreversion as the loss of reactivity in a patient who previously had a serologic test result positive for syphilis. We defined serologic failure as the lack of a 4-fold decrease in rapid plasma reagin titers 270-365 days after therapy or a 4-fold increase in titers > or =30 days after therapy. We used Cox proportional hazards models with statistical adjustments for multiple failure instances., Results: One hundred eighty subjects experienced 231 cases of syphilis. The median follow-up time was 5.3 years. A total of 71 episodes of serologic failure were documented. A CD4 cell count of <200 cells/mL at the time of syphilis diagnosis was associated with an increased risk of serologic failure (adjusted hazard ratio, 2.48; 95% confidence interval, 1.26-4.88). The receipt of highly active antiretroviral therapy was associated with a 60% reduction in the rate of serologic failure (adjusted hazard ratio, 0.40; 95% confidence interval, 0.21-0.75), independent of concomitant CD4 cell response. Rapid plasma reagin seroreversion was infrequent (16.1%) and inconsistent, and it was more likely to occur among patients who received macrolides., Conclusion: The use of highly active antiretroviral therapy to reverse immunosuppression and the routine use of macrolides for the prevention of opportunistic infections may reduce syphilis serologic failure rates among HIV-infected patients who have syphilis.

This study assessed the association between longitudinal patterns of illicit drug use and clinical progression of human immunodeficiency virus (HIV) disease. Confidential computer-based interviews, which addressed illicit drug use and other factors, were completed by HIV-infected participants in Baltimore, Maryland, at 6-month intervals from 1998 onward. To assess this association, the authors used a random-effects model in which clinically defined opportunistic conditions were linked to self-reported periods of drug use, enabling four categories of drug use to be distinguished: nonusers, intermittent users during abstinent periods, intermittent users during active periods, and persistent users. Included in the analysis were 1,851 participants who completed > or = 1 survey. For participants who used drugs intermittently over time, the risk of developing new opportunistic conditions during periods of abstinence was similar to that for those who never used drugs (odds ratio = 1.2, 95% confidence interval: 0.9, 1.7). In contrast, compared with that for nonusers, the risk of opportunistic infection was significantly higher for intermittent drug users during periods of active use (odds ratio = 2.2, 95% confidence interval: 1.4, 2.9) and for persistent drug users (odds ratio = 1.9, 95% confidence interval: 1.2, 2.8). Active drug use is temporally linked to HIV disease progression and mortality. Effectively targeting and treating active substance abuse in HIV treatment settings may provide a mechanism to improve clinical outcomes.

Infection Control surveillance revealed an abnormally high number of sputum samples growing Mycobacterium fortuitum from a single ward that houses the human immunodeficiency virus service. We investigated the outbreak using a retrospective case-control study and molecular epidemiology. A total of 47 patients were identified with >/=1 sputum sample that grew M. fortuitum. No significant demographic or clinical variables were found to be associated with colonization. Environmental investigation demonstrated that the M. fortuitum isolated from patients was identical to the ice machine isolates by pulsed-field gel electrophoresis. Fortunately, there has been no evidence of progressive pulmonary disease developing in our patients after >/=6 months of follow-up. All cases were thought to represent transient colonization and not infection. The ice machine was disconnected and cleaned successfully with vinegar and then bleach. Only when a 0.5-micrometer filter was installed were no further patients colonized or water cultures found to be positive.