Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 25.322
Filtrar
1.
Medicine (Baltimore) ; 98(35): e16866, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31464915

RESUMO

This study evaluated whether the interval from the first clinic visit until the start of antiretroviral treatment (ART) was correlated with common parameters of immunological recovery among patients with early HIV infection (EHI).We reviewed the medical records of patients with EHI who started ART using integrase strand-transfer inhibitors (ISTIs) within the first 6 months after diagnosis. Simple linear regression analyses were performed to determine whether the interval from the first visit to the start of ART was correlated with 1-year changes in CD4+ cell count, CD8+ cell count, CD4+ percentage, and CD4+/CD8+ ratio.Fifty-three patients with probable or definite EHI started ART using ISTIs between April 2014 and August 2016. Forty-nine patients completed 1 year of follow-up, including 48 men. The routes of HIV transmission were 1 case of needle sharing, 5 cases of heterosexual activity, and 43 cases of men who had sex with men. None of the immunological recovery parameters were correlated with time to the start of ART (CD4+ cell count: R = .12, P = .42; CD8+ cell count: R = .107, P = .5; CD4+ percentage: R = .14, P = .34; CD4+/CD8+ ratio: R = .23, P = .14). Furthermore, subgroup sensitivity analyses failed to detect significant correlations based on definite or probable diagnoses, treatment using elvitegravir or dolutegravir, or the time from HIV diagnosis to ART initiation.This series of EHI cases indicate that using ART with ISTI-based regimens is efficacious and well-tolerated. However, earlier initiation of treatment was not significantly correlated with common parameters of immunological recovery.


Assuntos
Infecções por HIV/tratamento farmacológico , Inibidores de Integrase de HIV/uso terapêutico , Adulto , Contagem de Linfócito CD4 , Relação CD4-CD8 , Feminino , Infecções por HIV/imunologia , Humanos , Modelos Lineares , Contagem de Linfócitos , Masculino , Fatores de Tempo , Resultado do Tratamento
3.
Nat Commun ; 10(1): 2753, 2019 07 02.
Artigo em Inglês | MEDLINE | ID: mdl-31266936

RESUMO

Elimination of HIV-1 requires clearance and removal of integrated proviral DNA from infected cells and tissues. Here, sequential long-acting slow-effective release antiviral therapy (LASER ART) and CRISPR-Cas9 demonstrate viral clearance in latent infectious reservoirs in HIV-1 infected humanized mice. HIV-1 subgenomic DNA fragments, spanning the long terminal repeats and the Gag gene, are excised in vivo, resulting in elimination of integrated proviral DNA; virus is not detected in blood, lymphoid tissue, bone marrow and brain by nested and digital-droplet PCR as well as RNAscope tests. No CRISPR-Cas9 mediated off-target effects are detected. Adoptive transfer of human immunocytes from dual treated, virus-free animals to uninfected humanized mice fails to produce infectious progeny virus. In contrast, HIV-1 is readily detected following sole LASER ART or CRISPR-Cas9 treatment. These data provide proof-of-concept that permanent viral elimination is possible.


Assuntos
Fármacos Anti-HIV/administração & dosagem , Sistemas CRISPR-Cas , Infecções por HIV/terapia , HIV-1/genética , Transferência Adotiva , Animais , Terapia Combinada , DNA Viral/genética , DNA Viral/imunologia , Edição de Genes , Infecções por HIV/tratamento farmacológico , Infecções por HIV/imunologia , Infecções por HIV/virologia , HIV-1/imunologia , HIV-1/fisiologia , Humanos , Camundongos , Resultado do Tratamento , Latência Viral
4.
Nat Commun ; 10(1): 2898, 2019 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-31263112

RESUMO

The HIV-1 envelope (Env) is the target for neutralizing antibodies and exists on the surface of virions in open or closed conformations. Difficult-to-neutralize viruses (tier 2) express Env in a closed conformation antigenic for broadly neutralizing antibodies (bnAbs) but not for third variable region (V3) antibodies. Here we show that select V3 macaque antibodies elicited by Env vaccination can neutralize 26% of otherwise tier 2 HIV-1 isolates in standardized virus panels. The V3 antibodies only bound to Env in its open conformation. Thus, Envs on tier 2 viruses sample a state where the V3 loop is not in its closed conformation position. Envelope second variable region length, glycosylation sites and V3 amino acids were signatures of neutralization sensitivity. This study determined that open conformations of Env with V3 exposed are present on a subset of otherwise neutralization-resistant virions, therefore neutralization of tier 2 HIV-1 does not always indicate bnAb induction.


