RESUMO
BACKGROUND: Recent evidence suggests the need to reframe healthcare delivery for patients with chronic conditions, with emphasis on minimizing healthcare footprint/workload on patients, caregivers, clinicians and health systems through the proposed Minimally Disruptive Medicine (MDM) care model named. HIV care models have evolved to further focus on understanding barriers and facilitators to care delivery while improving patient-centered outcomes (e.g., disease progression, adherence, access, quality of life). It is hypothesized that these models may provide an example of MDM care model in clinic practice. Therefore, this study aimed to observe and ascertain MDM-concordant and discordant elements that may exist within a tertiary-setting HIV clinic care model for patients living with HIV or AIDS (PLWHA). We also aimed to identify lessons learned from this setting to inform improving the feasibility and usefulness of MDM care model. METHODS: This qualitative case study occurred in multidisciplinary HIV comprehensive-care clinic within an urban tertiary-medical center. Participants included Adult PLWHA and informal caregivers (e.g. family/friends) attending the clinic for regular appointments were recruited. All clinic staff were eligible for recruitment. Measurements included; semi-guided interviews with patients, caregivers, or both; semi-guided interviews with varied clinicians (individually); and direct observations of clinical encounters (patient-clinicians), as well as staff daily operations in 2015-2017. The qualitative-data synthesis used iterative, mainly inductive thematic coding. RESULTS: Researcher interviews and observations data included 28 patients, 5 caregivers, and 14 care-team members. With few exceptions, the clinic care model elements aligned closely to the MDM model of care through supporting patient capacity/abilities (with some patients receiving minimal social support and limited assistance with reframing their biography) and minimizing workload/demands (with some patients challenged by the clinic hours of operation). CONCLUSIONS: The studied HIV clinic incorporated many of the MDM tenants, contributing to its validation, and informing gaps in knowledge. While these findings may support the design and implementation of care that is both minimally disruptive and maximally supportive, the impact of MDM on patient-important outcomes and different care settings require further studying.
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Atenção à Saúde , Infecções por HIV , Medicina , Adulto , Feminino , HIV , Infecções por HIV/terapia , Humanos , Masculino , Pesquisa Qualitativa , Qualidade de VidaRESUMO
Allogeneic hematopoietic cell transplantation (allo-HCT) is a potentially curative therapy for hematologic malignancies in persons living with HIV (PLHIV), however, uncertainties exist in many domains related to their care, including optimal donor selection, conditioning regimen, immunosuppression for graft-versus-host disease (GVHD), and long-term outcomes. We undertook a comprehensive systematic review from multiple databases to evaluate the foregoing uncertainties. The final sample comprised 49 patients (median age at HCT, 34 years; 46 males [93.8%]). Acute GVHD (aGVHD) was reported in 19 patients (59.3%) in the overall cohort, with grade II in 12 (37.5%) and grade III in 2 (6.2%). In the entire cohort, overall survival (OS) was 81.6% at 6 months and 56.6% at 12 months. Among 32 patients, the OS at 6 months was 73.3% for patients who received myeloablative conditioning (MAC) and 88.2% for those who received reduced-intensity conditioning (RIC), and OS at 12 months was 53.3% for MAC and 58.8% for RIC. Twenty-four patients were alive in complete remission on long-term follow-up, with 25 deaths reported. Fifteen deaths (60%) occurred due to relapse, including 3 (12%) from infection, 2 (8%) from GVHD, and 5 (20%) from other causes, including renal failure, respiratory failure, and liver failure. To our knowledge, this is the largest series of allo-HCT in PLHIV reported to date, and our results indicate that clinical outcomes (including engraftment, infection rate, and survival) are not significantly different from those in patients without HIV (historical controls). RIC regimens are associated with a slightly greater likelihood of survival compared with MAC regimens. Prospective trials are critically needed to evaluate the optimal conditioning regimens, ideal donor source, and most appropriate GVHD prophylaxis.
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Seleção do Doador , Doença Enxerto-Hospedeiro , Infecções por HIV , HIV-1 , Neoplasias Hematológicas , Transplante de Células-Tronco Hematopoéticas , Terapia de Imunossupressão , Condicionamento Pré-Transplante , Adulto , Aloenxertos , Intervalo Livre de Doença , Feminino , Doença Enxerto-Hospedeiro/mortalidade , Doença Enxerto-Hospedeiro/terapia , Infecções por HIV/mortalidade , Infecções por HIV/terapia , Neoplasias Hematológicas/mortalidade , Neoplasias Hematológicas/terapia , Humanos , Masculino , Taxa de SobrevidaRESUMO
As treatment of HIV has improved, people living with HIV (PLWH) have experienced a decreased risk of AIDS and AIDS-defining cancers (non-Hodgkin's lymphoma, Kaposi sarcoma, and cervical cancer), but the risk of Kaposi sarcoma in PLWH is still elevated about 500-fold compared with the general population in the United States. The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for AIDS-Related Kaposi Sarcoma provide diagnosis, treatment, and surveillance recommendations for PLWH who develop limited cutaneous Kaposi sarcoma and for those with advanced cutaneous, oral, visceral, or nodal disease.
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Infecções Oportunistas Relacionadas com a AIDS/diagnóstico , Infecções Oportunistas Relacionadas com a AIDS/terapia , Sarcoma de Kaposi/diagnóstico , Sarcoma de Kaposi/terapia , Infecções Oportunistas Relacionadas com a AIDS/epidemiologia , Infecções Oportunistas Relacionadas com a AIDS/etiologia , Humanos , Sarcoma de Kaposi/epidemiologia , Sarcoma de Kaposi/etiologiaAssuntos
Leishmaniose Visceral , Pancitopenia , Humanos , Pancitopenia/etiologia , Transplantados , Tosse/etiologia , Febre/etiologiaRESUMO
People living with HIV (PLWH) are diagnosed with cancer at an increased rate over the general population and generally have a higher mortality due to delayed diagnoses, advanced cancer stage, comorbidities, immunosuppression, and cancer treatment disparities. Lack of guidelines and provider education has led to substandard cancer care being offered to PLWH. To fill that gap, the NCCN Guidelines for Cancer in PLWH were developed; they provide treatment recommendations for PLWH who develop non-small cell lung cancer, anal cancer, Hodgkin lymphoma, and cervical cancer. In addition, the NCCN Guidelines outline advice regarding HIV management during cancer therapy; drug-drug interactions between antiretroviral treatments and cancer therapies; and workup, radiation therapy, surgical management, and supportive care in PLWH who have cancer.
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Infecções por HIV/tratamento farmacológico , Oncologia/normas , Neoplasias/tratamento farmacológico , Infecções Oportunistas/prevenção & controle , Fármacos Anti-HIV/farmacologia , Fármacos Anti-HIV/uso terapêutico , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Comorbidade , Interações Medicamentosas , Medicina Baseada em Evidências/métodos , Medicina Baseada em Evidências/normas , HIV/efeitos dos fármacos , HIV/isolamento & purificação , Infecções por HIV/epidemiologia , Infecções por HIV/imunologia , Infecções por HIV/virologia , Disparidades em Assistência à Saúde/normas , Humanos , Hospedeiro Imunocomprometido/efeitos dos fármacos , Hospedeiro Imunocomprometido/imunologia , Hospedeiro Imunocomprometido/efeitos da radiação , Oncologia/métodos , Neoplasias/epidemiologia , Neoplasias/imunologia , Neoplasias/virologia , Infecções Oportunistas/imunologia , Infecções Oportunistas/virologia , Cuidados Paliativos/métodos , Cuidados Paliativos/normas , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/prevenção & controle , Ensaios Clínicos Controlados Aleatórios como Assunto , Sociedades Médicas/normas , Procedimentos Cirúrgicos Operatórios/efeitos adversos , Procedimentos Cirúrgicos Operatórios/métodos , Procedimentos Cirúrgicos Operatórios/normas , Estados UnidosRESUMO
