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1.
J Med Virol ; 93(11): 6116-6123, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34375002

RESUMO

Virus invasion activates the host's innate immune response, inducing the production of numerous cytokines and interferons to eliminate pathogens. Except for viral DNA/RNA, viral proteins are also targets of pattern recognition receptors. Membrane-bound receptors such as Toll-like receptor (TLR)1, TLR2, TLR4, TLR6, and TLR10 relate to the recognition of viral proteins. Distinct TLRs perform both protective and detrimental roles for a specific virus. Here, we review viral proteins serving as pathogen-associated molecular patterns and their corresponding TLRs. These viruses are all enveloped, including respiratory syncytial virus, hepatitis C virus, measles virus, herpesvirus human immunodeficiency virus, and coronavirus, and can encode proteins to activate innate immunity in a TLR-dependent way. The TLR-viral protein relationship plays an important role in innate immunity activation. A detailed understanding of their pathways contributes to a novel direction for vaccine development.


Assuntos
Imunidade Inata , Padrões Moleculares Associados a Patógenos/metabolismo , Receptores Toll-Like/imunologia , Receptores Toll-Like/metabolismo , Proteínas Virais/metabolismo , Viroses/imunologia , Vírus/imunologia , Animais , HIV/imunologia , HIV/metabolismo , HIV/patogenicidade , Hepacivirus/imunologia , Hepacivirus/metabolismo , Hepacivirus/patogenicidade , Herpesviridae/imunologia , Herpesviridae/metabolismo , Herpesviridae/patogenicidade , Humanos , Vírus do Sarampo/imunologia , Vírus do Sarampo/metabolismo , Vírus do Sarampo/patogenicidade , Padrões Moleculares Associados a Patógenos/química , Vírus Sinciciais Respiratórios/imunologia , Vírus Sinciciais Respiratórios/metabolismo , Vírus Sinciciais Respiratórios/patogenicidade , SARS-CoV-2/imunologia , SARS-CoV-2/metabolismo , SARS-CoV-2/patogenicidade , Proteínas Virais/química , Viroses/virologia , Vírus/metabolismo , Vírus/patogenicidade
2.
Lancet Oncol ; 22(6): e240-e253, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-34087151

RESUMO

Non-AIDS-defining cancers are a growing source of morbidity for people with HIV globally. Although people living with HIV have a disproportionately increased risk of developing virally mediated cancers, cancer burden for common non-AIDS-defining cancers that are not virally associated and are linked to ageing, such as prostate cancer, is becoming higher than for virally mediated cancers. Ageing, behavioural, and HIV-specific factors drive the incidence and affect the outcomes of non-AIDS-defining cancers, presenting different challenges for addressing global morbidity and mortality from non-AIDS-defining cancer. Although large population-based studies have shown that people living with HIV with non-AIDS-defining cancers have poorer cancer outcomes than do people without HIV, current guidelines emphasise that people living with HIV with non-AIDS-defining cancers should receive standard, guideline-based treatment, and infectious disease and oncology providers should work closely to address potential drug interactions between antiretroviral therapy and antineoplastic treatment. Most trials target preventive measures focusing on non-AIDS-defining cancers. However, treatment trials for the optimal management of people living with HIV and non-AIDS-defining cancer, including interventions such as immunotherapies, are needed to improve non-AIDS-defining cancer outcomes.


Assuntos
Síndrome de Imunodeficiência Adquirida/terapia , Infecções por HIV/terapia , Neoplasias/terapia , Sarcoma de Kaposi/terapia , Síndrome de Imunodeficiência Adquirida/complicações , Síndrome de Imunodeficiência Adquirida/epidemiologia , Terapia Antirretroviral de Alta Atividade , HIV/patogenicidade , Infecções por HIV/epidemiologia , Infecções por HIV/virologia , Humanos , Imunoterapia/normas , Neoplasias/epidemiologia , Neoplasias/etiologia , Fatores de Risco , Sarcoma de Kaposi/epidemiologia , Sarcoma de Kaposi/etiologia , Sarcoma de Kaposi/patologia , Resultado do Tratamento
3.
Nat Med ; 27(6): 1006-1011, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-34099923

RESUMO

People with human immunodeficiency virus (HIV) have higher rates of certain comorbidities, particularly cardiovascular disease and cancer, than people without HIV1-5. In view of observations that somatic mutations associated with age-related clonal hematopoiesis (CH) are linked to similar comorbidities in the general population6-10, we hypothesized that CH may be more prevalent in people with HIV. To address this issue, we established a prospective cohort study, the ARCHIVE study (NCT04641013), in which 220 HIV-positive and 226 HIV-negative participants aged 55 years or older were recruited in Australia. Demographic characteristics, clinical data and peripheral blood were collected to assess the presence of CH mutations and to identify potential risk factors for and clinical sequelae of CH. In total, 135 CH mutations were identified in 100 (22.4%) of 446 participants. CH was more prevalent in HIV-positive participants than in HIV-negative participants (28.2% versus 16.8%, P = 0.004), overall and across all age groups; the adjusted odds ratio for having CH in those with HIV was 2.16 (95% confidence interval 1.34-3.48, P = 0.002). The most common genes mutated overall were DNMT3A (47.4%), TET2 (20.0%) and ASXL1 (13.3%). CH and HIV infection were independently associated with increases in blood parameters and biomarkers associated with inflammation. These data suggest a selective advantage for the emergence of CH in the context of chronic infection and inflammation related to HIV infection.


Assuntos
Doenças Cardiovasculares/genética , DNA (Citosina-5-)-Metiltransferases/genética , Proteínas de Ligação a DNA/genética , Infecções por HIV/genética , Proteínas Proto-Oncogênicas/genética , Proteínas Repressoras/genética , Idoso , Envelhecimento/genética , Envelhecimento/patologia , Doenças Cardiovasculares/complicações , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/virologia , Hematopoiese Clonal/genética , Feminino , HIV/patogenicidade , Infecções por HIV/complicações , Infecções por HIV/epidemiologia , Infecções por HIV/virologia , Humanos , Inflamação/genética , Inflamação/patologia , Inflamação/virologia , Masculino , Pessoa de Meia-Idade , Mutação/genética , Neoplasias/complicações , Neoplasias/epidemiologia , Neoplasias/genética , Neoplasias/virologia
4.
Viruses ; 13(5)2021 05 17.
Artigo em Inglês | MEDLINE | ID: mdl-34067925

RESUMO

By the middle of 2021, we are still immersed in the coronavirus disease 2019 (COVID-19) pandemic, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The concurrence of this new pandemic in regions where human immunodeficiency virus (HIV) and tuberculosis (TB) infections possess the same epidemiological consideration, has arisen concerns about the prognosis, clinical management, symptomatology, and treatment of patients with triple infection. At the same time, healthcare services previously devoted to diagnosis and treatment of TB and HIV are being jeopardized by the urgent need of resources and attention for COVID-19 patients. The aim of this review was to collect any article considering the three conditions (HIV, TB, and SARS-CoV-2), included in PubMed/Medline and published in the English language since the beginning of the COVID-19 pandemic. We focused on detailed descriptions of the unusual cases describing the three co-infections. Eighty-four out of 184 publications retrieved met our inclusion criteria, but only three of them reported cases (five in total) with the three concomitant infections. The clinical evolution, management, and therapy of all of them were not different from mild/severe cases with exclusive COVID-19; the outcome was not worse either, with recovery for the five patients. Cases of patients with COVID-19 besides HIV and TB infections are scarce in literature, but studies deliberately embracing the triple infection as a priori inclusion criterion should be carried out in order to provide a complete understanding of joint influence.


Assuntos
COVID-19/complicações , Coinfecção/epidemiologia , COVID-19/epidemiologia , Testes Diagnósticos de Rotina , HIV/patogenicidade , Infecções por HIV/complicações , Infecções por HIV/epidemiologia , Humanos , Mycobacterium tuberculosis/patogenicidade , Pandemias , SARS-CoV-2/patogenicidade , Tuberculose/complicações , Tuberculose/epidemiologia
5.
Am J Respir Cell Mol Biol ; 65(4): 413-429, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34014809

RESUMO

Extracellular vesicles (EVs) have emerged as important mediators in cell-cell communication; however, their relevance in pulmonary hypertension (PH) secondary to human immunodeficiency virus (HIV) infection is yet to be explored. Considering that circulating monocytes are the source of the increased number of perivascular macrophages surrounding the remodeled vessels in PH, this study aimed to identify the role of circulating small EVs and EVs released by HIV-infected human monocyte-derived macrophages in the development of PH. We report significantly higher numbers of plasma-derived EVs carrying higher levels of TGF-ß1 (transforming growth factor-ß1) in HIV-positive individuals with PH compared with individuals without PH. Importantly, levels of these TGF-ß1-loaded, plasma-derived EVs correlated with pulmonary arterial systolic pressures and CD4 counts but did not correlate with the Dl CO or viral load. Correspondingly, enhanced TGF-ß1-dependent pulmonary endothelial injury and smooth muscle hyperplasia were observed. HIV-1 infection of monocyte-derived macrophages in the presence of cocaine resulted in an increased number of TGF-ß1-high EVs, and intravenous injection of these EVs in rats led to increased right ventricle systolic pressure accompanied by myocardial injury and increased levels of serum ET-1 (endothelin-1), TNF-α, and cardiac troponin-I. Conversely, pretreatment of rats with TGF-ß receptor 1 inhibitor prevented these EV-mediated changes. Findings define the ability of macrophage-derived small EVs to cause pulmonary vascular modeling and PH via modulation of TGF-ß signaling and suggest clinical implications of circulating TGF-ß-high EVs as a potential biomarker of HIV-associated PH.


Assuntos
Infecções por HIV/complicações , HIV/patogenicidade , Fator de Crescimento Transformador beta1/metabolismo , Animais , Vesículas Extracelulares/virologia , Humanos , Hipertensão Pulmonar/virologia , Macrófagos/virologia , Masculino , Monócitos/virologia , Hipertensão Arterial Pulmonar/virologia , Ratos Endogâmicos F344 , Receptores de Fatores de Crescimento Transformadores beta/metabolismo , Remodelação Vascular/fisiologia
6.
PLoS One ; 16(5): e0251861, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33999968

RESUMO

Visceral Leishmaniasis and HIV-AIDS coinfection (VL/HIV) is considered a life-threatening pathology when undiagnosed and untreated, due to the immunosuppression caused by both diseases. Serological tests largely used for the VL diagnosis include the direct agglutination test (DAT), ELISA and immunochromatographic (ICT) assays. For VL diagnosis in HIV infections, different studies have shown that the use of the DAT assay facilitates the VL diagnosis in co-infected patients, since the performance of the most widely used ELISA and ICT tests, based on the recombinant protein rK39, are much less efficient in HIV co-infections. In this scenario, alternative recombinant antigens may help the development of new serological diagnostic methods which may improve the VL diagnosis for the co-infection cases. This work aimed to evaluate the use of the recombinant Lci2 antigen, related to, but antigenically more diverse than rK39, for VL diagnosis in co-infected sera through ELISA assays. A direct comparison between recombinant Lci2 and rK39 was thus carried out. The two proteins were first tested using indirect ELISA with sera from VL afflicted individuals and healthy controls, with similar performances. They were then tested with two different sets of VL/HIV co-infected cases and a significant drop in performance, for one of these groups, was observed for rK39 (32% sensitivity), but not for Lci2 (98% sensitivity). In fact, an almost perfect agreement (Kappa: 0.93) between the Lci2 ELISA and DAT was observed for the coinfected VL/HIV patients. Lci2 then has the potential to be used as a new tool for the VL diagnosis of VL/HIV co-infections.


Assuntos
Anticorpos Antiprotozoários/isolamento & purificação , Infecções por HIV/genética , Leishmania infantum/isolamento & purificação , Leishmaniose Visceral/diagnóstico , Proteínas Recombinantes/isolamento & purificação , Testes de Aglutinação , Anticorpos Antiprotozoários/imunologia , Antígenos de Protozoários/imunologia , Coinfecção/diagnóstico , Coinfecção/genética , Coinfecção/parasitologia , Ensaio de Imunoadsorção Enzimática , HIV/patogenicidade , Infecções por HIV/complicações , Infecções por HIV/parasitologia , Infecções por HIV/virologia , Humanos , Leishmania infantum/genética , Leishmania infantum/patogenicidade , Leishmaniose Visceral/genética , Leishmaniose Visceral/parasitologia , Leishmaniose Visceral/virologia , Proteínas de Protozoários/imunologia , Proteínas Recombinantes/genética
7.
Rev. cuba. med. trop ; 73(1): e505, tab, graf
Artigo em Espanhol | LILACS, CUMED | ID: biblio-1280325

RESUMO

Introducción: El sarcoma de Kaposi es una neoplasia oportunista asociada a la inmunodepresión causada por VIH, que se relaciona con la infección por VHH tipo 8. Objetivo: Describir la presentación del sarcoma de Kaposi en personas que viven con VIH en Guinea Ecuatorial. Métodos: Se realizó un estudio descriptivo de carácter retrospectivo para identificar la prevalencia y las características epidemiológicas y clínicas del sarcoma de Kaposi en las personas que viven con VIH que acuden a las unidades de referencia para el manejo de casos en Guinea Ecuatorial. Se revisaron las historias clínicas de una muestra aleatoria y representativa de 338 pacientes del grupo que ha recibido tratamiento en las unidades de referencia para enfermedades infecciosas de Bata, desde enero de 2007 a febrero de 2012. Resultados: Se identificaron 40 pacientes diagnosticados de sarcoma de Kaposi (prevalencia del 11, 83 por ciento). La mediana de la edad al diagnóstico de sarcoma de Kaposi fue de 43 años, siendo la ratio del sexo de 1/1. La media de linfocitos CD4 al diagnóstico fue de 166 (rango 21-375) y la frecuencia de afectación oral fue de 45 por ciento. En la mayoría de los pacientes (94,6 por ciento) la observación del sarcoma de Kaposi fue anterior al inicio del tratamiento antirretroviral. Las cifras de linfocitos T CD4/mm3 inferiores a 100 aparecían sobre todo en pacientes menores de 30 años, y esto era especialmente frecuente en el grupo de mujeres (OR 11, p <0,04, Ic 95 por ciento 0,8-148). Conclusiones: El sarcoma de Kaposi es una neoplasia prevalente en personas que viven con VIH seguidas en las unidades de referencia en Guinea Ecuatorial. En mujeres menores de 30 años podría existir un diagnóstico tardío(AU)


Introduction: Kaposi sarcoma is an opportunistic neoplasm associated to the immunosuppression caused by HIV and related to infection by HHV-8. Objective: Describe the presentation of Kaposi sarcoma in people living with HIV in Equatorial Guinea. Methods: A retrospective descriptive study was conducted to identify the prevalence and the clinical and epidemiological characteristics of Kaposi sarcoma in people living with HIV attending reference units for the management of cases in Equatorial Guinea. A review was carried out of the medical records of a random sample representative of 338 patients from the group receiving treatment at Bata reference unit for infectious diseases from January 2007 to February 2012. Results: A total 40 patients diagnosed with Kaposi sarcoma were identified (prevalence of 11,83 percent). Mean age at Kaposi sarcoma diagnosis was 43 years, with a 1/1 sex ratio. The mean CD4 lymphocyte count at diagnosis was 166 (range 21-375), whereas the frequency of oral damage was 45 percent. In most patients (94.6 percent) detection of Kaposi sarcoma was prior to the start of antiretroviral therapy. CD4 T lymphocyte levels / mm3 below 100 were mainly found in patients aged under 30 years, a fact particularly frequent among women (OR 11, p< 0.04, CI 95% 0.8-148). Conclusions: Kaposi sarcoma is a neoplasm prevailing in people living with HIV who attend reference units in Equatorial Guinea. Late diagnosis could exist among women aged under 30 years(AU)


Assuntos
Humanos , Sarcoma de Kaposi/complicações , Sarcoma de Kaposi/epidemiologia , HIV/patogenicidade , Herpesvirus Humano 8/crescimento & desenvolvimento , Epidemiologia Descritiva , Estudos Retrospectivos , Guiné Equatorial , Infecções Oportunistas Relacionadas com a AIDS/complicações
8.
PLoS One ; 16(3): e0247750, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33730043

RESUMO

BACKGROUND: On October 4, 2016, Hurricane Matthew struck southwest Haiti as a category 4 storm. The goal of this study was to evaluate the impact of the hurricane on tuberculosis (TB) services and patient outcomes in the three severely affected departments-Sud, Grand'Anse, and Nippes-of southwest Haiti. METHODS: We developed a standard questionnaire to assess a convenience sample of health facilities in the affected areas, a patient tracking form, and a line list for tracking all patients with drug-susceptible TB registered in care six months before the hurricane. We analyzed data from the national TB electronic surveillance system to determine outcomes for all patients receiving anti-TB treatment in the affected areas. We used logistic regression analysis to determine factors associated with treatment success. RESULTS: Of the 66 health facilities in the three affected departments, we assessed 31, accounting for 536 (45.7%) of 1,174 TB patients registered in care when Hurricane Matthew made landfall in Haiti. Three (9.7%) health facilities sustained moderate to severe damage, whereas 18 (58.1%) were closed for <1 week, and five (16.1%) for ≥1 week. Four weeks after the hurricane, 398 (73.1%) of the 536 patients in the assessed facilities were located. Treatment success in the affected departments one year after the hurricane was 81.4%. Receiving care outside the municipality of residence (adjusted odds ratio [aOR]: 0.46, 95% confidence interval [CI]: 0.27-0.80) and HIV positivity (aOR: 0.31, 95% CI: 0.19-0.51) or unknown HIV status (aOR: 0.49, 95% CI: 0.33-0.74) were associated with significantly lower rates of treatment success. CONCLUSIONS: Despite major challenges, a high percentage of patients receiving anti-TB treatment before the hurricane were located and successfully treated in southwest Haiti. The lessons learned and results presented here may help inform policies and guidelines in similar settings for effective TB control after a natural disaster.


Assuntos
Antituberculosos/uso terapêutico , Tempestades Ciclônicas , Infecções por HIV/tratamento farmacológico , Administração de Instituições de Saúde/estatística & dados numéricos , Tuberculose Pulmonar/tratamento farmacológico , Adolescente , Adulto , Coinfecção , Feminino , HIV/efeitos dos fármacos , HIV/crescimento & desenvolvimento , HIV/patogenicidade , Infecções por HIV/epidemiologia , Infecções por HIV/virologia , Haiti/epidemiologia , Instalações de Saúde , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Mycobacterium tuberculosis/efeitos dos fármacos , Mycobacterium tuberculosis/crescimento & desenvolvimento , Mycobacterium tuberculosis/patogenicidade , Estudos Retrospectivos , Inquéritos e Questionários , Resultado do Tratamento , Tuberculose Pulmonar/epidemiologia , Tuberculose Pulmonar/microbiologia
9.
Front Immunol ; 12: 634386, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33777022

RESUMO

Neutrophils are important components of the innate immune system that mediate pathogen defense by multiple processes including phagocytosis, release of proteolytic enzymes, production of reactive oxygen species, and neutrophil extracellular trap formation. Abnormalities of neutrophil count and function have been described in the setting of HIV infection, with the majority of antiretroviral agents (ARVs), excluding zidovudine, having been reported to correct neutropenia. Questions still remain, however, about their impact on neutrophil function, particularly the possibility of persistent neutrophil activation, which could predispose people living with HIV to chronic inflammatory disorders, even in the presence of virally-suppressive treatment. In this context, the effects of protease inhibitors and integrase strand transfer inhibitors, in particular, on neutrophil function remain poorly understood and deserve further study. Besides mediating hemostatic functions, platelets are increasingly recognized as critical role players in the immune response against infection. In the setting of HIV, these cells have been found to harbor the virus, even in the presence of antiretroviral therapy (ART) potentially promoting viral dissemination. While HIV-infected individuals often present with thrombocytopenia, they have also been reported to have increased platelet activation, as measured by an upregulation of expression of CD62P (P-selectin), CD40 ligand, glycoprotein IV, and RANTES. Despite ART-mediated viral suppression, HIV-infected individuals reportedly have sustained platelet activation and dysfunction. This, in turn, contributes to persistent immune activation and an inflammatory vascular environment, seemingly involving neutrophil-platelet-endothelium interactions that increase the risk for development of comorbidities such as cardiovascular disease (CVD) that has become the leading cause of morbidity and mortality in HIV-infected individuals on treatment, clearly underscoring the importance of unraveling the possible etiologic roles of ARVs. In this context, abacavir and ritonavir-boosted lopinavir and darunavir have all been linked to an increased risk of CVD. This narrative review is therefore focused primarily on the role of neutrophils and platelets in HIV transmission and disease, as well as on the effect of HIV and the most common ARVs on the numbers and functions of these cells, including neutrophil-platelet-endothelial interactions.


Assuntos
Fármacos Anti-HIV/uso terapêutico , Plaquetas/efeitos dos fármacos , Infecções por HIV/tratamento farmacológico , HIV/patogenicidade , Neutrófilos/efeitos dos fármacos , Animais , Plaquetas/imunologia , Plaquetas/metabolismo , Plaquetas/virologia , HIV/imunologia , Infecções por HIV/sangue , Infecções por HIV/imunologia , Infecções por HIV/virologia , Interações Hospedeiro-Patógeno , Humanos , Ativação de Neutrófilo/efeitos dos fármacos , Neutrófilos/imunologia , Neutrófilos/metabolismo , Neutrófilos/virologia , Ativação Plaquetária/efeitos dos fármacos , Resultado do Tratamento
10.
Lancet HIV ; 8(5): e284-e293, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33667411

RESUMO

BACKGROUND: Monitoring knowledge of HIV status among people living with HIV is essential for an effective national HIV response. This study estimates progress and gaps in reaching the UNAIDS 2020 target of 90% knowledge of status, and the efficiency of HIV testing services in sub-Saharan Africa, where two thirds of all people living with HIV reside. METHODS: For this modelling study, we used data from 183 population-based surveys (including more than 2·7 million participants) and national HIV testing programme reports (315 country-years) from 40 countries in sub-Saharan Africa as inputs into a mathematical model to examine trends in knowledge of status among people living with HIV, median time from HIV infection to diagnosis, HIV testing positivity, and proportion of new diagnoses among all positive tests, adjusting for retesting. We included data from 2000 to 2019, and projected results to 2020. FINDINGS: Across sub-Saharan Africa, knowledge of status steadily increased from 5·7% (95% credible interval [CrI] 4·6-7·0) in 2000 to 84% (82-86) in 2020. 12 countries and one region, southern Africa, reached the 90% target. In 2020, knowledge of status was lower among men (79%, 95% CrI 76-81) than women (87%, 85-89) across sub-Saharan Africa. People living with HIV aged 15-24 years were the least likely to know their status (65%, 62-69), but the largest gap in terms of absolute numbers was among men aged 35-49 years, with 701 000 (95% CrI 611 000-788 000) remaining undiagnosed. As knowledge of status increased from 2000 to 2020, the median time to diagnosis decreased from 9·6 years (9·1-10) to 2·6 years (1·8-3·5), HIV testing positivity declined from 9·0% (7·7-10) to 2·8% (2·1-3·9), and the proportion of first-time diagnoses among all positive tests dropped from 89% (77-96) to 42% (30-55). INTERPRETATION: On the path towards the next UNAIDS target of 95% diagnostic coverage by 2025, and in a context of declining positivity and yield of first-time diagnoses, disparities in knowledge of status must be addressed. Increasing knowledge of status and treatment coverage among older men could be crucial to reducing HIV incidence among women in sub-Saharan Africa, and by extension, reducing mother-to-child transmission. FUNDING: Steinberg Fund for Interdisciplinary Global Health Research (McGill University); Canadian Institutes of Health Research; Bill & Melinda Gates Foundation; Fonds the recherche du Québec-Santé; UNAIDS; UK Medical Research Council; MRC Centre for Global Infectious Disease Analysis; UK Foreign, Commonwealth & Development Office.


Assuntos
Infecções por HIV/diagnóstico , Infecções por HIV/epidemiologia , Teste de HIV/estatística & dados numéricos , Conhecimentos, Atitudes e Prática em Saúde , Transmissão Vertical de Doenças Infecciosas/prevenção & controle , Adolescente , Adulto , África ao Sul do Saara/epidemiologia , Idoso , Feminino , HIV/crescimento & desenvolvimento , HIV/patogenicidade , Infecções por HIV/mortalidade , Infecções por HIV/transmissão , Nível de Saúde , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Modelos Estatísticos , Análise de Sobrevida
11.
Lancet HIV ; 8(5): e274-e283, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33631101

RESUMO

BACKGROUND: Transgender people are disproportionately affected by HIV and other sexually transmitted infections (STIs) worldwide, and culturally competent prevention and treatment services are often unavailable or inaccessible. Despite recent improvements in national HIV responses for many key populations in east Africa, evidence of effective responses informed by transgender sexual health needs is sparse. We aimed to assess gender identity among men and transgender people who have sex with men in Kenya, and to explore its associations with sexual health-related outcomes, risk behaviours, and uptake of HIV prevention and care interventions. METHODS: We did a cross-sectional study in Nairobi, Kenya, and recruited adult cisgender men and transfeminine people who reported having sex with men, through respondent-driven sampling. Inclusion criteria were possession of a valid study coupon, being aged 18 years or older, having male sex assignment at birth or male gender identification currently, living within 50 km of Nairobi, and having had consensual anal or oral sexual activity with a man in the previous 12 months. Seed participants were identified by three community organisations that provide targeted health-care services to gay, bisexual, or other men who have sex with men (MSM) communities in Nairobi. We assessed gender identity, sociodemographics, sexual behaviour, and HIV prevention and care uptake, by self-completed survey. Participants were tested for HIV, syphilis, and rectal and urethral gonorrhoea and chlamydia. We compared prevalence of sexual health outcomes, risk behaviour, and HIV prevention and care service uptake among transfeminine and cisgender participants, using multivariable robust Poisson regression models, with gender identity as the independent variable. FINDINGS: Between May 4 and Dec 8, 2017, we enrolled 618 participants. Six participants did not answer the questions on sex assigned at birth and gender identity and so were excluded from the analyses. 522 (sample-weighted percentage 86%) of 612 participants were classified as cisgender men, 70 (11%) as transfeminine, and three (<1%) as transmasculine. 17 participants (2%) did not identify as male, female, or transgender. Compared with cisgender men, transfeminine people were more likely to be HIV-positive (28 [41%] of 70 transfeminine vs 151 [25%] of 521 cisgender men; p=0·0009) and to report current symptoms consistent with a rectal STI (eight [16%] of 67 vs 38 [7%] of 518; p=0·014). Transfeminine people reported higher numbers of recent male sexual partners (22 [27%] of 70 transfeminine people reported four or more male sexual partners in the past 3 months vs 112 [13%] of 522 cisgender men; p=0·042) and were more likely to report condomless anal intercourse with men (43 [62%] of 70 vs 208 [39%] of 522; p=0·0009) and receptive anal intercourse (54 [76%] of 70 vs 252 [46%] of 522; p<0·0001) in the past 3 months, and transactional sex with men (42 [57%] of 69 vs 240 [42%] of 518; p=0·023) and experience of sexual assault (16 [23%] of 69 vs 65 [11%] of 520; p=0·019) in the past 12 months. Use of pre-exposure prophylaxis and post-exposure prophylaxis was low in both groups. INTERPRETATION: Transfeminine people who have sex with men have a higher burden of HIV and associated risk behaviours compared with cisgender MSM in the same context, yet their uptake of prevention and care services is poor. Policies should acknowledge the specific needs of transfeminine people as distinct from cisgender MSM, and support health-care providers to address these needs. FUNDING: Evidence for HIV Prevention in Southern Africa (EHPSA), UK Aid.


Assuntos
Fármacos Anti-HIV/uso terapêutico , Infecções por HIV/epidemiologia , Infecções por HIV/psicologia , Homossexualidade Masculina/psicologia , Pessoas Transgênero/psicologia , Adolescente , Adulto , Terapia Antirretroviral de Alta Atividade , Estudos Transversais , Feminino , Identidade de Gênero , HIV/patogenicidade , Infecções por HIV/tratamento farmacológico , Infecções por HIV/transmissão , Humanos , Quênia/epidemiologia , Masculino , Pessoa de Meia-Idade , Profilaxia Pós-Exposição/ética , Profilaxia Pré-Exposição/ética , Parceiros Sexuais/psicologia , Minorias Sexuais e de Gênero/psicologia , Resultado do Tratamento
12.
PLoS One ; 16(2): e0246704, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33606700

RESUMO

INTRODUCTION: Estimation of hepatitis B virus (HBV), hepatitis C virus (HCV) and human immunodeficiency virus (HIV) transfusion risk in blood donors is essential for monitoring the safety of the blood supply and the impact of new screening tests. Due to improvements in donor selection and continuing progress in screening assays, residual risk of virus transmission has significantly decreased over the past years. It is not practical and sometimes even not possible to measure residual risk in blood donors directly and mathematical models are used. The aim of this study was to calculate the prevalence, incidence rates of HBV, HCV and HIV infections and analyse evolution of their transmission residual risk from 2004 to 2018 at the National Blood Center of Lithuania. MATERIALS AND METHODS: Data from the archives of the National Blood Center of Lithuania from 2004 to 2018 was retrospectively analysed. The residual risk was calculated for each virus and year by applying the incidence/window-period model suggested by World Health Organization. For the analysis of the residual risk yearly trends a linear regression was used. RESULTS: A total of 754,755 blood donors and 1,245,568 donations were included in the analysis and represented a 2.06 donations per donor over 15 years. Average residual risk for HBV, HCV and HIV respectively was 570.04, 807.14 and 35.72 per 1,00,000 donations. During the study period, there was statistically significant downward trend in the residual risk for every analysed virus. DISCUSSION: Residual risk of virus transmission has been steadily decreasing over past 15 years in Lithuanian donors, but the current risk remains quite high. It is difficult to establish how much the risk is affected by statistical assumptions or virus prevalence in general population. However, results of this study indicate the need of the population screening program of transfusion transmitted viruses.


Assuntos
Transfusão de Sangue/estatística & dados numéricos , Programas de Rastreamento/métodos , Reação Transfusional/epidemiologia , Doadores de Sangue/estatística & dados numéricos , Estudos de Coortes , HIV/patogenicidade , Infecções por HIV/epidemiologia , Hepacivirus/patogenicidade , Hepatite B/epidemiologia , Vírus da Hepatite B/patogenicidade , Hepatite C/epidemiologia , Humanos , Incidência , Lituânia/epidemiologia , Modelos Estatísticos , Prevalência , Estudos Retrospectivos , Fatores de Risco , Torque teno virus/patogenicidade , Reação Transfusional/virologia
13.
mSphere ; 6(1)2021 02 17.
Artigo em Inglês | MEDLINE | ID: mdl-33597174

RESUMO

Many viruses, such as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and human immunodeficiency virus (HIV), have a structure consisting of spikes protruding from an underlying spherical surface. Research in biological and colloidal sciences has revealed secrets of why spikes exist on virus surfaces. Specifically, the spikes favor virus attachment on surfaces via receptor-specific interactions (RSIs), mediate the membrane fusion, and determine or change viral tropism. The spikes also facilitate viruses to approach surfaces before attachment and subsequently escape back to the environment if RSIs do not occur (i.e., easy come and easy go). Therefore, virus spikes create the paradox of having a large capacity for binding with cells (high infectivity) and meanwhile great mobility in the environment. Such structure-function relationships have important implications for the fabrication of virus-like particles and analogous colloids (e.g., hedgehog- and raspberry-like particles) for applications such as the development of antiviral vaccines and drug delivery.


Assuntos
COVID-19/transmissão , SARS-CoV-2/fisiologia , SARS-CoV-2/patogenicidade , Glicoproteína da Espícula de Coronavírus/metabolismo , Animais , HIV/metabolismo , HIV/patogenicidade , Infecções por HIV/transmissão , Humanos , Proteínas Virais/metabolismo , Tropismo Viral/fisiologia , Internalização do Vírus
14.
Lancet HIV ; 8(2): e106-e113, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33539757

RESUMO

Ending the AIDS epidemic by 2030 will require addressing stigma more systematically and at a larger scale than current efforts. Existing global evidence shows that stigma is a barrier to achieving each of the 90-90-90 targets; it undermines HIV testing, linkage to care, treatment adherence, and viral load suppression. However, findings from both research studies and programmatic experience have helped to inform the growing body of knowledge regarding how to reduce stigma, leading to key principles for HIV stigma reduction. These principles include immediately addressing actionable drivers of stigma, centring groups affected by stigma at the core of the response, and engaging opinion leaders and building partnerships between affected groups and opinion leaders. Although there is still room to strengthen research on stigma measurement and reduction, in particular for intersectional stigma, the proliferation of evidence over the past several decades on how to measure and address stigma provides a solid foundation for immediate and comprehensive action.


Assuntos
Síndrome de Imunodeficiência Adquirida/prevenção & controle , Síndrome de Imunodeficiência Adquirida/psicologia , Epidemias/prevenção & controle , Medo/psicologia , Estigma Social , Síndrome de Imunodeficiência Adquirida/diagnóstico , Síndrome de Imunodeficiência Adquirida/virologia , Fármacos Anti-HIV/uso terapêutico , Feminino , HIV/efeitos dos fármacos , HIV/crescimento & desenvolvimento , HIV/patogenicidade , Teste de HIV/ética , Humanos , Masculino , Cooperação do Paciente/psicologia , Cooperação do Paciente/estatística & dados numéricos , Isolamento Social/psicologia , Cooperação e Adesão ao Tratamento/psicologia , Cooperação e Adesão ao Tratamento/estatística & dados numéricos , Carga Viral/efeitos dos fármacos
15.
PLoS Genet ; 17(1): e1009050, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33444376

RESUMO

HIV can evolve remarkably quickly in response to antiretroviral therapies and the immune system. This evolution stymies treatment effectiveness and prevents the development of an HIV vaccine. Consequently, there has been a great interest in using population genetics to disentangle the forces that govern the HIV adaptive landscape (selection, drift, mutation, and recombination). Traditional population genetics approaches look at the current state of genetic variation and infer the processes that can generate it. However, because HIV evolves rapidly, we can also sample populations repeatedly over time and watch evolution in action. In this paper, we demonstrate how time series data can bound evolutionary parameters in a way that complements and informs traditional population genetic approaches. Specifically, we focus on our recent paper (Feder et al., 2016, eLife), in which we show that, as improved HIV drugs have led to fewer patients failing therapy due to resistance evolution, less genetic diversity has been maintained following the fixation of drug resistance mutations. Because soft sweeps of multiple drug resistance mutations spreading simultaneously have been previously documented in response to the less effective HIV therapies used early in the epidemic, we interpret the maintenance of post-sweep diversity in response to poor therapies as further evidence of soft sweeps and therefore a high population mutation rate (θ) in these intra-patient HIV populations. Because improved drugs resulted in rarer resistance evolution accompanied by lower post-sweep diversity, we suggest that both observations can be explained by decreased population mutation rates and a resultant transition to hard selective sweeps. A recent paper (Harris et al., 2018, PLOS Genetics) proposed an alternative interpretation: Diversity maintenance following drug resistance evolution in response to poor therapies may have been driven by recombination during slow, hard selective sweeps of single mutations. Then, if better drugs have led to faster hard selective sweeps of resistance, recombination will have less time to rescue diversity during the sweep, recapitulating the decrease in post-sweep diversity as drugs have improved. In this paper, we use time series data to show that drug resistance evolution during ineffective treatment is very fast, providing new evidence that soft sweeps drove early HIV treatment failure.


Assuntos
Resistência à Doença/genética , Evolução Molecular , Infecções por HIV/genética , HIV/genética , Fármacos Anti-HIV/efeitos adversos , Terapia Antirretroviral de Alta Atividade/efeitos adversos , Variação Genética , Genética Populacional , HIV/efeitos dos fármacos , HIV/patogenicidade , Infecções por HIV/tratamento farmacológico , Infecções por HIV/virologia , Humanos , Mutação/genética , Taxa de Mutação , Seleção Genética/genética
16.
Mol Biol Rep ; 48(1): 691-699, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33409715

RESUMO

Lung cavitation is the classic hallmark of TB, which facilitates the disease development and transmission. It involves the degradation of lung parenchyma which is mainly made up of collagen fibers by metalloproteinases (MMPs) produced by activated monocyte-derived cells, neutrophils and stromal cells. The following population-based preliminary case-control study of adults with TB (50) and controls (112) without TB was used to investigate possible association between rs1800012 in COL1A1, rs12722 in COL5A1 genes and pulmonary TB in Kazakhstan. We examined 162 samples (50 cases and 112 controls) to study the associations between TB disease status and demographic variables along with single nucleotide polymorphisms related to COLA1 and COL5A1. The unadjusted χ2 and multivariable logistic regression was performed to find out relationships between SNP and other predictors. Preliminary findings suggest that there is a statistically significant association of age (AOR = 0.97, 95% CI:0.94-0.99, p value = 0.049), social status (AOR = 2.41, 95% CI:1.16-5.02, p value = 0.018), HIV status (AOR = 7.12, 95% CI:1.90-26.7, p value = 0.004) and heterozygous rs12722 SNP (AOR = 2.47, 95% CI:1.17-5.19, p value = 0.018) polymorphism of COL5A1 gene with TB susceptibility. The association of collagen genes with TB pathogenesis indicates that anti TB programs can include development of new drug regimens that include MMP inhibitors which has been found to be helpful in collagen remodeling and repair. Therapeutic targeting of MMPs will prevent extracellular matrix and collagen degradation and granuloma maturation.


Assuntos
Colágeno Tipo I/genética , Colágeno Tipo V/genética , Infecções por HIV/genética , Polimorfismo de Nucleotídeo Único , Tuberculose Pulmonar/genética , Adulto , Fatores Etários , Alelos , Estudos de Casos e Controles , Coinfecção , Feminino , Expressão Gênica , Frequência do Gene , Genótipo , HIV/crescimento & desenvolvimento , HIV/patogenicidade , Infecções por HIV/diagnóstico , Infecções por HIV/virologia , Heterozigoto , Humanos , Cazaquistão , Masculino , Pessoa de Meia-Idade , Mycobacterium tuberculosis/crescimento & desenvolvimento , Mycobacterium tuberculosis/patogenicidade , Tuberculose Pulmonar/diagnóstico , Tuberculose Pulmonar/microbiologia
18.
J Med Virol ; 93(2): 726-732, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-32692406

RESUMO

Since its first appearance in Wuhan, China, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has rapidly spread throughout the world and has become a global pandemic. Several medical comorbidities have been identified as risk factors for coronavirus disease 2019 (COVID-19). However, it remains unclear whether people living with human immunodefeciency virus (PLWH) are at an increased risk of COVID-19 and severe disease manifestation, with controversial suggestion that HIV-infected individuals could be protected from severe COVID-19 by means of antiretroviral therapy or HIV-related immunosuppression. Several cases of coinfection with HIV and SARS-CoV-2 have been reported from different parts of the globe. This review seeks to provide a holistic overview of SARS-CoV-2 infection in PLWH.


Assuntos
Fármacos Anti-HIV/uso terapêutico , COVID-19/epidemiologia , Infecções por HIV/epidemiologia , Hospedeiro Imunocomprometido , Pandemias , SARS-CoV-2/patogenicidade , Adulto , Terapia Antirretroviral de Alta Atividade/estatística & dados numéricos , Linfócitos T CD4-Positivos/efeitos dos fármacos , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD4-Positivos/virologia , COVID-19/imunologia , COVID-19/mortalidade , COVID-19/virologia , Coinfecção , Comorbidade , Diabetes Mellitus/epidemiologia , Diabetes Mellitus/fisiopatologia , Feminino , HIV/efeitos dos fármacos , HIV/crescimento & desenvolvimento , HIV/patogenicidade , Infecções por HIV/tratamento farmacológico , Infecções por HIV/mortalidade , Infecções por HIV/virologia , Humanos , Hipertensão/epidemiologia , Hipertensão/fisiopatologia , Masculino , Pessoa de Meia-Idade , SARS-CoV-2/imunologia , Análise de Sobrevida , Resultado do Tratamento
19.
PLoS One ; 15(12): e0243534, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33275646

RESUMO

The integrated counseling and testing center (ICTC) located in the district hospital, Unnao in the northern state of Uttar Pradesh (UP), India witnessed an increased detection of HIV among its attendees in July 2017. Subsequently, health camps were organized by the UP State AIDS Control Society in the villages and townships contributing to such detection. We conducted a case-control study to identify factors associated with this increased detection; 33 cases and 125 controls were enrolled. Cases were individuals, detected HIV sero-reactive during November 2017-April 2018 from three locations namely Premganj, Karimuddinpur and Chakmeerapur in the Bangarmau block of the district of Unnao. Controls hailed from the same geographical setting and tested HIV sero-nonreactive either in health camps or at ICTC centers from where the cases were detected. Misclassification bias was avoided by confirming HIV sero-status of both cases as well as controls prior to final analysis. Study participants were interviewed on various risk practices and invasive treatment procedures. They were also tested for HIV and other bio-markers reflecting unsafe injecting and sexual exposures such as hepatitis B surface antigen (HBsAg), anti-HCV antibody (HCV Ab), anti-herpes simplex-2 Immunoglobulin G (HSV-2 IgG) and rapid plasma regain (RPR) test for syphilis. Secondary data analysis on three time points during 2015 through 2018 revealed a rising trend of HIV among attendees of the ICTCs (ICTC-Hasanganj, ICTC-Unnao district hospital and ICTC- Nawabganj) catering to the entire district of Unnao. While there was a seven fold rise of HIV among ICTC attendees of Hasanganj (χ2 value for trend 23.83; p < 0.001), the rise in Unnao district hospital was twofold (χ2 value for trend 4.37; p < 0.05) and was tenfold at ICTC-Nawabganj (χ2 value for trend 5.23; p < 0.05) indicating risk of infection prevailing throughout the district. Primary data was generated through interviews and laboratory investigations as mentioned above. The median age of cases and controls was 50 year (minimum 18 -maximum 68; IQR 31-57) and 38 year (minimum 18 -maximum 78; IQR 29-50) respectively. Thirty six percent of the cases and 47% of controls were male. A significantly higher proportion of cases (85%) had HCV Ab compared to controls (56%; OR 4.4, 95% CI 1.5-12.1); none reported injection drug use. However, cases and controls did not differ significantly regarding presence of HSV-2 IgG (6% versus 8% respectively). Neither any significant difference existed between cases and controls in terms of receiving blood transfusion, undergoing invasive surgical procedures, tattooing, tonsuring of head or skin piercing. In multivariate logistic regression model, 'unsafe injection exposure during treatment-seeking'(AOR 6.61, 95% CI 1.80-24.18) and 'receipt of intramuscular injection in last five years' (AOR 7.20, 95% CI 1.48-34.88) were independently associated with HIV sero-reactive status. The monophyletic clustering of HIV sequences from 14 cases (HIV-1 pol gene amplified) indicated a common ancestry. Availability of auto-disabled syringes and needles, empowerment of the local communities and effective regulatory practices across care settings would serve as important intervention measures in this context.


Assuntos
Infecções por HIV/epidemiologia , Infecções por HIV/transmissão , Adulto , Estudos de Casos e Controles , Estudos Transversais , Surtos de Doenças , Contaminação de Equipamentos/prevenção & controle , Contaminação de Equipamentos/estatística & dados numéricos , Feminino , HIV/patogenicidade , Antígenos de Superfície da Hepatite B/sangue , Hepatite C/epidemiologia , Anticorpos Anti-Hepatite C/sangue , Humanos , Índia/epidemiologia , Masculino , Pessoa de Meia-Idade , Prevalência , Fatores de Risco , Comportamento Sexual/psicologia , Abuso de Substâncias por Via Intravenosa/epidemiologia , Sífilis/epidemiologia
20.
ACS Appl Mater Interfaces ; 12(50): 55614-55623, 2020 Dec 16.
Artigo em Inglês | MEDLINE | ID: mdl-33269927

RESUMO

Multiplexed detection of viral nucleic acids is important for rapid screening of viral infection. In this study, we present a molybdenum disulfide (MoS2) nanosheet-modified dendrimer droplet microarray (DMA) for rapid and sensitive detection of retroviral nucleic acids of human immunodeficiency virus-1 (HIV-1) and human immunodeficiency virus-2 (HIV-2) simultaneously. The DMA platform was fabricated by omniphobic-omniphilic patterning on a surface-grafted dendrimer substrate. Functionalized MoS2 nanosheets modified with fluorescent dye-labeled oligomer probes were prepatterned on positively charged amino-modified omniphilic spots to form a fluorescence resonance energy transfer (FRET) sensing microarray. With the formation of separated microdroplets of sample on the hydrophobic-hydrophilic micropattern, prepatterned oligomer probes specifically hybridized with the target HIV genes and detached from the MoS2 nanosheet surface due to weakening of the adsorption force, leading to fluorescence signal recovery. As a proof of concept, we used this microarray with a small sample size (<150 nL) for simultaneous detection of HIV-1 and HIV-2 nucleic acids with a limit of detection (LOD) of 50 pM. The multiplex detection capability was further demonstrated for simultaneous detection of five viral genes (HIV-1, HIV-2, ORFlab, and N genes of SARS-COV-2 and M gene of Influenza A). This work demonstrated the potential of this novel MoS2-DMA FRET sensing platform for high-throughput multiplexed viral nucleic acid screening.


Assuntos
Técnicas Biossensoriais , COVID-19/diagnóstico , Infecções por HIV/diagnóstico , HIV/isolamento & purificação , COVID-19/genética , COVID-19/virologia , Dissulfetos/química , Fluorescência , Transferência Ressonante de Energia de Fluorescência , HIV/patogenicidade , Infecções por HIV/genética , Infecções por HIV/virologia , Humanos , Molibdênio/química , Nanoestruturas/química , Ácidos Nucleicos/genética , Ácidos Nucleicos/isolamento & purificação , SARS-CoV-2/isolamento & purificação , SARS-CoV-2/patogenicidade
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