Assuntos
Anticorpos Anti-HIV/imunologia , Infecções por HIV/imunologia , HIV-1/imunologia , Produtos do Gene env do Vírus da Imunodeficiência Humana/imunologia , Motivos de Aminoácidos , Animais , Anticorpos Neutralizantes/imunologia , Glicosilação , Infecções por HIV/virologia , HIV-1/química , HIV-1/genética , Humanos , Macaca mulatta , Testes de Neutralização , Conformação Proteica , Produtos do Gene env do Vírus da Imunodeficiência Humana/química
5.
Medicine (Baltimore) ; 98(29): e16376, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31335686

RESUMO

The HIV subtype B is the most frequent in Brazil. The HIV subtype B' codes the amino acids glicine-tryptophan-glicine (GWG) instead of glicine-proline-glicine on the tip of gp120 V3 loop. This variant was associated to a slower HIV progression in mono-infected patients; however, there is no information in coinfected patients. This study evaluated the infection progression of HIV variant B' on the hepatitis C virus presence. RNA isolated from plasma of the 601 infected patients were used to human immunodeficiency virus (HIV) subtyping and to classify the virus according their syncytium-inducing ability. The HIV infection progression was evaluated by clinical and laboratorial data. The results showed a significant association between HIV B' variant and CD4 count and time of AIDS in HIV mono-infected patients. Notwithstanding the fact that we did not find a direct association between GWG variant and AIDS and in HIV coinfected patients no mitigating effect due to GWG presence was found. We did observe that the association between GWG variant and CD4 counts is lost in coinfected patients. This is first work showing influence of the HIV GWG variant in coinfected patients. Nevertheless, the presence of the GWG variant can indicate a better prognostic in the mono-infected patients.


Assuntos
Proteína gp120 do Envelope de HIV/genética , Infecções por HIV , HIV-1/genética , Hepatite C , Adulto , Brasil/epidemiologia , Contagem de Linfócito CD4/métodos , Coinfecção/epidemiologia , Coinfecção/virologia , Progressão da Doença , Feminino , Infecções por HIV/epidemiologia , Infecções por HIV/imunologia , Infecções por HIV/virologia , Hepacivirus/isolamento & purificação , Hepatite C/epidemiologia , Hepatite C/virologia , Humanos , Masculino , Prognóstico , RNA Viral/análise
6.
Medicine (Baltimore) ; 98(30): e16524, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31348267

RESUMO

Anti-hepatitis C virus (HCV) treatment for human immunodeficiency virus (HIV)/HCV co-positive patients with hemophilia A presents numerous problems in terms of safety and effectiveness. The emergence of direct-acting antiviral (DAA) regimens has led to tremendous changes in the management of HIV/HCV co-infection over the past few years, but the application of DAA in patients with hemophilia complicated with HIV/HCV co-infection has rarely been reported.We retrospectively analyzed the clinical course and outcome of hemophilia A patients with HIV/HCV co-infection receiving DAA with a focus on the virological response, changes in cluster of differentiation 4 lymphocyte (CD4) count, side effects, and impact on bleeding before and after DAA therapy.A total of 12 hemophilia A patients with HIV/HCV co-infection were included, 9 of which were severe. All the patients were in stable states with CD4 counts >200/mm and plasma HIV ribonucleic acid (RNA) suppressed (<40 IU/mL) while taking the antiretroviral regimen. Majority of the patients (n = 9, 75.0%) were infected with HCV genotype (GT) 1b, while 2 and 1 was infected with HCV GT 2i and HCV GT 3, respectively.After 12 weeks of DAA treatment, 11 patients (91.7%) obtained sustained virologic response within 24 weeks of discontinuation of treatment (SVR24), except 1 patient who was treated with sofosbuvir (SOF) + pegylated interferon + ribavirin (PR), which was then switched to daclatasvir (DCV) + asunaprevir (ASV) for 12 weeks; this patient then achieved SVR24. During DAA treatment, HIV RNA in all the patients was constantly suppressed, while CD4 counts showed no obvious change.The most common treatment-emergent adverse events were weakness and loss of appetite (generally mild). There was no evidence of an increased tendency of bleeding, and changes in response to replacement.DAA therapy offered a safe and well-tolerated management strategy for HIV/HCV co-infected patients with hemophilia A. An awareness of the potential drug-drug interactions (DDI) between DAA and combination antiretroviral therapy (cART) by clinicians is important for optimal management of co-infected patients.


