Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 5.267
Filtrar
1.
J Korean Med Sci ; 35(39): e358, 2020 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-33045775

RESUMO

Although some comorbidities, such as diabetes mellitus, lung disease, and chronic kidney disease, are known as risk factors for poor clinical outcome in patients with coronavirus disease 2019 (COVID-19), it is unknown if human immunodeficiency virus (HIV) patients with COVID-19 would have poor prognosis than others. Rare cases of HIV patients with COVID-19 have been reported. As of May 25th, 2020, over 11,000 patients have been diagnosed with COVID-19 and over 13,000 are living with HIV in Korea. Here, we present the first HIV patient with COVID-19 in Korea. The 29-year-old Korean man had been taking Genvoya® regularly for seven years and HIV was well suppressed with CD4 counts of 555/mm³. He had mild symptoms of sore throat, dry cough, loss of taste and smell. He received hydroxychloroquine while Genvoya® was continued. Pneumonia diagnosed in chest computed tomography improved without oxygen supplementation. He was discharged on hospital day 31. HIV patients are considered as immunocompromised, but this case suggests that well controlled HIV patients have satisfactory prognosis following proper medical care.


Assuntos
Infecções por Coronavirus/diagnóstico , Infecções por HIV/patologia , Pneumonia Viral/diagnóstico , Adulto , Betacoronavirus/genética , Betacoronavirus/isolamento & purificação , Contagem de Linfócito CD4 , Infecções por Coronavirus/complicações , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/virologia , Infecções por HIV/complicações , Humanos , Hidroxicloroquina/uso terapêutico , Masculino , Pandemias , Pneumonia Viral/complicações , Pneumonia Viral/tratamento farmacológico , Pneumonia Viral/virologia , Prognóstico , RNA Viral/genética , RNA Viral/metabolismo , Reação em Cadeia da Polimerase em Tempo Real , Tomografia Computadorizada por Raios X
2.
BMC Infect Dis ; 20(1): 732, 2020 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-33028241

RESUMO

BACKGROUND: Adolescent sexual debut and non-consensual sex have been linked to higher sexual risk and STI infection in adulthood among men who have sex with men (MSM) in high-income countries. This study aimed to examine adolescent and non-consensual anal sexual debut among Chinese MSM and to evaluate factors associated with adolescent sexual debut and non-consensual anal sex. METHODS: A cross-sectional study was conducted recently among Chinese men assigned male sex at birth, ≥18 years old, and who had ever engaged in anal sex with a man. Participants answered questions regarding socio-demographics, condomless sex, age at anal sexual debut with a man, and whether the first anal sex was consensual. Factors associated with an adolescent sexual debut (< 18 years old) and non-consensual sex at sexual debut were evaluated. We defined adolescent sexual debut as having anal sex with another man at 17 years old or younger, and the participants were asked whether their first male-to-male anal sex was non-consensual. RESULTS: Overall, 2031 eligible men completed the survey. The mean age of sexual debut was 20.7 (SD = 4.3) years old. 17.6% (358/2031) of men reported adolescent sexual debut, and 5.0% (101/2031) reported a non-consensual sexual debut. The adolescent sexual debut was associated with having more male sexual partners (adjusted OR 1.10, 95% CI 1.06-1.15) and condomless anal sex in the last three months (AOR = 1.71, 95% CI 1.34-2.18). MSM whose sexual debut was non-consensual were more likely to have condomless anal sex (AOR = 1.76, 95% CI 1.17-2.66), and to have reported an adolescent sexual debut (AOR = 2.72, 95% CI 1.75-4.21). CONCLUSIONS: Many Chinese MSM reported adolescent sexual debut and non-consensual sex, both of which are associated with sexual risk behaviors and drive STI transmission. These findings highlight the need for designing tailored interventions for MSM who experienced adolescent sexual debut and non-consensual sex at debut.


Assuntos
Homossexualidade Masculina/estatística & dados numéricos , Comportamento Sexual/estatística & dados numéricos , Adolescente , Adulto , Grupo com Ancestrais do Continente Asiático , China , Preservativos , Estudos Transversais , Infecções por HIV/patologia , Humanos , Masculino , Razão de Chances , Assunção de Riscos , Inquéritos e Questionários , Adulto Jovem
3.
Medicine (Baltimore) ; 99(40): e22408, 2020 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-33019417

RESUMO

The epidemiology of lymphomas has changed since the use of antiretroviral therapy. The incidence of Non-Hodgkin Lymphomas (NHL) has significantly decreased in high income countries but not in low and middle-income countries where AIDS-related events remain high. This observational study describes the characteristics, infectious complications and main outcomes of patients diagnosed with HIV and lymphoma at the Instituto Nacional de Cancerología.All adults >18 years diagnosed with HIV and lymphoma from January 2010 to December 2017 were included. Information on HIV and lymphoma was collected, as well as the occurrence of co-infections at diagnosis and during therapy. Multiple regression was done with NHL patients to evaluate independent variables associated to death.One hundred fifty three patients were included: 127 patients with NHL (83%) and 26 (17%) with Hodgkin lymphoma (HL). Of the NHL, 49 (38%) were diffuse large B cell Lymphomas (DLBCL), 35 (27%) plasmablastic, 28 (23%) Burkitt, 10 (8%) primary DLBCL of Central Nervous system, 3 (2%) T-cell lymphomas, and 2 (2%) pleural effusion lymphoma. Most patients were diagnosed in an advanced stage: 70% of NHL had a high International Prognostic Index (IPI); 68% of patients had <200 cells/mm. Almost 25% of NHL patients had an opportunistic infection at lymphoma diagnosis. During chemotherapy, 60% of all patients presented with at least 1 serious non-opportunistic infectious complication, and 50% presented 2 or more infectious complications, mostly bacterial infections. Thirty six percent of NHL and 23% of HL died. After adjusting for confounders, the variables associated with death were IPI and lymphoma type.HIV positive patients with lymphoma in our institution are diagnosed with an advanced stage and a high burden of infections complications. Death remains high and the variables strongly associated with death are those related to lymphoma prognosis such as lymphoma type and IPI.


Assuntos
Infecções por HIV/epidemiologia , Doença de Hodgkin/epidemiologia , Doença de Hodgkin/patologia , Linfoma não Hodgkin/epidemiologia , Linfoma não Hodgkin/patologia , Infecções Oportunistas/epidemiologia , Adulto , Feminino , Infecções por HIV/patologia , Humanos , Masculino , México/epidemiologia , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Infecções Oportunistas/microbiologia , Estudos Retrospectivos
4.
Medicine (Baltimore) ; 99(40): e22416, 2020 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-33019418

RESUMO

Human immunodeficiency virus (HIV) supresses immune system, primarily cell-mediated immunity. Cluster of differentiation 4 (CD4) cell count, viral load, and oral lesions are the most important laboratory parameters to evaluate the evolution of acquired immunodeficiency syndrome. The present study aims to determine the incidence of HIV-related oral lesions with CD4 cell count and viral load in Yunnan, China.A cross-sectional study was conducted from December 2007 to December 2009, in 1812 HIV positive patients from Department of Infectious Diseases in Kunming Third People's Hospital. CD4, CD8, and viral load data were collected and analyzed statistically using SPSS 11.3.Out of 1812 HIV positive patients, 929 (51.27%) were associated with 1 or more oral lesions. The most common oral lesions observed were Candida Pseudomembranous (13.75%), Candida erythematous (10.93%), Oral hairy leukoplakia (7.95%), Aphthous ulcer (6.18%), Herpes simplex infection (5.58%). In most patients with oral lesions, the CD4 cell count was < 200/µL. The incidence of oral lesions was lower when CD4 count was > 200/µL and with undetectable (P < .01) HIV viral load. Almost no oral lesions was observed when CD4 count > 500/µL (P < .01). With highly active antiretroviral therapy, reduction in HIV-related oral lesions was observed especially in Candida erythematous, Candida Pseudomembranous, Oral hairy leukoplakia, and Aphthous ulcer.The higher incidence of oral lesions with lower CD4 count (<200/µL) in HIV-infected patients indicated importance of CD4 cell count in identifying disease progression.


Assuntos
Contagem de Linfócito CD4/estatística & dados numéricos , Infecções por HIV/epidemiologia , Doenças da Boca/epidemiologia , Carga Viral/fisiologia , Síndrome de Imunodeficiência Adquirida/epidemiologia , Síndrome de Imunodeficiência Adquirida/patologia , Adulto , Terapia Antirretroviral de Alta Atividade/métodos , China/epidemiologia , Estudos Transversais , Feminino , Infecções por HIV/tratamento farmacológico , Infecções por HIV/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Doenças da Boca/microbiologia , Adulto Jovem
5.
BMC Infect Dis ; 20(1): 738, 2020 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-33028260

RESUMO

BACKGROUND: In accordance with international guidance for tuberculosis (TB) prevention, the Tanzanian Ministry of Health recommends isoniazid preventive therapy (IPT) for children aged 12 months and older who are living with HIV. Concerns about tolerability, adherence, and potential mistreatment of undiagnosed TB with monotherapy have limited uptake of IPT globally, especially among children, in whom diagnostic confirmation is challenging. We assessed IPT implementation and adherence at a pediatric HIV clinic in Tanzania. METHODS: In this prospective cohort study, eligible children living with HIV aged 1-15 years receiving care at the DarDar Pediatric Program in Dar es Salaam who screened negative for TB disease were offered a 6-month regimen of daily isoniazid. Patients could choose to receive IPT via facility- or community-based care. Parents/caregivers and children provided informed consent and verbal assent respectively. Isoniazid was dispensed with the child's antiretroviral therapy every 1-3 months. IPT adherence and treatment completion was determined by pill counts, appointment attendance, and self-report. Patients underwent TB symptom screening at every visit. RESULTS: We enrolled 66 children between July and December 2017. No patients/caregivers declined IPT. Most participants were female (n = 43, 65.1%) and the median age was 11 years (interquartile range [IQR] 8, 13). 63 (95.5%) participants chose the facility-based model; due to the small number of participants who chose the community-based model, valid comparisons between the two groups could not be made. Forty-nine participants (74.2%) completed IPT within 10 months. Among the remaining 17, 11 had IPT discontinued by their provider due to adverse drug reactions, 5 lacked documentation of completion, and 1 had unknown outcomes due to missing paperwork. Of those who completed IPT, the average monthly adherence was 98.0%. None of the participants were diagnosed with TB while taking IPT or during a median of 4 months of follow-up. CONCLUSIONS: High adherence and treatment completion rates can be achieved when IPT is integrated into routine, self-selected facility-based pediatric HIV care. Improved record-keeping may yield even higher completion rates. IPT was well tolerated and no cases of TB were detected. IPT for children living with HIV is feasible and should be implemented throughout Tanzania.


Assuntos
Antituberculosos/uso terapêutico , Infecções por HIV/patologia , Isoniazida/uso terapêutico , Tuberculose/prevenção & controle , Adolescente , Instituições de Assistência Ambulatorial , Antirretrovirais/uso terapêutico , Cuidadores/psicologia , Criança , Pré-Escolar , Feminino , Infecções por HIV/tratamento farmacológico , Humanos , Lactente , Masculino , Adesão à Medicação , Cooperação do Paciente , Estudos Prospectivos , Tanzânia , Resultado do Tratamento
7.
Molecules ; 25(21)2020 Oct 22.
Artigo em Inglês | MEDLINE | ID: mdl-33105694

RESUMO

Viral infections and associated diseases are responsible for a substantial number of mortality and public health problems around the world. Each year, infectious diseases kill 3.5 million people worldwide. The current pandemic caused by COVID-19 has become the greatest health hazard to people in their lifetime. There are many antiviral drugs and vaccines available against viruses, but they have many disadvantages, too. There are numerous side effects for conventional drugs, and active mutation also creates drug resistance against various viruses. This has led scientists to search herbs as a source for the discovery of more efficient new antivirals. According to the World Health Organization (WHO), 65% of the world population is in the practice of using plants and herbs as part of treatment modality. Additionally, plants have an advantage in drug discovery based on their long-term use by humans, and a reduced toxicity and abundance of bioactive compounds can be expected as a result. In this review, we have highlighted the important viruses, their drug targets, and their replication cycle. We provide in-depth and insightful information about the most favorable plant extracts and their derived phytochemicals against viral targets. Our major conclusion is that plant extracts and their isolated pure compounds are essential sources for the current viral infections and useful for future challenges.


Assuntos
Antivirais/uso terapêutico , Infecções por Coronavirus/tratamento farmacológico , Infecções por HIV/tratamento farmacológico , Hepatite C Crônica/tratamento farmacológico , Herpes Simples/tratamento farmacológico , Influenza Humana/tratamento farmacológico , Compostos Fitoquímicos/uso terapêutico , Pneumonia Viral/tratamento farmacológico , Antivirais/química , Antivirais/classificação , Antivirais/isolamento & purificação , Betacoronavirus/efeitos dos fármacos , Betacoronavirus/patogenicidade , Betacoronavirus/fisiologia , Infecções por Coronavirus/patologia , Infecções por Coronavirus/virologia , Descoberta de Drogas , HIV/efeitos dos fármacos , HIV/patogenicidade , HIV/fisiologia , Infecções por HIV/patologia , Infecções por HIV/virologia , Hepacivirus/efeitos dos fármacos , Hepacivirus/patogenicidade , Hepacivirus/fisiologia , Hepatite C Crônica/patologia , Hepatite C Crônica/virologia , Herpes Simples/patologia , Herpes Simples/virologia , Humanos , Influenza Humana/patologia , Influenza Humana/virologia , Orthomyxoviridae/efeitos dos fármacos , Orthomyxoviridae/patogenicidade , Orthomyxoviridae/fisiologia , Pandemias , Compostos Fitoquímicos/química , Compostos Fitoquímicos/classificação , Compostos Fitoquímicos/isolamento & purificação , Plantas Medicinais , Pneumonia Viral/patologia , Pneumonia Viral/virologia , Simplexvirus/efeitos dos fármacos , Simplexvirus/patogenicidade , Simplexvirus/fisiologia , Internalização do Vírus/efeitos dos fármacos , Replicação Viral/efeitos dos fármacos
8.
Sci Adv ; 6(35): eaba7910, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32923629

RESUMO

Targeting a universal host protein exploited by most viruses would be a game-changing strategy that offers broad-spectrum solution and rapid pandemic control including the current COVID-19. Here, we found a common YxxØ-motif of multiple viruses that exploits host AP2M1 for intracellular trafficking. A library chemical, N-(p-amylcinnamoyl)anthranilic acid (ACA), was identified to interrupt AP2M1-virus interaction and exhibit potent antiviral efficacy against a number of viruses in vitro and in vivo, including the influenza A viruses (IAVs), Zika virus (ZIKV), human immunodeficiency virus, and coronaviruses including MERS-CoV and SARS-CoV-2. YxxØ mutation, AP2M1 depletion, or disruption by ACA causes incorrect localization of viral proteins, which is exemplified by the failure of nuclear import of IAV nucleoprotein and diminished endoplasmic reticulum localization of ZIKV-NS3 and enterovirus-A71-2C proteins, thereby suppressing viral replication. Our study reveals an evolutionarily conserved mechanism of protein-protein interaction between host and virus that can serve as a broad-spectrum antiviral target.


Assuntos
Proteínas Adaptadoras de Transporte Vesicular/metabolismo , Antivirais/farmacologia , Cinamatos/farmacologia , Infecções por Coronavirus/tratamento farmacológico , Infecções por HIV/tratamento farmacológico , Influenza Humana/tratamento farmacológico , Pneumonia Viral/tratamento farmacológico , ortoaminobenzoatos/farmacologia , Células A549 , Animais , Betacoronavirus/efeitos dos fármacos , Sítios de Ligação/genética , Linhagem Celular Tumoral , Chlorocebus aethiops , Infecções por Coronavirus/patologia , Cães , Células HEK293 , Infecções por HIV/patologia , HIV-1/efeitos dos fármacos , Interações Hospedeiro-Patógeno/efeitos dos fármacos , Humanos , Vírus da Influenza A/efeitos dos fármacos , Influenza Humana/patologia , Células Madin Darby de Rim Canino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Camundongos Knockout , Coronavírus da Síndrome Respiratória do Oriente Médio/efeitos dos fármacos , Pandemias , Pneumonia Viral/patologia , Ligação Proteica/genética , Transporte Proteico/efeitos dos fármacos , RNA Viral/genética , Receptor de Interferon alfa e beta/genética , Fator de Crescimento Transformador beta1/metabolismo , Células Vero , Replicação Viral/efeitos dos fármacos , Zika virus/efeitos dos fármacos , Infecção por Zika virus/patologia
9.
PLoS One ; 15(9): e0238231, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32881883

RESUMO

BACKGROUND: In Ethiopia, uncomplicated severe acute malnutrition is managed through the outpatient therapeutic program at health posts level. This brings the services for the management of Severe Acute Malnutrition closer to the community by making services available at decentralized treatment points within the primary health care settings. So far, evidence of the treatment outcome of the program is limited. OBJECTIVE: The main aim of this study was to determine the magnitude of treatment outcomes of severe acute malnutrition and associated factors among under-five children at outpatient therapeutic feeding units in Gubalafto Wereda, Ethiopia, 2019. METHODS: This was a retrospective cohort study conducted on 600 children who had been managed for Severe Acute Malnutrition (SAM) under Outpatient Therapeutic Program (OTP) in Gubalafto Wereda from April to May/2019. The children were selected using systematic random sampling from 9 health posts. The structured, pre-tested, and adapted questionnaire was used to collect the data. The data was entered by using EPI-data Version 4.2 and exported to SPSS version 24.0 for analysis. Bivariate and Multivariate regression was also carried out to determine the association between dependent and independent variables. RESULTS: A total of 600 records of children with a diagnosis of severe acute malnutrition were reviewed. Of these cases of malnutrition, the recovery rate was found to be 65%. The death rate, default rate, and medical transfer were 2.0, 16.0, and 17.0 respectively. Immunized children had 6.85 times higher odds of recovery than children who were not immunized (AOR = 6.85 at 95% CI (3.68-12.76)). The likelihood of recovery was 3.78 times higher among children with new admission than those with re-admission (AOR = 3.78at 95% CI ((1.77-8.07))). Likewise, children provided with amoxicillin were 3.38 times recovered than their counterparts (AOR = 3.38 at 95% CI ((1.61-7.08))). SAM treatment in OTP is beneficial because of its local access for most severe cases since children reach early before developing complications as a result fatalities will be reduced. CONCLUSIONS: The recovery rate and medical transfer were lower than the sphere standard. Presence of cough, presence of diarrhea admission category, provision of amoxicillin, and immunization status were factors identified as significantly associated with treatment outcome of severe acute malnutrition. The impact on increasing the recovery rates of children treated using the OTP service indicates the potential benefits of increasing the capacity of such services across a target region on child mortality/recovery. Timely intervention is another benefit of a more local service like OTP. Building capacity of OTP service providers and regular monitoring of service provision based on the management protocol was recommended.


Assuntos
Assistência Ambulatorial/estatística & dados numéricos , Desnutrição Aguda Grave/terapia , Antibacterianos/uso terapêutico , Pré-Escolar , Diarreia/complicações , Diarreia/tratamento farmacológico , Diarreia/patologia , Etiópia , Feminino , Infecções por HIV/complicações , Infecções por HIV/patologia , Humanos , Lactente , Modelos Logísticos , Masculino , Razão de Chances , Estudos Retrospectivos , Desnutrição Aguda Grave/complicações , Desnutrição Aguda Grave/patologia , Resultado do Tratamento , Vacinação , Vitamina A/uso terapêutico
10.
PLoS One ; 15(9): e0238375, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32881916

RESUMO

BACKGROUND AND OBJECTIVES: Less than 10 percent of the more than one million people vulnerable to HIV are using pre-exposure prophylaxis (PrEP). Practitioners are critical to ensuring the delivery of PrEP across care settings. In this study, we target a group of prescribers focused on providing HIV care and seeking up-to-date information about HIV. We assessed their experiences prescribing PrEP, whether these experiences differed by clinical specialty, and examined associations between willingness to prescribe PrEP as a "best first step" and different hypothetical prescribing scenarios. SETTING AND METHODS: Between March and May 2015, we circulated a paper survey to 954 participants ((652 of whom met our inclusion criteria of being independent prescribers and 519 of those (80%) responded to the survey)) at continuing medical education advanced-level HIV courses in five locations across the US on practitioner practices and preferences of PrEP. We employed multivariable logistic regression analysis for binary and collapsed ordinal outcomes. RESULTS: Among this highly motivated group of practitioners, only 54% reported ever prescribing PrEP. Internal medicine practitioners were 1.6 times more likely than infectious disease practitioners to have prescribed PrEP (95% CI: 0.99-2.60, p = .0524) and age, years of training, and sex were significantly associated with prescribing experience. Based on clinical vignettes describing different hypothetical prescribing scenarios, practitioners who viewed PrEP as the first clinical step for persons who inject drugs (PWID) were twice as likely to have also considered PrEP as the first clinical option for safer conception, and vice-a-versa (95% CI: 1.4-3.2, p < .001). Practitioners considering PrEP as the first preventive option for MSM were nearly six times as likely to also consider PrEP as the first clinical step for PWID, and vice-a-versa (95% CI: 2.28-13.56, p = .0002). CONCLUSIONS: Our findings indicate that even among a subset of HIV-focused practitioners, PrEP prescribing is not routine. This group of practitioners could be an optimal group to engage individuals that could most benefit from PrEP.


Assuntos
Infecções por HIV/prevenção & controle , Médicos/psicologia , Profilaxia Pré-Exposição , Prescrições/estatística & dados numéricos , Adulto , Feminino , Infecções por HIV/patologia , Homossexualidade Masculina , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Inquéritos e Questionários , Estados Unidos
11.
PLoS One ; 15(9): e0238347, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32870938

RESUMO

Highly exposed seronegative (HESN) individuals present a unique setting to study mechanisms of protection against HIV acquisition. As natural killer (NK) cell activation and function have been implicated as a correlate of protection in HESN individuals, we sought to better understand the features of NK cells that may confer protection. We used mass cytometry to phenotypically profile NK cells from a cohort of Beninese sex workers and healthy controls. We found that NK cells from HESN women had increased expression of NKG2A, NKp30 and LILRB1, as well as the Fc receptor CD16, and decreased expression of DNAM-1, CD94, Siglec-7, and NKp44. Using functional assessments of NK cells from healthy donors against autologous HIV-infected CD4+ T cells, we observed that NKp30+ and Siglec-7+ cells had improved functional activity. Further, we found that NK cells from HESN women trended towards increased antibody-dependent cellular cytotoxicity (ADCC) activity; this activity correlated with increased CD16 expression. Overall, we identify features of NK cells in HESN women that may contribute to protection from HIV infection. Follow up studies with larger cohorts are warranted to confirm these findings.


Assuntos
Infecções por HIV/patologia , Células Matadoras Naturais/metabolismo , Adulto , Citotoxicidade Celular Dependente de Anticorpos/imunologia , Antígenos de Diferenciação Mielomonocítica/metabolismo , Feminino , Proteínas Ligadas por GPI/genética , Proteínas Ligadas por GPI/metabolismo , Genótipo , Infecções por HIV/imunologia , Humanos , Células Matadoras Naturais/citologia , Células Matadoras Naturais/imunologia , Lectinas/metabolismo , Modelos Lineares , Receptor 3 Desencadeador da Citotoxicidade Natural/metabolismo , Fenótipo , Receptores de IgG/genética , Receptores de IgG/metabolismo , Profissionais do Sexo
12.
PLoS Pathog ; 16(9): e1008853, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32886726

RESUMO

HIV-1 transmission is associated with a severe bottleneck in which a limited number of variants from a pool of genetically diverse quasispecies establishes infection. The IAVI protocol C cohort of discordant couples, female sex workers, other heterosexuals and men who have sex with men (MSM) present varying risks of HIV infection, diverse HIV-1 subtypes and represent a unique opportunity to characterize transmitted/founder viruses (TF) where disease outcome is known. To identify the TF, the HIV-1 repertoire of 38 MSM participants' samples was sequenced close to transmission (median 21 days post infection, IQR 18-41) and assessment of multivariant infection done. Patient derived gag genes were cloned into an NL4.3 provirus to generate chimeric viruses which were characterized for replicative capacity (RC). Finally, an evaluation of how the TF virus predicted disease progression and modified the immune response at both acute and chronic HIV-1 infection was done. There was higher prevalence of multivariant infection compared with previously described heterosexual cohorts. A link was identified between multivariant infection and replicative capacity conferred by gag, whereby TF gag tended to be of lower replicative capacity in multivariant infection (p = 0.02) suggesting an overall lowering of fitness requirements during infection with multiple variants. Notwithstanding, multivariant infection was associated with rapid CD4+ T cell decline and perturbances in the CD4+ T cell and B cell compartments compared to single variant infection, which were reversible upon control of viremia. Strategies aimed at identifying and mitigating multivariant infection could contribute toward improving HIV-1 prognosis and this may involve strategies that tighten the stringency of the transmission bottleneck such as treatment of STI. Furthermore, the sequences and chimeric viruses help with TF based experimental vaccine immunogen design and can be used in functional assays to probe effective immune responses against TF.


Assuntos
Linfócitos T CD4-Positivos/imunologia , Efeito Fundador , Infecções por HIV , HIV-1/fisiologia , Replicação Viral , Produtos do Gene gag do Vírus da Imunodeficiência Humana , Doença Aguda , Adolescente , Adulto , Linfócitos B/imunologia , Linfócitos B/patologia , Linfócitos T CD4-Positivos/patologia , Linfócitos T CD4-Positivos/virologia , Feminino , Infecções por HIV/genética , Infecções por HIV/imunologia , Infecções por HIV/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Viremia/genética , Viremia/imunologia , Viremia/patologia , Replicação Viral/genética , Replicação Viral/imunologia , Produtos do Gene gag do Vírus da Imunodeficiência Humana/genética , Produtos do Gene gag do Vírus da Imunodeficiência Humana/imunologia
13.
BMC Infect Dis ; 20(1): 588, 2020 Aug 08.
Artigo em Inglês | MEDLINE | ID: mdl-32770955

RESUMO

BACKGROUND: Scale-up of hepatitis C virus (HCV) treatment for HIV/HCV coinfected individuals is occurring in Spain, the vast majority (> 85%) with a reported history of injecting drug use and a smaller population of co-infected men who have sex with men (MSM). We assess impact of recent treatment scale-up to people living with HIV (PLWH) and implications for achieving the WHO HCV incidence elimination target (80% reduction 2015-2030) among PLWH and overall in Andalusia, Spain, using dynamic modeling. METHODS: A dynamic transmission model of HCV/HIV coinfection was developed. The model was stratified by people who inject drugs (PWID) and MSM. The PWID component included dynamic HCV transmission from the HCV-monoinfected population. The model was calibrated to Andalusia based on published data and the HERACLES cohort (prospective cohort of HIV/HCV coinfected individuals representing > 99% coinfected individuals in care in Andalusia). From HERACLES, we incorporated HCV treatment among diagnosed PLWH of 10.5%/year from 2004 to 2014, and DAAs at 33%/year from 2015 with 94.8% SVR. We project the impact of current and scaled-up HCV treatment for PLWH on HCV prevalence and incidence among PLWH and overall. RESULTS: Current treatment rates among PLWH (scaled-up since 2015) could substantially reduce the number of diagnosed coinfected individuals (mean 76% relative reduction from 2015 to 2030), but have little impact on new diagnosed coinfections (12% relative reduction). However, DAA scale-up to PWLH in 2015 would have minimal future impact on new diagnosed coinfections (mean 9% relative decrease from 2015 to 2030). Similarly, new cases of HCV would only reduce by a mean relative 29% among all PWID and MSM due to ongoing infection/reinfection. Diagnosing/treating all PLWH annually from 2020 would increase the number of new HCV infections among PWLH by 28% and reduce the number of new HCV infections by 39% among the broader population by 2030. CONCLUSION: Targeted scale-up of HCV treatment to PLWH can dramatically reduce prevalence among this group but will likely have little impact on the annual number of newly diagnosed HIV/HCV coinfections. HCV microelimination efforts among PWLH in Andalusia and settings where a large proportion of PLWH have a history of injecting drug use will require scaled-up HCV diagnosis and treatment among PLWH and the broader population at risk.


Assuntos
Infecções por HIV/patologia , Hepatite C/diagnóstico , Modelos Teóricos , Antivirais/uso terapêutico , Estudos de Coortes , Coinfecção/epidemiologia , Coinfecção/patologia , Hepatite C/tratamento farmacológico , Hepatite C/epidemiologia , Homossexualidade Masculina , Humanos , Masculino , Prevalência , Estudos Prospectivos , Espanha/epidemiologia , Transtornos Relacionados ao Uso de Substâncias/patologia , Resposta Viral Sustentada
14.
BMC Infect Dis ; 20(1): 563, 2020 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-32738895

RESUMO

BACKGROUND: Despite several intervention programmes in South Africa, risky sexual behaviours among women of reproductive age remain a public health concern, making them vulnerable to unintended pregnancies and/or sexually transmitted infections (STIs), including human immunodeficiency virus (HIV) infection. The aim of this study was to investigate the predictors of risky sexual behaviours among women of reproductive age in a high HIV-burden township in KwaZulu-Natal, South Africa. METHODS: In a cross-sectional study, 471 women of reproductive age (18-49 years, mean: 25.83) in 10 public health clinics in Umlazi Township, responded to a structured questionnaire. Data were coded, entered into Epi Data Manager and exported to Stata for analysis. A Pearson Chi-square tests and logistic regression models (bivariate and multivariate) were employed to assess the level of the association between the predictor and outcome variables and the p-value < 0.05 was considered statistically significant. RESULTS: More than half (51.80%) of the women were aged 18-24 years and only a handful (18.26%) had a tertiary qualification. The majority were single (88.96%) and the unemployed accounted for 53.50%. This study found that women who had talked about condoms with their partner in the past 12 months were more likely (p = < 0.0001) to have used condoms during their last sexual intercourse. Older women (p = 0.035) were more likely to have used a condom at last sex, compared to younger women. However, women who were exposed to physical partner violence (hitting and/or slapping), those who had been diagnosed with HIV and those whose sexual partners were diagnosed with HIV, did not show a significant association with condom use at last sex. CONCLUSION: Exposure to physical partner violence and poor partner discussions about condoms are key deterrents to condom usage. Holistic interventions are required in order to address the risky behaviours, and consequently reduce sexually transmitted infections and/or unintended pregnancies.


Assuntos
Infecções por HIV/patologia , Comportamento Sexual , Adolescente , Adulto , Fatores Etários , Preservativos/estatística & dados numéricos , Estudos Transversais , Feminino , Infecções por HIV/epidemiologia , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Razão de Chances , Delitos Sexuais , África do Sul/epidemiologia , Inquéritos e Questionários , Adulto Jovem
15.
BMC Infect Dis ; 20(1): 569, 2020 Aug 04.
Artigo em Inglês | MEDLINE | ID: mdl-32753067

RESUMO

BACKGROUND: HIV-1 produces defective mutants in the process of reproduction. The significance of the mutants has not been well investigated. METHODS: The plasmids of wild type (HIV-1NL4-3) and Env-defective (HIV-1SG3ΔEnv) HIV-1 were co-transfected into HEK293T cells. The progeny virus was collected to infect MT4 cells. The env gene and near-full-length genome (NFLG) of HIV-1 were amplified and sequenced. The phylogenetic diversity, recombinant patterns and hotspots, and the functionality of HIV-1 Env were determined. RESULTS: A total of 42 env genes and 8 NFLGs were successfully amplified and sequenced. Five types of recombinant patterns of env were identified and the same recombinant sites were detected in different patterns. The recombination hotspots were found distributing mainly in conservative regions of env. The recombination between genes of HIV-1NL4-3 and HIV-1SG3Δenv increased the variety of viral quasispecies and resulted in progeny viruses with relative lower infectious ability than that of HIVNL4-3. The defective env genes as well as NFLG could be detected after 20 passages. CONCLUSION: The existence of the defective HIV-1 promotes the phylogenetic evolution of the virus, thus increasing the diversity of virus population. The role of defective genes may be converted from junk genes to useful materials and cannot be neglected in the study of HIV-1 reservoir.


Assuntos
Evolução Molecular , Infecções por HIV/patologia , HIV-1/fisiologia , Produtos do Gene env do Vírus da Imunodeficiência Humana/genética , Células HEK293 , Infecções por HIV/virologia , HIV-1/classificação , HIV-1/genética , Humanos , Filogenia , Plasmídeos/genética , Plasmídeos/metabolismo , Recombinação Genética , Produtos do Gene env do Vírus da Imunodeficiência Humana/química , Produtos do Gene env do Vírus da Imunodeficiência Humana/metabolismo
16.
BMC Infect Dis ; 20(1): 591, 2020 Aug 10.
Artigo em Inglês | MEDLINE | ID: mdl-32778057

RESUMO

BACKGROUND: Men who have sex with men (MSM) bear a disproportionate burden of HIV in Malawi. Early prevention efforts in Malawi have been largely focused on preventing heterosexual and vertical transmission of HIV, and MSM have rarely been the specific benefactors of these efforts, despite facing both higher prevalence of HIV coupled with multiple barriers to prevention and care. To better facilitate the design of culturally relevant HIV prevention programs and prioritize resources among MSM in resource limited settings, the objective of this analysis was to estimate the relationship between social factors and HIV related risk behaviors and mental health. METHODS: 338 MSM were recruited using respondent-driven sampling in Blantyre, Malawi from April 2011 to March 2012. Structural equation models were built to test the association between six latent factors: participation in social activities, social support, stigma and human rights violations, depression symptomatology, condom use, and sexual risk behaviors, including concurrent sexual partnerships and total number of partners. RESULTS: The mean age of participants was 25 years old. Almost 50% (158/338) of the participants were unemployed and 11% (37/338) were married or cohabiting with women. More than 30% (120/338) of the participants reported sexual behavior stigma and 30% (102/338) reported depression symptomatology. Almost 50% (153/338) of the participants reported any kind of HIV-related risk behaviors and 30% (110/338) participated in one of the recorded social activities. Significant associations were identified between stigma and risk behaviors (ß = 0.14, p = 0.03); stigma and depression symptomatology (ß = 0.62, p = 0.01); participation in social activities and depression symptomatology (ß = 0.17, p = 0.01). CONCLUSION: Results suggest MSM reporting stigma are more likely to report sexual risk practices associated with HIV/STI transmission and depressive symptoms, while those reporting participation in social activities related to HIV education are less likely to be depressed. Furthermore, interventions at the community level to support group empowerment and engagement may further reduce risks of HIV transmission and improve mental health outcomes. Taken together, these results suggest the potential additive benefits of mental health services integrated within comprehensive HIV prevention packages to optimize both HIV-related outcomes and general quality of life among MSM in Malawi.


Assuntos
Infecções por HIV/patologia , Homossexualidade Masculina/psicologia , Modelos Teóricos , Adulto , Depressão/patologia , Infecções por HIV/epidemiologia , Humanos , Malaui , Masculino , Saúde Mental , Prevalência , Assunção de Riscos , Comportamento Sexual , Estigma Social , Adulto Jovem
17.
Lancet Haematol ; 7(9): e690-e696, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32791043

RESUMO

People living with HIV are a global population with increased cancer risk but their access to modern immunotherapies for cancer treatment has been limited by socioeconomic factors and inadequate research to support safety and efficacy in this population. These immunotherapies include immune checkpoint inhibitors and advances in cellular immunotherapy, particularly chimeric antigen receptor (CAR) T-cell therapy. Despite the field of cancer immunotherapy rapidly expanding with ongoing clinical trials, people with HIV are often excluded from such trials. In 2019, post-approval evaluation of anti-CD19 CAR T-cell therapy in people with HIV and aggressive B-cell lymphoma showed the feasibility of CAR T-cell therapy for cancer in this excluded group. Along with expanded treatment options for people with HIV is the ability to assess the effects of immunotherapy on the latent HIV reservoir, with certain immunotherapies showing the ability to alleviate this burden. This Series paper addresses the increased cancer burden in people with HIV, the increasing evidence for the safety and efficacy of immunotherapies in the context of HIV and cancer, and opportunities for novel applications of CAR-T therapy for the treatment of both haematological malignancies and HIV.


Assuntos
Infecções por HIV/patologia , Neoplasias Hematológicas/terapia , Receptores de Antígenos Quiméricos/metabolismo , Linfócitos T/transplante , Antígenos CD19/imunologia , Terapia Baseada em Transplante de Células e Tecidos , Infecções por HIV/complicações , Neoplasias Hematológicas/complicações , Neoplasias Hematológicas/mortalidade , Humanos , Imunoterapia Adotiva , Taxa de Sobrevida , Linfócitos T/citologia , Linfócitos T/metabolismo
18.
Lancet Haematol ; 7(9): e679-e689, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32791044

RESUMO

Although the incidence of HIV-associated lymphomas decreased after the introduction of effective combination antiretroviral therapy, they became the most common AIDS-related cancer in high-income countries. Moreover, as people living with HIV live longer, a wide range of non-AIDS-related cancer has emerged, including other haematological malignancies. Nonetheless, combination antiretroviral therapy has offered people with HIV the opportunity to receive the same therapies as those provided to the general population, and intensive curative therapies have become the standard. However, several population-based studies highlight a major health-care disparity between people with HIV and those without, with people who are HIV positive often excluded from using innovative therapies and participating in prospective trials. In addition, patients from low-income countries frequently receive inappropriate treatment. The hope is that with increased awareness of effective curative options these disparities will decrease, and people with HIV will be given the same therapeutic opportunities and enrolled in clinical trials alongside patients who are HIV negative.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Infecções por HIV/patologia , Neoplasias Hematológicas/tratamento farmacológico , Antirretrovirais/uso terapêutico , Saúde Global , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , Neoplasias Hematológicas/complicações , Neoplasias Hematológicas/mortalidade , Neoplasias Hematológicas/patologia , Humanos , Gradação de Tumores , Intervalo Livre de Progressão , Taxa de Sobrevida
19.
PLoS Pathog ; 16(8): e1008752, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32760121

RESUMO

Members of the family of pyrin and HIN domain containing (PYHIN) proteins play an emerging role in innate immunity. While absent in melanoma 2 (AIM2) acts a cytosolic sensor of non-self DNA and plays a key role in inflammasome assembly, the γ-interferon-inducible protein 16 (IFI16) restricts retroviral gene expression by sequestering the transcription factor Sp1. Here, we show that the remaining two human PYHIN proteins, i.e. myeloid cell nuclear differentiation antigen (MNDA) and pyrin and HIN domain family member 1 (PYHIN1 or IFIX) share this antiretroviral function of IFI16. On average, knock-down of each of these three nuclear PYHIN proteins increased infectious HIV-1 yield from human macrophages by more than an order of magnitude. Similarly, knock-down of IFI16 strongly increased virus transcription and production in primary CD4+ T cells. The N-terminal pyrin domain (PYD) plus linker region containing a nuclear localization signal (NLS) were generally required and sufficient for Sp1 sequestration and anti-HIV-1 activity of IFI16, MNDA and PYHIN1. Replacement of the linker region of AIM2 by the NLS-containing linker of IFI16 resulted in a predominantly nuclear localization and conferred direct antiviral activity to AIM2 while attenuating its ability to form inflammasomes. The reverse change caused nuclear-to-cytoplasmic relocalization of IFI16 and impaired its antiretroviral activity but did not result in inflammasome assembly. We further show that the Zn-finger domain of Sp1 is critical for the interaction with IFI16 supporting that pyrin domains compete with DNA for Sp1 binding. Finally, we found that human PYHIN proteins also inhibit Hepatitis B virus and simian vacuolating virus 40 as well as the LINE-1 retrotransposon. Altogether, our data show that IFI16, PYHIN1 and MNDA restrict HIV-1 and other viral pathogens by interfering with Sp1-dependent gene expression and support an important role of nuclear PYHIN proteins in innate antiviral immunity.


Assuntos
Linfócitos T CD4-Positivos/imunologia , Núcleo Celular/metabolismo , Infecções por HIV/prevenção & controle , HIV-1/imunologia , Macrófagos/imunologia , Proteínas Nucleares/metabolismo , Fator de Transcrição Sp1/metabolismo , Linfócitos T CD4-Positivos/metabolismo , Linfócitos T CD4-Positivos/virologia , Núcleo Celular/genética , DNA Viral/genética , Células HEK293 , Infecções por HIV/imunologia , Infecções por HIV/patologia , Infecções por HIV/virologia , HIV-1/genética , HIV-1/isolamento & purificação , Células Hep G2 , Humanos , Imunidade Inata/imunologia , Inflamassomos/genética , Inflamassomos/imunologia , Macrófagos/metabolismo , Macrófagos/virologia , Proteínas Nucleares/genética , Fator de Transcrição Sp1/genética , Replicação Viral
20.
PLoS One ; 15(8): e0236362, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32797053

RESUMO

BACKGROUND: Tuberculosis (TB) is among the top 10 causes of mortality and the first killer among infectious diseases worldwide. One of the factors fuelling the TB epidemic is the global rise of multidrug resistant TB (MDR-TB). The aim of this study was to determine the magnitude and factors associated with MDR-TB in the Tigray Region, Ethiopia. METHOD: This study employed a facility-based cross-sectional study design, which was conducted between July 2018 and August 2019. The inclusion criteria for the study participants were GeneXpert-positive who were not under treatment for TB, PTB patients' ≥15 years of age and who provided written informed consent. A total of 300 participants were enrolled in the study, with a structured questionnaire used to collect data on clinical, sociodemographic and behavioral factors. Sputum samples were collected and processed for acid-fast bacilli staining, culture and drug susceptibility testing. Drug susceptibility testing was performed using a line probe assay. Logistic regression was used to analyze associations between outcome and predictor variables. RESULTS: The overall proportion of MDR-TB was 16.7% (11.6% and 32.7% for new and previously treated patients, respectively). Of the total MDR-TB isolates, 5.3% were pre-XDR-TB. The proportion of MDR-TB/HIV co-infection was 21.1%. A previous history of TB treatment AOR 3.75; 95% CI (0.7-2.24), cigarette smoking AOR 6.09; CI (1.65-2.50) and patients who had an intermittent fever (AOR = 2.54, 95% CI = 1.21-5.4) were strongly associated with MDR-TB development. CONCLUSIONS: The magnitude of MDR-TB observed among new and previously treated patients is very alarming, which calls for an urgent need for intervention. The high proportion of MDR-TB among newly diagnosed cases indicates ongoing transmission, which suggests the need for enhanced TB control program performance to interrupt transmission. The increased proportion of MDR-TB among previously treated cases indicates a need for better patient management to prevent the evolution of drug resistance. Assessing the TB control program performance gaps and an optimal implementation of the WHO recommended priority actions for the management of drug-resistant TB, is imperative to help reduce the current high MDR-TB burden in the study region.


Assuntos
Infecções por HIV/tratamento farmacológico , Mycobacterium tuberculosis/efeitos dos fármacos , Tuberculose Resistente a Múltiplos Medicamentos/tratamento farmacológico , Tuberculose Pulmonar/tratamento farmacológico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Antituberculosos/uso terapêutico , Estudos Transversais , Etiópia/epidemiologia , Feminino , Infecções por HIV/epidemiologia , Infecções por HIV/microbiologia , Infecções por HIV/patologia , Humanos , Isoniazida/uso terapêutico , Masculino , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Mycobacterium tuberculosis/patogenicidade , Rifampina/uso terapêutico , Fatores de Risco , Escarro/efeitos dos fármacos , Escarro/microbiologia , Tuberculose Resistente a Múltiplos Medicamentos/epidemiologia , Tuberculose Resistente a Múltiplos Medicamentos/microbiologia , Tuberculose Resistente a Múltiplos Medicamentos/patologia , Tuberculose Pulmonar/epidemiologia , Tuberculose Pulmonar/microbiologia , Tuberculose Pulmonar/patologia , Adulto Jovem
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA