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  1 / 298130 MEDLINE  
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[PMID]:27789052
[Au] Autor:Timsit FJ; Janier M; Vernay-Vaïsse C; Bouscarat F; Fouéré S; Dupin N; Section MST de la SFD
[Ad] Dirección:Centre clinique et biologique des MST, hôpital Saint-Louis, 42, rue Bichat, 75010 Paris, France. Electronic address: centre.mst@aphp.fr.
[Ti] Título:[Primary HIV infection].
[Ti] Título:Primo-infection VIH..
[So] Fuente:Ann Dermatol Venereol;, 2016 Oct 24.
[Is] ISSN:0151-9638
[Cp] País de publicación:France
[La] Idioma:FRE
[Pt] Tipo de publicación:JOURNAL ARTICLE
[Em] Mes de ingreso:1610
[Cu] Fecha actualización por clase:161030
[Lr] Fecha última revisión:161030
[St] Status:Publisher


  2 / 298130 MEDLINE  
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[PMID]:27610559
[Au] Autor:Crowe JE
[Ad] Dirección:Departments of Pediatrics, Pathology, Microbiology, and Immunology and Vanderbilt Vaccine Center, Vanderbilt University Medical Center, Nashville, TN 37232, USA. Electronic address: james.crowe@vanderbilt.edu.
[Ti] Título:Teaching a Clone to Walk, One Step at a Time.
[So] Fuente:Cell;166(6):1360-1, 2016 Sep 8.
[Is] ISSN:0092-8674
[Cp] País de publicación:United States
[La] Idioma:ENG
[Ab] Resumen:Development of broad HIV neutralizing antibodies during infection requires prolonged exposure to viral variants. A series of three studies published in this issue of Cell and a related paper in Immunity report new HIV structure-based design efforts focused on sequential boosting regimens with antigens of increasing maturation that point the way forward for an effective HIV vaccine strategy.
[Mh] Términos MeSH primario: Vacunas contra el SIDA/inmunología
Infecciones por VIH/inmunología
[Mh] Términos MeSH secundario: Anticuerpos Neutralizantes/inmunología
Anticuerpos Anti-VIH/inmunología
VIH-1/inmunología
Humanos
[Pt] Tipo de publicación:JOURNAL ARTICLE; COMMENT
[Nm] Nombre de substancia:
0 (AIDS Vaccines); 0 (Antibodies, Neutralizing); 0 (HIV Antibodies)
[Em] Mes de ingreso:1610
[Cu] Fecha actualización por clase:161027
[Lr] Fecha última revisión:161027
[Sb] Subgrupo de revista:IM
[Da] Fecha de ingreso para procesamiento:016910
[St] Status:MEDLINE


  3 / 298130 MEDLINE  
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[PMID]:27565339
[Au] Autor:Freed EO
[Ad] Dirección:Virus-Cell Interaction Section, HIV Dynamics and Replication Program, Center for Cancer Research, National Cancer Institute, Frederick, MD 21702, USA. Electronic address: efreed@nih.gov.
[Ti] Título:Getting IN on Viral RNA Condensation and Virion Maturation.
[So] Fuente:Cell;166(5):1082-3, 2016 Aug 25.
[Is] ISSN:0092-8674
[Cp] País de publicación:United States
[La] Idioma:ENG
[Ab] Resumen:The retroviral enzyme integrase plays an essential role in the virus replication cycle by catalyzing the covalent insertion of newly synthesized viral DNA into the host cell chromosome early after infection. Now, Kessl et al. report a second function of integrase: binding to the viral RNA genome in virion particles late in the virus replication cycle to promote particle maturation.
[Mh] Términos MeSH primario: VIH-1/enzimología
ARN Viral/genética
[Mh] Términos MeSH secundario: Línea Celular
ADN Viral/metabolismo
Virión/genética
Replicación Viral/genética
[Pt] Tipo de publicación:JOURNAL ARTICLE; COMMENT
[Nm] Nombre de substancia:
0 (DNA, Viral); 0 (RNA, Viral)
[Em] Mes de ingreso:1610
[Cu] Fecha actualización por clase:161027
[Lr] Fecha última revisión:161027
[Sb] Subgrupo de revista:IM
[Da] Fecha de ingreso para procesamiento:016827
[St] Status:MEDLINE


  4 / 298130 MEDLINE  
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[PMID]:27119235
[Au] Autor:Gopal S
[Ad] Dirección:From the Malawi Cancer Consortium and the University of North Carolina Project-Malawi, Lilongwe, and the University of Malawi College of Medicine, Blantyre - all in Malawi; and the Lineberger Comprehensive Cancer Center, University of North Carolina Institute for Global Health and Infectious Diseases, and University of North Carolina Gillings School of Global Public Health - all in Chapel Hill.