Assuntos
Antivirais/uso terapêutico , Coinfecção/tratamento farmacológico , Infecções por HIV/tratamento farmacológico , Hemofilia A/tratamento farmacológico , Hepatite C/tratamento farmacológico , Adulto , Contagem de Linfócito CD4 , Coinfecção/imunologia , Coinfecção/virologia , Quimioterapia Combinada , Infecções por HIV/imunologia , Infecções por HIV/virologia , HIV-1 , Hemofilia A/imunologia , Hemofilia A/virologia , Hepacivirus , Hepatite C/imunologia , Hepatite C/virologia , Humanos , Imidazóis/uso terapêutico , Interferons/uso terapêutico , Isoquinolinas/uso terapêutico , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Ribavirina/uso terapêutico , Sofosbuvir/uso terapêutico , Sulfonamidas/uso terapêutico , Resposta Viral Sustentada
7.
Nat Commun ; 10(1): 2759, 2019 06 21.
Artigo em Inglês | MEDLINE | ID: mdl-31227717

RESUMO

Langerhans cells (LC) are thought to be the only mononuclear phagocyte population in the epidermis where they detect pathogens. Here, we show that CD11c+ dendritic cells (DCs) are also present. These cells are transcriptionally similar to dermal cDC2 but are more efficient antigen-presenting cells. Compared to LCs, epidermal CD11c+ DCs are enriched in anogenital tissues where they preferentially interact with HIV, express the higher levels of HIV entry receptor CCR5, support the higher levels of HIV uptake and replication and are more efficient at transmitting the virus to CD4 T cells. Importantly, these findings are observed using both a lab-adapted and transmitted/founder strain of HIV. We also describe a CD33low cell population, which is transcriptionally similar to LCs but does not appear to function as antigen-presenting cells or acts as HIV target cells. Our findings reveal that epidermal DCs in anogenital tissues potentially play a key role in sexual transmission of HIV.


Assuntos
Células Dendríticas/virologia , Células Epidérmicas/virologia , Infecções por HIV/transmissão , HIV-1/imunologia , Apresentação do Antígeno/imunologia , Antígeno CD11c/metabolismo , Células Cultivadas , Células Dendríticas/imunologia , Células Dendríticas/metabolismo , Células Epidérmicas/imunologia , Células Epidérmicas/metabolismo , Epiderme/imunologia , Feminino , Infecções por HIV/imunologia , Infecções por HIV/virologia , HIV-1/patogenicidade , Voluntários Saudáveis , Humanos , Masculino , Cultura Primária de Células , Receptores CCR5/metabolismo , Lectina 3 Semelhante a Ig de Ligação ao Ácido Siálico/metabolismo , Linfócitos T/imunologia , Internalização do Vírus
9.
BMC Public Health ; 19(1): 771, 2019 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-31208459

RESUMO

BACKGROUND: Access to antiretroviral therapy (ART) in Ethiopia has been scaled up since the introduction of the service in 2003. Free ART was launched in 2005, resulting in fewer new human immunodeficiency virus (HIV) infections and deaths from acquired immunodeficiency syndrome (AIDS). However, immunological and clinical failures for first-line ART due to poor adherence and other factors have received less attention. Thus, this study aims to determine the magnitude and associated factors of clinical and immunological failure among HIV-positive adults after six months of first-line ART in Dire Dawa, Eastern Ethiopia. METHODS: A facility-based cross-sectional study was conducted using secondary data of patients on ART in all health facilities providing ART services in Dire Dawa. A total of 949 samples were collected. The data were entered into Epidata version 3.02, and the analysis was performed using SPSS version 16.0. Univariate and multivariate analyses were performed to determine the magnitude of clinical and immunological failure and identify factors significantly associated with the outcome variable. RESULTS: The magnitude of clinical and immunological failure was 22.7% (n = 215). Of these, 33 (15%) patients were switched to second-line ART. CD4 count ≤100 cells/mm3 (AOR: 1.78, 95% CI: 1.18-2.69), poor adherence (AOR: 2.5, 95% CI: 1.19-5.25), restarting after interruption of ART (AOR: 1.93, 95% CI: 1.23-3.07), regimen change (AOR: 1.50, 95% CI: 1.05-2.15), ambulatory/bedridden functional status at the last visit on ART (AOR: 2.41, 95% CI: 1.22-4.75) and patients who died (AOR: 3.94, 95% CI: 1.64-9.45) had higher odds of failure. CONCLUSION: The magnitude of clinical and immunological failure was high. To curb this problem, initiation of ART before the occurrence of severe immune suppression, early detection and management of failure and improved adherence support mechanisms are recommended. Restarting treatment after interruption and regimen changes-should-be-made-cautiously.


Assuntos
Antirretrovirais/uso terapêutico , Infecções por HIV/tratamento farmacológico , Infecções por HIV/imunologia , Adolescente , Adulto , Estudos Transversais , Etiópia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Falha de Tratamento , Adulto Jovem
10.
Pan Afr Med J ; 32: 105, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31223395

RESUMO

Haemophagocytic lymphohistiocytosis (HLH) in Human Immunodeficiency Virus (HIV) infected individuals can either be due to the disease itself or due to associated infections/malignancies. The treatment for HLH requires immunosuppressive therapy but administering immunosuppressive therapy to an already immunosuppressed patient (HIV infection) is complex. We present two such cases of HLH in patients infected with HIV. In the first case, no alternate cause for HLH was found even after extensive investigations and it was attributed to the uncontrolled HIV replication. Patient was started on dexamethasone for the same but succumbed to hospital acquired pneumonia. The second patient was diagnosed with Hodgkin's lymphoma but he succumbed to his illness before initiating immunosuppressive therapy for HLH. We report these cases to highlight the dilemma and a need for further research in this direction.


Assuntos
Infecções por HIV/complicações , Imunossupressores/efeitos adversos , Linfo-Histiocitose Hemofagocítica/tratamento farmacológico , Adulto , Dexametasona/administração & dosagem , Dexametasona/efeitos adversos , Feminino , Infecções por HIV/imunologia , Humanos , Imunossupressores/administração & dosagem , Linfo-Histiocitose Hemofagocítica/etiologia , Masculino , Pessoa de Meia-Idade
11.
Acta Cytol ; 63(5): 352-360, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31234174

RESUMO

OBJECTIVE: We aimed to evaluate the sensitivity of fine needle aspiration (FNA) for the diagnosis of Hodgkin's lymphoma (HL) in HIV-infected patients. STUDY DESIGN: An electronic search was conducted to retrospectively identify patients diagnosed with HL who underwent FNA followed by confirmatory biopsy. FNAs were categorized as negative, atypical/suspicious/positive, or nondiagnostic. Diagnostic sensitivity in HIV+ and HIV- patients was statistically compared via Fisher's exact test, with a p value <0.05 considered significant. RESULTS: Thirty-six patients meeting inclusion criteria were identified (24 HIV- and 12 HIV+). Average age was 36.0 ± 11.5 and 36.5 ± 7.4 years (means ± SD) in HIV- and HIV+ patients, respectively. The male-to-female ratio was 1.4:1 in HIV- patients versus 3:1 in HIV+ patients. Among these 36 patients, a total of 42 FNAs were performed. Overall sensitivity of FNA was 66.7% (95% confidence interval: 52.4-80.9%). When stratified by HIV status, a statistically significant difference in FNA sensitivity was detected, as sen-sitivity was 84.6% (70.8-98.4%) in HIV- patients versus only 37.5% (13.8-61.2%) in HIV+ patients (p =0.003). CONCLUSION: The diagnostic sensitivity of FNA biopsy was significantly attenuated in the HIV+ cohort. In HIV-infected patients presenting with lymphadenopathy, increased clinical suspicion of HL is critical to avoid misdiagnosis.


Assuntos
Biópsia por Agulha Fina , Infecções por HIV/virologia , Doença de Hodgkin/patologia , Adulto , Biomarcadores Tumorais/análise , Diagnóstico Diferencial , Feminino , Infecções por HIV/diagnóstico , Infecções por HIV/imunologia , Doença de Hodgkin/imunologia , Doença de Hodgkin/virologia , Humanos , Hospedeiro Imunocomprometido , Imuno-Histoquímica , Antígeno Ki-1/análise , Antígenos Comuns de Leucócito/análise , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Reprodutibilidade dos Testes , Estudos Retrospectivos
12.
BMC Infect Dis ; 19(1): 359, 2019 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-31035959