BACKGROUND: Notwithstanding 1 documented case of HIV-1 cure following allogeneic stem cell transplantation (allo-SCT), several subsequent cases of allo-SCT in HIV-1 positive individuals have failed to cure HIV-1 infection. The aim of our study was to describe changes in the HIV reservoir in a single chronically HIV-infected patient on suppressive antiretroviral therapy who underwent allo-SCT for treatment of acute lymphoblastic leukemia. METHODS AND FINDINGS: We prospectively collected peripheral blood mononuclear cells (PBMCs) by leukapheresis from a 55-year-old man with chronic HIV infection before and after allo-SCT to measure the size of the HIV-1 reservoir and characterize viral phylogeny and phenotypic changes in immune cells. At day 784 post-transplant, when HIV-1 was undetectable by multiple measures-including PCR measurements of both total and integrated HIV-1 DNA, replication-competent virus measurement by large cell input quantitative viral outgrowth assay, and in situ hybridization of colon tissue-the patient consented to an analytic treatment interruption (ATI) with frequent clinical monitoring. He remained aviremic off antiretroviral therapy until ATI day 288, when a low-level virus rebound of 60 HIV-1 copies/ml occurred, which increased to 1,640 HIV-1 copies/ml 5 days later, prompting reinitiation of ART. Rebounding plasma HIV-1 sequences were phylogenetically distinct from proviral HIV-1 DNA detected in circulating PBMCs before transplantation. The main limitations of this study are the insensitivity of reservoir measurements, and the fact that it describes a single case. CONCLUSIONS: allo-SCT led to a significant reduction in the size of the HIV-1 reservoir and a >9-month-long ART-free remission from HIV-1 replication. Phylogenetic analyses suggest that the origin of rebound virus was distinct from the viruses identified pre-transplant in the PBMCs.
Assuntos
Infecções por HIV/terapia , Carga Viral/efeitos dos fármacos , Antirretrovirais/uso terapêutico , HIV/genética , Infecções por HIV/virologia , HIV-1/genética , Humanos , Leucócitos Mononucleares , Masculino , Pessoa de Meia-Idade , Filogenia , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Transplante de Células-Tronco/métodos , Carga Viral/fisiologiaRESUMO
UNLABELLED: Understanding how some HIV-infected cells resist the cytotoxicity of HIV replication is crucial to enabling HIV cure efforts. HIV killing of CD4 T cells that replicate HIV can involve HIV protease-mediated cleavage of procaspase 8 to generate a fragment (Casp8p41) that directly binds and activates the mitochondrial proapoptotic protein BAK. Here, we demonstrate that Casp8p41 also binds with nanomolar affinity to the antiapoptotic protein Bcl-2, which sequesters Casp8p41 and prevents apoptosis. Further, we show that central memory CD4 T cells (TCM) from HIV-infected individuals have heightened expression of BCL-2 relative to procaspase 8, possibly explaining the persistence of HIV-infected TCMdespite generation of Casp8p41. Consistent with this hypothesis, the selective BCL-2 antagonist venetoclax induced minimal killing of uninfected CD4 T cells but markedly increased the death of CD4 T cells and diminished cell-associated HIV DNA when CD4 T cells from antiretroviral therapy (ART)-suppressed HIV patients were induced with αCD3/αCD28 to reactivate HIVex vivo Thus, priming CD4 T cells from ART suppressed HIV patients with a BCL-2 antagonist, followed by HIV reactivation, achieves reductions in cell-associated HIV DNA, whereas HIV reactivation alone does not. IMPORTANCE: HIV infection is incurable due to a long-lived reservoir of HIV(+)memory CD4 T cells, and no clinically relevant interventions have been identified that reduce the number of these HIV DNA-containing cells. Since postintegration HIV replication can result in HIV protease generation of Casp8p41, which activates BAK, causing infected CD4 T cell death, we sought to determine whether this occurs in memory CD4 T cells. Here, we demonstrate that memory CD4 T cells can generate Casp8p41 and yet are intrinsically resistant to death induced by diverse stimuli, including Casp8p41. Furthermore, BCL-2 expression is relatively increased in these cells and directly binds and inhibits Casp8p41's proapoptotic effects. Antagonizing BCL-2 with venetoclax derepresses this antagonism, resulting in death, preferentially in HIV DNA containing cells, since only these cells generate Casp8p41. Thus, BCL-2 antagonism is a clinically relevant intervention with the potential to reduce HIV reservoir size in patients.
Assuntos
Linfócitos T CD4-Positivos/imunologia , Caspase 8/metabolismo , Infecções por HIV/imunologia , HIV-1/imunologia , Proteína Killer-Antagonista Homóloga a bcl-2/antagonistas & inibidores , Apoptose , Compostos Bicíclicos Heterocíclicos com Pontes/farmacologia , Inibidores de Caspase/metabolismo , Morte Celular/efeitos dos fármacos , Células HEK293 , HIV-1/efeitos dos fármacos , HIV-1/fisiologia , Humanos , Memória Imunológica , Células Jurkat , Fragmentos de Peptídeos/antagonistas & inibidores , Fragmentos de Peptídeos/imunologia , Ligação Proteica , Sulfonamidas/farmacologia , Carga Viral , Ativação Viral/efeitos dos fármacosRESUMO
Dermatologists and their staff are at risk for needlestick injuries and exposures to body fluids. Despite the availability of treatment to reduce the risk of blood-borne infection, many exposures go unreported. This paper identifies current recommendations and the specific details for response to occupational exposures to HIV, hepatitis B virus, and hepatitis C virus in the dermatology office. Issues surrounding each virus are discussed individually, and a summary step-by-step algorithm of how to proceed in the event of an occupational exposure is presented. In addition, a focused Practice Improvement Activity that is based on this paper and provides Maintenance of Certification credit has been developed. To view and participate, visit https://secure.dataharborsolutions.com/abdermorg/.
Assuntos
Patógenos Transmitidos pelo Sangue , Transmissão de Doença Infecciosa do Paciente para o Profissional/prevenção & controle , Ferimentos Penetrantes Produzidos por Agulha/prevenção & controle , Exposição Ocupacional/efeitos adversos , Saúde Ocupacional , Dermatologia , Infecções por HIV/transmissão , Hepacivirus/isolamento & purificação , Hepatite B/transmissão , Vírus da Hepatite B/isolamento & purificação , Hepatite C/transmissão , Humanos , Masculino , Ferimentos Penetrantes Produzidos por Agulha/epidemiologia , Visita a Consultório MédicoRESUMO
BACKGROUND: Universal human immunodeficiency virus (HIV) screening remains low in many clinical practices despite published guidelines recommending screening for all patients between ages 13-65. Electronic clinical decision support tools have improved screening rates for many chronic diseases. We designed a quality improvement project to improve the rate of universal HIV screening of adult patients in a Midwest primary care practice using a clinical decision support tool. METHODS: We conducted this quality improvement project in Rochester, Minnesota from January 1, 2014 to December 31, 2014. Baseline primary care practice HIV screening data were acquired from January 1, 2014 to April 30, 2014. We surveyed providers and educated them about current CDC recommended screening guidelines. We then added an HIV screening alert to an existing electronic clinical decision support tool and post-intervention HIV screening rates were obtained from May 1, 2014 to December 31, 2014. The primary quality outcome being assessed was change in universal HIV screening rates. RESULTS: Twelve thousand five hundred ninety-six unique patients were eligible for HIV screening in 2014; 327 were screened for HIV. 6,070 and 6,526 patients were seen before and after the intervention, respectively. 1.80 % of eligible patients and 3.34 % of eligible patients were screened prior to and after the intervention, respectively (difference of -1.54 % [-2.1 %, -0.99 %], p < 0.0001); OR 1.89 (1.50, 2.38). Prior to the intervention, African Americans were more likely to have been screened for HIV (OR 3.86 (2.22, 6.71; p < 0.001) than Whites, but this effect decreased significantly after the intervention (OR 1.90 (1.12, 3.21; p = 0.03). CONCLUSIONS: These data showed that an electronic alert almost doubled the rates of universal HIV screening by primary care providers in a Midwestern practice and reduced racial disparities, but there is still substantial room for improvement in universal screening practices. Opportunities for universal HIV screening remain abundant, as many providers either do not understand the importance of screening average risk patients or do not remember to discuss it. Alerts to remind providers of current guidelines and help identify screening opportunities can be helpful.
Assuntos
Tomada de Decisão Clínica , Técnicas de Apoio para a Decisão , Infecções por HIV/diagnóstico , Atenção Primária à Saúde/normas , Melhoria de Qualidade/normas , Adolescente , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Minnesota , Adulto JovemRESUMO
After a primary immune response, T cell memory occurs when a subset of Ag-specific T cells resists peripheral selection by acquiring resistance to TCR-induced death. Recent data have implicated Bcl-2 interacting mediator of death (Bim) as an essential mediator of the contraction phase of T cell immunity. In this article, we describe that stromal-derived factor-1α (SDF-1α) ligation of CXCR4 on activated T cells promotes two parallel processes that favor survival, phospho-inactivation of Foxo3A, as well as Bim extralong isoform (Bim(EL)) degradation, both in an Akt- and Erk-dependent manner. Activated primary CD4 T cells treated with SDF-1α therefore become resistant to the proapoptotic effects of TCR ligation or IL-2 deprivation and accumulate cells of a memory phenotype. Unlike SDF-1α, gp120 ligation of CXCR4 has the opposite effect because it causes p38-dependent Bim(EL) upregulation. However, when activated CD4 T cells are treated with both gp120 and SDF-1α, the SDF-1α-driven effects of Bim(EL) degradation and acquired resistance to TCR-induced death predominate. These results provide a novel causal link between SDF-1α-induced chemotaxis, degradation of Bim(EL), and the development of CD4 T cell memory.
Assuntos
Proteínas Reguladoras de Apoptose/imunologia , Linfócitos T CD4-Positivos/imunologia , Quimiocina CXCL12/imunologia , Memória Imunológica/imunologia , Proteínas de Membrana/imunologia , Proteínas Proto-Oncogênicas/imunologia , Apoptose/imunologia , Proteínas Reguladoras de Apoptose/metabolismo , Proteína 11 Semelhante a Bcl-2 , Linfócitos T CD4-Positivos/metabolismo , Quimiocina CXCL12/metabolismo , Quimiotaxia de Leucócito/imunologia , Citometria de Fluxo , Humanos , Immunoblotting , Imunoprecipitação , Ativação Linfocitária/imunologia , Proteínas de Membrana/metabolismo , Isoformas de Proteínas , Proteínas Proto-Oncogênicas/metabolismo , Receptores CXCR4/imunologia , Receptores CXCR4/metabolismo , Transdução de Sinais/imunologia , Transfecção , Regulação para CimaRESUMO
This experimental laboratory-based study evaluated two disinfectants' efficacy against replication-competent severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) on three surfaces. Disinfectants were effictive at eliminating the presence, viability, and subsequent replication of SARS-CoV-2 on all surfaces. Although SARS-CoV-2 likely spreads primarily via airborne transmission, layered mitigation should include high-touch surface disinfection.
Assuntos
COVID-19 , Desinfetantes , Humanos , SARS-CoV-2 , Desinfetantes/farmacologia , COVID-19/prevenção & controle , DesinfecçãoRESUMO
OBJECTIVE: Our study aimed to assess the impact of pharmacogenomic panel testing in people with HIV (PWH). DESIGN: Prospective, observational intervention assessment. METHODS: One hundred PWH were provided a comprehensive pharmacogenomic panel during routine care visits within the HIV specialty clinic of a large academic medical center. The panel determined the presence of specific genetic variants that could predict response or toxicity to commonly prescribed antiretroviral therapy (ART) and non-ART medications. An HIV specialty pharmacist reviewed the results with participants and the care team. The pharmacist (1) recommended clinically actionable interventions based on the participants' current drug therapy, (2) assessed for genetic explanations for prior medication failures, adverse effects, or intolerances, and (3) advised on potential future clinically actionable care interventions based on individual genetic phenotypes. RESULTS: Ninety-six participants (median age 53 years, 74% white, 84% men, 89% viral load <50âcopies/ml) completed panel testing, yielding 682 clinically relevant pharmacogenomic results (133 major, 549 mild-moderate). Ninety participants (89 on ART) completed follow-up visits with 65 (72%) receiving clinical recommendations based on current medication profiles. Of the 105 clinical recommendations, 70% advised additional monitoring for efficacy or toxicity, and 10% advised alteration of drug therapy. Panel results offered explanation for prior ART inefficacy in one participant and ART intolerance in 29%. Genetic explanation for non-ART toxicity was seen in 21% of participants, with genetic contributors to inefficacy of non-ART therapy identified in 39% of participants. CONCLUSION: Preliminary data in a small cohort of PWH demonstrates benefit of routine pharmacogenomic panel testing.
Assuntos
Fármacos Anti-HIV , Infecções por HIV , Humanos , Fármacos Anti-HIV/uso terapêutico , Infecções por HIV/tratamento farmacológico , Conduta do Tratamento Medicamentoso , Farmacogenética , Estudos Prospectivos , Carga ViralRESUMO
Virus-host interactions are characterized by the selection of adaptive mechanisms by which to evade pathogenic and defense mechanisms, respectively. In primary T cells infected with HIV, HIV infection up-regulates TNF-related apoptosis inducing ligand (TRAIL) and death-inducing TRAIL receptors, but blockade of TRAIL:TRAIL receptor interaction does not alter HIV-induced cell death. Instead, HIV infection results in a novel splice variant that we call TRAIL-short (TRAIL-s), which antagonizes TRAIL-R2. In HIV patients, plasma TRAIL-s concentration increases with increasing viral load and renders cells resistant to TRAIL-induced death. Knockdown of TRAIL-s abrogates this resistance. We propose that TRAIL-s is a novel adaptive mechanism of apoptosis resistance acquired by HIV-infected cells to avoid their elimination by TRAIL-dependent effector mechanism.
Assuntos
Processamento Alternativo , Infecções por HIV/sangue , HIV , Receptores do Ligante Indutor de Apoptose Relacionado a TNF/sangue , Linfócitos T/metabolismo , Ligante Indutor de Apoptose Relacionado a TNF/antagonistas & inibidores , Ligante Indutor de Apoptose Relacionado a TNF/metabolismo , Apoptose/genética , Feminino , Células HEK293 , Infecções por HIV/genética , Humanos , Células Jurkat , Masculino , Receptores do Ligante Indutor de Apoptose Relacionado a TNF/genética , Receptores do Ligante Indutor de Apoptose Relacionado a TNF/isolamento & purificação , Ligante Indutor de Apoptose Relacionado a TNF/genéticaRESUMO
HIV is an independent risk factor for lung disease, including chronic obstructive pulmonary disease (COPD) and emphysema. Angiotensin receptor blockers may be beneficial in COPD and emphysema through pathways that have been implicated in HIV-related lung disease. We performed a randomized comparison of the effects of losartan versus placebo on the plasma concentrations of the pneumoproteins, surfactant protein D (SPD) and club cell secretory protein (CCSP), in people living with HIV (PLWH). A total of 108 PLWH were included (52 assigned to losartan and 56 assigned to placebo). We found no difference in the change from baseline in log2 concentrations of CCSP or SPD over 1 year of follow-up. For SPD, we found a strong interaction by CD4+ counts, where those with CD4+ counts >350 cells/mm3 treated with losartan had more reduction (improvement) in SPD concentration than those treated with placebo (p value for interaction <.001). In conclusion, we did not find a beneficial effect of losartan on pneumoprotein concentrations in PLWH, but PLWH with higher CD4+ counts may have improvement in SPD when treated with losartan.
Assuntos
Infecções por HIV , Doença Pulmonar Obstrutiva Crônica , Método Duplo-Cego , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , Humanos , Losartan/uso terapêutico , Projetos Piloto , Doença Pulmonar Obstrutiva Crônica/complicações , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Doença Pulmonar Obstrutiva Crônica/metabolismoRESUMO
Combination anti-retroviral therapy has drastically improved solid organ transplantation outcomes in persons living with HIV. DAA therapy has led to the successful eradication of HCV. While recent data have suggested improvement in outcomes in HIV/HCV-coinfected liver transplant recipients, temporal trends in patient survival within pre- and post-DAA eras are yet to be elucidated. The UNOS database was utilized to identify deceased donor liver transplant recipients between 1 January 2000 and 30 September 2020 and stratify them by HIV and HCV infection status. A total of 85,730 patients met the inclusion criteria. One-year and five-year patient survival improved (93% and 80%, respectively) for all transplants performed post-2015. For HIV/HCV-coinfected recipients, survival improved significantly from 78% (pre-2015) to 92% (post-2015). Multivariate regression analyses identified advanced recipient age, Black race, diabetes mellitus and decompensated cirrhosis as risk factors associated with higher one-year mortality. Liver transplant outcomes in HIV/HCV-coinfected liver transplant recipients have significantly improved over the last quinquennium in the setting of the highly effective combination of ART and DAA therapy. The presence of HIV, HCV, HIV/HCV-coinfection and active HCV viremia at the time of transplant do not cause higher mortality risk in liver transplant recipients in the current era.
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While the full impact of COVID-19 is not yet clear, early studies have indicated that upwards of 10% of patients experience COVID-19 symptoms longer than 3 weeks, known as Long-Hauler's Syndrome or PACS (postacute sequelae of SARS-CoV-2 infection). There is little known about risk factors or predictors of susceptibility for Long-Hauler's Syndrome, but older adults are at greater risk for severe outcomes and mortality from COVID-19. The pillars of aging (including cellular senescence, telomere dysfunction, impaired proteostasis, mitochondrial dysfunction, deregulated nutrient sensing, genomic instability, progenitor cell exhaustion, altered intercellular communication, and epigenetic alterations) that contribute to age-related dysfunction and chronic diseases (the "Geroscience Hypothesis") may interfere with defenses against viral infection and consequences of these infections. Heightening of the low-grade inflammation that is associated with aging may generate an exaggerated response to an acute COVID-19 infection. Innate immune system dysfunction that leads to decreased senescent cell removal and/or increased senescent cell formation could contribute to accumulation of senescent cells with both aging and viral infections. These processes may contribute to increased risk for long-term COVID-19 sequelae in older or chronically ill patients. Hence, senolytics and other geroscience interventions that may prolong healthspan and alleviate chronic diseases and multimorbidity linked to fundamental aging processes might be an option for delaying, preventing, or alleviating Long-Hauler's Syndrome.
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Envelhecimento/fisiologia , COVID-19/fisiopatologia , Idoso , COVID-19/virologia , Doença Crônica , Humanos , SARS-CoV-2/isolamento & purificaçãoRESUMO
In patients with HIV, the use of highly active antiretroviral therapy has improved life expectancy. At the same time, this increase in life expectancy has been associated with a higher frequency of chronic kidney disease due to factors other than HIV infection. Besides HIV-associated nephropathy, a number of different types of immune complex and non-immune complex-mediated processes have been identified on kidney biopsies, including vascular disease (nephrosclerosis), diabetes, and drug-related renal injury. In this setting, renal biopsy needs to be considered in order to obtain the correct diagnosis in individual patients with HIV and kidney impairment. Many issues regarding the optimal treatment of the different pathological processes affecting the kidneys of these patients have remained unresolved. Further research is needed in order to optimize treatment and renal outcomes in patients with HIV and kidney disease.
Assuntos
Nefropatia Associada a AIDS/tratamento farmacológico , HIV-1 , Nefropatias/tratamento farmacológico , Nefropatia Associada a AIDS/imunologia , Nefropatia Associada a AIDS/patologia , Corticosteroides/uso terapêutico , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Animais , Terapia Antirretroviral de Alta Atividade/métodos , Humanos , Imunossupressores/uso terapêutico , Nefropatias/imunologia , Nefropatias/patologia , Ensaios Clínicos Controlados Aleatórios como Assunto/métodos , Resultado do TratamentoRESUMO
Surface disinfection is part of a larger mitigation strategy to prevent the spread of the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) virus causing coronavirus disease-2019 (COVID-19). Research evaluating the time, nature, and extent of surface disinfection of replication-competent viruses is needed. We evaluated the efficacy of two disinfectants against a replication-competent SARS-CoV-2 surrogate on three common public surfaces. Vesicular stomatitis virus expressing green fluorescent protein (VSV-GFP) was our replication-competent SARS-CoV-2 surrogate. Disinfection occurred using Super Sani-Cloth Germicidal Disposable Wipes and Oxivir Tb spray per manufacturer instructions to test the efficacy at reducing the presence, viability, and later replication of VSV-GFP on stainless steel, laminate wood, and porcelain surfaces using standardized methods after recovery and toxicity testing. During the main trials, we placed 100 µL spots of VSV-GFP at viral titers of 108, 107, and 106 PFU/mL on each surface prior to disinfection. Trials were completed in triplicate and post-disinfection measurements on each surface were compared to the measurements of non-disinfected surfaces. Disinfectants were considered efficacious when ≥3-log10 reduction in the number of infectious VSV-GFP virus units was observed on a given surface during all trials. Both disinfectants produced a ≥3.23-log10 reduction in infectious VSV-GFP virus unit numbers, with all trials showing no viable, replication-competent VSV-GFP present on any tested surface. The two disinfectants eliminated the presence, viability, and later replication of VSV-GFP, our SARS-CoV-2 surrogate, on all surfaces. This information suggests that, if following manufacturer instructions, overcleaning surfaces with multiple disinfectant solutions may be unnecessary.
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COVID-19 , Desinfetantes , Estomatite Vesicular , Animais , Desinfetantes/farmacologia , Humanos , SARS-CoV-2 , Vírus da Estomatite Vesicular IndianaRESUMO
A global multi-disciplinary faculty was established to work collaboratively and provide virtual technical assistance, using a point-of-care continuing education model, to clinicians across the world engaged in the care of patients with either HIV infection or tuberculosis. Ancillary offerings included live or virtual lectures, case-based conferences, and courses. In spite of the considerable disruption of the program due to the COVID-19 pandemic, we engaged and assisted a substantial number of clinicians across the world and provided meaningful contributions to their continuous professional development and patient care. In light of the ongoing pandemic, virtual technical assistance models such as this should be scaled to continue essential high-quality HIV/TB services.
RESUMO
BACKGROUND: Persistent inflammation and incomplete immune recovery among persons with HIV (PHIV) are associated with increased disease risk. We hypothesized that the angiotensin receptor blocker (ARB) losartan would reduce inflammation by mitigating nuclear factor (NF)κB responses and promote T-cell recovery via inhibition of transforming growth factor-beta (TGFß)-mediated fibrosis. METHODS: Losartan (100âmg) versus placebo over 12 months was investigated in a randomized (1â:â1) placebo-controlled trial, among PHIV age at least 50 years, receiving antiretroviral therapy (ART), with HIV RNA less than 200âcopies/ml and CD4+ cell count 600âcells/µl or less. Inflammation, fibrosis and myocardial biomarkers were measured in blood using ELISA, electrochemiluminescence and immunoturbidimetric methods, and T-cell and monocyte phenotypes were assessed with flow cytometry among a subset of participants. Changes over follow-up in (log-2 transformed) biomarkers and cell phenotypes (untransformed) were compared between losartan and placebo arms using linear mixed models. RESULTS: Among 108 PHIV (nâ=â52 to losartan; nâ=â56 to placebo), 97% had a month 12 visit. Median age was 57 years and baseline CD4+ cell count was 408âcells/µl. Losartan treatment was not associated with an improvement in interleukin-6 levels, or other blood measures of inflammation, immune activation, fibrosis activity or myocardial function. CD4+ and CD8+ T cells also did not differ by treatment group. Losartan reduced SBP and DBP by 6 and 5âmmHg, respectively. CONCLUSION: Among older PHIV with viral suppression, losartan did not improve blood measures of inflammation nor T-cell immune recovery. Losartan treatment is unlikely to reduce inflammation associated comorbidities to a clinically meaningful degree, beyond the benefits from lowering blood pressure. CLINICALTRIALSGOV: NCT02049307.