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1.
Int J Med Sci ; 18(3): 846-851, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33437221

RESUMO

In the last 50 years we have experienced two big pandemics, the HIV pandemic and the pandemic caused by SARS-CoV-2. Both pandemics are caused by RNA viruses and have reached us from animals. These two viruses are different in the transmission mode and in the symptoms they generate. However, they have important similarities: the fear in the population, increase in proinflammatory cytokines that generate intestinal microbiota modifications or NETosis production by polymorphonuclear neutrophils, among others. They have been implicated in the clinical, prognostic and therapeutic attitudes.


Assuntos
/epidemiologia , Infecções por HIV/epidemiologia , HIV-1/patogenicidade , Pandemias/história , /patogenicidade , /imunologia , /transmissão , Citocinas/sangue , Citocinas/imunologia , Armadilhas Extracelulares/imunologia , Armadilhas Extracelulares/metabolismo , Medo , Carga Global da Doença/estatística & dados numéricos , Infecções por HIV/imunologia , Infecções por HIV/psicologia , Infecções por HIV/transmissão , HIV-1/imunologia , HIV-1/isolamento & purificação , História do Século XX , História do Século XXI , Interações Hospedeiro-Patógeno/imunologia , Humanos , Mediadores da Inflamação/sangue , Mediadores da Inflamação/imunologia , Mortalidade , Neutrófilos/imunologia , Neutrófilos/metabolismo , Pandemias/estatística & dados numéricos , Prognóstico , /isolamento & purificação
2.
Biosens Bioelectron ; 171: 112753, 2021 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-33120235

RESUMO

A polyethyleneimine (PEI)-assisted copper in-situ growth (CISG) strategy was proposed as a controlled signal amplification strategy to enhance the sensitivity of gold nanoparticle-based lateral flow sensors (AuNP-LFS). The controlled signal amplification is achieved by introducing PEI as a structure-directing agent to regulate the thermodynamics of anisotropic Cu nanoshell growth on the AuNP surface, thus controlling shape and size of the resultant AuNP@Cu core-shell nanostructures and confining free reduction and self-nucleation of Cu2+ for improved reproducibility and decreased false positives. The PEI-CISG-enhanced AuNP-LFS showed ultrahigh sensitivities with the detection limits of 50 fg mL-1 for HIV-1 capsid p24 antigen and 6 CFU mL-1 for Escherichia coli O157:H7. We further demonstrated its clinical diagnostic efficacy by configuring PEI-CISG into a commercial AuNP-LFS detection kit for SARS-CoV-2 antibody detection. Altogether, this work provides a reliable signal amplification platform to dramatically enhance the sensitivity of AuNP-LFS for rapid and accurate diagnostics of various infectious diseases.


Assuntos
Técnicas Biossensoriais/métodos , Cobre/química , Infecções por Coronavirus/diagnóstico , Infecções por Escherichia coli/diagnóstico , Ouro/química , Infecções por HIV/diagnóstico , Pneumonia Viral/diagnóstico , Betacoronavirus/isolamento & purificação , Técnicas Biossensoriais/instrumentação , Técnicas de Laboratório Clínico , Desenho de Equipamento , Escherichia coli O157/isolamento & purificação , Proteína do Núcleo p24 do HIV/análise , HIV-1/isolamento & purificação , Humanos , Limite de Detecção , Nanopartículas Metálicas/química , Nanopartículas Metálicas/ultraestrutura , Oxirredução , Pandemias , Polietilenoimina/química , Fitas Reagentes/análise
3.
Curr Opin HIV AIDS ; 16(1): 3-10, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33186228

RESUMO

PURPOSE OF REVIEW: In response to the HIV-AIDS pandemic, great strides have been made in developing molecular methods that accurately quantify nucleic acid products of HIV-1 at different stages of viral replication and to assess HIV-1 sequence diversity and its effect on susceptibility to small molecule inhibitors and neutralizing antibodies. Here, we review how knowledge gained from these approaches, including viral RNA quantification and sequence analyses, have been rapidly applied to study SARS-CoV-2 and the COVID-19 pandemic. RECENT FINDINGS: Recent studies have shown detection of SARS-CoV-2 RNA in blood of infected individuals by reverse transcriptase PCR (RT-PCR); and, as in HIV-1 infection, there is growing evidence that the level of viral RNA in plasma may be related to COVID disease severity. Unlike HIV-1, SARS-CoV-2 sequences are highly conserved limiting SARS-CoV-2 sequencing applications to investigating interpatient genetic diversity for phylogenetic analysis. Sensitive sequencing technologies, originally developed for HIV-1, will be needed to investigate intrapatient SARS-CoV-2 genetic variation in response to antiviral therapeutics and vaccines. SUMMARY: Methods used for HIV-1 have been rapidly applied to SARS-CoV-2/COVID-19 to understand pathogenesis and prognosis. Further application of such methods should improve precision of therapy and outcome.


Assuntos
/virologia , Infecções por HIV/virologia , HIV-1/isolamento & purificação , RNA Viral/genética , /isolamento & purificação , /sangue , Infecções por HIV/sangue , Infecções por HIV/diagnóstico , HIV-1/genética , Humanos , RNA Viral/sangue , /genética
4.
Medicine (Baltimore) ; 99(50): e23206, 2020 Dec 11.
Artigo em Inglês | MEDLINE | ID: mdl-33327237

RESUMO

INTRODUCTION: Human Immunodeficiency Virus (HIV) infection remains prevalent co-morbidity, and among fracture patients. Few studies have investigated the role of exercise interventions in preventing bone demineralization in people who have fractures and HIV. If exercise exposed, HIV-infected individuals may experience improved bone health outcomes (BMD), function, quality of life (QoL). The study will aim to assess the impact of home based exercises on bone mineral density, functional capacity, QoL, and some serological markers of health in HIV infection among Nigerians and South Africans. METHODS AND DESIGN: The study is an assessor-blinded randomized controlled trial. Patients managed with internal and external fixation for femoral shaft fracture at the study sites will be recruited to participate in the study. The participants will be recruited 2 weeks post-discharge at the follow-up clinic with the orthopaedic surgeon. The study population will consist of all persons with femoral fracture and HIV-positive and negative (HIV-positive medically confirmed) aged 18 to 60 years attending the above-named health facilities. For the HIV-positive participants, a documented positive HIV result, as well as a history of being followed-up at the HIV treatment and care center. A developed home based exercise programme will be implemented in the experimental group while the control group continues with the usual rehabilitation programme. The primary outcome measures will be function, gait, bone mineral density, physical activity, and QoL. DISCUSSION: The proposed trial will compare the effect of a home-based physical exercise-training programme in the management of femoral fracture to the usual physiotherapy management programmes with specific outcomes of bone mineral density, function, and inflammatory markers. TRIAL REGISTRATION: The study was prospectively registered with the Pan African Clinical Trials Registry (Reference number - PACTR201910562118957) on October 21, 2019. (https://pactr.samrc.ac.za/TrialDisplay.aspx?TrialID=9425).


Assuntos
Exercício Físico/fisiologia , Fraturas do Fêmur/reabilitação , Fraturas Ósseas/etiologia , Fraturas Ósseas/reabilitação , Infecções por HIV/complicações , Adulto , Densidade Óssea/fisiologia , Terapia por Exercício/métodos , Feminino , Fraturas do Fêmur/cirurgia , Fixação de Fratura/métodos , Fraturas Ósseas/cirurgia , Marcha/fisiologia , Infecções por HIV/sangue , Infecções por HIV/epidemiologia , Infecções por HIV/virologia , HIV-1/isolamento & purificação , Humanos , Masculino , Pessoa de Meia-Idade , Nigéria/epidemiologia , Avaliação de Resultados em Cuidados de Saúde , Prevalência , Qualidade de Vida , África do Sul/epidemiologia
5.
BMC Infect Dis ; 20(1): 772, 2020 Oct 19.
Artigo em Inglês | MEDLINE | ID: mdl-33076868

RESUMO

BACKGROUND: CRF_BC recombinants, including CRF07_BC and CRF08_BC, were considered the predominant subtypes in China. Since the discovery of HIV-1 circulating recombinant form CRF 85_BC in Southwest China in 2016, this BC recombinant forms had been reported in different regions of China. However, the history and magnitude of CRF85_BC transmission were still to be investigated. METHOD: We conducted the most recent molecular epidemiology of HIV-1 among newly reported HIV-1 infected patients in Sichuan in 2019 by sequencing and phylogenetic analysis of 1291 pol sequences. Then, we used maximum likelihood approach and the Bayesian Markov chain Monte Carlo (MCMC) sampling of pol sequences to reconstruct the phylogeographic and demographic dynamics of the CRF85_BC. RESULTS: HIV-1 CRF85_BC (68/1291, 5.27%) became the fourth most prevalent strain revealing a significant increase in local population. CRF85_BC were only found in heterosexually infected individuals and the majority of CRF85_BC (95.45%) were circulating among the people living with HIV aged 50 years and over (PLHIV50+), suggesting a unique prevalent pattern. The founder lineages of CRF85_BC were likely to have first emerged in Yunnan, a province of Southwest China bordering Sichuan, in the early 2000s. It then spread exponentially to various places (including Guangxi, Sichuan, et al) and became endemic around 2008.6 (2006.7-2010.2) in Sichuan. CONCLUSION: Taken together, our findings on HIV-1 subtype CRF85_BC infections provided new insights into the spread of this virus and extended the understanding of the HIV epidemic in China.


Assuntos
Infecções por HIV/transmissão , Infecções por HIV/virologia , HIV-1/classificação , Adulto , Teorema de Bayes , China/epidemiologia , Epidemias , Feminino , Genótipo , Infecções por HIV/epidemiologia , HIV-1/genética , HIV-1/isolamento & purificação , Heterossexualidade , Humanos , Funções Verossimilhança , Masculino , Pessoa de Meia-Idade , Epidemiologia Molecular , Filogenia , Filogeografia
6.
PLoS One ; 15(9): e0239157, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32960910

RESUMO

CD4dimCD8bright T cells, a genuine population of CD8+ T cells, are highly activated and cytolytic. Recently, the low affinity IgG Fc fragment receptor CD32a was described as marker of HIV latency while others reported that CD32a is associated with T cell activation. Given that we have previously established that CD4dimCD8bright T cells are highly activated, mediate anti-HIV responses, and are infected by HIV, we assessed here CD32 expression on CD4dimCD8bright T cells in context of HIV. CD32 frequency on peripheral CD4dimCD8bright and CD4+ T cells was determined by flow cytometry among HIV negative and HIV positive patients. We report that among HIV- individuals, mean CD32 percent expression was 60% on CD4dimCD8bright T cells and 17% on CD4+ T cells (p<0.01). Among HIV+ patients, mean CD32 percent expression was 54% on CD4dimCD8bright T cells and 12% on CD4+ T cells (p<0.001). CD32 expression on CD4dimCD8bright T cells did not correlate with CD4 count and viral load and was not different by HIV serostatus. CD32 was also higher on other double positive T cell populations in both HIV negative and HIV positive donors in comparison to their single positive T cell counterpart. Together, these studies indicate that CD32 is enriched on double positive T cells regardless of HIV serostatus. The functional role of CD32 on these double positive T cells remains to be elucidated.


Assuntos
Linfócitos T CD8-Positivos/imunologia , Infecções por HIV/sangue , Receptores de IgG/metabolismo , Subpopulações de Linfócitos T/imunologia , Fármacos Anti-HIV/uso terapêutico , Contagem de Linfócito CD4 , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD4-Positivos/metabolismo , Linfócitos T CD8-Positivos/metabolismo , Separação Celular , Citometria de Fluxo , Infecções por HIV/tratamento farmacológico , Infecções por HIV/imunologia , Infecções por HIV/virologia , HIV-1/isolamento & purificação , Humanos , Receptores de IgG/imunologia , Subpopulações de Linfócitos T/metabolismo , Carga Viral
7.
PLoS One ; 15(9): e0237469, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32870911

RESUMO

BACKGROUND: It is estimated that approximately half of new HIV diagnoses among heterosexual migrants in Victoria, Australia, were acquired post-migration. We investigated the characteristics of phylogenetic clusters in notified cases of HIV among heterosexual migrants. METHODS: Partial HIV pol sequences obtained from routine clinical genotype tests were linked to Victorian HIV notifications with the following exposures listed on the notification form: heterosexual sexual contact, injecting drug use, bisexual sexual contact, male-to male sexual contact or heterosexual sexual contact in combination with injecting drug use, unknown exposure. Those with heterosexual sexual contact as the only exposure were the focus of this study, with the other exposures included to better understand transmission networks. Additional reference sequences were extracted from the Los Alamos database. Maximum likelihood methods were used to infer the phylogeny and the robustness of the resulting tree was assessed using bootstrap analysis. Phylogenetic clusters were defined on the basis of bootstrap and genetic distance. RESULTS: HIV pol sequences were available for 332 of 445 HIV notifications attributed to only heterosexual sexual contact in Victoria from 2005-2014. Forty-three phylogenetic clusters containing at least one heterosexual migrant were detected, 30 (70%) of which were pairs. The characteristics of these phylogenetic clusters varied considerably by cluster size. Pairs were more likely to be composed of people living with HIV from a single country of birth (p = 0.032). Larger clusters (n≥3) were more likely to contain people born in Australian/New Zealand (p = 0.002), migrants from more than one country of birth (p = 0.013) and viral subtype-B, the most common subtype in Australia (p = 0.006). Pairs were significantly more likely to contain females (p = 0.037) and less likely to include HIV diagnoses with male-to-male sexual contact reported as a possible exposure (p<0.001) compared to larger clusters (n≥3). CONCLUSION: Migrants appear to be at elevated risk of HIV acquisition, in part due to intimate relationships between migrants from the same country of origin, and in part due to risks associated with the broader Australian HIV epidemic. However, there was no evidence of large transmission clusters driven by heterosexual transmission between migrants. A multipronged approach to prevention of HIV among migrants is warranted.


Assuntos
Infecções por HIV/epidemiologia , HIV/genética , Filogenia , Adulto , Austrália/epidemiologia , Análise por Conglomerados , Feminino , HIV/isolamento & purificação , Infecções por HIV/diagnóstico , HIV-1/genética , HIV-1/isolamento & purificação , Heterossexualidade , Humanos , Masculino , Pessoa de Meia-Idade , Migrantes , Produtos do Gene pol do Vírus da Imunodeficiência Humana/genética
8.
PLoS One ; 15(9): e0238282, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32915788

RESUMO

The number, intensity and order of emergence of HIV-1 specific antibodies in serum or plasma were associated with the stage of HIV-1 infection. In this study, we retrospectively analyzed the HIV-1 confirmatory results tested by western blot (WB) or recombination immunoblot assay (RIBA) in Wuhan, 2012-2018, to access the profiles of HIV-1 specific antibodies. A total of 14432 HIV-suspected serum or plasma samples collected from local hospitals and other HIV screening laboratories were further screened by two 4th generation enzyme-linked immunosorbent assay (ELISA) kits in our laboratory, of which 11068 specimens (76.69%) had at least one positive ELISA result and thereby were finally confirmed with WB or RIBA. RIBA had identified 652 (81.09%) positive and 13 (1.62%) indeterminate cases from July 1, 2014 to January 7, 2015, while WB had identified 8358 (81.43%) positive and 643 (6.26%) indeterminate cases in the other times during 2012-2018. The indeterminate rate of WB was significant higher than that of RIBA (p<0.001). Although the number of HIV-1 infected subjects increased significantly from 2012 (n = 911) to 2018 (n = 1578), the positive rate of HIV-1 antibodies decreased markedly from 70.08% in 2012 to 58.79% in 2018 (p<0.001). The most commonly observed antibody profile was gp160+gp120+p66+(p55+)p51+gp41+p31+p24+p17+ (4131, 49.43%) for WB-MP and gp160+gp120+gp41+p31+p24+p17+ (382, 58.59%) for RIBA-WANTAI, and the absence of reactivity to three possible serologic markers for recent HIV-1 infection, p31, p66, and p51, increased significantly from 2012 to 2018, with the overall rate of 17.03%, 9.40%, and 15.15%, respectively. The suspected acute HIV-1 infection was also observed to be increased in recent years, with an overall rate of 1.00%. Our results indicated the detection rate had decreased for HIV-1 infection, but increased for suspected recent and acute HIV-1 infection during 2012-2018, reflecting the efforts of intervention among high risk population.


Assuntos
Anticorpos Anti-HIV/sangue , Proteína gp120 do Envelope de HIV/imunologia , Proteína gp160 do Envelope de HIV/imunologia , Infecções por HIV/diagnóstico , Soropositividade para HIV/epidemiologia , HIV-1/imunologia , Adolescente , Adulto , Criança , China/epidemiologia , Ensaio de Imunoadsorção Enzimática , Feminino , Anticorpos Anti-HIV/imunologia , Infecções por HIV/sangue , Infecções por HIV/epidemiologia , HIV-1/isolamento & purificação , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Testes Sorológicos , Fatores de Tempo , Adulto Jovem
9.
PLoS Pathog ; 16(8): e1008752, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32760121

RESUMO

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


Assuntos
Linfócitos T CD4-Positivos/imunologia , Núcleo Celular/metabolismo , Infecções por HIV/prevenção & controle , HIV-1/imunologia , Macrófagos/imunologia , Proteínas Nucleares/metabolismo , Fator de Transcrição Sp1/metabolismo , Linfócitos T CD4-Positivos/metabolismo , Linfócitos T CD4-Positivos/virologia , Núcleo Celular/genética , DNA Viral/genética , Células HEK293 , Infecções por HIV/imunologia , Infecções por HIV/patologia , Infecções por HIV/virologia , HIV-1/genética , HIV-1/isolamento & purificação , Células Hep G2 , Humanos , Imunidade Inata/imunologia , Inflamassomos/genética , Inflamassomos/imunologia , Macrófagos/metabolismo , Macrófagos/virologia , Proteínas Nucleares/genética , Fator de Transcrição Sp1/genética , Replicação Viral
10.
PLoS One ; 15(8): e0236156, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32804970

RESUMO

BACKGROUND: HIV drug resistance (HIVDR) poses a threat to the HIV epidemic control in Zambia especially in sub-populations such as the 15-24 years where there is poor virological suppression. Understanding the prevalence and patterns of HIVDR in this population (15-24 years) will contribute to defining effective antiretroviral therapy (ART) regimens, improving clinical decision making, and supporting behavioral change interventions needed to achieve HIV epidemic control. METHODS: A cross-sectional analysis of study enrollment data from the Project YES! Youth Engaging for Success randomized controlled trial was conducted. Participants were 15 to 24 years old, who knew their HIV status, and had been on ART for at least 6 months. All participants completed a survey and underwent viral load (VL) testing. Participants with viral failure (VL ≥1,000 copies/mL) underwent HIVDR testing which included analysis of mutations in the protease and reverse transcriptase genes. RESULTS: A total of 99 out of 273 analyzed participants receiving ART had VL failure, of whom 77 had successful HIVDR amplification and analysis. Out of the 77, 75% (58) had at least one drug resistant mutation, among which 83% (48/58) required a drug change. Among the 58 with HIVDR mutations, the prevalence of at least one HIVDR mutation to nucleoside reverse transcriptase inhibitors (NRTIs), non-nucleoside reverse transcriptase inhibitors (NNRTIs) and protease inhibitors (PIs) were 81%, 65.5% and 1.7%. The mutation M184V which confers resistance to NRTI drugs of lamivudine (3TC) and emtricitabine (FTC) was the most common (81%) among NRTI associated mutations followed by K65R (34.5%) which is associated with both tenofovir disoproxil fumarate (TDF) and tenofovir alafenamide fumarate (TAF) resistance. Thymidine analogue mutations (TAMs) which confer resistance primarily to zidovudine (AZT), stavudine (d4T) and other NRTIs were observed at 32.8%. Common TAMs were K70RTQNE (32.8%), K219QE (22.4%), D67N (17.2%) and T215IT (15.5%). The most common NNRTI associated mutation was the K103N (65.5%) which confers resistance to both efavirenz (EFV) and nevirapine (NVP). There was a relatively high occurrence of other NNRTI mutations V106A (36.2%), as well as Y188C (36.2%) and Y181C (36.2%) which confer resistance to etravirine. CONCLUSIONS: There is a high prevalence of HIVDR including TAMs despite majority of these patients (90.48%) being on AZT or d4T sparing first line ART among the youth. Emergence of these mutations including the NNRTI associated mutations (Y181C and Y188C) may compromise future second- and third-line regimens in the absence of routine HIVDR testing. HIVDR monitoring at start of ART or at first-line failure can better inform clinical decision making and ART programing.


Assuntos
Fármacos Anti-HIV/farmacologia , Farmacorresistência Viral/genética , Infecções por HIV/tratamento farmacológico , HIV-1/isolamento & purificação , Adolescente , Fármacos Anti-HIV/uso terapêutico , Tomada de Decisão Clínica , Estudos Transversais , Feminino , Infecções por HIV/epidemiologia , HIV-1/genética , Humanos , Masculino , Mutação , Prevalência , RNA Viral/genética , RNA Viral/isolamento & purificação , Ensaios Clínicos Controlados Aleatórios como Assunto , Timidina/genética , Carga Viral/efeitos dos fármacos , Adulto Jovem , Zâmbia
11.
Nature ; 585(7824): 261-267, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32848246

RESUMO

Sustained, drug-free control of HIV-1 replication is naturally achieved in less than 0.5% of infected individuals (here termed 'elite controllers'), despite the presence of a replication-competent viral reservoir1. Inducing such an ability to spontaneously maintain undetectable plasma viraemia is a major objective of HIV-1 cure research, but the characteristics of proviral reservoirs in elite controllers remain to be determined. Here, using next-generation sequencing of near-full-length single HIV-1 genomes and corresponding chromosomal integration sites, we show that the proviral reservoirs of elite controllers frequently consist of oligoclonal to near-monoclonal clusters of intact proviral sequences. In contrast to individuals treated with long-term antiretroviral therapy, intact proviral sequences from elite controllers were integrated at highly distinct sites in the human genome and were preferentially located in centromeric satellite DNA or in Krüppel-associated box domain-containing zinc finger genes on chromosome 19, both of which are associated with heterochromatin features. Moreover, the integration sites of intact proviral sequences from elite controllers showed an increased distance to transcriptional start sites and accessible chromatin of the host genome and were enriched in repressive chromatin marks. These data suggest that a distinct configuration of the proviral reservoir represents a structural correlate of natural viral control, and that the quality, rather than the quantity, of viral reservoirs can be an important distinguishing feature for a functional cure of HIV-1 infection. Moreover, in one elite controller, we were unable to detect intact proviral sequences despite analysing more than 1.5 billion peripheral blood mononuclear cells, which raises the possibility that a sterilizing cure of HIV-1 infection, which has previously been observed only following allogeneic haematopoietic stem cell transplantation2,3, may be feasible in rare instances.


Assuntos
Inativação Gênica , Infecções por HIV/genética , Infecções por HIV/virologia , HIV-1/genética , Heterocromatina/genética , Provírus/genética , Integração Viral/genética , Latência Viral/genética , Adulto , Idoso , Centrômero/genética , Cromossomos Humanos Par 19/genética , DNA Satélite/genética , Feminino , Genoma Viral/genética , Infecções por HIV/sangue , HIV-1/isolamento & purificação , Heterocromatina/metabolismo , Humanos , Masculino , Pessoa de Meia-Idade , Provírus/isolamento & purificação , Proteínas Repressoras/genética , Sítio de Iniciação de Transcrição
12.
PLoS One ; 15(8): e0237560, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32857765

RESUMO

Pakistan is considered by the World Health Organization to currently have a "concentrated" HIV-1 epidemic due to a rapid rise in infections among people who inject drugs (PWID). Prevalence among the country's nearly 105,000 PWID is estimated to be 37.8% but has been shown to be higher in several large urban centers. A lack of public health resources, the common use of professional injectors and unsafe injection practices are believed to have fueled the outbreak. Here we evaluate the molecular characteristics of HIV-1 sequences (n = 290) from PWID in several Pakistani cities to examine transmission dynamics and the association between rates of HIV-1 transmission with regards to regional trends in opioid trafficking. Tip-to-tip (patristic) distance based phylogenetic cluster inferences and BEAST2 Bayesian phylodynamic analyses of time-stamped data were performed on HIV-1 pol sequences generated from dried blood spots collected from 1,453 PWID as part of a cross-sectional survey conducted in Pakistan during 2014/2015. Overall, subtype A1 strains were dominant (75.2%) followed by CRF02_AG (14.1%), recombinants/unassigned (7.2%), CRF35_AD (2.1%), G (1.0%) and C (0.3%). Nearly three quarters of the PWID HIV-1 sequences belonged to one of five distinct phylogenetic clusters. Just below half (44.4%) of individuals in the largest cluster (n = 118) did seek help injecting from professional injectors which was previously identified as a strong correlate of HIV-1 infection. Spikes in estimated HIV-1 effective population sizes coincided with increases in opium poppy cultivation in Afghanistan, Pakistan's western neighbor. Structured coalescent analysis was undertaken in order to investigate the spatial relationship of HIV-1 transmission among the various cities under study. In general terms, our analysis placed the city of Larkana at the center of the PWID HIV-1 epidemic in Pakistan which is consistent with previous epidemiological data.


Assuntos
Analgésicos Opioides/administração & dosagem , Infecções por HIV/epidemiologia , Infecções por HIV/transmissão , HIV-1/isolamento & purificação , Transtornos Relacionados ao Uso de Opioides/epidemiologia , Filogenia , Abuso de Substâncias por Via Intravenosa/epidemiologia , Adulto , Estudos Transversais , Feminino , Infecções por HIV/virologia , Soropositividade para HIV , Humanos , Masculino , Transtornos Relacionados ao Uso de Opioides/virologia , Paquistão/epidemiologia , Adulto Jovem
13.
J Chromatogr A ; 1627: 461378, 2020 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-32823092

RESUMO

Downstream processing (DSP) of large bionanoparticles is still a challenge. The present study aims to systematically compare some of the most commonly used DSP strategies for capture and purification of enveloped viruses and virus-like particles (eVLPs) by using the same staring material and analytical tools. As a model, Human Immunodeficiency Virus-1 (HIV-1) gag VLPs produced in CHO cells were used. Four different DSP strategies were tested. An anion-exchange monolith and a membrane adsorber, for direct capture and purification of eVLPs, and a polymer-grafted anion-exchange resin and a heparin-affinity resin for eVLP purification after a first flow-through step to remove small impurities. All tested strategies were suitable for capture and purification of eVLPs. The performance of the different strategies was evaluated regarding its binding capacity, ability to separate different particle populations and product purity. The highest binding capacity regarding total particles was obtained using the anion exchange membrane adsorber (5.3 × 1012 part/mL membrane), however this method did not allow the separation of different particle populations. Despite having a lower binding capacity (1.5 × 1011 part/mL column) and requiring a pre-processing step with flow-through chromatography, Heparin-affinity chromatography showed the best performance regarding separation of different particle populations, allowing not only the separation of HIV-1 gag VLPs from host cell derived bionanoparticles but also from chromatin. This work additionally shows the importance of thorough sample characterization combining several biochemical and biophysical methods in eVLP DSP.


Assuntos
Convecção , HIV-1/isolamento & purificação , Adsorção , Animais , Ânions , Células CHO , Cromatina/metabolismo , Cromatografia de Afinidade , Cricetinae , Cricetulus , HIV-1/ultraestrutura , Histonas/metabolismo , Humanos , Microesferas , Nanopartículas/química , Nanopartículas/ultraestrutura , Polímeros/química , Porosidade , Vírion/isolamento & purificação , Vírion/ultraestrutura
14.
Zhonghua Liu Xing Bing Xue Za Zhi ; 41(7): 1121-1125, 2020 Jul 10.
Artigo em Chinês | MEDLINE | ID: mdl-32741182

RESUMO

Objective: To analyze the characteristics of HIV-1 molecular network in men who have sex with men (MSM) from 2016 to 2018 in Kunming, Yunnan province, explore the risk factors associated with HIV-1 transmission network and provide evidence for the effective implementation of intervention. Methods: A total of 540 samples of newly reported HIV-1 positive MSM were consecutively collected in Kunming from 2016 to 2018, the pol gene fragments were amplified by nested polymerase chain reaction (PCR). HIV-1 molecular networks were constructed according to the bootstrap value of the maximum likelihood evolutionary tree over 95% and the genetic distance less than 3%. The factors associated with the subjects entering network and network growth were further analyzed. Results: Among 459 successfully sequenced samples, seven genotypes were found, in which CRF07_BC (49.2%, 226/459) and CRF01_AE (40.3%, 185/459 ) were predominant. Other genotypes included URFs (4.8%, 22/459), CRF08_BC (3.1%, 14/459), CRF55_01B (1.7%, 8/459), B (0.7%, 3/459) and CRF68_01B (0.2%, 1/459). A total of 163 sequences entered the network, with an entry rate of 35.5%(163/459), forming 56 clusters with the number of individuals in the cluster was between 2 and 13. The analysis of the factors associated with entering network showed that the MSM who married and had multiple homosexual partners were more likely to be found in HIV-1 molecular networks. Multivariate logistic regression analysis showed that the number of sexual partners was the factor for the growth of HIV-1 molecular network. According to the criteria for the emergence of three or more newly reported cases in every year, six transmission clusters were judged as active transmission clusters, in which MSM who were not Kunming natives, had sexually transmitted diseases (STD), were divorced and students were the key targets of intervention. Conclusions: HIV-1 genotypes in MSM in Kunming were becoming complex, the risk factors associated with transmission networks in MSM in Kunming included being married and having multiple partners, the intervention targets in active transmission clusters included MSM who were not Kunming natives, had STD, were divorced and students. This study provided the basis for applying HIV-1 molecular networks to real-time intervention in this population.


Assuntos
Infecções por HIV/virologia , HIV-1/genética , Homossexualidade Masculina/estatística & dados numéricos , China/epidemiologia , Genótipo , Infecções por HIV/epidemiologia , HIV-1/isolamento & purificação , Humanos , Masculino
16.
PLoS One ; 15(7): e0235958, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32692778

RESUMO

BACKGROUND: With the scale-up of antiretroviral therapy (ART), pre-treatment drug resistance (PDR) appears ≥10% amongst ART-initiators in many developing countries, including Cameroon. Northwest region-Cameroon having the second epidemiological burden of HIV infection, generating data on PDR in these geographical settings, will enhance evidence-based decision-making. OBJECTIVES: We sought to ascertain levels of PDR and HIV-1 clade dispersal in rural and urban settings, and their potential association with subtype distribution and CD4-staging. METHODS: A cross-sectional study was conducted from February to May 2017 among patients recently diagnosed with HIV-infection and initiating ART at the Bamenda regional Hospital (urban setting) and the Mbingo Baptist hospital (rural setting). Protease and reverse transcriptase sequencing was performed using an in-house protocol and pre-treatment drug resistance mutations were interpreted using Stanford HIVdb.v8.3. Phylogeny was performed for subtype assignation. RESULTS: A total of 61 patient sequences were generated from ART initiators (median age: 37 years old; 57.4% female; median CD4 cell count: 184 [IQR: 35-387] in urban vs. 161 [IQR: 96-322] cells/mm3 in rural). Overall, the level of PDR was 9.8% (6/61). Of note, burden of PDR was almost doubled in urban (12.9% [4/31]) compared to rural setting 6.7% (2/30), p = 0.352). Fifteen (15) PDR mutations were found among four patients the urban settings [6 resistance mutations to NRTIs:[M41L (2), E44D (1), K65R (1), K70E (1), M184V/I (2), K219R (1)] and 6 resistance mutations to NNRTIs: K103N (1), E138A/G (2), V179E (1), M230L (1), K238T (1), P225H (1)] against two (02) mutations found in two patients in the rural setting[2 resistant mutations to NNRTIs: E138A (1) and Y188H (1)]. The rural setting showed more genetic diversity (8 subtypes) than the urban setting (5 subtypes), with CRF02_AG being the most prevalent clade (72.1% [44/61]). Of note, level of PDR was similar between patients infected with CRF02_AG and non-CRF02_AG infected (9.1% [4/44]) vs. 11.8% [2/17]), p = 1.000). Moreover, PDR appeared higher in patients with CD4 cell count <200 cells/mm3 compared to those with CD4 cell count ≥200 cells/mm3 (14.7% [5/34]) vs. 3.7% [1/27]), p = 0.214). CONCLUSIONS: PDR is at a moderate rate in the Northwest region of Cameroon, with higher burden within urban populations. CRF02_AG is the most predominant clade in both urban and rural settings. No effect of HIV molecular epidemiology and CD4-staging on the presence of PDR in patients living in these settings was found. Our findings suggest close monitoring, NNRTI-sparing regimens or sequencing for patients initiating ART, especially in urban settings.


Assuntos
Fármacos Anti-HIV/uso terapêutico , Farmacorresistência Viral/genética , Variação Genética/efeitos dos fármacos , Infecções por HIV/tratamento farmacológico , HIV-1/efeitos dos fármacos , HIV-1/genética , Carga Viral/efeitos dos fármacos , Adulto , Camarões/epidemiologia , Estudos Transversais , Feminino , Genótipo , Infecções por HIV/epidemiologia , Infecções por HIV/genética , Infecções por HIV/virologia , HIV-1/isolamento & purificação , Humanos , Masculino , População Rural , População Urbana , Carga Viral/genética
17.
PLoS One ; 15(7): e0236162, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32697807

RESUMO

HIV cerebrospinal fluid (CSF) escape is defined by a concentration of HIV-1 RNA in CSF above the lower limit of quantification of the employed assay and equal to or greater than the plasma HIV-1 RNA level in the presence of treatment-related plasma viral suppression, while CSF discordance is similarly defined by equal or higher CSF than plasma HIV-1 RNA in untreated individuals. During secondary CSF escape or discordance, disproportionate CSF HIV-1 RNA develops in relation to another infection in addition to HIV-1. We performed a retrospective review of people living with HIV receiving clinical care at Sahlgrenska Infectious Diseases Clinic in Gothenburg, Sweden who developed uncomplicated herpes zoster (HZ) and underwent a research lumbar puncture (LP) within the ensuing 150 days. Based on treatment status and the relationship between CSF and plasma HIV-1 RNA concentrations, they were divided into 4 groups: i) antiretroviral treated with CSF escape (N = 4), ii) treated without CSF escape (N = 5), iii) untreated with CSF discordance (N = 8), and iv) untreated without CSF discordance (N = 8). We augmented these with two additional cases of secondary CSF escape related to neuroborreliosis and HSV-2 encephalitis and analyzed these two non-HZ cases for factors contributing to CSF HIV-1 RNA concentrations. HIV-1 CSF escape and discordance were associated with higher CSF white blood cell (WBC) counts than their non-escape (P = 0.0087) and non-discordant (P = 0.0017) counterparts, and the CSF WBC counts correlated with the CSF HIV-1 RNA levels in both the treated (P = 0.0047) and untreated (P = 0.002) group pairs. Moreover, the CSF WBC counts correlated with the CSF:plasma HIV-1 RNA ratios of the entire group of 27 subjects (P = <0.0001) indicating a strong effect of the CSF WBC count on the relation of the CSF to plasma HIV-1 RNA concentrations across the entire sample set. The inflammatory response to HZ and its augmenting effect on CSF HIV-1 RNA was found up to 5 months after the HZ outbreak in the cross-sectional sample and, was present for one year after HZ in one individual followed longitudinally. We suggest that HZ provides a 'model' of secondary CSF escape and discordance. Likely, the inflammatory response to HZ pathology provoked local HIV-1 production by enhanced trafficking or activation of HIV-1-infected CD4+ T lymphocytes. Whereas treatment and other systemic factors determined the plasma HIV-1 RNA concentrations, in this setting the CSF WBC counts established the relation of the CSF HIV-1 RNA levels to this plasma set-point.


Assuntos
Encefalite/etiologia , Infecções por HIV/complicações , HIV-1/isolamento & purificação , Herpes Zoster/etiologia , Leucocitose/etiologia , RNA Viral/líquido cefalorraquidiano , Adulto , Estudos Transversais , Encefalite/líquido cefalorraquidiano , Encefalite/patologia , Feminino , Infecções por HIV/virologia , Herpes Zoster/líquido cefalorraquidiano , Herpes Zoster/patologia , Herpesvirus Humano 3/isolamento & purificação , Humanos , Leucocitose/líquido cefalorraquidiano , Leucocitose/patologia , Estudos Longitudinais , Masculino , Estudos Retrospectivos
18.
Sci Rep ; 10(1): 8699, 2020 05 26.
Artigo em Inglês | MEDLINE | ID: mdl-32457309

RESUMO

Sub-Saharan Africa carries the largest burden of pediatric HIV infection. The success of second line anti-retroviral treatment and related factors among African children is not well-defined. Objectives: We aimed to identify the rate and determinants of second line anti-retroviral treatment failure among children and adolescents on follow-up at an Ethiopian tertiary teaching hospital. A retrospective observational cohort study was conducted at Tikur Anbessa Specialized Hospital, Addis Ababa. Structured forms were used to collect socio-demographic, clinical and diagnostic data. Descriptive statistics and bivariate analysis were used to describe the magnitude of the problem and its associations. A total of 76 children and adolescents taking second line anti-retroviral treatment were analyzed (mean age: 16.1 years). Failure of therapy was seen in 14/76 while four were eligible for a switch to third line anti-retrovirals. Mean duration on second line treatment till virologic failure was diagnosed was 17.6 months while mean viral load upon requiring a third line regimen was 82,131.3 copies/ml. Second line antiretroviral treatment virologic failure was significantly associated with the age of the child or adolescent. A high rate of virologic failure exists among the study population. Findings underline need for provision of third line anti-retroviral drugs in Ethiopia. Challenges for delivering a standard care were irregular viral load testing and delayed initiation of second line treatment after failure of first line regimens.


Assuntos
Antirretrovirais/uso terapêutico , Infecções por HIV/tratamento farmacológico , Adolescente , Criança , Pré-Escolar , Estudos de Coortes , Etiópia , Infecções por HIV/patologia , Infecções por HIV/virologia , HIV-1/isolamento & purificação , HIV-1/fisiologia , Humanos , Estudos Retrospectivos , Centros de Atenção Terciária , Falha de Tratamento , Carga Viral
19.
PLoS One ; 15(4): e0231761, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32353005

RESUMO

BACKGROUND: Cellular immunometabolism among people living with HIV (PLWH) on antiretroviral therapy (ART) remains under investigated. We assessed the relationships between mitochondrial oxidative phosphorylation (OXPHOS) in peripheral blood mononuclear cells (PBMCs) and blood parameters associated with HIV immune dysregulation. METHODS: PLWH ≥40 years old and on stable ART ≥3 months were enrolled (N = 149). OXPHOS complex I (CI, NADH dehydrogenase) and complex IV (CIV, cytochrome c oxidase) protein levels in PBMCs were quantified using immunoassays. Monocyte subsets and markers of T-cell activation, senescence, and exhaustion were measured on PBMC by flow cytometry. Plasma inflammatory mediators were quantified using a multiplex assay. HIV-uninfected group (N = 44) of similar age, gender, and ethnicity had available OXPHOS levels. RESULTS: PLWH had a median age of 51 years. Majority were male (88.6%), Caucasian (57.7%), and with undetectable plasma HIV RNA <50 copies/mL (84.6%). Median CI level was lower in PLWH compared with the HIV-seronegative group (65.5 vs 155.0 optical density/µg protein x 103, p <0.0001). There was no significant difference in median CIV levels. Lower OXPHOS levels correlated with lower CD4% and CD4/CD8 ratio. On multivariable linear regression adjusted for age, current use of zidovudine/didanosine, and HIV RNA (detectable versus undetectable), lower OXPHOS levels were significantly associated with higher MPO, SAA, SAP, and sVCAM, and higher frequencies of intermediate (CD14++CD16+) monocytes and TIGIT+TIM3+ CD4 T-cell (p<0.01). CONCLUSION: CI PBMC protein levels were decreased in PLWH on ART. Decreased OXPHOS correlated with disease severity and inflammation. Further studies on the relationship between immunometabolism and immune dysregulation in HIV are warranted.


Assuntos
Fármacos Anti-HIV/uso terapêutico , Infecções por HIV/imunologia , HIV-1/imunologia , Leucócitos Mononucleares/imunologia , Mitocôndrias/metabolismo , Fosforilação Oxidativa , Relação CD4-CD8 , Estudos Transversais , Feminino , Infecções por HIV/diagnóstico , Infecções por HIV/tratamento farmacológico , Infecções por HIV/virologia , HIV-1/genética , HIV-1/isolamento & purificação , Hawaii , Interações Hospedeiro-Patógeno/imunologia , Humanos , Leucócitos Mononucleares/citologia , Ativação Linfocitária , Masculino , Pessoa de Meia-Idade , Mitocôndrias/imunologia , RNA Viral/isolamento & purificação , Índice de Gravidade de Doença
20.
BMC Infect Dis ; 20(1): 313, 2020 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-32345262

RESUMO

BACKGROUND: There is increasing evidence that HIV-1 genetic diversity can have an impact on drug resistance. The aim of this study is to investigate the epidemiological situation of CRF65_cpx and the impact of natural polymorphisms of this variant on genotypic resistance. METHODS: We used the BLAST search program followed by phylogenetic analysis to identify additional CRF65_cpx pol sequences from the Los Alamos HIV Sequence Database. Maximum likelihood phylogeny was estimated to clarify the epidemiological relationship of CRF65_cpx strains. Genotypic resistance was determined by submitting sequences to the Stanford HIV Drug Resistance Database. RESULTS: A total of 32 CRF65_cpx pol sequences were obtained. The CRF65_cpx strains were detected in seven provinces with large geographic distance. Yunnan CRF65_cpx sequences were mainly derived from a heterosexual risk group, whereas the CRF65_cpx sequences in other provinces were almost exclusively derived from an MSM population. With one exception of V179E, the other 31 strains harbored V179D mutation. The combination of V179D and K103R, conferring intermediate resistance to EFV and NVP, was detected in seven treatment-naive MSM patients. CONCLUSIONS: This study confirmed the expansion CRF65_cpx in China. Furthermore, we found the natural presence of the V179D and K103R/V179D mutations associated with resistance to NNRTIs in HIV-1 CRF65_cpx. Our findings highlight the contribution of polymorphic mutations to drug resistance and underscore the challenges in treating patients harboring CRF65_cpx strains.


Assuntos
Farmacorresistência Viral/genética , Infecções por HIV/tratamento farmacológico , HIV-1/genética , Inibidores da Transcriptase Reversa/uso terapêutico , Produtos do Gene pol do Vírus da Imunodeficiência Humana/genética , Adulto , Feminino , Genótipo , HIV-1/classificação , HIV-1/isolamento & purificação , Homossexualidade Masculina , Humanos , Funções Verossimilhança , Masculino , Pessoa de Meia-Idade , Mutação , Filogenia , Produtos do Gene pol do Vírus da Imunodeficiência Humana/classificação , Produtos do Gene pol do Vírus da Imunodeficiência Humana/metabolismo
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