RESUMO

BACKGROUND: Pro-inflammatory cytokines expressed in human immune deficiency virus (HIV) infection, may induce oxidative stress likely to compromise the patency of the airways or damage the lung tissues/cardiac function. However, physical (aerobic and/or resistance) exercise-induced release of heat shock protein, immune function alteration or reduced tissue hypoxia, have been highlighted as possible mechanisms by which increasing physical activity may reduce plasma pro-inflammatory cytokines in uninfected individuals and should be appraised in the literature for evidence of similar benefits in people living with HIV (PLWH). Therefore, we evaluated the effects of physical exercises on 1) inflammatory biomarkers and 2) cardiopulmonary function (VO2 Max) in PLWH. METHOD: A systematic review was conducted using the Cochrane Collaboration protocol. Searching databases, up to January 2018. Only randomized control trials investigating the effects of either aerobic or resistance or a combination of both exercise types with a control/other intervention(s) for a period of at least 4 weeks among adults living with HIV, were included. Two independent reviewers determined the eligibility of the studies. Data were extracted and risk of bias (ROB) was assessed with the Cochrane Collaboration ROB tool. Meta-analyses were conducted with random effect models using the Review Manager (RevMan) computer software. RESULT: Twenty-three studies met inclusion criteria (n = 1073 participants at study completion) comprising male and female with age range 18-65 years. Three meta-analyses across three sub-groups comparisons were performed. The result showed no significant change in biomarkers of inflammation (IL-6 and IL-1ß) unlike a significant (Z = 3.80, p < 0.0001) improvement in VO2 Max. Overall, the GRADE evidence for this review was of moderate quality. CONCLUSION: There was evidence that engaging in either aerobic or resistance exercise, or a combination of both exercises, two to five times per week can lead to a significant improvement in cardiopulmonary function but not biomarkers of inflammation (IL-6 and IL-1ß). However, this should not be interpreted as "No evidence of effect" because the individual trial studies did not attain sufficient power to detect treatment effects. The moderate grade evidence for this review suggests that further research may likely have an important impact on our confidence in the estimate of effects and may change the estimate.


Assuntos
Biomarcadores/metabolismo , Exercício , Infecções por HIV/diagnóstico , Pulmão/metabolismo , Miocárdio/metabolismo , Proteína C-Reativa/metabolismo , Citocinas/metabolismo , Infecções por HIV/imunologia , Humanos
13.
Nat Commun ; 10(1): 2005, 2019 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-31043606

RESUMO

A long-acting injectable formulation of the HIV integrase inhibitor cabotegravir (CAB-LA) is currently in clinical development for PrEP. Although the long plasma half-life of CAB-LA is an important attribute for PrEP, it also raises concerns about drug resistance emergence if someone becomes infected with HIV, or if PrEP is initiated during undiagnosed acute infection. Here we use a macaque model of SHIV infection to model risks of drug resistance to CAB-LA PrEP. Six macaques infected with SHIV received CAB-LA before seroconversion. We show integrase mutations G118R, E92G/Q, or G140R in plasma from 3/6 macaques as early as day 57, and identify G118R and E92Q in viruses from vaginal and rectal fluids. G118R and G140R confer > 800-fold resistance to CAB and cross-resistance to all licensed integrase inhibitors. Our results emphasize the need for appropriate HIV testing strategies before and possibly shortly after initiating CAB LA PrEP to exclude acute infection.


Assuntos
Farmacorresistência Viral/genética , Infecções por HIV/prevenção & controle , Inibidores de Integrase de HIV/farmacologia , Profilaxia Pré-Exposição/métodos , Piridonas/farmacologia , Síndrome de Imunodeficiência Adquirida dos Símios/prevenção & controle , Doença Aguda , Animais , Modelos Animais de Doenças , Farmacorresistência Viral/efeitos dos fármacos , Feminino , Células HEK293 , Infecções por HIV/sangue , Infecções por HIV/imunologia , Infecções por HIV/virologia , Integrase de HIV/genética , Inibidores de Integrase de HIV/sangue , Inibidores de Integrase de HIV/uso terapêutico , HIV-1/efeitos dos fármacos , HIV-1/genética , Meia-Vida , Humanos , Macaca , Masculino , Piridonas/sangue , Piridonas/uso terapêutico , Soroconversão , Síndrome de Imunodeficiência Adquirida dos Símios/sangue , Síndrome de Imunodeficiência Adquirida dos Símios/imunologia , Síndrome de Imunodeficiência Adquirida dos Símios/virologia , Vírus da Imunodeficiência Símia/efeitos dos fármacos , Vírus da Imunodeficiência Símia/genética , Vírus da Imunodeficiência Símia/imunologia , Fatores de Tempo
14.
Pan Afr Med J ; 32: 2, 2019.
Artigo em Francês | MEDLINE | ID: mdl-31068996

RESUMO

Introduction: This study aimed to evaluate the performances of the MUSE® flow cytometer compared with the reference GUAVA® flow cytometer. Methods: We conducted an experimental study on HIV-infected patient samples. Venous blood samples, collected in a K3 EDTA tube, were analyzed within 24-48 hours by MUSE® and GUAVA® cytometers at the International Center for medical diagnosis (Centre International de Diagnostic médical) in Yaoundé. Results: In total, 227 samples were analyzed. There was a strong intraclass correlation (p<0.0001) between MUSE® and GUAVA® cytometers with a correlation coefficient 0.998 (95% CI: 0,998-0,999) for the absolute values and 0,992 (95% CI: 0,989-0,994) for the percentages. A strong positive linear correlation (p=0.0001) was found between MUSE® and GUAVA® cytometers with linear regression slope r2 = 0.98 (95% CI=0,97-0,99) for the absolute values and r2= 0.98 (95% CI= 0.96-1,00) for the percentages. The biases were -4,80 cells/µl (-101.31-91.71) for the absolute values and -0.89% (IC: -6,08-4.3) for the percentages. The percentage of data points outside the limits of agreement was 12/227 (5.29%) and 10/227 (4.41%) respectively for the absolute values and percentages. Cohen's kappa coefficient was 0.92 and the area under the curve was 0,9975 (CI 95%: 0.99-1). Conclusion: MUSE®AUTO CD4/CD4% cytometer is a powerful instrument because its results are consistent with those obtained by the reference cytometer. It can enable tracking of patients infected with HIV, in particular in the developing countries.


Assuntos
Contagem de Linfócito CD4/métodos , Linfócitos T CD4-Positivos/imunologia , Citometria de Fluxo/métodos , Infecções por HIV/diagnóstico , Adulto , Contagem de Linfócito CD4/instrumentação , Camarões , Feminino , Citometria de Fluxo/instrumentação , Infecções por HIV/imunologia , Humanos , Modelos Lineares , Masculino , Pessoa de Meia-Idade
15.
Nat Commun ; 10(1): 2296, 2019 05 24.
Artigo em Inglês | MEDLINE | ID: mdl-31127086

RESUMO

Schistosoma mansoni (Sm) infection has been linked with an increased risk of HIV acquisition in women. Therefore, defining the mechanism(s) by which Sm alters HIV susceptibility might lead to new HIV prevention strategies. Here, we analyze the impact of standard Sm therapy in HIV-uninfected Sm+ Ugandan adult women on genital HIV susceptibility and mucosal and systemic immunology. Schistosomiasis treatment induces a profound reduction of HIV entry into cervical and blood CD4+ T cells that is sustained for up to two months, despite transient systemic and mucosal immune activation and elevated genital IL-1α levels. Genital IFN-α2a levels are also elevated post-treatment, and IFN-α2a blocks HIV entry into primary CD4+ T cells ex vivo. Transcriptomic analysis of blood mononuclear cells post-Sm treatment shows IFN-I pathway up-regulation and partial reversal of Sm-dysregulated interferon signaling. These findings indicate that Sm therapy may reduce HIV susceptibility for women with Sm infection, potentially through de-repression of IFN-I pathways.


Assuntos
Linfócitos T CD4-Positivos/parasitologia , HIV/efeitos dos fármacos , Esquistossomose mansoni/tratamento farmacológico , Esquistossomicidas/uso terapêutico , Internalização do Vírus/efeitos dos fármacos , Adulto , Animais , Linfócitos T CD4-Positivos/imunologia , Células Cultivadas , Colo do Útero/citologia , Colo do Útero/imunologia , Colo do Útero/patologia , Suscetibilidade a Doenças , Feminino , HIV/fisiologia , Infecções por HIV/imunologia , Infecções por HIV/prevenção & controle , Infecções por HIV/virologia , Humanos , Interferon-alfa/imunologia , Interferon-alfa/metabolismo , Praziquantel/farmacologia , Praziquantel/uso terapêutico , Cultura Primária de Células , Schistosoma mansoni/imunologia , Schistosoma mansoni/isolamento & purificação , Esquistossomose mansoni/sangue , Esquistossomose mansoni/imunologia , Esquistossomose mansoni/parasitologia , Esquistossomicidas/farmacologia , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/imunologia , Uganda , Regulação para Cima , Esfregaço Vaginal , Adulto Jovem
17.
BMC Infect Dis ; 19(1): 401, 2019 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-31072394

RESUMO

BACKGROUND: France is the European country with the lowest level of confidence in vaccines. Measurement of patients' acceptability towards a future therapeutic HIV vaccine is critically important. Thus, the aim of this study was to evaluate patients' acceptability of a future therapeutic HIV vaccine in a representative cohort of French patients living with HIV-AIDS (PLWHs). METHODS: This multicentre study used quantitative and qualitative methods to assess PLWHs' opinions and their potential acceptance of a future therapeutic HIV vaccine. Cross-sectional study on 220 HIV-1 infected outpatients, aged 18-75 years. RESULTS: The participants' characteristics were similar to those of the overall French PLWH population. Responses from the questionnaires showed high indices of acceptance: the mean score for acceptability on the Visual Analog Scale VAS was 8.4 of 10, and 92% of patients agreed to be vaccinated if a therapeutic vaccine became available. Acceptability depended on the expected characteristics of the vaccine, notably the duration of its effectiveness: 44% of participants expected it to be effective for life. This acceptance was not associated with socio-demographic, clinical (mode of contamination, duration of disease), quality of life, or illness-perception parameters. Acceptability was also strongly correlated with confidence in the treating physician. CONCLUSION: The PLWHs within our cohort had high indices of acceptance to a future therapeutic HIV vaccine. TRIAL REGISTRATION: This study was retroactively registered on ClinicalTrials.gov with ID: NCT02077101 in February 21, 2014.


Assuntos
Vacinas contra a AIDS/administração & dosagem , Infecções por HIV/psicologia , Aceitação pelo Paciente de Cuidados de Saúde , Vacinas contra a AIDS/imunologia , Adolescente , Adulto , Idoso , Estudos Transversais , Feminino , Previsões , França , Infecções por HIV/imunologia , Infecções por HIV/prevenção & controle , Humanos , Masculino , Pessoa de Meia-Idade , Inquéritos e Questionários , Adulto Jovem
18.
Nat Immunol ; 20(6): 711-723, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-31061530

RESUMO

Resting CD4+ T cells are highly resistant to the production of human immunodeficiency virus type 1 (HIV-1). However, the mechanism by which resting CD4+ T cells restrict such production in the late viral replication phase of infection has remained unclear. In this study, we found that the cell membrane metalloprotease TRAB domain-containing protein 2A (TRABD2A) inhibited this production in resting CD4+ T cells by degrading the virion structural precursor polyprotein Gag at the plasma membrane. Depletion or inhibition of metalloprotease activity by TRABD2A profoundly enhanced HIV-1 production in resting CD4+ T cells. TRABD2A expression was much higher in resting CD4+ T cells than in activated CD4+ T cells and was considerably reduced by T cell activation. Moreover, reexpressing TRABD2A reinforced the resistance of activated CD4+ T cells to the production of HIV-1 progeny. Collectively, these results elucidate the molecular mechanism employed by resting CD4+ T cells to potently restrict the assembly and production of HIV-1 progeny.


Assuntos
Linfócitos T CD4-Positivos/imunologia , Infecções por HIV/genética , Infecções por HIV/imunologia , Infecções por HIV/virologia , HIV-1/fisiologia , Metaloproteases/genética , Replicação Viral , Produtos do Gene gag do Vírus da Imunodeficiência Humana/metabolismo , Animais , Linfócitos T CD4-Positivos/metabolismo , Cátions , Linhagem Celular , Ativação Enzimática , Expressão Gênica , Interações Hospedeiro-Patógeno/genética , Interações Hospedeiro-Patógeno/imunologia , Humanos , Proteínas de Membrana/metabolismo , Metaloproteases/antagonistas & inibidores , Metaloproteases/metabolismo , Família Multigênica , Proteólise , Proteína 1 com Domínio SAM e Domínio HD/genética , Proteína 1 com Domínio SAM e Domínio HD/metabolismo , Carga Viral
19.
Arch Virol ; 164(8): 2083-2090, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31134354

RESUMO

Although a few studies have been done on transmissible blood-borne viral infections in high-risk groups, little attention has been given to assessing the infection status of the general population in Afghanistan. To investigate the epidemiological status in the general population, we tested the serological markers of hepatitis B virus (HBV), hepatitis C virus (HCV), hepatitis delta virus (HDV), human immunodeficiency virus 1 (HIV-1) and human T-cell leukemia virus (HTLV) infections. In total, 492 samples were selected randomly from Nangarhar, Herat, Mazar-e Sharif, Kandahar, and Kabul from subjects between 25 and 70 years old. The samples were tested for the presence of HBsAg, anti-HBs, anti-HBc, anti-HDV, anti-HCV, anti-HIV-1 and anti-HTLV I/II antibodies using chemiluminescent immunoassays on Abbott Architect automated platforms. In addition, 220 HBsAg-positive samples identified among 5897 samples from the general population of the same regions of Afghanistan were included in the study and tested for both HBsAg and anti-HDV to investigate HDV prevalence in the country. Viral loads of HBV, HCV and HDV were determined in all seropositive samples using Ampliprep/Cobas TaqMan HBV, HCV, Test Roche (CA, USA), and an in-house method, respectively. Out of 492 samples, 31 (6.3%), 136 (27.6%) and 149 (30.3%) were found to be positive for HBsAg, anti-HBs and anti-HBc, respectively. Anti-HDV positivity was detected in five (2.1%) out of 234 HBsAg-positive samples (including 14 of the randomly selected samples that were not among the 220 previously identified as HBsAg positive). Only eight out of 492 (1.6%) subjects were positive for anti-HCV antibodies. Seven out of 489 (1.4%) were positive for anti-HIV-1 antibodies, and three out of 466 cases (0.6%) were positive for anti-HTLV I/II antibodies. These results suggest that Afghanistan is an intermediate endemic region for HBV, HDV and HCV infection. The prevalence of HIV-1 seems to be significantly higher than the global prevalence and that of the eastern Mediterranean region. In addition, the HTLV I/II screening results suggest that these viruses should be monitored in Afghanistan to confirm the trend observed in the current study.


Assuntos
Viroses/epidemiologia , Adulto , Afeganistão/epidemiologia , DNA Viral/genética , Feminino , Infecções por HIV/epidemiologia , Infecções por HIV/imunologia , HIV-1/imunologia , Hepacivirus/imunologia , Anticorpos Anti-Hepatite/imunologia , Hepatite B/epidemiologia , Hepatite B/imunologia , Anticorpos Anti-Hepatite B/imunologia , Antígenos de Superfície da Hepatite B/imunologia , Vírus da Hepatite B/imunologia , Hepatite C/epidemiologia , Hepatite C/imunologia , Anticorpos Anti-Hepatite C/imunologia , Hepatite D/epidemiologia , Hepatite D/imunologia , Vírus Delta da Hepatite/imunologia , Humanos , Masculino , Pessoa de Meia-Idade , Carga Viral/métodos , Viroses/imunologia
20.
Cell Mol Life Sci ; 76(18): 3583-3600, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31129856

RESUMO

35 years since identification of HIV as the causative agent of AIDS, and 35 million deaths associated with this disease, significant effort is now directed towards the development of potential cures. Current anti-retroviral (ART) therapies for HIV/AIDS can suppress virus replication to undetectable levels, and infected individuals can live symptom free so long as treatment is maintained. However, removal of therapy allows rapid re-emergence of virus from a highly stable reservoir of latently infected cells that exist as a barrier to elimination of the infection with current ART. Prospects of a cure for HIV infection are significantly encouraged by two serendipitous cases where individuals have entered remission following stem cell transplantation from compatible HIV-resistant donors. However, development of a routine cure that could become available to millions of infected individuals will require a means of specifically purging cells harboring latent HIV, preventing replication of latent provirus, or destruction of provirus genomes by gene editing. Elimination of latently infected cells will require a means of exposing this population, which may involve identification of a natural specific biomarker or therapeutic intervention to force their exposure by reactivation of virus expression. Accordingly, the proposed "Shock and Kill" strategy involves treatment with latency-reversing agents (LRA) to induce HIV provirus expression thus exposing these cells to killing by cellular immunity or apoptosis. Current efforts to enable this strategy are directed at developing improved combinations of LRA to produce broad and robust induction of HIV provirus and enhancing the elimination of cells where replication has been reactivated by targeted immune modulation. Alternative strategies may involve preventing re-emergence virus from latently infected cells by "Lock and Block" intervention, where transcription of provirus is inhibited to prevent virus spread or disruption of the HIV provirus genome by genome editing.


Assuntos
Reservatórios de Doenças/virologia , Infecções por HIV/terapia , HIV-1/fisiologia , Antirretrovirais/uso terapêutico , Edição de Genes , Infecções por HIV/tratamento farmacológico , Infecções por HIV/imunologia , Humanos , Imunidade Celular , Imunoterapia , Proteínas Recombinantes/uso terapêutico , Latência Viral
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA