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  1 / 305030 MEDLINE  
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[PMID]:29099110
[Au] Autor:Zamudio-Rodríguez A; Aguilar-Navarro S; Avila-Funes JA
[Ad] Dirección:Maestrías y Doctorados en Ciencias Médicas, Odontológicas y de la Salud, Epidemiología Clínica, Universidad Nacional Autónoma de México.
[Ti] Título:Deterioro cognitivo en adultos mayores con VIH/sida y síndrome de fragilidad.
[So] Fuente:Gac Med Mex;153(5):598-607, 2017.
[Is] ISSN:0016-3813
[Cp] País de publicación:Mexico
[La] Idioma:eng
[Ab] Resumen:In 2014, 17% of newly diagnosed HIV infection cases in the United States were made in people over 50 years of age; actually, it is expected that in the near future this population group will be the most affected. This epidemiological change can be explained by the increased incidence of HIV infection in people over 50 years, but also by its higher prevalence due to treatment advances. As HIV infection has become a chronic one, new challenges have emerged. For instance, early-onset "geriatric syndromes," such as frailty, have been recognized in these patients. Frailty refers to a physiological state of vulnerability that increases the risk of adverse health-related outcomes. Frail individuals have higher risk of cognitive impairment; however, it is not known if early-onset frailty in those infected by HIV could also increase the risk of cognitive impairment in this already vulnerable population. The purpose of this review article is to describe, from an epidemiological point of view, the relationship between the changes promoted by HIV and the syndrome of frailty on cognitive function.
[Pt] Tipo de publicación:JOURNAL ARTICLE
[Em] Mes de ingreso:1711
[Cu] Fecha actualización por clase:171103
[Lr] Fecha última revisión:171103
[St] Status:In-Data-Review
[do] DOI:10.24875/GMM.17002875


  2 / 305030 MEDLINE  
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[PMID]:29092761
[Au] Autor:Leblanc J; Hejblum G; Costagliola D; Durand-Zaleski I; Lert F; de Truchis P; Verbeke G; Rousseau A; Piquet H; Simon F; Pateron D; Simon T; Crémieux AC; DICI-VIH (Dépistage Infirmier CIblé du VIH) Group
[Ad] Dirección:Assistance Publique-Hôpitaux de Paris, Groupe Hospitalier des Hôpitaux Universitaires Est Parisien, Clinical Research Center of East of Paris, Paris, France; Université Paris Saclay-Université Versailles St Quentin, INSERM UMR 1173, Garches, France. Electronic address: judith.leblanc@aphp.fr.
[Ti] Título:Targeted HIV Screening in Eight Emergency Departments: The DICI-VIH Cluster-Randomized Two-Period Crossover Trial.
[So] Fuente:Ann Emerg Med;, 2017 Oct 30.
[Is] ISSN:1097-6760
[Cp] País de publicación:United States
[La] Idioma:eng
[Ab] Resumen:STUDY OBJECTIVE: This study compares the effectiveness and cost-effectiveness of nurse-driven targeted HIV screening alongside physician-directed diagnostic testing (intervention strategy) with diagnostic testing alone (control strategy) in 8 emergency departments. METHODS: In this cluster-randomized, 2-period, crossover trial, 18- to 64-year-old patients presenting for reasons other than potential exposure to HIV were included. The strategy applied first was randomly assigned. During both periods, diagnostic testing was prescribed by physicians following usual care. During the intervention periods, patients were asked to complete a self-administered questionnaire. According to their answers, the triage nurse suggested performing a rapid test to patients belonging to a high-risk group. The primary outcome was the proportion of new diagnoses among included patients, which further refers to effectiveness. A secondary outcome was the intervention's incremental cost (health care system perspective) per additional diagnosis. RESULTS: During the intervention periods, 74,161 patients were included, 16,468 completed the questionnaire, 4,341 belonged to high-risk groups, and 2,818 were tested by nurses, yielding 13 new diagnoses. Combined with 9 diagnoses confirmed through 97 diagnostic tests, 22 new diagnoses were established. During the control periods, 74,166 patients were included, 92 were tested, and 6 received a new diagnosis. The proportion of new diagnoses among included patients was higher during the intervention than in the control periods (3.0 per 10,000 versus 0.8 per 10,000; difference 2.2 per 10,000, 95% CI 1.3 to 3.6; relative risk 3.7, 95% CI 1.4 to 9.8). The incremental cost was €1,324 per additional new diagnosis. CONCLUSION: The combined strategy of targeted screening and diagnostic testing was effective.
