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1.
PLoS Pathog ; 17(9): e1009581, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34529720

RESUMO

The switch between HIV latency and productive transcription is regulated by an auto-feedback mechanism initiated by the viral trans-activator Tat, which functions to recruit the host transcription elongation factor P-TEFb to proviral HIV. A heterodimeric complex of CDK9 and one of three cyclin T subunits, P-TEFb is expressed at vanishingly low levels in resting memory CD4+ T cells and cellular mechanisms controlling its availability are central to regulation of the emergence of HIV from latency. Using a well-characterized primary T-cell model of HIV latency alongside healthy donor memory CD4+ T cells, we characterized specific T-cell receptor (TCR) signaling pathways that regulate the generation of transcriptionally active P-TEFb, defined as the coordinate expression of cyclin T1 and phospho-Ser175 CDK9. Protein kinase C (PKC) agonists, such as ingenol and prostratin, stimulated active P-TEFb expression and reactivated latent HIV with minimal cytotoxicity, even in the absence of intracellular calcium mobilization with an ionophore. Unexpectedly, inhibition-based experiments demonstrated that PKC agonists and TCR-mobilized diacylglycerol signal through MAP kinases ERK1/2 rather than through PKC to effect the reactivation of both P-TEFb and latent HIV. Single-cell and bulk RNA-seq analyses revealed that of the four known isoforms of the Ras guanine nucleotide exchange factor RasGRP, RasGRP1 is by far the predominantly expressed diacylglycerol-dependent isoform in CD4+ T cells. RasGRP1 should therefore mediate the activation of ERK1/2 via Ras-Raf signaling upon TCR co-stimulation or PKC agonist challenge. Combined inhibition of the PI3K-mTORC2-AKT-mTORC1 pathway and the ERK1/2 activator MEK prior to TCR co-stimulation abrogated active P-TEFb expression and substantially suppressed latent HIV reactivation. Therefore, contrary to prevailing models, the coordinate reactivation of P-TEFb and latent HIV in primary T cells following either TCR co-stimulation or PKC agonist challenge is independent of PKC but rather involves two complementary signaling arms of the TCR cascade, namely, RasGRP1-Ras-Raf-MEK-ERK1/2 and PI3K-mTORC2-AKT-mTORC1.


Assuntos
Linfócitos T CD4-Positivos/metabolismo , HIV/fisiologia , Fator B de Elongação Transcricional Positiva/metabolismo , Proteína Quinase C/metabolismo , Latência Viral/fisiologia , Linfócitos T CD4-Positivos/virologia , Infecções por HIV/metabolismo , Infecções por HIV/virologia , Humanos , Transdução de Sinais/fisiologia , Ativação Viral/fisiologia
2.
PLoS One ; 16(8): e0255566, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34339464

RESUMO

BACKGROUND: Closing the gap of unmet for family planning is crucial to eliminate new pediatric HIV infections likewise to improve maternal and child health among reproductive-age women living with HIV. However, studies conducted on unmet need for family planning among reproductive-age women living with HIV showed inconsistent and non-conclusive findings on the magnitude of the problem. Moreover, there was no meta-analysis conducted in this area. So this systematic review and meta-analysis were conducted to estimate the pooled prevalence unmet need for family planning among reproductive-age women living with HIV in Ethiopia. METHODS: The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline was followed to review both published and unpublished studies in Ethiopia. All studies in PubMed, Cochrane Library, Hinari, Google Scholar, CINAHL, and Global Health databases were searched. Meta-analysis was performed using STATA 14 software. The heterogeneity and publication bias were assessed using the I2 statistics and Egger regression asymmetry test, respectively. Forest plots were used to present the pooled prevalence with a 95% confidence interval (CI). RESULTS: This review included 7 studies, and 3333 study participants. The pooled prevalence of unmet need for family planning among reproductive-age women living with HIV in Ethiopia was 25.13% (95%CI: 19.97, 30.29). The pooled prevalence of unmet need for spacing and limiting was 13.91% (95%CI: 10.11, 17.72) and 9.11% (95%CI: 6.43, 11.78), respectively. CONCLUSIONS: One-fourths of reproductive-age women living with HIV had an unmet need for family planning. A variety of programmatic investments are needed to achieve more meaningful progress toward the reduction of unmet need for family planning among reproductive-age women living with HIV.


Assuntos
Comportamento Contraceptivo , Serviços de Planejamento Familiar/estatística & dados numéricos , Infecções por HIV/epidemiologia , HIV/fisiologia , Necessidades e Demandas de Serviços de Saúde/estatística & dados numéricos , Reprodução , Educação Sexual/métodos , Feminino , Infecções por HIV/tratamento farmacológico , Infecções por HIV/virologia , Humanos , Gravidez
3.
Elife ; 102021 08 03.
Artigo em Inglês | MEDLINE | ID: mdl-34342266

RESUMO

Background: People who inject drugs (PWID) account for some of the most explosive human immunodeficiency virus (HIV) and hepatitis C virus (HCV) epidemics globally. While individual drivers of infection are well understood, less is known about network factors, with minimal data beyond direct ties. Methods: 2512 PWID in New Delhi, India were recruited in 2017-19 using a sociometric network design. Sampling was initiated with 10 indexes who recruited named injection partners (people who they injected with in the prior month). Each recruit then recruited their named injection partners following the same process with cross-network linkages established by biometric data. Participants responded to a survey, including information on injection venues, and provided a blood sample. Factors associated with HIV/HCV infection were identified using logistic regression. Results: The median age was 26; 99% were male. Baseline HIV prevalence was 37.0% and 46.8% were actively infected with HCV (HCV RNA positive). The odds of prevalent HIV and active HCV infection decreased with each additional degree of separation from an infected alter (HIV AOR: 0.87; HCV AOR: 0.90) and increased among those who injected at a specific venue (HIV AOR: 1.50; HCV AOR: 1.69) independent of individual-level factors (p<0.001). In addition, sociometric factors, for example, network distance to an infected alter, were statistically significant predictors even when considering immediate egocentric ties. Conclusions: These data demonstrate an extremely high burden of HIV and HCV infection and a highly interconnected injection and spatial network structure. Incorporating network and spatial data into the design/implementation of interventions may help interrupt transmission while improving efficiency. Funding: National Institute on Drug Abuse and the Johns Hopkins University Center for AIDS Research.


Assuntos
Coinfecção/transmissão , Infecções por HIV/transmissão , Hepatite C/transmissão , Adulto , Coinfecção/epidemiologia , Coinfecção/virologia , Estudos Transversais , Feminino , HIV/fisiologia , Infecções por HIV/epidemiologia , Infecções por HIV/virologia , Hepacivirus/fisiologia , Hepatite C/epidemiologia , Hepatite C/virologia , Humanos , Índia/epidemiologia , Masculino , Prevalência , Análise de Rede Social , Adulto Jovem
4.
J Gen Virol ; 102(8)2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34424156

RESUMO

Viruses may exploit the cardiovascular system to facilitate transmission or within-host dissemination, and the symptoms of many viral diseases stem at least in part from a loss of vascular integrity. The microvascular architecture is comprised of an endothelial cell barrier ensheathed by perivascular cells (pericytes). Pericytes are antigen-presenting cells (APCs) and play crucial roles in angiogenesis and the maintenance of microvascular integrity through complex reciprocal contact-mediated and paracrine crosstalk with endothelial cells. We here review the emerging ways that viruses interact with pericytes and pay consideration to how these interactions influence microvascular function and viral pathogenesis. Major outcomes of virus-pericyte interactions include vascular leakage or haemorrhage, organ tropism facilitated by barrier disruption, including viral penetration of the blood-brain barrier and placenta, as well as inflammatory, neurological, cognitive and developmental sequelae. The underlying pathogenic mechanisms may include direct infection of pericytes, pericyte modulation by secreted viral gene products and/or the dysregulation of paracrine signalling from or to pericytes. Viruses we cover include the herpesvirus human cytomegalovirus (HCMV, Human betaherpesvirus 5), the retrovirus human immunodeficiency virus (HIV; causative agent of acquired immunodeficiency syndrome, AIDS, and HIV-associated neurocognitive disorder, HAND), the flaviviruses dengue virus (DENV), Japanese encephalitis virus (JEV) and Zika virus (ZIKV), and the coronavirus severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2; causative agent of coronavirus disease 2019, COVID-19). We touch on promising pericyte-focussed therapies for treating the diseases caused by these important human pathogens, many of which are emerging viruses or are causing new or long-standing global pandemics.


Assuntos
Fenômenos Fisiológicos Celulares , Suscetibilidade a Doenças , Interações Hospedeiro-Patógeno , Pericitos/virologia , Viroses/metabolismo , Viroses/virologia , Animais , Comunicação Celular , Vírus da Dengue/fisiologia , Gerenciamento Clínico , Células Endoteliais/virologia , Endotélio/metabolismo , Endotélio/virologia , HIV/fisiologia , Humanos , Comunicação Parácrina , SARS-CoV-2/fisiologia , Viroses/diagnóstico , Viroses/terapia , Fenômenos Fisiológicos Virais
5.
PLoS Med ; 18(5): e1003651, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-34029346

RESUMO

Peter Ehrenkranz and co-authors present a cyclical cascade of care for people with HIV infection, aiming to facilitate assessment of outcomes.


Assuntos
Síndrome de Imunodeficiência Adquirida/terapia , Atenção à Saúde/normas , HIV/fisiologia , Objetivos , Humanos , Nações Unidas
6.
Front Immunol ; 12: 682624, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34025682

RESUMO

Ubiquitination is a process that acts upon every step of the HIV replication cycle. The activity, subcellular localization, and stability of HIV dependency factors as well as negative modulators can be affected by ubiquitination. These modifications consequently have an impact on the progression and outcome of infection. Additionally, recent findings suggest new roles for ubiquitination in the interplay between HIV and the cellular environment, specifically in the interactions between HIV, autophagy and apoptosis. On one hand, autophagy is a defense mechanism against HIV that promotes the degradation of the viral protein Gag, likely through ubiquitination. Gag is an essential structural protein that drives virion assembly and release. Interestingly, the ubiquitination of Gag is vital for HIV replication. Hence, this post-translational modification in Gag represents a double-edged sword: necessary for virion biogenesis, but potentially detrimental under conditions of autophagy activation. On the other hand, HIV uses Nef to circumvent autophagy-mediated restriction by promoting the ubiquitination of the autophagy inhibitor BCL2 through Parkin/PRKN. Although the Nef-promoted ubiquitination of BCL2 occurs in both the endoplasmic reticulum (ER) and mitochondria, only ER-associated ubiquitinated BCL2 arrests the progression of autophagy. Importantly, both mitochondrial BCL2 and PRKN are tightly connected to mitochondrial function and apoptosis. Hence, by enhancing the PRKN-mediated ubiquitination of BCL2 at the mitochondria, HIV might promote apoptosis. Moreover, this effect of Nef might account for HIV-associated disorders. In this article, we outline our current knowledge and provide perspectives of how ubiquitination impacts the molecular interactions between HIV, autophagy and apoptosis.


Assuntos
Apoptose , Autofagia , Infecções por HIV/metabolismo , Infecções por HIV/virologia , Interações Hospedeiro-Patógeno , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Produtos do Gene nef do Vírus da Imunodeficiência Humana/metabolismo , HIV/fisiologia , Humanos , Complexo de Endopeptidases do Proteassoma/metabolismo , Proteólise , Ubiquitinação
7.
J Med Virol ; 93(8): 4992-5000, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-33818800

RESUMO

In hepatitis C virus (HCV)/human immunodeficiency virus (HIV) co-infected patients, HIV enhances HCV replication and liver damage. Several microRNAs (miRNAs), active in pro-fibrotic and inflammatory pathways, have been implicated in the pathogenesis of this phenomenon. However, these miRNAs have been tested only in explanted cirrhotic livers, when the liver damage has become chronic and irreversible. No data are available on the early phase of viral infection, such as early after liver transplantation (LT). In the present study, the expression of miR-101, miR-122, miR-155, miR-192, miR-200c, miR-338, and miR-532 was determined by quantitative real-time polymerase chain reaction in liver biopsies of HCV (n = 19) and HCV/HIV-infected (n = 20) LT recipients, as well as in a control group (n = 18) of noninfected patients, transplanted for alcoholic cirrhosis. The timing of liver biopsy was 6 months post-LT. None of the patients was treated with direct-acting anti-HCV drugs. All co-infected recipients had suppressed HIV viral load. Grading and staging were assessed according to the Ishak Classification. HCV and HIV viral load were measured in the sera. miR-101 (p = .03), miR-122 (p = .012), and miR-192 (p = .038) were significantly downregulated in HCV/HIV co-infected and HCV mono-infected recipients when compared with noninfected recipients, and such downregulation was more pronounced in co-infected ones. Moreover, in co-infected recipients but not in mono-infected ones, miR-101 inversely correlated with the peripheral HCV-RNA levels (r = .41, p = .04) and miR-122 inversely correlated with peripheral HCV-RNA levels (r = .49, p = .03) and with the histological grading (r = .51, p = .02).  In conclusion, as early as 6 months after LT, the presence of HIV-HCV co-infection enhanced a significant downregulation of certain miRNAs that showed a direct correlation with HCV viral load and liver inflammation.


Assuntos
Coinfecção/terapia , Infecções por HIV/terapia , Hepatite C/terapia , Transplante de Fígado , Fígado/metabolismo , MicroRNAs/metabolismo , Adulto , Aloenxertos/metabolismo , Aloenxertos/patologia , Aloenxertos/virologia , Coinfecção/genética , Coinfecção/patologia , Coinfecção/virologia , Feminino , HIV/fisiologia , Infecções por HIV/genética , Infecções por HIV/patologia , Infecções por HIV/virologia , Hepacivirus/fisiologia , Hepatite C/genética , Hepatite C/patologia , Hepatite C/virologia , Humanos , Fígado/patologia , Fígado/virologia , Cirrose Hepática Alcoólica/genética , Cirrose Hepática Alcoólica/patologia , Cirrose Hepática Alcoólica/terapia , Masculino , MicroRNAs/genética , Pessoa de Meia-Idade , RNA Viral/genética , RNA Viral/metabolismo , Carga Viral
8.
PLoS One ; 16(4): e0249953, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33852629

RESUMO

INTRODUCTION: New HIV infection during pre-conception and pregnancy is a significant contributor of mother-to-child transmission of HIV in South Africa. This study estimated HIV incidence (defined as new infection within the last one year from the time of the survey which included both new infections occurred during pregnancy or just before pregnancy) among pregnant women and described the characteristics of recently infected pregnant women at national level. METHODS: Between 1 October and 15 November 2017, we conducted a national cross-sectional survey among pregnant women aged 15-49 years old attending antenatal care at 1,595 public facilities. Blood specimens were collected from pregnant women and tested for HIV in a centralised laboratory. Plasma viral load and Limiting Antigen Avidity Enzyme Immunosorbent Assay (LAg) tests were further performed on HIV positive specimens to differentiate between recent and long-term infections. Recent infection was defined as infection that occurred within one year from the date of collection of blood specimen for the survey. Data on age, age of partner, and marital status were collected through interviews. Women whose specimens were classified as recent by LAg assay and with viral loads >1,000 copies/mL were considered as recently infected. The calculated proportion of HIV positive women with recent infection was adjusted for assay-specific parameters to estimate annual incidence. Survey multinomial logistic regression was used to examine factors associated with being recently infected using HIV negative women as a reference group. Age-disparate relationship was defined as having a partner 5 or more years older. RESULTS: Of 10,049 HIV positive participants with LAg and viral load data, 1.4% (136) were identified as recently infected. The annual HIV incidence was 1.5% (95% confidence interval (CI): 1.2-1.7). In multivariable analyses, being single (adjusted odds ratio, aOR: 3.4, 95% CI: 1.8-6.2) or cohabiting (aOR: 3.8, 95% CI: 1.8-7.7), compared to being married as well as being in an age-disparate relationship among young women (aOR: 3.1, 95% CI: 2.0-4.7; reference group: young women (15-24years) whose partners were not 5 years or more older) were associated with higher odds of recent infection. CONCLUSIONS: Compared to previous studies among pregnant women, the incidence estimated in this study was substantially lower. However, the UNAIDS target to reduce incidence by 75% by 2020 (which is equivalent to reducing incidence to <1%) has not been met. The implementation of HIV prevention and treatment interventions should be intensified, targeting young women engaged in age-disparate relationship and unmarried women to fast track progress towards the UNAIDS target.


Assuntos
Infecções por HIV/epidemiologia , Adolescente , Adulto , Fatores Etários , Estudos Transversais , Feminino , HIV/isolamento & purificação , HIV/fisiologia , Infecções por HIV/tratamento farmacológico , Infecções por HIV/patologia , Infecções por HIV/prevenção & controle , Humanos , Incidência , Entrevistas como Assunto , Modelos Logísticos , Pessoa de Meia-Idade , Razão de Chances , Gravidez , Gestantes , Cuidado Pré-Natal , Parceiros Sexuais , África do Sul/epidemiologia , Carga Viral , Adulto Jovem
9.
PLoS Pathog ; 17(4): e1009522, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33872331

RESUMO

Although HIV infection inhibits interferon responses in its target cells in vitro, interferon signatures can be detected in vivo soon after sexual transmission, mainly attributed to plasmacytoid dendritic cells (pDCs). In this study, we examined the physiological contributions of pDCs to early HIV acquisition using coculture models of pDCs with myeloid DCs, macrophages and the resting central, transitional and effector memory CD4 T cell subsets. pDCs impacted infection in a cell-specific manner. In myeloid cells, HIV infection was decreased via antiviral effects, cell maturation and downregulation of CCR5 expression. In contrast, in resting memory CD4 T cells, pDCs induced a subset-specific increase in intracellular HIV p24 protein expression without any activation or increase in CCR5 expression, as measured by flow cytometry. This increase was due to reactivation rather than enhanced viral spread, as blocking HIV entry via CCR5 did not alter the increased intracellular p24 expression. Furthermore, the load and proportion of cells expressing HIV DNA were restricted in the presence of pDCs while reverse transcriptase and p24 ELISA assays showed no increase in particle associated reverse transcriptase or extracellular p24 production. In addition, pDCs also markedly induced the expression of CD69 on infected CD4 T cells and other markers of CD4 T cell tissue retention. These phenotypic changes showed marked parallels with resident memory CD4 T cells isolated from anogenital tissue using enzymatic digestion. Production of IFNα by pDCs was the main driving factor for all these results. Thus, pDCs may reduce HIV spread during initial mucosal acquisition by inhibiting replication in myeloid cells while reactivating latent virus in resting memory CD4 T cells and retaining them for immune clearance.


Assuntos
Células Dendríticas/virologia , Infecções por HIV/virologia , HIV/imunologia , Interferon-alfa/metabolismo , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD4-Positivos/virologia , Células Dendríticas/imunologia , Citometria de Fluxo , HIV/genética , HIV/fisiologia , Proteína do Núcleo p24 do HIV/genética , Proteína do Núcleo p24 do HIV/metabolismo , Infecções por HIV/imunologia , Humanos , Células Mieloides/imunologia , Células Mieloides/virologia , Fenótipo
10.
Artigo em Inglês | MEDLINE | ID: mdl-33865542

RESUMO

The increased life expectancy of people living with HIV (PLWH) receiving antiretroviral treatment (ART) has transformed HIV infection into a chronic disease. However, patients may be at risk of accelerated aging and the accumulation of cellular damage, which may trigger the development of cancer. We evaluated genomic instability in HIV-positive individuals with different viral loads receiving antiretroviral treatment (ART) and in HIV ART-naïve individuals. We included 67 participants divided into four groups: group 1 (n = 24) HIV patients receiving reverse-transcriptase inhibitors (tenofovir/ emtricitabine/ efavirenz and abacavir/ lamivudine/ efavirenz), group 2 (n = 22) HIV patients receiving protease inhibitors combined with other antiretroviral drugs (tenofovir/ emtricitabine with ritonavir/ atazanavir or lopinavir/ ritonavir, and darunavir/ ritonavir/ raltegravir), group 3 (n = 13) HIV ART-naïve patients, and group 4 (n = 8) healthy individuals (controls). Nuclear abnormalities in buccal mucosal samples (micronuclei, binucleated cells, nuclear buds, karyorrhexis, karyolysis, and pyknosis) were quantified. Simultaneously, blood samples were taken to quantify CD4+, CD8+, and HIV viral load. There was a significant age difference between HIV ART-naïve patients and receiving ART groups. Infection time was longer in HIV patients with ART than in ART-naïve patients. There were no differences in sex, smoking, alcohol consumption, or number of micronucleated cells between the study groups. We found higher frequencies of binucleated cells and nuclear buds in HIV patients, HIV ART-naïve, and HIV ART patients compared to the control group. We found a positive correlation between nuclear buds and CD4/CD8 ratio in the HIV ART-naïve group. In conclusion, PLWH showed increased genomic instability. The CD4/CD8 ratio affects the numbers of nuclear buds and binucleated cells. These findings are pertinent to mechanisms of damage and possible strategies to mitigate carcinogenesis in PLWH.


Assuntos
Instabilidade Genômica , Infecções por HIV/genética , Adulto , Fármacos Anti-HIV/efeitos adversos , Fármacos Anti-HIV/uso terapêutico , Contagem de Linfócito CD4 , Relação CD4-CD8 , Feminino , Instabilidade Genômica/efeitos dos fármacos , HIV/efeitos dos fármacos , HIV/fisiologia , Infecções por HIV/tratamento farmacológico , Infecções por HIV/imunologia , Infecções por HIV/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Inibidores da Transcriptase Reversa/efeitos adversos , Inibidores da Transcriptase Reversa/uso terapêutico , Carga Viral/efeitos dos fármacos , Carga Viral/fisiologia , Adulto Jovem
11.
Int J Mol Sci ; 22(7)2021 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-33918134

RESUMO

The persistence of latent HIV provirus pools in different resting CD4+ cell subsets remains the greatest obstacle in the current efforts to treat and cure HIV infection. Recent efforts to purge out latently infected memory CD4+ T-cells using latency-reversing agents have failed in clinical trials. This review discusses the epigenetic and non-epigenetic mechanisms of HIV latency control, major limitations of the current approaches of using latency-reversing agents to reactivate HIV latency in resting CD4+ T-cells, and potential solutions to these limitations.


Assuntos
Linfócitos T CD4-Positivos/virologia , Epigênese Genética/imunologia , HIV/fisiologia , Interações Hospedeiro-Patógeno/imunologia , Latência Viral , Humanos , Memória Imunológica , NF-kappa B/fisiologia , Fator B de Elongação Transcricional Positiva/fisiologia , Reinfecção
12.
Viruses ; 13(3)2021 02 25.
Artigo em Inglês | MEDLINE | ID: mdl-33669141

RESUMO

Viruses are highly dependent on the host they infect. Their dependence triggers processes of virus-host co-adaptation, enabling viruses to explore host resources whilst escaping immunity. Scientists have tackled viral-host interplay at differing levels of complexity-in individual hosts, organs, tissues and cells-and seminal studies advanced our understanding about viral lifecycles, intra- or inter-species transmission, and means to control infections. Recently, it emerged as important to address the physical properties of the materials in biological systems; membrane-bound organelles are only one of many ways to separate molecules from the cellular milieu. By achieving a type of compartmentalization lacking membranes known as biomolecular condensates, biological systems developed alternative mechanisms of controlling reactions. The identification that many biological condensates display liquid properties led to the proposal that liquid-liquid phase separation (LLPS) drives their formation. The concept of LLPS is a paradigm shift in cellular structure and organization. There is an unprecedented momentum to revisit long-standing questions in virology and to explore novel antiviral strategies. In the first part of this review, we focus on the state-of-the-art about biomolecular condensates. In the second part, we capture what is known about RNA virus-phase biology and discuss future perspectives of this emerging field in virology.


Assuntos
Interações Hospedeiro-Patógeno/fisiologia , Fenômenos Fisiológicos Virais , Animais , Fenômenos Biofísicos , HIV/fisiologia , Humanos , Vírus da Influenza A/fisiologia , Morbillivirus/fisiologia , Organelas/virologia , SARS-CoV-2/fisiologia , Vesiculovirus/fisiologia , Viroses/virologia , Internalização do Vírus
13.
Bull Cancer ; 108(4): 369-376, 2021 Apr.
Artigo em Francês | MEDLINE | ID: mdl-33714539

RESUMO

HIV testing is recommended at time of cancer diagnosis, HBV and HCV screening because of the risk of reactivation with certain anticancer drugs.This is a cross-sectional study. The objectives were to assess the screening practices in cancer patients and the satisfaction of professionals in the event of use of the CancerHIV network. A questionnaire drafted by the CancerHIV expert and the OncoPaca-Corse Regional Cancer Network (RCN) was distributed in the region at the end of 2018 (part 1: V1) before being extended to the national level via the CancerHIV network (part 2: V2). Participation reached 160 and 130 respondents (V1 and V2, respectively). At the initial cancer assessment, 23% of respondents declared that they systematically screened for HIV at V1 (V2: 17%), 25% for HBV (V2: 20%) and 24% for HCV (V2: 19%). Before immunotherapy, the rates were 54% for HIV in V1 (V2: 52%), 57% for HBV (V2: 60%) and 55% for HCV (V2: 57%). Among the respondents, satisfaction when requesting a regional or national remedy was high (almost 100%). Screening for HIV, HBV and HCV allows supervised prescription of immunosuppressive or cytotoxic treatment to a potentially immunosuppressed patient. This study, resulting of an original collaboration between a RCN and a national expert network, underlines the lack of screening at the 2 examined stages of patient care, and the need for raising practitioners' awareness to recommendations.


Assuntos
Infecções por HIV/diagnóstico , Hepatite B/diagnóstico , Hepatite C/diagnóstico , Programas de Rastreamento/métodos , Neoplasias/complicações , Antineoplásicos/efeitos adversos , Antineoplásicos/farmacologia , Estudos Transversais , Feminino , França/epidemiologia , HIV/fisiologia , Infecções por HIV/complicações , Infecções por HIV/epidemiologia , Hepacivirus/fisiologia , Hepatite B/complicações , Hepatite B/epidemiologia , Vírus da Hepatite B/fisiologia , Hepatite C/complicações , Hepatite C/epidemiologia , Humanos , Imunoterapia/efeitos adversos , Masculino , Programas de Rastreamento/estatística & dados numéricos , Neoplasias/terapia , Inquéritos e Questionários , Ativação Viral/efeitos dos fármacos , Ativação Viral/imunologia
14.
mBio ; 12(2)2021 03 23.
Artigo em Inglês | MEDLINE | ID: mdl-33758093

RESUMO

The oral microbiome is considered an important factor in health and disease. We recently reported significant effects of HIV and several other clinical variables on the oral bacterial communities in a large cohort of HIV-positive and -negative individuals. The purpose of the present study was to similarly analyze the oral mycobiome in the same cohort. To identify fungi, the internal transcribed spacer 2 (ITS2) of the fungal rRNA genes was sequenced using oral rinse samples from 149 HIV-positive and 88 HIV-negative subjects that had previously undergone bacterial amplicon sequencing. Quantitative PCR was performed for total fungal content and total bacterial content. Interestingly, samples often showed predominance of a single fungal species with four major clusters predominated by Candida albicans, Candida dubliniensis, Malassezia restricta, or Saccharomyces cerevisiae Quantitative PCR analysis showed the Candida-dominated sample clusters had significantly higher total fungal abundance than the Malassezia or Saccharomyces species. Of the 25 clinical variables evaluated for potential influences on the oral mycobiome, significant effects were associated with caries status, geographical site of sampling, sex, HIV under highly active antiretroviral therapy (HAART), and missing teeth, in rank order of statistical significance. Investigating specific interactions between fungi and bacteria in the samples often showed Candida species positively correlated with Firmicutes or Actinobacteria and negatively correlated with Fusobacteria, Proteobacteria, and Bacteroidetes Our data suggest that the oral mycobiome, while diverse, is often dominated by a limited number of species per individual; is affected by several clinical variables, including HIV positivity and HAART; and shows genera-specific associations with bacterial groups.IMPORTANCE The oral microbiome is likely a key element of homeostasis in the oral cavity. With >600 bacterial species and >160 fungal species comprising the oral microbiome, influences on its composition can have an impact on both local and systemic health. We recently reported significant effects of HIV and several other clinical variables on the oral bacterial community in a large cohort of HIV-positive and -negative subjects. We describe here a comprehensive analysis of the oral mycobiome in the same cohort. Similar to the bacterial community, HIV under highly active antiretroviral therapy (HAART) had a significant impact on the mycobiome composition, but with less impact compared to other clinical variables. Additionally, unlike the oral bacterial microbiome, the oral mycobiome is often dominated by a single species with 4 major clusters of fungal communities. Together, these results suggest the oral mycobiome has distinct properties compared with the oral bacterial community, although both are equally impacted by HIV.


Assuntos
Terapia Antirretroviral de Alta Atividade , Infecções por HIV/tratamento farmacológico , HIV/fisiologia , Boca/microbiologia , Boca/virologia , Análise Multivariada , Micobioma/genética , Bactérias/classificação , Bactérias/genética , Bactérias/metabolismo , Estudos de Coortes , DNA Intergênico/genética , Feminino , Fungos/classificação , Fungos/genética , Fungos/metabolismo , HIV/genética , Infecções por HIV/virologia , Humanos , Masculino , Micobioma/fisiologia
15.
PLoS One ; 16(2): e0246135, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33577551

RESUMO

INTRODUCTION: Several methods have been proposed to estimate the time of HIV seroconversion, including those based on CD4 cell depletion models. However, previous models have failed to consider the heterogeneity that exists in CD4 trajectories among different sub-populations. Our objective was to estimate the time from HIV seroconversion relative to the HIV diagnosis date in a population-based cohort of people living with HIV (PLWH) in the province of British Columbia, Canada. METHODS: We used linked administrative and clinical data from the British Columbia Seek and Treat for Optimal Prevention of HIV/AIDS (STOP HIV/AIDS) cohort, which contains longitudinal individual-level data on all PLWH ever diagnosed in the province. Eligible participants were aged ≥18 years and diagnosed with HIV between 1989 and 2013. The outcome was pre-antiretroviral treatment CD4 cell count measurements assessed every six months. Models were stratified by age and stage of HIV infection at diagnosis. Several explanatory variables were considered including longitudinal viral load measurements. Longitudinal CD4, square root transformed, was modeled via a non-linear mixed effects model; time was modeled using an exponential decay function. We assumed a Gaussian distribution (identity link), an AR(1) correlation structure, and a random intercept and slope for the longitudinal viral load measurements. Due to the population variation in CD4 count among uninfected individuals, we assumed 500 to 1500 cells/mm3 as the normal range when estimating the time of HIV seroconversion. RESULTS: Longitudinal data on 1,253 individuals were analysed: 80% male, 33% White, and the median age at diagnosis was 38 years (25th-75th percentile [Q1-Q3], 31 to 45). CD4 decay differed by stage of infection at diagnosis and age, with those ≥50 years in Stages 1 and 2 experiencing a faster decline in CD4 over time. The median duration of infection from seroconversion until HIV diagnosis was 6.9 (Q1-Q3, 3.9 to 10.1) years. CONCLUSIONS: Considering the heterogeneity that exists in individual CD4 cell trajectories in a population, we presented a methodology that only relies on routinely collected HIV-related data, which can be further extended to estimate other epidemic measures.


Assuntos
Soropositividade para HIV/diagnóstico , Soropositividade para HIV/imunologia , HIV/fisiologia , Adulto , Fatores Etários , Colúmbia Britânica , Contagem de Linfócito CD4 , Progressão da Doença , Feminino , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Soroconversão , Carga Viral
16.
Int J Infect Dis ; 104: 526-531, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33434664

RESUMO

BACKGROUND: Timely viral load (VL) testing is critical in the care of pregnant women living with HIV and receiving anti-retroviral therapy (ART). There is paucity of data regarding the Time to First Viral Load (TFVL) testing in resource-limited settings. METHODS: We extracted clinical and VL test data from records of a cohort of ART-naïve pregnant women living with HIV who initiated Option B + and were retained in care between 01 Jan 2015 and 31 Dec 2015. The data were verified against laboratory VL registers. TFVL (in months) was calculated based on the time difference between the date of ART initiation and FVL test. Descriptive and Cox regression analyses of data up to 30 Sep 2017 (33 months later) were done. RESULTS: Of the 622 records retrieved, 424 women were retained in care. Of 424 women retained in care, 182/424 (43%) had at least one VL result post ART initiation while 242/424 (57%) had no VL performed. Only 30/182 (16.5%) had a second VL. At six, nine, and twelve months, only 8/424 (1.9%), 47/424 (11.1%), and 94/424 (22.2%) had VL testing performed respectively post ART initiation. The median TFVL testing was 12.7 months (95 CI 11.6-13.7) post ART initiation. Across the five clinics, patient factors (age, gravidity, gestational age, marital status, and adherence at 12 months) were not significant predictors. CONCLUSION: A dismal 1.9% rate of achieving WHO-recommended TFVL testing and a median TFVL testing of twelve months post ART initiation were observed. The non-association of patient factors to these observations may suggest a serious need to review health system factors likely associated with these observations and their effective interventions.


Assuntos
Fármacos Anti-HIV/uso terapêutico , Infecções por HIV/virologia , HIV/fisiologia , Complicações Infecciosas na Gravidez/virologia , Carga Viral , Adulto , Centros Comunitários de Saúde , Feminino , Infecções por HIV/tratamento farmacológico , Humanos , Programas Nacionais de Saúde , Gravidez , Complicações Infecciosas na Gravidez/tratamento farmacológico , Estudos Retrospectivos , Uganda , Adulto Jovem
17.
Food Chem ; 347: 128932, 2021 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-33465692

RESUMO

The human immunodeficiency virus interacts with the cluster of differentiation 4 receptors and one of the two chemokine receptors (CCR5 and CXCR4) to gain entry in human cells. Both the co-receptors are essential for viral entry, replication, and are considered critical targets for antiviral drugs. In this study, bioactive molecules from different Himalayan plants were screened considering their potential to bind with the CCR5 and CXCR4 co-receptors. We utilized computational and thermodynamic parameters to validate the binding of the selected biomolecules to the active site of the co-receptors. The molecules Butyl 2-ethylhexyl phthalate and Dactylorhin-A showed a higher binding affinity with CCR5 co-receptor than the standard antagonist Maraviroc. Moreover, Pseudohypericin, Amarogentin, and Dactylorhin-E exhibited stronger interactions with CXCR4 than the co-crystallized inhibitor Isothiourea-1 t. Hence, we suggest that these molecules could be developed as potential inhibitors of the CCR5 and CXCR4 co-receptors. However, this require further in-vitro and in-vivo validation.


Assuntos
Fármacos Anti-HIV/farmacologia , HIV/efeitos dos fármacos , HIV/fisiologia , Internalização do Vírus/efeitos dos fármacos , Fármacos Anti-HIV/metabolismo , HIV/metabolismo , Humanos , Receptores CCR5/metabolismo , Receptores CXCR4/metabolismo
18.
Am J Med Sci ; 361(1): 90-97, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-32773107

RESUMO

BACKGROUND: Despite anti-retroviral therapy, HIV-1 infection increases the risk of pneumonia and causes oxidative stress and defective alveolar macrophage (AM) immune function. We have previously determined that HIV-1 proteins inhibit antioxidant defenses and impair AM phagocytosis by suppressing nuclear factor (erythroid-derived 2)-like 2 (Nrf2). Given its known effects on Nrf2, we hypothesize miR-144 mediates the HIV-1 induced suppression of Nrf2. METHODS: Primary AMs isolated from HIV-1 transgenic (HIV-1 Tg) rats and wild type littermates (WT) as well as human monocyte-derived macrophages (MDMs) infected ex vivo with HIV-1 were used. We modulated miR-144 expression using a miR-144 mimic or an inhibitor to assay its effects on Nrf2/ARE activity and AM functions in vitro and in vivo. RESULTS: MiR-144 expression was increased in AMs from HIV-1 Tg rats and in HIV-1-infected human MDMs compared to cells from WT rats and non-infected human MDMs, respectively. Increasing miR-144 with a miR-144 mimic inhibited the expression of Nrf2 and its downstream effectors in WT rat macrophages and consequently impaired their bacterial phagocytic capacity and H2O2 scavenging ability. These effects on Nrf2 expression and AM function were reversed by antagonizing miR-144 ex vivo or in the airways of HIV-1 Tg rats in vivo, but this protection was abrogated by silencing Nrf2 expression. CONCLUSIONS: Our results suggest that inhibiting miR-144 or interfering with its deleterious effects on Nrf2 attenuates HIV-1-mediated AM immune dysfunction and improves lung health in individuals with HIV.


Assuntos
Infecções por HIV/fisiopatologia , HIV/fisiologia , Macrófagos Alveolares/metabolismo , MicroRNAs/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , Animais , Feminino , Infecções por HIV/metabolismo , Masculino , Ratos
19.
Curr Opin HIV AIDS ; 16(1): 63-73, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33186229

RESUMO

PURPOSE OF REVIEW: We examine the interplay between the HIV and COVID-19 epidemics, including the impact of HIV on COVID-19 susceptibility and severe disease, the effect of the COVID-19 epidemic on HIV prevention and treatment, and the influence of the HIV epidemic on responses to COVID-19. RECENT FINDINGS: Evidence to date does not suggest that people living with HIV (PLWH) have a markedly higher susceptibility to SARS-CoV-2 infection, with disparities in the social determinants of health and comorbidities likely having a greater influence. The majority of literature has not supported a higher risk for severe disease among PLWH in Europe and the United States, although a large, population-based study in South Africa reported a higher rate of death due to COVID-19. Higher rates of comorbidities associated with COVID-19 disease severity among PLWH is an urgent concern. COVID-19 is leading to decreased access to HIV prevention services and HIV testing, and worsening HIV treatment access and virologic suppression, which could lead to worsening HIV epidemic control. CONCLUSION: COVID-19 is threatening gains against the HIV epidemic, including the U.S. Ending the HIV Epidemic goals. The ongoing collision of these two global pandemics will continue to need both study and interventions to mitigate the effects of COVID-19 on HIV efforts worldwide.


Assuntos
COVID-19/virologia , Infecções por HIV/virologia , HIV/fisiologia , SARS-CoV-2/fisiologia , COVID-19/complicações , COVID-19/epidemiologia , COVID-19/mortalidade , Europa (Continente)/epidemiologia , HIV/genética , Infecções por HIV/complicações , Infecções por HIV/epidemiologia , Infecções por HIV/mortalidade , Humanos , Pandemias , SARS-CoV-2/genética , África do Sul/epidemiologia , Estados Unidos/epidemiologia
20.
Curr Opin HIV AIDS ; 16(1): 48-53, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33278160

RESUMO

PURPOSE OF REVIEW: The global pandemic caused by the severe acute respiratory virus coronavirus 2 (SARS-CoV-2) has a male bias in mortality likely driven by both gender and sex-based differences between male and female individuals. This is consistent with sex and gender-based features of HIV infection and overlap between the two diseases will highlight potential mechanistic pathways of disease and guide research questions and policy interventions. In this review, the emerging findings from SARS-CoV-2 infection will be placed in the context of sex and gender research in the more mature HIV epidemic. RECENT FINDINGS: This review will focus on the new field of literature on prevention, immunopathogenesis and treatment of SARS-CoV-2 referencing relevant articles in HIV for context from a broader time period, consistent with the evolving understanding of sex and gender in HIV infection. Sex-specific features of epidemiology and immunopathogenesis reported in COVID-19 disease will be discussed and potential sex and gender-specific factors of relevance to prevention and treatment will be emphasized. SUMMARY: Multilayered impacts of sex and gender on HIV infection have illuminated pathways of disease and identified important goals for public health interventions. SARS-CoV-2 has strong evidence for a male bias in disease severity and exploring that difference will yield important insights.


Assuntos
COVID-19/virologia , SARS-CoV-2/fisiologia , Animais , COVID-19/epidemiologia , Feminino , HIV/genética , HIV/fisiologia , Infecções por HIV/virologia , Humanos , Masculino , Pandemias , SARS-CoV-2/genética , Fatores Sexuais
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