RESUMO
CCR5-tropic simian/human immunodeficiency viruses (SHIV) with clade C transmitted/founder envelopes represent a critical tool for the investigation of HIV experimental vaccines and microbicides in nonhuman primates, although many such isolates lead to spontaneous viral control post infection. Here, we generated a high-titer stock of pathogenic SHIV-C109p5 by serial passage in two rhesus macaques (RM) and tested its virulence in aged monkeys. The co-receptor usage was confirmed before infecting five geriatric rhesus macaques (four female and one male). Plasma viral loads were monitored by reverse transcriptase-quantitative PCR (RT-qPCR), cytokines by multiplex analysis, and biomarkers of gastrointestinal damage by enzyme-linked immunosorbent assay. Antibodies and cell-mediated responses were also measured. Viral dissemination into tissues was determined by RNAscope. Intravenous SHIV-C109p5 infection of aged RMs leads to high plasma viremia and rapid disease progression; rapid decrease in CD4+ T cells, CD4+CD8+ T cells, and plasmacytoid dendritic cells; and wasting necessitating euthanasia between 3 and 12 weeks post infection. Virus-specific cellular immune responses were detected only in the two monkeys that survived 4 weeks post infection. These were Gag-specific TNFα+CD8+, MIP1ß+CD4+, Env-specific IFN-γ+CD4+, and CD107a+ T cell responses. Four out of five monkeys had elevated intestinal fatty acid binding protein levels at the viral peak, while regenerating islet-derived protein 3α showed marked increases at later time points in the three animals surviving the longest, suggesting gut antimicrobial peptide production in response to microbial translocation post infection. Plasma levels of monocyte chemoattractant protein-1, interleukin-15, and interleukin-12/23 were also elevated. Viral replication in gut and secondary lymphoid tissues was extensive.IMPORTANCESimian/human immunodeficiency viruses (SHIV) are important reagents to study prevention of virus acquisition in nonhuman primate models of HIV infection, especially those representing transmitted/founder (T/F) viruses. However, many R5-tropic SHIV have limited fitness in vivo leading to many monkeys spontaneously controlling the virus post acute infection. Here, we report the generation of a pathogenic SHIV clade C T/F stock by in vivo passage leading to sustained viral load set points, a necessity to study pathogenicity. Unexpectedly, administration of this SHIV to elderly rhesus macaques led to extensive viral replication and fast disease progression, despite maintenance of a strict R5 tropism. Such age-dependent rapid disease progression had previously been reported for simian immunodeficiency virus but not for R5-tropic SHIV infections.
Assuntos
Infecções por HIV , HIV , Síndrome de Imunodeficiência Adquirida dos Símios , Vírus da Imunodeficiência Símia , Replicação Viral , Animais , Feminino , Masculino , Proteínas Adaptadoras de Transdução de Sinal/imunologia , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Envelhecimento , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD4-Positivos/patologia , Linfócitos T CD8-Positivos/imunologia , Linfócitos T CD8-Positivos/patologia , Quimiocina CCL2/imunologia , Quimiocina CCL2/metabolismo , Células Dendríticas/imunologia , Células Dendríticas/patologia , Progressão da Doença , HIV/classificação , HIV/crescimento & desenvolvimento , HIV/patogenicidade , HIV/fisiologia , Infecções por HIV/imunologia , Infecções por HIV/patologia , Infecções por HIV/virologia , Interferon gama/imunologia , Interferon gama/metabolismo , Interleucinas/imunologia , Interleucinas/metabolismo , Intestinos/virologia , Tecido Linfoide/virologia , Macaca mulatta/imunologia , Macaca mulatta/metabolismo , Inoculações Seriadas , Síndrome de Imunodeficiência Adquirida dos Símios/imunologia , Síndrome de Imunodeficiência Adquirida dos Símios/patologia , Síndrome de Imunodeficiência Adquirida dos Símios/virologia , Vírus da Imunodeficiência Símia/classificação , Vírus da Imunodeficiência Símia/crescimento & desenvolvimento , Vírus da Imunodeficiência Símia/patogenicidade , Vírus da Imunodeficiência Símia/fisiologia , Fator de Necrose Tumoral alfa/imunologia , Fator de Necrose Tumoral alfa/metabolismo , Carga Viral , Tropismo Viral , Virulência , Receptores CCR5/metabolismoRESUMO
As viruses are obligatory intracellular parasites, any step during their life cycle strictly depends on successful interaction with their particular host cells. In particular, their interaction with cellular membranes is of crucial importance for most steps in the viral replication cycle. Such interactions are initiated by uptake of viral particles and subsequent trafficking to intracellular compartments to access their replication compartments which provide a spatially confined environment concentrating viral and cellular components, and subsequently, employ cellular membranes for assembly and exit of viral progeny. The ability of viruses to actively modulate lipid composition such as sphingolipids (SLs) is essential for successful completion of the viral life cycle. In addition to their structural and biophysical properties of cellular membranes, some sphingolipid (SL) species are bioactive and as such, take part in cellular signaling processes involved in regulating viral replication. It is especially due to the progress made in tools to study accumulation and dynamics of SLs, which visualize their compartmentalization and identify interaction partners at a cellular level, as well as the availability of genetic knockout systems, that the role of particular SL species in the viral replication process can be analyzed and, most importantly, be explored as targets for therapeutic intervention.
Assuntos
Esfingolipídeos/metabolismo , Viroses , Transporte Biológico , Membrana Celular/química , Ceramidas/metabolismo , Sistemas de Liberação de Medicamentos , HIV/crescimento & desenvolvimento , Interações entre Hospedeiro e Microrganismos , Membranas Intracelulares/química , SARS-CoV-2/crescimento & desenvolvimento , Vírion , Replicação Viral , Vírus/crescimento & desenvolvimentoRESUMO
Human immunodeficiency viruses (HIVs) are retroviruses that replicate effectively in human CD4+ cells and cause the development of acquired immune deficiency syndrome (AIDS). On the other hand, type 1 long interspersed elements (LINE-1s or L1s) are the only active retroelements that can replicate autonomously in human cells. They, along with other active yet nonautonomous retroelements, have been associated with autoimmune diseases. There are many similarities between HIV and LINE-1. Being derived (or evolved) from ancient retroviruses, both HIV and LINE-1 replicate through a process termed reverse transcription, activate endogenous DNA and RNA sensors, trigger innate immune activation to promote interferon (IFN) expression, and are suppressed by protein products of interferon-stimulated genes (ISGs). However, these similarities make it difficult to decipher or even speculate the relationship between HIV and LINE-1, especially regarding the involvement of the IFN signaling system. In this review, we summarize previous findings on the relationships between HIV and innate immune activation as well as between LINE-1 and IFN upregulation. We also attempt to elucidate the interplay among HIV, LINE-1, and the IFN signaling system in hopes of guiding future research directions for viral suppression and immune regulation.
Assuntos
Infecções por HIV/virologia , HIV/patogenicidade , Imunidade Inata , Interferons/metabolismo , Elementos Nucleotídeos Longos e Dispersos , Animais , HIV/genética , HIV/crescimento & desenvolvimento , HIV/imunologia , Infecções por HIV/genética , Infecções por HIV/imunologia , Infecções por HIV/metabolismo , Interações Hospedeiro-Patógeno , Humanos , Evasão da Resposta Imune , Interferons/genética , Transdução de Sinais , Replicação ViralRESUMO
Background: It remains unclear whether combination antiretroviral therapy (ART) regimens differ in their ability to fully suppress human immunodeficiency virus (HIV) replication. Here, we report the results of two cross-sectional studies that compared levels of cell-associated (CA) HIV markers between individuals receiving suppressive ART containing either a non-nucleoside reverse transcriptase inhibitor (NNRTI) or a protease inhibitor (PI). Methods: CA HIV unspliced RNA and total HIV DNA were quantified in two cohorts (n = 100, n = 124) of individuals treated with triple ART regimens consisting of two nucleoside reverse transcriptase inhibitors (NRTIs) plus either an NNRTI or a PI. To compare CA HIV RNA and DNA levels between the regimens, we built multivariable models adjusting for age, gender, current and nadir CD4+ count, plasma viral load zenith, duration of virological suppression, NRTI backbone composition, low-level plasma HIV RNA detectability, and electronically measured adherence to ART. Results: In both cohorts, levels of CA HIV RNA and DNA strongly correlated (rho = 0.70 and rho = 0.54) and both markers were lower in NNRTI-treated than in PI-treated individuals. In the multivariable analysis, CA RNA in both cohorts remained significantly reduced in NNRTI-treated individuals (padj = 0.02 in both cohorts), with a similar but weaker association between the ART regimen and total HIV DNA (padj = 0.048 and padj = 0.10). No differences in CA HIV RNA or DNA levels were observed between individual NNRTIs or individual PIs, but CA HIV RNA was lower in individuals treated with either nevirapine or efavirenz, compared to PI-treated individuals. Conclusions: All current classes of antiretroviral drugs only prevent infection of new cells but do not inhibit HIV RNA transcription in long-lived reservoir cells. Therefore, these differences in CA HIV RNA and DNA levels by treatment regimen suggest that NNRTIs are more potent in suppressing HIV residual replication than PIs, which may result in a smaller viral reservoir size. Funding: This work was supported by ZonMw (09120011910035) and FP7 Health (305522).
Assuntos
DNA Viral/genética , Infecções por HIV/tratamento farmacológico , Inibidores da Protease de HIV/uso terapêutico , HIV/efeitos dos fármacos , RNA Viral/genética , Inibidores da Transcriptase Reversa/uso terapêutico , Replicação Viral/efeitos dos fármacos , Adulto , Estudos Transversais , Quimioterapia Combinada , Europa (Continente) , Feminino , HIV/genética , HIV/crescimento & desenvolvimento , Infecções por HIV/diagnóstico , Infecções por HIV/virologia , Humanos , Masculino , Pessoa de Meia-Idade , Ensaios Clínicos Controlados Aleatórios como Assunto , Fatores de Tempo , Resultado do Tratamento , Carga ViralRESUMO
INTRODUCTION: This study produces an estimate of the proportion of eligible PrEP users among people of Sub-Saharan African background based on the Belgian PrEP eligibility criteria and examines associations with socio-economic and demographic characteristics. METHODS: We performed logistic regression analysis on data of a representative community-based survey conducted among Sub-Saharan African communities (n = 685) living in Antwerp. RESULTS: Almost a third (30.3%) of the respondents were eligible to use PrEP. Those who were male, single, lower educated, undocumented, and had experienced forced sex were more likely to be eligible for PrEP use. The findings highlight the importance of taking intra-, interpersonal and structural HIV risk factors into account. CONCLUSIONS: The study shows high unmet PrEP needs in this population, especially among those with high vulnerability for HIV acquisition. A better understanding of barriers to PrEP use in this population group is needed to allow for equitable access.
Assuntos
Fármacos Anti-HIV/uso terapêutico , Infecções por HIV/prevenção & controle , Profilaxia Pré-Exposição/organização & administração , Assunção de Riscos , Adulto , África Subsaariana/etnologia , Fármacos Anti-HIV/economia , Bélgica/epidemiologia , Estudos Transversais , Feminino , HIV/crescimento & desenvolvimento , HIV/patogenicidade , Infecções por HIV/epidemiologia , Infecções por HIV/psicologia , Infecções por HIV/virologia , Humanos , Masculino , Profilaxia Pré-Exposição/ética , Migrantes/psicologiaRESUMO
People with human immunodeficiency virus (HIV) often have neurocognitive impairment. People with HIV make riskier decisions when the outcome probabilities are known, and have abnormal neural architecture underlying risky decision making. However, ambiguous decision making, when the outcome probabilities are unknown, is more common in daily life, but the neural architecture underlying ambiguous decision making in people with HIV is unknown. Eighteen people with HIV and 20 controls completed a decision making task while undergoing functional magnetic resonance imaging scanning. Participants chose between a certain reward and uncertain reward with a known (risky) or unknown (ambiguous) probability of winning. There were three levels of risk: high, medium, and low. Ambiguous > risky brain activity was compared between groups. Ambiguous > risky brain activity was correlated with emotional/psychiatric functioning in people with HIV. Both groups were similarly ambiguity-averse. People with HIV were more risk-averse than controls and chose the high-risk uncertain option less often. People with HIV had hypoactivity in the precuneus, posterior cingulate cortex (PCC), and fusiform gyrus during ambiguous > medium risk decision making. Ambiguous > medium risk brain activity was negatively correlated with emotional/psychiatric functioning in individuals with HIV. To make ambiguous decisions, people with HIV underrecruit key regions of the default mode network, which are thought to integrate internally and externally derived information to come to a decision. These regions and related cognitive processes may be candidates for interventions to improve decision-making outcomes in people with HIV.
Assuntos
Tomada de Decisões , Giro do Cíngulo/fisiopatologia , Infecções por HIV/fisiopatologia , Lobo Parietal/fisiopatologia , Assunção de Riscos , Lobo Temporal/fisiopatologia , Adulto , Estudos de Casos e Controles , Feminino , Jogos Experimentais , Giro do Cíngulo/diagnóstico por imagem , Giro do Cíngulo/virologia , HIV/crescimento & desenvolvimento , HIV/patogenicidade , Infecções por HIV/diagnóstico por imagem , Infecções por HIV/psicologia , Infecções por HIV/virologia , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Lobo Parietal/diagnóstico por imagem , Lobo Parietal/virologia , Testes Psicológicos , Recompensa , Lobo Temporal/diagnóstico por imagem , Lobo Temporal/virologiaRESUMO
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/microbiologiaRESUMO
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 701â000 (95% CrI 611â000-788â000) 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 Subsaariana/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 SobrevidaRESUMO
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 da Imunodeficiência Adquirida/prevenção & controle , Síndrome da Imunodeficiência Adquirida/psicologia , Epidemias/prevenção & controle , Medo/psicologia , Estigma Social , Síndrome da Imunodeficiência Adquirida/diagnóstico , Síndrome da 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 fármacosRESUMO
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 , Cadeia alfa 1 do Colágeno Tipo I , 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/microbiologiaRESUMO
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 TratamentoAssuntos
Fármacos Anti-HIV/uso terapêutico , COVID-19/epidemiologia , Infecções por HIV/epidemiologia , Hospedeiro Imunocomprometido , Pandemias , SARS-CoV-2/patogenicidade , 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 , HIV/efeitos dos fármacos , HIV/crescimento & desenvolvimento , HIV/patogenicidade , Infecções por HIV/tratamento farmacológico , Infecções por HIV/mortalidade , Infecções por HIV/virologia , Humanos , SARS-CoV-2/imunologia , Análise de Sobrevida , Resultado do TratamentoAssuntos
Infecções por Vírus Epstein-Barr/tratamento farmacológico , Gengiva/patologia , Infecções por HIV/tratamento farmacológico , Mandíbula/patologia , Linfoma Plasmablástico/tratamento farmacológico , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Terapia Antirretroviral de Alta Atividade/métodos , Biópsia , Ciclofosfamida/uso terapêutico , Doxorrubicina/uso terapêutico , Infecções por Vírus Epstein-Barr/diagnóstico por imagem , Infecções por Vírus Epstein-Barr/patologia , Infecções por Vírus Epstein-Barr/virologia , Raios gama , Gengiva/diagnóstico por imagem , Gengiva/efeitos dos fármacos , Gengiva/virologia , HIV/efeitos dos fármacos , HIV/crescimento & desenvolvimento , Infecções por HIV/diagnóstico por imagem , Infecções por HIV/patologia , Infecções por HIV/virologia , Herpesvirus Humano 4/efeitos dos fármacos , Herpesvirus Humano 4/crescimento & desenvolvimento , Humanos , Masculino , Mandíbula/diagnóstico por imagem , Mandíbula/efeitos dos fármacos , Mandíbula/virologia , Linfoma Plasmablástico/diagnóstico por imagem , Linfoma Plasmablástico/patologia , Linfoma Plasmablástico/virologia , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Prednisona/uso terapêutico , Costelas/diagnóstico por imagem , Costelas/efeitos dos fármacos , Costelas/patologia , Costelas/virologia , Escápula/diagnóstico por imagem , Escápula/efeitos dos fármacos , Escápula/patologia , Escápula/virologia , Vincristina/uso terapêuticoRESUMO
BACKGROUND: The replication-competent human immunodeficiency virus (HIV) reservoir is the major barrier to cure. The quantitative viral outgrowth assay (QVOA), the gold-standard method to quantify replication-competent HIV, is resource intensive, which limits its application in large clinical trials. The intact proviral DNA assay (IPDA) requires minimal cell input relative to QVOA and quantifies both defective and intact proviral HIV DNA, the latter potentially serving as a surrogate marker for replication-competent provirus. However, there are limited cross-sectional and longitudinal data on the relationship between IPDA and QVOA measurements. METHODS: QVOA and IPDA measurements were performed on 156 resting CD4 T-cell (rCD4) samples from 83 antiretroviral therapy-suppressed HIV-positive participants. Longitudinal QVOA and IPDA measurements were performed on rCD4 from 29 of these participants. RESULTS: Frequencies of intact, defective, and total proviruses were positively associated with frequencies of replication-competent HIV. Longitudinally, decreases in intact proviral frequencies were strikingly similar to that of replication-competent virus in most participants. In contrast, defective proviral DNA frequencies appeared relatively stable over time in most individuals. CONCLUSIONS: Changes in frequencies of IPDA-derived intact proviral DNA and replication-competent HIV measured by QVOA are similar. IPDA is a promising high-throughput approach to estimate changes in the frequency of the replication-competent reservoir.
Assuntos
Antirretrovirais/uso terapêutico , DNA Viral/análise , HIV/isolamento & purificação , Provírus/isolamento & purificação , Adulto , Estudos Transversais , Feminino , HIV/efeitos dos fármacos , HIV/crescimento & desenvolvimento , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Provírus/crescimento & desenvolvimento , Estudos RetrospectivosRESUMO
BACKGROUND: The COVID-19 has been a severe pandemic all around the world. Nowadays the patient with co-infection of HIV and SARS-CoV-2 was rarely reported. Here we reported a special case with HIV and SARS-CoV-2 co-infection, which showed a prolonged viral shedding duration. CASE PRESENTATION: The patient was infected with HIV 8 years ago through sexual transmission and had the normal CD4+T cell count. She was found SARS-CoV-2 positive using real-time Polymerase Chain Reaction (RT-PCR) during the epidemic. Most importantly, the patient had a prolonged viral shedding duration of SARS-CoV-2 about 28 days. CONCLUSION: The viral shedding duration may be prolonged in people living with HIV. The 14 days isolation strategy might not be long enough for them. The isolation or discharge of these patients needs further confirmation for preventing epidemics.
Assuntos
Antirretrovirais/uso terapêutico , Betacoronavirus/isolamento & purificação , Infecções por Coronavirus/diagnóstico , Infecções por HIV/complicações , Pneumonia Viral/diagnóstico , Eliminação de Partículas Virais , Alcinos , Benzoxazinas/administração & dosagem , Betacoronavirus/genética , Betacoronavirus/imunologia , Proteína C-Reativa/análise , Contagem de Linfócito CD4 , COVID-19 , Calafrios , Infecções por Coronavirus/diagnóstico por imagem , Infecções por Coronavirus/tratamento farmacológico , Ciclopropanos , Fadiga , Feminino , Febre , HIV/crescimento & desenvolvimento , Infecções por HIV/tratamento farmacológico , Infecções por HIV/imunologia , Humanos , Hospedeiro Imunocomprometido , Imunoglobulina M/sangue , Lamivudina/administração & dosagem , Pessoa de Meia-Idade , Pandemias , Faringite , Pneumonia Viral/diagnóstico por imagem , Pneumonia Viral/tratamento farmacológico , Reação em Cadeia da Polimerase em Tempo Real , SARS-CoV-2 , Escarro/virologia , Fatores de Tempo , Tomografia Computadorizada por Raios X , Eliminação de Partículas Virais/imunologia , Zidovudina/administração & dosagemRESUMO
BACKGROUND: Serum cytokine levels over the course of HIV infection usually increase with immunosuppression and decrease after antiretroviral treatment (ART). OBJECTIVES: The aim of the study is to compare cytokine levels between HIV-infected patients (HIP) and controls and investigate the relationship between CD4+T cell count, HIV-RNA levels, and cytokine levels. METHODS: The study subjects comprised ART-naive HIP (n=30) with no comorbidities and age-and sex-matched healthy controls. We measured levels of IL-6, IL-1ß, TNF-α, and IFN-γ in serum samples of HIP at the beginning and at month 6 of ART and in controls. RESULTS: The mean age of the study subjects was 38.7 ±10.3 years, with men making up 86.7% of the study subjects (n=26). IL-6, IL-1ß, and TNF-α levels were significantly higher in both ART-naive (p<0.001, p=0.002, p=0.001) and ART-experienced HIP (p<0.001) than controls. The IFN-γ level was lower in both ART-naive and ART-experienced HIP compared to controls (p=0.082 and p=0.002). There was a positive correlation between the CD4+T cell count and serum concentration of IFN- γ(r=0.320, p<0.05). While the serum IFN-γ concentration showed a negative correlation with the HIVRNA level(r=-0.412, p<0.001), the serum IL-1ß, IL-6, and TNF-α concentrations showed a positive correlation with the HIV-RNA level (r=0.349, p<0.001; r:0.54, p<0.001; r:0.438, p<0.00). CONCLUSION: Although serum concentrations of IL-6, IL-1ß and TNF-α showed a significant decrease after ART, they were still significantly higher than the controls. IFN-γ responded differently to ART compared to the other cytokines, indicating that it may play a distinct and important role in the pathogenesis of HIV infection.
Assuntos
Antirretrovirais/uso terapêutico , Infecções por HIV/tratamento farmacológico , HIV/efeitos dos fármacos , HIV/crescimento & desenvolvimento , HIV/genética , Adulto , Linfócitos T CD4-Positivos/virologia , Citocinas/metabolismo , Feminino , Infecções por HIV/virologia , Humanos , Interleucina-1beta/metabolismo , Interleucina-6/metabolismo , Masculino , Pessoa de Meia-IdadeRESUMO
BACKGROUND: Disseminated Kaposi sarcoma (DKS) is present in patients with advanced HIV infection in whom co-infection with other opportunistic pathogens can occur. Bone marrow (BM) aspirate and biopsy comprise a robust diagnostic tool in patients with fever, cytopenias, and abnormal liver tests. However, the yield in patients with DKS has not been determined. OBJECTIVE: The aim of this study was to evaluate the utility of BM aspirate and biopsy in patients with DKS. METHODS: We included 40 male patients with a recent diagnosis of DKS. BM aspirate and biopsy was performed as part of the workup to rule out co-infections. RESULTS: In four patients, Mycobacterium avium complex (MAC) was recovered from culture. In other four patients, intracellular yeasts were observed in the Grocott stain, diagnosed as Histoplasma. The yield of BM was calculated in 20%. Only 12 patients (30%) had fever and 11 (27.5%) had pancytopenia. Alkaline phosphatase (ALP) above normal values and C-reactive protein (CRP) were higher in patients with positive results for BM than in those with negative results (63% vs. 21.9%, and 3.0 vs. 1.2 mg/L; p = 0.03 in both comparisons). No differences were found when complete blood-count abnormalities were compared. CONCLUSION: We recommend performing a BM aspirate for stains, culture, and biopsy in all HIV patients with DKS, as this will permit the early diagnosis of co-infections and prevent further complications in those who receive chemotherapy.
Assuntos
Infecções Oportunistas Relacionadas com a AIDS/diagnóstico , Medula Óssea/microbiologia , Infecções por HIV/diagnóstico , Histoplasma/crescimento & desenvolvimento , Histoplasmose/diagnóstico , Sarcoma de Kaposi/diagnóstico , Infecções Oportunistas Relacionadas com a AIDS/microbiologia , Infecções Oportunistas Relacionadas com a AIDS/patologia , Infecções Oportunistas Relacionadas com a AIDS/virologia , Adulto , Fosfatase Alcalina/metabolismo , Biomarcadores/metabolismo , Biópsia , Hemocultura , Medula Óssea/metabolismo , Medula Óssea/cirurgia , Medula Óssea/virologia , Proteína C-Reativa/metabolismo , HIV/crescimento & desenvolvimento , HIV/patogenicidade , Infecções por HIV/microbiologia , Infecções por HIV/patologia , Infecções por HIV/virologia , Histoplasma/isolamento & purificação , Histoplasma/patogenicidade , Histoplasmose/microbiologia , Histoplasmose/patologia , Histoplasmose/virologia , Humanos , Masculino , Pessoa de Meia-Idade , Sarcoma de Kaposi/microbiologia , Sarcoma de Kaposi/patologia , Sarcoma de Kaposi/virologiaRESUMO
BACKGROUND: Emergence of Kaposi's Sarcoma in the cases other than HIV, following the use of immunosuppressant drugs, demonstrates that it is related to weak immunity. The fact that this malignancy does not occur in every HIV-positive patient suggests that genetic predisposition may also be effective. Replacement of one of the base pairs of adenine, guanine, cytosine, and thymine that constitute the DNA sequence in the human genome with another base pair can affect susceptibility to disease, response to treatment, and immunity. OBJECTIVE: The purpose of this study is to analyze the Single Nucleotide Polymorphism that could predispose to Kaposi's sarcoma of an HIV-infected patient and to identify which nucleotides such SNPs correspond to, using the microarray technology. MATERIALS AND METHODS: The blood samples of individuals, one of whom was diagnosed with Kaposi's Sarcoma HIV (+) visiting the outpatient clinic of infectious diseases polyclinic of Harran University Research and Practice Hospital and of a healthy individual with no Kaposi's Sarcoma, were used in the study. Following the DNA isolation of the blood samples taken from the respective individuals, a SNP analysis was conducted on the microarray device. 204,000 SNPs obtained were scanned later on in the databases in an attempt to identify the SNPs related to Kaposi's Sarcoma. RESULTS: In the 204,000 SNP screenings, we scrutinized the SNPs that differ in the case of Kaposi's Sarcoma [KS (+) and HIV (+)] on the basis of Control [KS(-) and HIV(-)] and HIV+ [KS(-)], and two SNPs of the ENDRA gene, three SNPs of the ADRA1A gene, six SNPs of the STIM1 gene, four SNPs of the EFNB2 gene, and one SNP of the CD209 gene were found to be different. However, when it comes to all SNPs (all the 204.000 SNPs) screened in terms of allele, it was observed that the AA and BB alleles were lower in the patient with Kaposi's Sarcoma [KS (+) and HIV (+)] compared to other groups and AB alleles were found to be higher than others in the patient with Kaposi's sarcoma [KS] (+) and HIV (+)]. CONCLUSION: In the microarray study we have conducted, 204,000 SNPs were screened for Control (HIV-) HIV (+) and HIV (+) patient with Kaposi's Sarcoma. It was found that 32,362 of those SNPs had different alleles in the Kaposi's Sarcoma [KS + HIV (+)] patient, while they had the same ones in the control [KS (-) and HIV (-)] and HIV + [KS (-)] group. 16 of the 32,362 SNPs took place among the genes related to Kaposi's Sarcoma. In the cases of Kaposi's Sarcoma with suspected diagnosis, it can be used as a beneficial laboratory test.
Assuntos
Moléculas de Adesão Celular/genética , Efrina-B2/genética , Infecções por HIV/genética , Lectinas Tipo C/genética , Proteínas de Neoplasias/genética , Receptor de Endotelina A/genética , Receptores Adrenérgicos alfa 1/genética , Receptores de Superfície Celular/genética , Sarcoma de Kaposi/genética , Molécula 1 de Interação Estromal/genética , Adulto , Alelos , Estudos de Casos e Controles , Moléculas de Adesão Celular/imunologia , Efrina-B2/imunologia , Expressão Gênica , Predisposição Genética para Doença , HIV/crescimento & desenvolvimento , HIV/patogenicidade , Infecções por HIV/complicações , Infecções por HIV/imunologia , Infecções por HIV/virologia , Interações Hospedeiro-Patógeno/genética , Interações Hospedeiro-Patógeno/imunologia , Humanos , Lectinas Tipo C/imunologia , Masculino , Análise em Microsséries , Pessoa de Meia-Idade , Proteínas de Neoplasias/imunologia , Polimorfismo de Nucleotídeo Único , Receptor de Endotelina A/imunologia , Receptores Adrenérgicos alfa 1/imunologia , Receptores de Superfície Celular/imunologia , Sarcoma de Kaposi/complicações , Sarcoma de Kaposi/imunologia , Sarcoma de Kaposi/virologia , Molécula 1 de Interação Estromal/imunologiaRESUMO
Hepatic steatosis (HS) is frequently observed in HIV-infected patients. It is not known whether HIV infection is an independent risk factor for HS development. We aimed to analyze whether HIV coinfection was associated with a higher frequency of HS in patients with chronic hepatitis C. This was a retrospective cross-sectional study. 574 subjects with chronic hepatitis C virus (HCV) infection were included, 246 (43%) of them coinfected with HIV. All of them underwent transient elastography with controlled attenuation parameter (CAP) measurement. HS was defined as CAP ≥ 248 dB/m. 147 individuals (45%) showed HS in the HCV-monoinfected group and 100 (40.7%) in the HIV/HCV-coinfected group (p = 0.318). HS was associated with body mass index (BMI) [<25 Kg/m2 vs. ≥25 Kg/m2, 67 (23.5%) vs. 171 (62.9%); p = 0.001], with plasma HDL-cholesterol [<50 mg/dL vs. ≥50 mg/dL, 122 (48.6%) vs. 95 (37.5%), p = 0.012], with plasma triglycerides [<150 mg/dL vs. ≥150 mg/dL, 168 (40.2%) vs. 65 (52.4%); p = 0.016] and with plasma total cholesterol [<200 mg/dL vs. ≥200 mg/dL, 181 (41%) vs. 53 (52.5%); p = 0.035]. In the multivariate analysis, HS was associated with BMI [adjusted OR (AOR) = 1.264 (1.194-1.339); p = 0.001], age [AOR = 1.029 (1.001-1.058); p = 0.047] and HCV genotype 3 infection [AOR = 1.901 (1.081-2.594); p = 0.026]. HIV coinfection was not associated with HS [AOR = 1.166 (0.719-1.892); p = 0.534]. In conclusion, HIV coinfection is not related with an increased frequency of HS in HCV-infected patients.
Assuntos
Fígado Gorduroso/epidemiologia , Infecções por HIV/epidemiologia , HIV/patogenicidade , Hepacivirus/patogenicidade , Hepatite C Crônica/epidemiologia , Fígado/patologia , Índice de Massa Corporal , HDL-Colesterol/sangue , LDL-Colesterol/sangue , Coinfecção , Estudos Transversais , Técnicas de Imagem por Elasticidade , Fígado Gorduroso/diagnóstico por imagem , Fígado Gorduroso/patologia , Fígado Gorduroso/virologia , Feminino , HIV/crescimento & desenvolvimento , Infecções por HIV/diagnóstico por imagem , Infecções por HIV/patologia , Infecções por HIV/virologia , Hepacivirus/crescimento & desenvolvimento , Hepatite C Crônica/diagnóstico por imagem , Hepatite C Crônica/patologia , Hepatite C Crônica/virologia , Humanos , Fígado/diagnóstico por imagem , Fígado/virologia , Masculino , Pessoa de Meia-Idade , Prevalência , Estudos Retrospectivos , Fatores de Risco , Espanha/epidemiologia , Triglicerídeos/sangueRESUMO
BACKGROUND: In China, although quite a few bold programmes have been made for HIV/AIDS, the epidemic has still shown an increasing trend. OBJECTIVES: The study was aimed to investigate the characteristics of new HIV/AIDS and the major factors of false positives (FP) for HIV testing. METHODS: A retrospective review was performed in a teaching hospital in Xi'an between 2013 and 2018. The overall characteristics and trends of new HIV/AIDS were described. Moreover, the major factors of FP were determined by the Pareto analysis. RESULTS: A total of 469 new HIV/AIDS were diagnosed, with an increasing prevalence of the new HIV/AIDS from 0.0626% (41/65503) in 2013 to 0.0827% (115/139046) in 2018. Of them, the majority occurred in the males (88.50%), people aged 21-50 years (76.97%), migrants (60.98%), and sexual contact route (88.70%). There was a rapid increase in the annual number of new HIV/AIDS and increasing trends in groups of young individuals, students, and homosexual mode; however, a downward trend in the percentage of injecting drug use was also observed. Over 50 years old and patients from oncology, obstetrics, hepatobiliary surgery, nephrology, cardiology, and infectious disease constituted the major factors of FP. CONCLUSION: The HIV/AIDS epidemic in Xi'an is still evolving, therefore, effective strategies, appropriate education and scaling up HIV testing should be developed. In addition, old adults and specific departments were associated with FP.