[Ti] Título:Moonshot to Malawi.
[So] Fuente:N Engl J Med;374(17):1604-5, 2016 Apr 28.
[Is] ISSN:0028-4793
[Cp] País de publicación:United States
[La] Idioma:ENG
[Mh] Términos MeSH primario: Neoplasias/terapia
[Mh] Términos MeSH secundario: Femenino
Infecciones por VIH/complicaciones
Infecciones por VIH/epidemiología
Conocimientos, Actitudes y Práctica en Salud
Humanos
Malaui/epidemiología
Masculino
Neoplasias/diagnóstico
Neoplasias/epidemiología
Neoplasias/prevención & control
Prevalencia
Salud Pública
Apoyo a la Investigación como Asunto
Neoplasias del Cuello Uterino/prevención & control
[Pt] Tipo de publicación:JOURNAL ARTICLE
[Em] Mes de ingreso:1605
[Cu] Fecha actualización por clase:161028
[Lr] Fecha última revisión:161028
[Sb] Subgrupo de revista:AIM; IM
[Da] Fecha de ingreso para procesamiento:016428
[St] Status:MEDLINE
[do] DOI:10.1056/NEJMp1601982


  5 / 298130 MEDLINE  
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[PMID]:27049052
[Au] Autor:Althoff KN; Rebeiro PF; Hanna DB; Padgett D; Horberg MA; Grinsztejn B; Abraham AG; Hogg R; Gill MJ; Wolff MJ; Mayor A; Rachlis A; Williams C; Sterling TR; Kitahata MM; Buchacz K; Thorne JE; Cesar C; Cordero FM; Rourke SB; Sierra-Madero J; Pape JW; Cahn P; McGowan C; North American Aids Cohort Collaboration on Research and Design (NA-ACCORD) and Caribbean, Central and South America Network for Hiv Epidemiology (CCASAnet)
[Ad] Dirección:Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA; kalthoff@jhu.edu.
[Ti] Título:A picture is worth a thousand words: maps of HIV indicators to inform research, programs, and policy from NA-ACCORD and CCASAnet clinical cohorts.
[So] Fuente:J Int AIDS Soc;19(1):20707, 2016.
[Is] ISSN:1758-2652
[Cp] País de publicación:Switzerland
[La] Idioma:ENG
[Ab] Resumen:INTRODUCTION: Maps are powerful tools for visualization of differences in health indicators by geographical region, but multi-country maps of HIV indicators do not exist, perhaps due to lack of consistent data across countries. Our objective was to create maps of four HIV indicators in North, Central, and South American countries. METHODS: Using data from the North American AIDS Cohort Collaboration on Research and Design (NA-ACCORD) and the Caribbean, Central, and South America network for HIV epidemiology (CCASAnet), we mapped median CD4 at presentation for HIV clinical care, proportion retained in HIV primary care, proportion prescribed antiretroviral therapy (ART), and the proportion with suppressed plasma HIV viral load (VL) from 2010 to 2012 for North, Central, and South America. The 15 Canadian and US clinical cohorts and 7 clinical cohorts in Argentina, Brazil, Chile, Haiti, Honduras, Mexico, and Peru represented approximately 2-7% of persons known to be living with HIV in these countries. RESULTS: Study populations were selected for each indicator: median CD4 at presentation for care was estimated among 14,811 adults; retention was estimated among 87,979 adults; ART use was estimated among 84,757 adults; and suppressed VL was estimated among 51,118 adults. Only three US states and the District of Columbia had a median CD4 at presentation >350 cells/mm(3). Haiti, Mexico, and several states had >85% retention in care; lower (50-74%) retention in care was observed in the US West, South, and Mid-Atlantic, and in Argentina, Brazil, and Peru. ART use was highest (90%) in Mexico. The percentages of patients with suppressed VL in the US South and Northeast were lower than in most of Central and South America. CONCLUSIONS: These maps provide visualization of gaps in the quality of HIV care and allow for comparison between and within countries as well as monitoring policy and programme goals within geographical boundaries.
[Mh] Términos MeSH primario: Infecciones por VIH/quimioterapia
[Mh] Términos MeSH secundario: Adulto
Recuento de Linfocito CD4
Estudios de Cohortes
Conducta Cooperativa
Estudios Transversales
Femenino
Infecciones por VIH/epidemiología
Infecciones por VIH/inmunología
Política de Salud
Humanos
Masculino
Mediana Edad
Proyectos de Investigación
[Pt] Tipo de publicación:JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL; RESEARCH SUPPORT, N.I.H., INTRAMURAL; RESEARCH SUPPORT, NON-U.S. GOV'T; RESEARCH SUPPORT, U.S. GOV'T, P.H.S.
[Em] Mes de ingreso:1609
[Cu] Fecha actualización por clase:161028
[Lr] Fecha última revisión:161028
[Sb] Subgrupo de revista:IM; X
[Da] Fecha de ingreso para procesamiento:201646
[St] Status:MEDLINE
[do] DOI:10.7448/IAS.19.1.20707


  6 / 298130 MEDLINE  
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Araujo, Sergio
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[PMID]:27039183
[Au] Autor:Riello FN; Brígido RT; Araújo S; Moreira TA; Goulart LR; Goulart IM
[Ad] Dirección:National Reference Center for Sanitary Dermatology and Leprosy (CREDESH) Clinical Hospital Federal University of Uberlândia, Uberlândia, Minas Gerais, Brazil.
[Ti] Título:Diagnosis of mycobacterial infections based on acid-fast bacilli test and bacterial growth time and implications on treatment and disease outcome.
[So] Fuente:BMC Infect Dis;16:142, 2016 Apr 01.
[Is] ISSN:1471-2334
[Cp] País de publicación:England
[La] Idioma:ENG
[Ab] Resumen:BACKGROUND: The establishment of therapeutic regimens for mycobacteriosis depends on the accurate identification of Mycobacterium species, and misdiagnosis can result in inappropriate treatment and increased mortality of patients. Differential diagnosis among Mycobacterium species has been made by conventional phenotypic and biochemical tests after a long culture period. Specialized molecular diagnostics of mycobacteria allows rapid detection and species identification; however, such tests are not available in public health programs. Our aim was to demonstrate the clinical implications of erroneous diagnosis by performing molecular genotyping of mycobacterial infections in patients that were diagnosed based on symptoms, culture and bacilloscopy. METHODS: Culture samples of mycobacterial infections from 55 patients clinically diagnosed as tuberculosis in 2013 and 2014, based on conventional methods, were identified by PCR -RFLP and results are discussed. RESULTS: We have confirmed 35 (63.6%) positive samples as M. tuberculosis, but 18 (32.7%) were identified as non-tuberculous mycobacteria (M. avium type 1, M. avium type 2, M. kansasii type 1 type 1, M. mucogenicum, M. chelonae, M. terrae type 3, and 1 unknown RFLP pattern) and two were negative. Regarding clinical diagnosis, 61.8% (34/55) was classified as pulmonary tuberculosis. It is important to emphasize that 36.4% (20/55) of samples were misdiagnosed by conventional methods, and 11 (61.1%) of the HIV positive patients (18/55) were NTM-coinfected. CONCLUSION: The identification of species in mycobacterial infections is essential for correct diagnosis and choice of treatment regimen, and misdiagnosis by conventional tools can lead to chronic disease, increased resistance and death.
[Mh] Términos MeSH primario: Infecciones por Mycobacterium/diagnóstico
Mycobacterium/genética
Tuberculosis/diagnóstico
[Mh] Términos MeSH secundario: Adulto
Anciano
Anciano de 80 o más Años
ADN Bacteriano/análisis
Femenino
Genotipo
Infecciones por VIH/complicaciones
Infecciones por VIH/diagnóstico
Humanos
Masculino
Mediana Edad
Mycobacterium/aislamiento & purificación
Infecciones por Mycobacterium/complicaciones
Infecciones por Mycobacterium/microbiología
Reacción en Cadena de la Polimerasa
Tuberculosis/microbiología
Adulto Joven
[Pt] Tipo de publicación:JOURNAL ARTICLE
[Nm] Nombre de substancia:
0 (DNA, Bacterial)
[Em] Mes de ingreso:1610
[Cu] Fecha actualización por clase:161027
[Lr] Fecha última revisión:161027
[Sb] Subgrupo de revista:IM
[Da] Fecha de ingreso para procesamiento:201644
[St] Status:MEDLINE
[do] DOI:10.1186/s12879-016-1474-6


  7 / 298130 MEDLINE  
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[PMID]:26996992
[Au] Autor:Cesar C; Koethe JR; Giganti MJ; Rebeiro P; Althoff KN; Napravnik S; Mayor A; Grinsztejn B; Wolff M; Padgett D; Sierra-Madero J; Gotuzzo E; Sterling TR; Willig J; Levison J; Kitahata M; Rodriguez-Barradas MC; Moore RD; McGowan C; Shepherd BE; Cahn P; Caribbean, Central and South America Network for HIV epidemiology (CCASAnet) and North American AIDS Cohort Collaboration on Research and Design (NA-ACCORD)
[Ad] Dirección:Investigaciones Clínicas, Fundación Huésped, Buenos Aires, Argentina; carina.cesar@huesped.org.ar.
[Ti] Título:Health outcomes among HIV-positive Latinos initiating antiretroviral therapy in North America versus Central and South America.
[So] Fuente:J Int AIDS Soc;19(1):20684, 2016.
[Is] ISSN:1758-2652
[Cp] País de publicación:Switzerland
[La] Idioma:ENG
[Ab] Resumen:INTRODUCTION: Latinos living with HIV in the Americas share a common ethnic and cultural heritage. In North America, Latinos have a relatively high rate of new HIV infections but lower rates of engagement at all stages of the care continuum, whereas in Latin America antiretroviral therapy (ART) services continue to expand to meet treatment needs. In this analysis, we compare HIV treatment outcomes between Latinos receiving ART in North America versus Latin America. METHODS: HIV-positive adults initiating ART at Caribbean, Central and South America Network for HIV (CCASAnet) sites were compared to Latino patients (based on country of origin or ethnic identity) starting treatment at North American AIDS Cohort Collaboration on Research and Design (NA-ACCORD) sites in the United States and Canada between 2000 and 2011. Cox proportional hazards models compared mortality, treatment interruption, antiretroviral regimen change, virologic failure and loss to follow-up between cohorts. RESULTS: The study included 8400 CCASAnet and 2786 NA-ACCORD patients initiating ART. CCASAnet patients were younger (median 35 vs. 37 years), more likely to be female (27% vs. 20%) and had lower nadir CD4 count (median 148 vs. 195 cells/µL, p<0.001 for all). In multivariable analyses, CCASAnet patients had a higher risk of mortality after ART initiation (adjusted hazard ratio (AHR) 1.61; 95% confidence interval (CI): 1.32 to 1.96), particularly during the first year, but a lower hazard of treatment interruption (AHR: 0.46; 95% CI: 0.42 to 0.50), change to second-line ART (AHR: 0.56; 95% CI: 0.51 to 0.62) and virologic failure (AHR: 0.52; 95% CI: 0.48 to 0.57). CONCLUSIONS: HIV-positive Latinos initiating ART in Latin America have greater continuity of treatment but are at higher risk of death than Latinos in North America. Factors underlying these differences, such as HIV testing, linkage and access to care, warrant further investigation.
[Mh] Términos MeSH primario: Fármacos Anti-VIH/uso terapéutico
Infecciones por VIH/quimioterapia
[Mh] Términos MeSH secundario: Adulto
Canadá
Femenino
Hispanoamericanos
Humanos
Masculino
América del Norte
Modelos de Riesgos Proporcionales
América del Sur
Resultado del Tratamiento
Estados Unidos
[Pt] Tipo de publicación:COMPARATIVE STUDY; JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL; RESEARCH SUPPORT, N.I.H., INTRAMURAL; RESEARCH SUPPORT, NON-U.S. GOV'T; RESEARCH SUPPORT, U.S. GOV'T, P.H.S.
[Nm] Nombre de substancia:
0 (Anti-HIV Agents)
[Em] Mes de ingreso:1609
[Cu] Fecha actualización por clase:161028
[Lr] Fecha última revisión:161028
[Sb] Subgrupo de revista:IM; X
[Da] Fecha de ingreso para procesamiento:016321
[St] Status:MEDLINE
[do] DOI:10.7448/IAS.19.1.20684


  8 / 298130 MEDLINE  
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[PMID]:26983786
[Au] Autor:Du VY; Bansal A; Carlson J; Salazar-Gonzalez JF; Salazar MG; Ladell K; Gras S; Josephs TM; Heath SL; Price DA; Rossjohn J; Hunter E; Goepfert PA
[Ad] Dirección:Department of Medicine, University of Alabama at Birmingham, Birmingham, AL 35294;
[Ti] Título:HIV-1-Specific CD8 T Cells Exhibit Limited Cross-Reactivity during Acute Infection.
[So] Fuente:J Immunol;196(8):3276-86, 2016 Apr 15.
[Is] ISSN:0022-1767
[Cp] País de publicación:United States
[La] Idioma:ENG
[Ab] Resumen:Prior work has demonstrated that HIV-1-specific CD8 T cells can cross-recognize variant epitopes. However, most of these studies were performed in the context of chronic infection, where the presence of viral quasispecies makes it difficult to ascertain the true nature of the original antigenic stimulus. To overcome this limitation, we evaluated the extent of CD8 T cell cross-reactivity in patients with acute HIV-1 clade B infection. In each case, we determined the transmitted founder virus sequence to identify the autologous epitopes restricted by individual HLA class I molecules. Our data show that cross-reactive CD8 T cells are infrequent during the acute phase of HIV-1 infection. Moreover, in the uncommon instances where cross-reactive responses were detected, the variant epitopes were poorly recognized in cytotoxicity assays. Molecular analysis revealed that similar antigenic structures could be cross-recognized by identical CD8 T cell clonotypes mobilized in vivo, yet even subtle differences in a single TCR-accessible peptide residue were sufficient to disrupt variant-specific reactivity. These findings demonstrate that CD8 T cells are highly specific for autologous epitopes during acute HIV-1 infection. Polyvalent vaccines may therefore be required to provide optimal immune cover against this genetically labile pathogen.
[Mh] Términos MeSH primario: Linfocitos T CD8-positivos/inmunología
Reacciones Cruzadas/inmunología
Epítopos de Linfocito T/inmunología
VIH-1/inmunología
Antígeno HLA-B7/inmunología
[Mh] Términos MeSH secundario: Línea Celular
Cristalografía por Rayos X
Epítopos de Linfocito T/ultraestructura
Infecciones por VIH/inmunología
Infecciones por VIH/virología
VIH-1/clasificación
Antígeno HLA-B27/inmunología
Antígeno HLA-B27/ultraestructura
Antígeno HLA-B7/ultraestructura
Humanos
[Pt] Tipo de publicación:JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nombre de substancia:
0 (Epitopes, T-Lymphocyte); 0 (HLA-B*07:02 antigen); 0 (HLA-B*27:05 antigen); 0 (HLA-B27 Antigen); 0 (HLA-B7 Antigen)
[Em] Mes de ingreso:1608
[Cu] Fecha actualización por clase:161027
[Lr] Fecha última revisión:161027
[Sb] Subgrupo de revista:AIM; IM
[Da] Fecha de ingreso para procesamiento:201645
[St] Status:MEDLINE
[do] DOI:10.4049/jimmunol.1502411


  9 / 298130 MEDLINE  
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[PMID]:26882502
[Au] Autor:Feder AF; Rhee SY; Holmes SP; Shafer RW; Petrov DA; Pennings PS
[Ad] Dirección:Department of Biology, Stanford University, Stanford, United States.
[Ti] Título:More effective drugs lead to harder selective sweeps in the evolution of drug resistance in HIV-1.
[So] Fuente:Elife;5, 2016 Feb 15.
[Is] ISSN:2050-084X
[Cp] País de publicación:England
[La] Idioma:ENG
[Ab] Resumen:In the early days of HIV treatment, drug resistance occurred rapidly and predictably in all patients, but under modern treatments, resistance arises slowly, if at all. The probability of resistance should be controlled by the rate of generation of resistance mutations. If many adaptive mutations arise simultaneously, then adaptation proceeds by soft selective sweeps in which multiple adaptive mutations spread concomitantly, but if adaptive mutations occur rarely in the population, then a single adaptive mutation should spread alone in a hard selective sweep. Here, we use 6717 HIV-1 consensus sequences from patients treated with first-line therapies between 1989 and 2013 to confirm that the transition from fast to slow evolution of drug resistance was indeed accompanied with the expected transition from soft to hard selective sweeps. This suggests more generally that evolution proceeds via hard sweeps if resistance is unlikely and via soft sweeps if it is likely.
[Mh] Términos MeSH primario: Fármacos Anti-VIH/farmacología
Fármacos Anti-VIH/uso terapéutico
Farmacorresistencia Viral
Infecciones por VIH/quimioterapia
Infecciones por VIH/virología
VIH-1/efectos de drogas
Selección Genética
[Mh] Términos MeSH secundario: Adaptación Biológica
Genotipo
Humanos
Tasa de Mutación
[Pt] Tipo de publicación:JOURNAL ARTICLE
[Nm] Nombre de substancia:
0 (Anti-HIV Agents)
[Em] Mes de ingreso:1610
[Cu] Fecha actualización por clase:161027
[Lr] Fecha última revisión:161027
[Sb] Subgrupo de revista:IM
[Da] Fecha de ingreso para procesamiento:016217
[St] Status:MEDLINE


  10 / 298130 MEDLINE  
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[PMID]:26845675
[Au] Autor:Appay V; Kelleher AD
[Ad] Dirección:aSorbonne Universités, UPMC Univ Paris 06, DHU FAST, CR7, Centre d'Immunologie et des Maladies Infectieuses (CIMI-Paris) bINSERM, U1135, CIMI-Paris, Paris, France cThe Kirby Institute of Infectious Diseases in Society, UNSW Australia dSt Vincent's Centre for Applied Medical Research, Darlinghurst, Sydney, NSW, Australia.
[Ti] Título:Immune activation and immune aging in HIV infection.
[So] Fuente:Curr Opin HIV AIDS;11(2):242-9, 2016 Mar.
[Is] ISSN:1746-6318
[Cp] País de publicación:United States
[La] Idioma:ENG
[Ab] Resumen:PURPOSE OF REVIEW: The development of serious non-AIDS-related pathologies typically associated with aging, and the premature immune aging that characterizes HIV-1-infected patients, even with suppressive antiretroviral therapy, have raised increasing concerns in recent years. Deciphering the causes of these phenomena is key for our understanding of HIV pathogenesis and for the clinical care of patients living with the virus. RECENT FINDINGS: An important basis for the immune parallels between HIV infection and aging lies in the exhaustion of the lymphopoietic capacity of infected individuals, which eventually affects all compartments of the immune system. The alleged cause for these immune alterations, and the onset of age-related comorbidities, is the systemic chronic immune activation that is established in patients. However, there is a multiplicity of contributors to this immune activation. SUMMARY: Our understanding of the precise link between immune activation and aging in HIV infection is complicated by the influence of coinfections and life style factors. Developing rational interventions to reduce the hyper-inflammatory status of HIV-1-infected patients requires a clearer delineation of the factors contributing to the increased levels of systemic immune activation.
[Mh] Términos MeSH primario: Envejecimiento/inmunología
Infecciones por VIH
VIH-1/inmunología
Inflamación/inmunología
[Mh] Términos MeSH secundario: Comorbilidad
Infecciones por VIH/complicaciones
Infecciones por VIH/inmunología
Humanos
[Pt] Tipo de publicación:JOURNAL ARTICLE; REVIEW
[Em] Mes de ingreso:1610
[Cu] Fecha actualización por clase:161027
[Lr] Fecha última revisión:161027
[Sb] Subgrupo de revista:IM; X
[Da] Fecha de ingreso para procesamiento:201625
[St] Status:MEDLINE
[do] DOI:10.1097/COH.0000000000000240



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