[Pt] Tipo de publicación:JOURNAL ARTICLE
[Em] Mes de ingreso:1711
[Cu] Fecha actualización por clase:171102
[Lr] Fecha última revisión:171102
[St] Status:Publisher


  3 / 305030 MEDLINE  
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[PMID]:28923796
[Au] Autor:Veilleux O; Lee TC; McDonald EG
[Ad] Dirección:Department of Medicine (Veilleux, Lee, McDonald), McGill University; Clinical Practice Assessment Unit (Lee, McDonald), McGill University Health Centre, Montréal, Que.
[Ti] Título:Rebound adrenal insufficiency after withdrawal of ritonavir in a 65-year-old man using inhaled budesonide.
[So] Fuente:CMAJ;189(37):E1188-E1191, 2017 09 18.
[Is] ISSN:1488-2329
[Cp] País de publicación:Canada
[La] Idioma:eng
[Mh] Términos MeSH primario: Insuficiencia Suprarrenal/etiología
Asma/quimioterapia
Budesonida/administración & dosificación
Infecciones por VIH/quimioterapia
Ritonavir/uso terapéutico
Privación de Tratamiento
[Mh] Términos MeSH secundario: Administración por Inhalación
Anciano
Asma/complicaciones
Broncodilatadores/administración & dosificación
Infecciones por VIH/complicaciones
Inhibidores de la Proteasa del VIH
Humanos
Masculino
[Pt] Tipo de publicación:CASE REPORTS; JOURNAL ARTICLE
[Nm] Nombre de substancia:
0 (Bronchodilator Agents); 0 (HIV Protease Inhibitors); 51333-22-3 (Budesonide); O3J8G9O825 (Ritonavir)
[Em] Mes de ingreso:1711
[Cu] Fecha actualización por clase:171102
[Lr] Fecha última revisión:171102
[Sb] Subgrupo de revista:AIM; IM
[Da] Fecha de ingreso para procesamiento:170919
[St] Status:MEDLINE
[do] DOI:10.1503/cmaj.170415


  4 / 305030 MEDLINE  
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[PMID]:28878089
[Au] Autor:Leitman EM; Willberg CB; Tsai MH; Chen H; Buus S; Chen F; Riddell L; Haas D; Fellay J; Goedert JJ; Piechocka-Trocha A; Walker BD; Martin J; Deeks S; Wolinsky SM; Martinson J; Martin M; Qi Y; Sáez-Cirión A; Yang OO; Matthews PC; Carrington M; Goulder PJR
[Ad] Dirección:Department of Paediatrics, University of Oxford, Oxford, United Kingdom ellen_leitman@hms.harvard.edu.
[Ti] Título:HLA-B*14:02-Restricted Env-Specific CD8 T-Cell Activity Has Highly Potent Antiviral Efficacy Associated with Immune Control of HIV Infection.
[So] Fuente:J Virol;91(22), 2017 Nov 15.
[Is] ISSN:1098-5514
[Cp] País de publicación:United States
[La] Idioma:eng
[Ab] Resumen:Immune control of human immunodeficiency virus type 1 (HIV) infection is typically associated with effective Gag-specific CD8 T-cell responses. We here focus on HLA-B*14, which protects against HIV disease progression, but the immunodominant HLA-B*14-restricted anti-HIV response is Env specific (ERYLKDQQL, HLA-B*14-EL9). A subdominant HLA-B*14-restricted response targets Gag (DRYFKTLRA, HLA-B*14-DA9). Using HLA-B*14/peptide-saporin-conjugated tetramers, we show that HLA-B*14-EL9 is substantially more potent at inhibiting viral replication than HLA-B*14-DA9. HLA-B*14-EL9 also has significantly higher functional avidity ( < 0.0001) and drives stronger selection pressure on the virus than HLA-B*14-DA9. However, these differences were HLA-B*14 subtype specific, applying only to HLA-B*14:02 and not to HLA-B*14:01. Furthermore, the HLA-B*14-associated protection against HIV disease progression is significantly greater for HLA-B*14:02 than for HLA-B*14:01, consistent with the superior antiviral efficacy of the HLA-B*14-EL9 response. Thus, although Gag-specific CD8 T-cell responses may usually have greater anti-HIV efficacy, factors independent of protein specificity, including functional avidity of individual responses, are also critically important to immune control of HIV. In HIV infection, although cytotoxic T lymphocytes (CTL) play a potentially critical role in eradication of viral reservoirs, the features that constitute an effective response remain poorly defined. We focus on HLA-B*14, unique among HLAs associated with control of HIV in that the dominant CTL response is Env specific, not Gag specific. We demonstrate that Env-specific HLA-B*14-restricted activity is substantially more efficacious than the subdominant HLA-B*14-restricted Gag response. Env immunodominance over Gag and strong Env-mediated selection pressure on HIV are observed only in subjects expressing HLA-B*14:02, and not HLA-B*14:01. This reflects the increased functional avidity of the Env response over Gag, substantially more marked for HLA-B*14:02. Finally, we show that HLA-B*14:02 is significantly more strongly associated with viremic control than HLA-B*14:01. These findings indicate that, although Gag-specific CTL may usually have greater anti-HIV efficacy than Env responses, factors independent of protein specificity, including functional avidity, may carry greater weight in mediating effective control of HIV.
[Mh] Términos MeSH primario: Proteínas gp160 de Envoltorio del VIH/inmunología
Infecciones por VIH/inmunología
VIH-1/inmunología
Antígeno HLA-B14/inmunología
Inmunidad Celular
Péptidos/inmunología
Productos del Gen gag del Virus de la Inmunodeficiencia Humana/inmunología
[Mh] Términos MeSH secundario: Adulto
Linfocitos T CD8-positivos
Infecciones por VIH/patología
Infecciones por VIH/terapia
Humanos
[Pt] Tipo de publicación:CLINICAL TRIAL; JOURNAL ARTICLE; MULTICENTER STUDY
[Nm] Nombre de substancia:
0 (HIV Envelope Protein gp160); 0 (HLA-B*14:01 antigen); 0 (HLA-B*14:02 antigen); 0 (HLA-B14 Antigen); 0 (Peptides); 0 (gag Gene Products, Human Immunodeficiency Virus)
[Em] Mes de ingreso:1711
[Cu] Fecha actualización por clase:171102
[Lr] Fecha última revisión:171102
[Sb] Subgrupo de revista:IM
[Da] Fecha de ingreso para procesamiento:170907
[St] Status:MEDLINE


  5 / 305030 MEDLINE  
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[PMID]:28878072
[Au] Autor:Sullivan JT; Sulli C; Nilo A; Yasmeen A; Ozorowski G; Sanders RW; Ward AB; Klasse PJ; Moore JP; Doranz BJ
[Ad] Dirección:Integral Molecular, Philadelphia, Pennsylvania, USA.
[Ti] Título:High-Throughput Protein Engineering Improves the Antigenicity and Stability of Soluble HIV-1 Envelope Glycoprotein SOSIP Trimers.
[So] Fuente:J Virol;91(22), 2017 Nov 15.
[Is] ISSN:1098-5514
[Cp] País de publicación:United States
[La] Idioma:eng
[Ab] Resumen:Soluble envelope glycoprotein (Env) trimers (SOSIP.664 gp140) are attractive HIV-1 vaccine candidates, with structures that mimic the native membrane-bound Env spike (gp160). Since engineering trimers can be limited by the difficulty of rationally predicting beneficial mutations, here we used a more comprehensive mutagenesis approach with the goal of identifying trimer variants with improved antigenic and stability properties. We created 341 cysteine pairs at predicted points of stabilization throughout gp140, 149 proline residue substitutions at every residue of the gp41 ectodomain, and 362 space-filling residue substitutions at every hydrophobic and aromatic residue in gp140. The parental protein target, the clade B strain B41 SOSIP.664 gp140, does not bind the broadly neutralizing antibody PGT151 and so was used here to identify improved variants that also provide insight into the structural basis for Env antigenicity. Each of the 852 mutants was expressed in human cells and screened for antigenicity using four different monoclonal antibodies (MAbs), including PGT151. We identified 29 trimer variants with antigenic improvements derived from each of the three mutagenesis strategies. We selected four variants (Q203F, T538F, I548F, and M629P) for more comprehensive biochemical, structural, and antigenicity analyses. The T538F substitution had the most beneficial effect overall, including restoration of the PGT151 epitope. The improved B41 SOSIP.664 trimer variants identified here may be useful for vaccine and structural studies. Soluble Env trimers have become attractive HIV-1 vaccine candidates, but the prototype designs are capable of further improvement through protein engineering. Using a high-throughput screening technology (shotgun mutagenesis) to create and evaluate 852 variants, we were able to identify sequence changes that were beneficial to the antigenicity and stability of soluble trimers based on the clade B B41 gene. The strategies described here may be useful for identifying a wider range of antigenically and structurally improved soluble trimers based on multiple genotypes for use in programs intended to create a broadly protective HIV-1 vaccine.
[Mh] Términos MeSH primario: Vacunas contra el SIDA/inmunología
Sustitución de Aminoácidos
Proteínas gp160 de Envoltorio del VIH/inmunología
VIH-1/inmunología
Mutagénesis
Mutación Missense
[Mh] Términos MeSH secundario: Vacunas contra el SIDA/genética
Anticuerpos Monoclonales de Origen Murino/inmunología
Anticuerpos Neutralizantes/inmunología
Células HEK293
Anticuerpos Anti-VIH/inmunología
Proteínas gp160 de Envoltorio del VIH/genética
VIH-1/genética
Humanos
[Pt] Tipo de publicación:JOURNAL ARTICLE
[Nm] Nombre de substancia:
0 (AIDS Vaccines); 0 (Antibodies, Monoclonal, Murine-Derived); 0 (Antibodies, Neutralizing); 0 (HIV Antibodies); 0 (HIV Envelope Protein gp160)
[Em] Mes de ingreso:1711
[Cu] Fecha actualización por clase:171102
[Lr] Fecha última revisión:171102
[Sb] Subgrupo de revista:IM
[Da] Fecha de ingreso para procesamiento:170907
[St] Status:MEDLINE


  6 / 305030 MEDLINE  
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[PMID]:28865865
[Au] Autor:Brewer JD; Elston DM; Vidimos AT; Rizza SA; Miller SJ
[Ad] Dirección:Division of Dermatologic Surgery, Mayo Clinic, Rochester, Minnesota. Electronic address: brewer.jerry@mayo.edu.
[Ti] Título:Managing sharps injuries and other occupational exposures to HIV, HBV, and HCV in the dermatology office.
[So] Fuente:J Am Acad Dermatol;77(5):946-951.e6, 2017 Nov.
[Is] ISSN:1097-6787
[Cp] País de publicación:United States
[La] Idioma:eng
[Ab] Resumen: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/.
[Mh] Términos MeSH primario: Patógenos Transmitidos por la Sangre
Transmisión de Enfermedad Infecciosa de Paciente a Profesional/prevención & control
Lesiones por Pinchazo de Aguja/prevención & control
Exposición Profesional/efectos adversos
Salud Laboral
[Mh] Términos MeSH secundario: Dermatología
Infecciones por VIH/transmisión
Hepacivirus/aislamiento & purificación
Hepatitis B/transmisión
Virus de la Hepatitis B/aislamiento & purificación
Hepatitis C/transmisión
Humanos
Masculino
Lesiones por Pinchazo de Aguja/epidemiología
Visita a Consultorio Médico
[Pt] Tipo de publicación:COMPARATIVE STUDY; JOURNAL ARTICLE; REVIEW
[Em] Mes de ingreso:1711
[Cu] Fecha actualización por clase:171102
[Lr] Fecha última revisión:171102
[Sb] Subgrupo de revista:IM
[Da] Fecha de ingreso para procesamiento:170903
[St] Status:MEDLINE


  7 / 305030 MEDLINE  
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[PMID]:28828489
[Au] Autor:Gulick RM; Wilkin TJ; Chen YQ; Landovitz RJ; Amico KR; Young AM; Richardson P; Marzinke MA; Hendrix CW; Eshleman SH; McGowan I; Cottle LM; Andrade A; Marcus C; Klingman KL; Chege W; Rinehart AR; Rooney JF; Andrew P; Salata RA; Siegel M; Manabe YC; Frank I; Ho K; Santana J; Stekler JD; Swaminathan S; McCauley M; Hodder S; Mayer KH
[Ad] Dirección:From Weill Cornell Medicine, New York, New York; Fred Hutchinson Cancer Research Center and University of Washington, Seattle, Washington; University of California, Los Angeles, Los Angeles, California; University of Michigan, Ann Arbor, Michigan; Johns Hopkins University School of Medicine, Baltimo
[Ti] Título:Safety and Tolerability of Maraviroc-Containing Regimens to Prevent HIV Infection in Women: A Phase 2 Randomized Trial.
[So] Fuente:Ann Intern Med;167(6):384-393, 2017 Sep 19.
[Is] ISSN:1539-3704
[Cp] País de publicación:United States
[La] Idioma:eng
[Ab] Resumen:Background: Maraviroc (MVC) is a candidate drug for HIV preexposure prophylaxis (PrEP). Objective: To assess the safety and tolerability of MVC-containing PrEP over 48 weeks in U.S. women at risk for HIV infection. Design: Phase 2 randomized, controlled, double-blinded study of 4 antiretroviral regimens used as PrEP. (ClinicalTrials.gov: NCT01505114). Setting: 12 clinical research sites of the HIV Prevention Trials Network and AIDS Clinical Trials Group. Participants: HIV-uninfected women reporting condomless vaginal or anal intercourse with at least 1 man with HIV infection or unknown serostatus within 90 days. Intervention: MVC only, MVC-emtricitabine (FTC), MVC-tenofovir disoproxil fumarate (TDF), and TDF-FTC (control). Measurements: At each visit, clinical and laboratory (including HIV) assessments were done. Primary outcomes were grade 3 and 4 adverse events and time to permanent discontinuation of the study regimen. All randomly assigned participants were analyzed according to their original assignment. Results: Among 188 participants, 85% completed follow-up, 11% withdrew early, and 4% were lost to follow-up; 19% discontinued their regimen prematurely. The number discontinuing and the time to discontinuation did not differ among regimens. Grade 3 or 4 adverse events occurred in 5 (MVC), 13 (MVC-FTC), 9 (MVC-TDF), and 8 (TDF-FTC) participants; rates did not differ among regimens. One death (by suicide) occurred in the MVC-TDF group but was judged not to be related to study drugs. Of available plasma samples at week 48 (n = 126), 60% showed detectable drug concentrations. No new HIV infections occurred. Limitations: Participants were not necessarily at high risk for HIV infection. The regimen comprised 3 pills taken daily. The study was not powered for efficacy. Conclusion: Maraviroc-containing PrEP regimens were safe and well-tolerated compared with TDF-FTC in U.S. women. No new HIV infections occurred, although whether this was due to study drugs or low risk in the population is uncertain. Maraviroc-containing PrEP for women may warrant further study. Primary Funding Source: National Institutes of Health.
[Mh] Términos MeSH primario: Ciclohexanos/efectos adversos
Ciclohexanos/uso terapéutico
Inhibidores de Fusión de VIH/efectos adversos
Inhibidores de Fusión de VIH/uso terapéutico
Infecciones por VIH/prevención & control
Profilaxis Pre-Exposición
Triazoles/efectos adversos
Triazoles/uso terapéutico
[Mh] Términos MeSH secundario: Adolescente
Adulto
Método Doble Ciego
Femenino
Estudios de Seguimiento
Humanos
Mediana Edad
Pacientes Desistentes del Tratamiento
Estudios Prospectivos
Resultado del Tratamiento
Adulto Joven
[Pt] Tipo de publicación:CLINICAL TRIAL, PHASE II; JOURNAL ARTICLE; RANDOMIZED CONTROLLED TRIAL
[Nm] Nombre de substancia:
0 (Cyclohexanes); 0 (HIV Fusion Inhibitors); 0 (Triazoles); MD6P741W8A (maraviroc)
[Em] Mes de ingreso:1709
[Cu] Fecha actualización por clase:171103
[Lr] Fecha última revisión:171103
[Sb] Subgrupo de revista:AIM; IM
[Da] Fecha de ingreso para procesamiento:170822
[St] Status:MEDLINE
[do] DOI:10.7326/M17-0520


  8 / 305030 MEDLINE  
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[PMID]:28774464
[Au] Autor:Anderson AM; Schein TN; Kalapila A; Lai L; Waldrop-Valverde D; Moore RC; Franklin D; Letendre SL; Barnum SR
[Ad] Dirección:Department of Medicine, Emory University School of Medicine, Atlanta, GA, United States. Electronic address: aande2@emory.edu.
[Ti] Título:Soluble membrane attack complex in the blood and cerebrospinal fluid of HIV-infected individuals, relationship to HIV RNA, and comparison with HIV negatives.
[So] Fuente:J Neuroimmunol;311:35-39, 2017 Oct 15.
[Is] ISSN:1872-8421
[Cp] País de publicación:Netherlands
[La] Idioma:eng
[Ab] Resumen:The soluble membrane attack complex (sMAC) represents the terminal product of the complement cascade. We enrolled 47 HIV+ adults (12 of whom underwent a second visit at least 24weeks after starting therapy) as well as 11 HIV negative controls. At baseline, cerebrospinal fluid (CSF) sMAC was detectable in 27.7% of HIV+ individuals. CSF sMAC correlated with CSF HIV RNA levels and was more likely to be detectable in HIV+ individuals on cART compared to HIV negative controls. In HIV+ participants, there were negative association trends between sMAC and neurocognitive performance but these did not reach statistical significance.
[Mh] Términos MeSH primario: Complejo de Ataque a Membrana del Sistema Complemento/metabolismo
Infecciones por VIH/sangre
Infecciones por VIH/líquido cefalorraquídeo
VIH-1/genética
ARN/líquido cefalorraquídeo
[Mh] Términos MeSH secundario: Adulto
Antirretrovirales/uso terapéutico
Linfocitos T CD4-Positivos/patología
Linfocitos T CD4-Positivos/virología
Trastornos del Conocimiento/etiología
Trastornos del Conocimiento/virología
Femenino
Infecciones por VIH/complicaciones
Infecciones por VIH/quimioterapia
Humanos
Estudios Longitudinales
Masculino
Mediana Edad
Estadística como Asunto
[Pt] Tipo de publicación:JOURNAL ARTICLE
[Nm] Nombre de substancia:
0 (Anti-Retroviral Agents); 0 (Complement Membrane Attack Complex); 63231-63-0 (RNA)
[Em] Mes de ingreso:1709
[Cu] Fecha actualización por clase:171103
[Lr] Fecha última revisión:171103
[Sb] Subgrupo de revista:IM
[Da] Fecha de ingreso para procesamiento:170804
[St] Status:MEDLINE


  9 / 305030 MEDLINE  
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[PMID]:28637761
[Au] Autor:Naidoo VL; Mann JK; Noble C; Adland E; Carlson JM; Thomas J; Brumme CJ; Thobakgale-Tshabalala CF; Brumme ZL; Brockman MA; Goulder PJR; Ndung'u T
[Ad] Dirección:HIV Pathogenesis Programme, Doris Duke Medical Research Institute, Nelson R. Mandela School of Medicine, University of KwaZulu-Natal, Durban, South Africa.
[Ti] Título:Mother-to-Child HIV Transmission Bottleneck Selects for Consensus Virus with Lower Gag-Protease-Driven Replication Capacity.
[So] Fuente:J Virol;91(17), 2017 Sep 01.
[Is] ISSN:1098-5514
[Cp] País de publicación:United States
[La] Idioma:eng
[Ab] Resumen:In the large majority of cases, HIV infection is established by a single variant, and understanding the characteristics of successfully transmitted variants is relevant to prevention strategies. Few studies have investigated the viral determinants of mother-to-child transmission. To determine the impact of Gag-protease-driven viral replication capacity on mother-to-child transmission, the replication capacities of 148 recombinant viruses encoding plasma-derived Gag-protease from 53 nontransmitter mothers, 48 transmitter mothers, and 47 infected infants were assayed in an HIV-1-inducible green fluorescent protein reporter cell line. All study participants were infected with HIV-1 subtype C. There was no significant difference in replication capacities between the nontransmitter ( = 53) and transmitter ( = 44) mothers ( = 0.48). Infant-derived Gag-protease NL4-3 recombinant viruses ( = 41) were found to have a significantly lower Gag-protease-driven replication capacity than that of viruses derived from the mothers ( < 0.0001 by a paired test). High percent similarities to consensus subtype C Gag, p17, p24, and protease sequences were also found in the infants ( = 28) in comparison to their mothers ( = 0.07, = 0.002, = 0.03, and = 0.02, respectively, as determined by a paired test). These data suggest that of the viral quasispecies found in mothers, the HIV mother-to-child transmission bottleneck favors the transmission of consensus-like viruses with lower viral replication capacities. Understanding the characteristics of successfully transmitted HIV variants has important implications for preventative interventions. Little is known about the viral determinants of HIV mother-to-child transmission (MTCT). We addressed the role of viral replication capacity driven by Gag, a major structural protein that is a significant determinant of overall viral replicative ability and an important target of the host immune response, in the MTCT bottleneck. This study advances our understanding of the genetic bottleneck in MTCT by revealing that viruses transmitted to infants have a lower replicative ability as well as a higher similarity to the population consensus (in this case HIV subtype C) than those of their mothers. Furthermore, the observation that "consensus-like" virus sequences correspond to lower replication abilities yet appear to be preferentially transmitted suggests that viral characteristics favoring transmission are decoupled from those that enhance replicative capacity.
[Mh] Términos MeSH primario: Infecciones por VIH/transmisión
VIH-1/fisiología
Transmisión Vertical de Enfermedad Infecciosa
Replicación Viral
Productos del Gen gag del Virus de la Inmunodeficiencia Humana/genética
[Mh] Términos MeSH secundario: Progresión de la Enfermedad
Femenino
Infecciones por VIH/virología
VIH-1/clasificación
Humanos
Lactante
Modelos Logísticos
Masculino
Sudáfrica
[Pt] Tipo de publicación:JOURNAL ARTICLE
[Nm] Nombre de substancia:
0 (gag Gene Products, Human Immunodeficiency Virus)
[Em] Mes de ingreso:1708
[Cu] Fecha actualización por clase:171103
[Lr] Fecha última revisión:171103
[Sb] Subgrupo de revista:IM
[Da] Fecha de ingreso para procesamiento:170622
[St] Status:MEDLINE


  10 / 305030 MEDLINE  
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[PMID]:28407813
[Au] Autor:Audet CM; Salato J; Vermund SH; Amico KR
[Ad] Dirección:Vanderbilt Institute for Global Health, Vanderbilt University Medical Center, Nashville, TN, USA. carolyn.m.audet@vanderbilt.edu.
[Ti] Título:Adapting an adherence support workers intervention: engaging traditional healers as adherence partners for persons enrolled in HIV care and treatment in rural Mozambique.
[So] Fuente:Implement Sci;12(1):50, 2017 Apr 13.
[Is] ISSN:1748-5908
[Cp] País de publicación:England
[La] Idioma:eng
[Ab] Resumen:BACKGROUND: Systematic adaptation of evidence-informed interventions that increase retention in care and improve adherence to antiretroviral therapy (ART) are essential to ending the HIV epidemic in rural sub-Saharan Africa. We selected and adapted an adherence support worker intervention employed in Malawi for use by traditional healers in rural Mozambique. Given the levels of trust and dependence previously expressed by persons living with HIV (PLHIV) for traditional medicine, we adapted the program to engage traditional healers within the allopathic health system. METHODS: Adaption followed a theoretically driven approach to intervention adaption: the Assessment-Decision-Administration-Production-Topical Experts-Integration-Training-Testing (ADAPT-ITT) model. Three rounds of performance feedback, based on theater presentations of the adapted intervention for stakeholders and idea generation, were completed with 12 groups from March to July 2016 to develop the final model. We offered healer support to 180 newly diagnosed HIV-infected patients. RESULTS: Traditional healers were an acceptable group of community health workers to assist with patient adherence and retention. Traditional healers, clinicians, and interested community members suggested novel strategies to tailor the adherence support worker intervention, revealing a local culture of HIV denialism, aversion to the health system, and dislike of healthcare providers, as well as a preference for traditional treatments. Proposed changes to the intervention included modifications to the training language and topics, expanded community-based activities to support acceptability of an HIV diagnosis and to facilitate partner disclosure, and accompaniment to the health facility by healers to encourage delivery of respectful clinical care. PLHIV, healers, and clinicians deemed the intervention socially acceptable during focus groups. We subsequently recruited 180 newly diagnosed HIV-infected patients into the program: 170 (94%) accepted. CONCLUSIONS: Systematic translation of interventions, even between regions with similar social and economic environments, is an important first step to successful program implementation. Efforts previously limited to community health workers can be tailored for use by traditional healers-an underutilized and often maligned health workforce. It proved feasible to use theater-based performances to demonstrate delivery of the intervention in low-literacy populations, generating discussions about social norms, community concerns, and the merits of an acceptable strategy to improve retention and adherence to ART.
[Mh] Términos MeSH primario: Antivirales/uso terapéutico
Infecciones por VIH/quimioterapia
Medicina Tradicional Africana/métodos
Cooperación del Paciente/estadística & datos numéricos
Evaluación de Programas y Proyectos de Salud
Apoyo Social
[Mh] Términos MeSH secundario: Adulto
Servicios de Salud Comunitaria
Femenino
Infecciones por VIH/terapia
Humanos
Masculino
Mediana Edad
Mozambique
Población Rural
Adulto Joven
[Pt] Tipo de publicación:JOURNAL ARTICLE
[Nm] Nombre de substancia:
0 (Antiviral Agents)
[Em] Mes de ingreso:1711
[Cu] Fecha actualización por clase:171102
[Lr] Fecha última revisión:171102
[Sb] Subgrupo de revista:IM
[Da] Fecha de ingreso para procesamiento:170414
[St] Status:MEDLINE
[do] DOI:10.1186/s13012-017-0582-z



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