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1.
Mikrobiyol Bul ; 55(1): 17-29, 2021 Jan.
Artigo em Turco | MEDLINE | ID: mdl-33590978

RESUMO

Shortly after the first detection of human immundeficiency virus (HIV) infection in USA in 1981, the number of cases have increased gradually from all around the world. Turkey's high capacity for tourism and the unique geographic location extending between Europe and Asia, provides convenience for the passage of individuals across the countries and sexually transmitted infections including HIV, as well. According to the official data of the Ministry of Health; there are 25809 HIV positive and 1958 AIDS cases as of November 30, 2020, after the epidemic started in 1985 in Turkey. Despite the decrease in the number of newly detected HIV cases as a result of serious measures taken for the transmission of infection worldwide, the increase in the number of cases still continues in our country. Shortening the reporting period and starting treatment as soon as possible in the diagnosis of infection is critical for the control of the epidemic. For this purpose, Centers for Disease Control and Prevention (CDC) published a new test algorithm in 2010, which suggested the use of the Geenius™ HIV ½ supplemental assay test instead of western blot tests, which have been used for many years to verify HIV screening test positivity. In this study, we aimed to report the experience of the National HIV-Acquiner Immundeficiency Syndrome(AIDS) and Viral Hepatitis Reference Laboratories of Turkey in the first year of transition to the new HIV algorithm and to evaluate the diagnostic performance of Geenius™ HIV ó and line immunassay (LIA) s. A total of 2090 anti-HIV positive patient sera sent to National HIV-AIDS and Viral Hepatitis Reference Laboratories of Turkey, Ankara for HIV confirmation were included in the study. All samples were retested with a fourth-generation enzyme linked immunosorbent assay (ELISA) test (VIDAS® HIV-1/2 Duo Ultra assay, BioMerieux, France) followed by the confirmatory tests; Geenius™ HIV 1/2 confirmatory assay (BioRad, Redmond, WA) and Line-immunoassay (INNO-LIA HIV ½ Score, Fujirebio, reverse transcriptase polymerase chain reaction (RT-PCR) (artus HI Virus-1 RT-PCR, Qiagen, Germany) test and in-house HIV-2 RNA and proviral DNA PCR. The sensitivity, specificity, and the agreement of the each assay were compared. Cohen's Kappa analysis was used for the evaluation of the agreement between the tests. According to the new algorithm which recommended Geenius™ test besides HIV-1 RNA test, 1707 (81.7%) HIV-1 positive samples were identified. Of these samples; 95.9% and 95.02% were identified as HIV-1 positive by GeeniusTM and INNO-LIA, respectively. However, 2.5% of the positive samples were negative with Geenius™ and 3.5% with INNO-LIA. One and a half percentage (1.5%) of these samples were detected with Geenius™ and 1.4% with INNO-LIA as indeterminant. When all the positive samples determined with ELISA were evaluated; it was detected that,1.3% were indeterminate by Geenius™ test and 2.4% by the INNO-LIA test. When the INNO-LIA test was regarded as the gold standard method; sensitivity, specificity, positive predictive and negative predictive values of the Geenius™ test were as follows; 99.7%, 96.1%, 98.9%, and 99.1%. The agreement between INNO-LIA and Geenius™ tests was found to be 98.95% (κ= 0.969; very good). When the Geenius™ and HIV-1 PCR tests were evaluated together for the confirmation; the sensitivities of Geenius™ and INNO-LIA tests were 99.8% and 98.3%, specificities were 89.8% and 85.3%, respectively. Slight positive bands were detected in the gp36 or gp140 bands, the HIV-2 specific envelope proteins, were detected in seven samples, However, the positivity disappeared after the dilution of the samples and it was accepted as false positivite reaction due to the absence of HIV-2 RNA and proviral DNA in these samples. In conclusion; we concluded that Geenius ™ and INNO-LIA tests have a perfect agreement in HIV diagnosis and due to the rapid and reliable results provided for the HIV test protocol, Geenius™ test can be used safely as an alternative to the immunoblot tests. HIV-1 RNA testing must be performed in all HIV confirmation centers in order to detect acute HIV cases in the fast and early period which are the main reason for the updates in HIV diagnosis.


Assuntos
Algoritmos , Infecções por HIV , Imunoensaio , Anticorpos Anti-HIV/sangue , Infecções por HIV/diagnóstico , Infecções por HIV/epidemiologia , Infecções por HIV/virologia , HIV-1/imunologia , HIV-2/imunologia , Humanos , Imunoensaio/normas , Sensibilidade e Especificidade , Turquia/epidemiologia
2.
PLoS One ; 15(10): e0239607, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33017442

RESUMO

BACKGROUND: HIV self-testing (HIVST) is an additional approach to increasing uptake of HIV testing services. The practicability and accuracy of and the preference for the capillary blood self-test (Exacto Test HIV) versus the oral fluid self-test (OraQuick HIV self-test) were compared among untrained individuals in the Democratic Republic of the Congo (DRC). METHODS: This multicenter cross-sectional study (2019) used face-to-face, tablet-based, structured questionnaires in a facility-based HIVST approach. Volunteers from the general public who were at high risk of HIV infection, who were between 18 and 49 years of age, and who had signed an informed consent form were eligible for the study. The successful performance and correct interpretation of the self-test results were the main outcomes of the practicability evaluation. The successful performance of the HIV self-test was conditioned by the presence of the control band. The sensitivity and specificity of the participant-interpreted results compared to the laboratory results were estimated for accuracy. Preference for either type of self-test was assessed. Logistic regression models were used to examine factors associated with participants' preference. RESULTS: A total of 528 participants were included in this survey. The rate of successful performance of the HIV self-tests was high, with the blood test (99.6%) and the oral-fluid test (99.4%) yielding an absolute difference of 0.2% (95% CI: -1.8 to 1.1; P = 0.568). The rate of correct interpretation of the HIV self-test results was 84.4% with the blood test versus 83.8% with the oral-fluid test (difference = 0.6; 95% CI: -0.2 to 1.7; P = 0.425). Misinterpretation (25.4% for the blood test and 25.6% for the oral-fluid test) and inability to interpret (20.4% for the blood test and 21.1% for the oral-fluid test) test results were significantly more prevalent with invalid tests. The Exacto Test HIV self-test and the OraQuick HIV self-test showed 100% and 99.2% sensitivity, and 98.9% and 98.1% specificity, respectively. Preference for oral-fluid-based HIVST was greater than that for blood-based HIVST (85.6% versus 78.6%; P = 0.008). Preference for the blood test was greater among participants with a university education (86.1%; aOR = 2.4 [95% CI: 1.1 to 4.9]; P = 0.016), a higher risk of HIV infection (88.1%; aOR = 2.3 [95% CI: 1.0 to 5.3]; P = 0.047), and knowledge about the existence of HIVST (89.3%; aOR = 2.2 [95% CI: 1.0 to 5.0]; P = 0.05). CONCLUSION: Our field observations demonstrate that blood-based and oral-fluid-based HIVST are both practicable approaches with a high and comparable rate of accuracy in the study setting. Although preference for the oral-fluid test was generally greater, preference for the blood test was greater among participants with a university education, a high risk of HIV infection, and knowledge about the existence of HIVST. Both approaches seem complementary in the sense that users can choose the type of self-test that best suits them for a similar result. Taken together, our observations support the use of the two HIV self-test kits in the DRC.


Assuntos
Sorodiagnóstico da AIDS/métodos , Infecções por HIV/diagnóstico , Sorodiagnóstico da AIDS/estatística & dados numéricos , Adolescente , Adulto , Líquidos Corporais/imunologia , Estudos Transversais , República Democrática do Congo , Feminino , Anticorpos Anti-HIV/análise , Anticorpos Anti-HIV/sangue , Infecções por HIV/sangue , Infecções por HIV/imunologia , Humanos , Masculino , Pessoa de Meia-Idade , Boca/imunologia , Participação do Paciente , Autocuidado , Inquéritos e Questionários , Adulto Jovem
3.
BMC Infect Dis ; 20(1): 655, 2020 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-32894072

RESUMO

BACKGROUND: People who use drugs including people who inject drugs (PWUD/ID), sex workers (SWs) and men who have sex with men (MSM) are at increased risk of HIV and viral hepatitis infection. Limited epidemiological data on the infections exists in key populations (KPs) in South Africa. We investigated the prevalence of hepatitis B (HBV), hepatitis C (HCV) and HIV and selected risk factors among these KPs to inform effective responses. METHODS: We used convenience sampling to recruit a targeted 3500 KPs accessing HIV-related health services across Cape Town (SWs, MSM, PWUD/ID), Durban (SWs, PWUD/ID), Pietermaritzburg (SWs), Mthatha (SWs), Port Elizabeth (SWs), Johannesburg (MSM) and Pretoria (MSM and PWUD/ID) into a cross-sectional survey. An interviewer questionnaire to assess socio-demographic characteristics, drug use and sexual risk practices, was administered. HBV surface antigen (HBsAg); HCV antibody, viral load and genotype, and HIV antibody, was tested. RESULTS: Among the 3439 people included in the study (1528 SWs, 746 MSM, 1165 PWUD/ID) the median age was 29 years, most participants were black African (60%), and 24% reported homelessness. 82% reported substance use in the last month, including alcohol (46%) and heroin (33%). 75% were sexually active in the previous month, with condom use at last sex at 74%. HIV prevalence was 37% (highest among SWs at 47%), HBsAg prevalence 4% (similar across KPs) and HCV prevalence was 16% (highest among PWUD/ID at 46%). CONCLUSIONS: HBV, HCV and HIV pose a health burden for KPs in South Africa. While HIV is key for all included KPs, HCV is of particular importance to PWUD/ID. For KPs, HBV vaccination and behavioural change interventions that support consistent condom and lubricant access and use are needed. Coverage of opioid substitution therapy and needle and syringe services, and access to HCV treatment for PWUD/ID need to be expanded.


Assuntos
Infecções por HIV/epidemiologia , HIV/imunologia , Hepacivirus/genética , Hepacivirus/imunologia , Vírus da Hepatite B/imunologia , Hepatite B/epidemiologia , Hepatite C/epidemiologia , Adulto , Estudos Transversais , Feminino , Genótipo , Anticorpos Anti-HIV/sangue , Infecções por HIV/tratamento farmacológico , Infecções por HIV/etiologia , Infecções por HIV/prevenção & controle , Hepatite B/etiologia , Antígenos de Superfície da Hepatite B/sangue , Hepatite C/etiologia , Anticorpos Anti-Hepatite C/sangue , Homossexualidade Masculina , Humanos , Masculino , Prevalência , Estudos Prospectivos , Fatores de Risco , Profissionais do Sexo , Minorias Sexuais e de Gênero , África do Sul/epidemiologia , Abuso de Substâncias por Via Intravenosa/complicações , Carga Viral , Adulto Jovem
4.
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
6.
PLoS One ; 15(8): e0237580, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32790740

RESUMO

BACKGROUND: HIV screening (i.e. antigen/antibody) tests are followed by a supplemental (i.e. antibody-only) if the screen is positive. Discrepant results can result from two scenarios: a false-positive screening test or acute HIV infection. These scenarios can be distinguished by a molecular HIV test, but due to contamination concerns, our laboratory recently implemented a policy requiring a second specimen dedicated for molecular HIV testing. Our objective was to (1) characterize the effect of this policy on the time-to-diagnosis for patients with discrepant screening and supplemental test results, and (2) explore "strength of positivity" as an interim predictor of screening test accuracy while awaiting confirmatory test results. METHODS: Data from our laboratory information system, electronic health record, and instrument logs were used to collate data for all HIV testing performed at Barnes-Jewish Hospital (BJH) between January 1, 2014 and October 18, 2017. RESULTS: Requiring a dedicated specimen for molecular testing significantly increased the time-to-diagnosis for patients with discrepant screening and supplemental HIV tests (p = 0.0084). This policy also contributed to loss-to-followup, with 0/35 discrepant cases lost-to-followup prior to policy implementation compared to 2/10 after implementation. However, by optimizing the signal-to-cutoff (S/CO) ratio of the screening test, we were able to more accurately distinguish false-positives from acute-HIV prior to molecular testing (sensitivity of 100%, specificity of 89%). CONCLUSIONS: We propose utilizing quantitative fourth-generation assay results (S/CO) ratios as a predictor of infection true positivity in situations where the screening assay is reactive but the supplemental test is negative and confirmatory molecular results are not immediately available.


Assuntos
Sorodiagnóstico da AIDS/normas , Anticorpos Anti-HIV/sangue , Antígenos HIV/imunologia , Infecções por HIV/diagnóstico , Infecções por HIV/prevenção & controle , HIV-1/imunologia , Programas de Rastreamento/métodos , Algoritmos , Reações Falso-Positivas , Anticorpos Anti-HIV/imunologia , Infecções por HIV/sangue , Infecções por HIV/virologia , Humanos
7.
PLoS One ; 15(8): e0237438, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32790799

RESUMO

Rapid tests (RTs), also known as point-of-care tests, usually release results within 30 minutes with no need for a qualified staff, equipment, or laboratory structure. The Brazilian Ministry of Health published a resolution in 2013, recommending the use of RTs for the diagnosis of HIV infection, where one positive RT must be followed by another different RT. This was meant to increase the chance of proper diagnosis in specific settings and special populations. However, data comparing and validating the different HIV RTs available in Brazil are scarce. Therefore, the present study seeks to evaluate eight anti-HIV RTs available in the Brazilian market regarding their analytical performance: sensitivity, specificity, positive and negative predictive values, positive and negative likelihood ratios, and accuracy. We also evaluated the agreement between kits (Kappa index) and the quality of the reading pattern of the tests. This was an observational, analytical, and concordance study, in which previously defined positive and negative samples, based on their serological pattern for anti-HIV antibodies (chemiluminescent immunoassay-ECLIA-used as screening and Western Blot used as the confirmatory test) were tested. Analytical performance and Kappa index were calculated, considering a 95% CI and p<0.05. This study identified differences in the performances of the eight tested kits. Six out of eight RTs showed good performance and can be used in the routine laboratory and health care units as screening tests. Regarding the quality of the RT band reading pattern, two brands had several samples showing quite faint bands, thus compromising its use in clinical and laboratory settings.


Assuntos
Infecções por HIV/diagnóstico , Imunoensaio/métodos , Anticorpos Anti-HIV/sangue , Humanos , Medições Luminescentes , Sistemas Automatizados de Assistência Junto ao Leito , Kit de Reagentes para Diagnóstico , Sensibilidade e Especificidade
8.
J Cancer Res Ther ; 16(3): 619-623, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32719277

RESUMO

Introduction: Patients receiving treatment for head-and-neck squamous cell carcinoma (HNSCC) also may have coexisting viral infections caused by HIV, HBV, and HCV (seropositive). There is scarce literature regarding the clinical presentation and treatment outcomes for these patients with coexisting viral infections (seropositive HNSCC). We conducted this study to assess the clinical presentation and treatment outcomes (overall survival [OS] and disease-specific survival [DSS]) of seropositive HNSCC patients. Methodology: This was a retrospective cohort study on seropositive HNSCC patients registered at our center from 2012 to 2014. The viral infections were identified by the presence of the antibodies to these viruses in the patient's blood samples. Results: Out of the 19,137 HNSCC patients registered, 156 patients had HBV, HCV, and/or HIV infection. Among these, HBV infection was the most common (n = 86/156, 55.1%) followed by HIV infection (n = 36/156, 23.1%) and HCV infection (n = 29/156, 18.6%). The oral cavity was the most common subsite involved. Majority of these patients presented at an advanced stage (advanced T stage - 71.8% and node positive - 62.2%). The majority of the patients received curative-intent treatment (65.4%). The OS at 3 years for these HNSCC patients with coexisting HIV, HBV, and HCV infection was 60%, 62.6%, and 57.5%, respectively, and their DSS at 3 years was 58.8%, 78.6%, and 53.8%, respectively. Conclusions: Seropositive patients with HNSCC often present in the advanced stage but have a good survival if treated appropriately.


Assuntos
Soropositividade para HIV/epidemiologia , Neoplasias de Cabeça e Pescoço/epidemiologia , Hepatite B/epidemiologia , Hepatite C/epidemiologia , Carcinoma de Células Escamosas de Cabeça e Pescoço/epidemiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Anticorpos Anti-HIV/sangue , Soropositividade para HIV/imunologia , Soropositividade para HIV/patologia , Soropositividade para HIV/virologia , Neoplasias de Cabeça e Pescoço/sangue , Neoplasias de Cabeça e Pescoço/patologia , Neoplasias de Cabeça e Pescoço/virologia , Hepatite B/imunologia , Hepatite B/patologia , Hepatite B/virologia , Anticorpos Anti-Hepatite B/sangue , Hepatite C/imunologia , Hepatite C/patologia , Hepatite C/virologia , Anticorpos Anti-Hepatite C/sangue , Humanos , Índia/epidemiologia , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Estudos Retrospectivos , Carcinoma de Células Escamosas de Cabeça e Pescoço/sangue , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia , Carcinoma de Células Escamosas de Cabeça e Pescoço/virologia , Taxa de Sobrevida
9.
Nat Commun ; 11(1): 3195, 2020 06 24.
Artigo em Inglês | MEDLINE | ID: mdl-32581216

RESUMO

Penile acquisition of HIV accounts for most infections among men globally. Nevertheless, candidate HIV interventions for men advance to clinical trials without preclinical efficacy data, due primarily to a paucity of relevant animal models of penile HIV infection. Using our recently developed macaque model, we show that a single subcutaneous administration of broadly neutralizing antibody (bNAb) 10-1074 conferred durable protection against repeated penile exposures to simian-human immunodeficiency virus (SHIVSF162P3). Macaques co-administered bNAbs 10-1074 and 3BNC117, or 3BNC117 alone, also exhibited significant protection against repeated vaginal SHIVAD8-EO exposures. Regression modeling estimated that individual plasma bNAb concentrations of 5 µg ml-1 correlated with ≥99.9% relative reduction in SHIV infection probability via penile (10-1074) or vaginal (10-1074 or 3BNC117) challenge routes. These results demonstrate that comparably large reductions in penile and vaginal SHIV infection risk among macaques were achieved at clinically relevant plasma bNAb concentrations and inform dose selection for the development of bNAbs as long-acting pre-exposure prophylaxis candidates for use by men and women.


Assuntos
Vacinas contra a AIDS/administração & dosagem , Anticorpos Amplamente Neutralizantes/administração & dosagem , Anticorpos Anti-HIV/administração & dosagem , Síndrome de Imunodeficiência Adquirida dos Símios/prevenção & controle , Síndrome de Imunodeficiência Adquirida dos Símios/transmissão , Vírus da Imunodeficiência Símia/imunologia , Vacinas contra a AIDS/sangue , Animais , Anticorpos Amplamente Neutralizantes/sangue , Modelos Animais de Doenças , Feminino , Anticorpos Anti-HIV/sangue , Infecções por HIV/prevenção & controle , Infecções por HIV/transmissão , Meia-Vida , Imunização Passiva , Macaca mulatta , Masculino , Pênis/imunologia , Pênis/virologia , Profilaxia Pré-Exposição , Vagina/imunologia , Vagina/virologia
10.
Lancet HIV ; 7(5): e359-e365, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32386722

RESUMO

Several assays have been developed to measure and characterise the replication-competent HIV-1 reservoir, which constitutes the barrier to cure. To date, the application of these assays to studies in children and in limited-resource settings has been minimal, primarily because of their expense, the large required blood volumes, and labour-intensive technologies. For children vertically infected with HIV-1 who initiated suppressive antiretroviral therapy (ART) regimens in infancy, HIV-1-specific antibody concentrations are associated with viral persistence and could be used to estimate the size of the residual latent reservoir on ART. This strategy could be particularly useful for screening children on suppressive ART for enrolment into therapeutic vaccine trials and other protocols aimed at achieving HIV-1 remission.


Assuntos
Anticorpos Anti-HIV/sangue , Infecções por HIV/imunologia , Infecções por HIV/virologia , HIV-1/imunologia , Transmissão Vertical de Doença Infecciosa , Carga Viral , Fármacos Anti-HIV/uso terapêutico , DNA Viral/sangue , Infecções por HIV/tratamento farmacológico , Infecções por HIV/transmissão , Humanos , Lactente
12.
Mol Immunol ; 119: 106-122, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-32007753

RESUMO

A licensed vaccine against human immunodeficiency virus-1 (HIV-1) infection has not become available up to now. Hence, it is more rational to use immune-informatics tools for prediction of T cell epitopes (in silico study) and development of an effective epitope-driven vaccine against hypervariable pathogens. Multiepitope vaccines were considered as the next generation of an effective vaccine against HIV-1 infection. In the current study, we developed two different constructs encoding T cell epitopes derived from Nef, Vif, Vpu, Gp160 and P24 proteins in BALB/c mice. To overcome their poor immunogenicity, four different cell penetrating peptides (MPG and HR9 for DNA delivery, and CyLoP-1 and LDP-NLS for protein delivery), Montanide adjuvant, and heterologous prime-boost immunization strategy were utilized. The generation of cytokines, Granzyme B, and total IgG and its subclasses was determined using ELISA. Our data indicated that the levels of IFN-γ and Granzyme B in mice injected with Nef-Vif-Gp160-P24 multiepitope constructs were higher than those immunized with Nef-Vpu-Gp160-P24 multiepitope constructs. Moreover, the heterologous DNA priming/ multiepitope peptide boosting in both Nef-Vif-Gp160-P24 and Nef-Vpu-Gp160-P24 regimens induced significantly high antigen-specific IgG2a and IgG2b responses in comparison with other groups. There was no significant difference between MPG and HR9 as well as CyLoP-1 and LDP-NLS as a delivery system for enhancement of immune responses. Generally, the heterologous DNA prime/ multiepitope peptide boost modalities for both constructs could significantly enhance the levels of IgG2a, IgG2b, IFN-γ, and Granzyme B directed toward Th1 immune responses as compared to homologous prime/ boost with DNA or polypeptide constructs.


Assuntos
Vacinas contra a AIDS/imunologia , Epitopos de Linfócito T/imunologia , HIV-1/imunologia , Proteínas do Vírus da Imunodeficiência Humana/imunologia , Animais , Citocinas/sangue , Epitopos de Linfócito B/imunologia , Feminino , Granzimas/metabolismo , Anticorpos Anti-HIV/sangue , Anticorpos Anti-HIV/imunologia , Imunogenicidade da Vacina , Camundongos Endogâmicos BALB C , Modelos Moleculares
13.
Nat Commun ; 11(1): 948, 2020 02 19.
Artigo em Inglês | MEDLINE | ID: mdl-32075963

RESUMO

Eliciting protective titers of HIV-1 broadly neutralizing antibodies (bnAbs) is a goal of HIV-1 vaccine development, but current vaccine strategies have yet to induce bnAbs in humans. Many bnAbs isolated from HIV-1-infected individuals are encoded by immunoglobulin gene rearrangments with infrequent naive B cell precursors and with unusual genetic features that may be subject to host regulatory control. Here, we administer antibodies targeting immune cell regulatory receptors CTLA-4, PD-1 or OX40 along with HIV envelope (Env) vaccines to rhesus macaques and bnAb immunoglobulin knock-in (KI) mice expressing diverse precursors of CD4 binding site HIV-1 bnAbs. CTLA-4 blockade augments HIV-1 Env antibody responses in macaques, and in a bnAb-precursor mouse model, CTLA-4 blocking or OX40 agonist antibodies increase germinal center B and T follicular helper cells and plasma neutralizing antibodies. Thus, modulation of CTLA-4 or OX40 immune checkpoints during vaccination can promote germinal center activity and enhance HIV-1 Env antibody responses.


Assuntos
Vacinas contra a AIDS/imunologia , Anticorpos Neutralizantes/imunologia , Anticorpos Anti-HIV/imunologia , HIV-1/imunologia , Fatores Imunológicos/imunologia , Vacinação/métodos , Vacinas contra a AIDS/administração & dosagem , Animais , Anticorpos Bloqueadores/administração & dosagem , Anticorpos Bloqueadores/imunologia , Anticorpos Neutralizantes/sangue , Linfócitos B/imunologia , Antígenos CD4/genética , Antígeno CTLA-4/antagonistas & inibidores , Antígeno CTLA-4/imunologia , Anticorpos Anti-HIV/sangue , Infecções por HIV/imunologia , Humanos , Fatores Imunológicos/administração & dosagem , Ativação Linfocitária , Macaca mulatta/imunologia , Camundongos , Camundongos Transgênicos , Receptores OX40/agonistas , Receptores OX40/imunologia , Linfócitos T Auxiliares-Indutores/imunologia , Transcriptoma , Produtos do Gene env do Vírus da Imunodeficiência Humana/imunologia
14.
Epidemiol Infect ; 148: e53, 2020 02 19.
Artigo em Inglês | MEDLINE | ID: mdl-32070438

RESUMO

Accurate methods for determining the duration of HIV infection at the individual level are valuable in many settings, including many critical research studies and in clinical practice (especially for acute infection). Since first published in 2003, the 'Fiebig staging system' has been used as the primary way of classifying early HIV infection into five sequential stages based on HIV test result patterns in newly diagnosed individuals. However, Fiebig stages can only be assigned to individuals who produce both a negative and a positive test result on the same day, on specific pairs of tests of varying 'sensitivity'. Further, in the past 16 years HIV-testing technology has evolved substantially, and three of the five key assays used to define Fiebig stages are no longer widely used. To address these limitations, we developed an improved and more general framework for estimating the duration of HIV infection by interpreting any combination of diagnostic test results, whether obtained on single or multiple days, into an estimated date of detectable infection, or EDDI. A key advantage of the EDDI method over Fiebig staging is that it allows for the generation of a point estimate, as well as an associated credibility interval for the date of first detectable infection, for any person who has at least one positive and one negative HIV test of any kind. The tests do not have to be run on the same day; they do not have to be run during the acute phase of infection and the method does not rely on any special pairing of tests to define 'stages' of infection. The size of the interval surrounding the EDDI (and therefore the precision of the estimate itself) depends largely on the length of time between negative and positive tests. The EDDI approach is also flexible, seamlessly incorporating any assay for which there is a reasonable diagnostic delay estimate. An open-source, free online tool includes a user-updatable curated database of published diagnostic delays. HIV diagnostics have evolved tremendously since that original publication more than 15 years ago, and it is time to similarly evolve the methods used to estimate timing of infection. The EDDI method is a flexible and rigorous way to estimate the timing of HIV infection in a continuously evolving diagnostic landscape.


Assuntos
Infecções por HIV/diagnóstico , Diagnóstico Tardio , Diagnóstico Precoce , Anticorpos Anti-HIV/sangue , Infecções por HIV/epidemiologia , Infecções por HIV/imunologia , Infecções por HIV/virologia , Humanos , Modelos Biológicos , Prognóstico , Índice de Gravidade de Doença , Carga Viral/estatística & dados numéricos
15.
J Immunol ; 204(6): 1543-1561, 2020 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-32066595

RESUMO

Elicitation of broadly neutralizing Ab (bNAb) responses toward the conserved HIV-1 envelope (Env) CD4 binding site (CD4bs) by vaccination is an important goal for vaccine development and yet to be achieved. The outcome of previous immunogenicity studies suggests that the limited accessibility of the CD4bs and the presence of predominant nonneutralizing determinants (nND) on Env may impede the elicitation of bNAbs and their precursors by vaccination. In this study, we designed a panel of novel immunogens that 1) preferentially expose the CD4bs by selective elimination of glycosylation sites flanking the CD4bs, and 2) minimize the nND immune response by engineering fusion proteins consisting of gp120 Core and one or two CD4-induced (CD4i) mAbs for masking nND epitopes, referred to as gp120-CD4i fusion proteins. As expected, the fusion proteins possess improved antigenicity with retained affinity for VRC01-class, CD4bs-directed bNAbs and dampened affinity for nonneutralizing Abs. We immunized C57BL/6 mice with these fusion proteins and found that overall the fusion proteins elicit more focused CD4bs Ab response than prototypical gp120 Core by serological analysis. Consistently, we found that mice immunized with selected gp120-CD4i fusion proteins have higher frequencies of germinal center-activated B cells and CD4bs-directed memory B cells than those inoculated with parental immunogens. We isolated three mAbs from mice immunized with selected gp120-CD4i fusion proteins and found that their footprints on Env are similar to VRC01-class bNAbs. Thus, using gp120-CD4i fusion proteins with selective glycan deletion as immunogens could focus Ab response toward CD4bs epitope.


Assuntos
Vacinas contra a AIDS/imunologia , Anticorpos Neutralizantes/sangue , Anticorpos Anti-HIV/sangue , Proteína gp120 do Envelope de HIV/imunologia , Infecções por HIV/prevenção & controle , HIV-1/imunologia , Vacinas contra a AIDS/administração & dosagem , Vacinas contra a AIDS/genética , Animais , Anticorpos Monoclonais/administração & dosagem , Anticorpos Monoclonais/genética , Anticorpos Monoclonais/imunologia , Anticorpos Neutralizantes/imunologia , Sítios de Ligação de Anticorpos/genética , Sítios de Ligação de Anticorpos/imunologia , Antígenos CD4/imunologia , Antígenos CD4/metabolismo , Epitopos de Linfócito T/genética , Epitopos de Linfócito T/imunologia , Feminino , Anticorpos Anti-HIV/imunologia , Proteína gp120 do Envelope de HIV/genética , Infecções por HIV/sangue , Infecções por HIV/imunologia , Infecções por HIV/virologia , HIV-1/genética , Humanos , Imunogenicidade da Vacina , Camundongos , Modelos Animais , Proteínas Recombinantes de Fusão/administração & dosagem , Proteínas Recombinantes de Fusão/genética , Proteínas Recombinantes de Fusão/imunologia , Vacinas Sintéticas/administração & dosagem , Vacinas Sintéticas/genética , Vacinas Sintéticas/imunologia
16.
J Acquir Immune Defic Syndr ; 83(3): 260-266, 2020 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-31917751

RESUMO

BACKGROUND: Previous studies have shown low frequencies of seroreactivity to HIV diagnostic assays for infected infants treated with antiretroviral therapy (ART) early in infection. METHODS: Fifty-eight HIV-infected infants treated with ART at a median age of 1.9 months (range: 0.2-5.4) for up to 4 years of life were assessed for seroreactivity to 4 routinely used HIV clinical immunoassays (IA): Second-generation (2ndG) IA and 2 rapid diagnostic tests (RDT), based on third-generation principles, measuring antibody only and a fourth-generation (4thG) antigen/antibody IA. HIV Western blot assay was also performed to assess HIV-specific antibodies. RESULTS: The 2ndG IA demonstrated the highest frequency of seroreactivity in children (69%) followed by the 4thG IA (40%) and the RDT (26%) after one year of ART. Infants initiating ART during ages 3-6 months (N = 15) showed a greater frequency (range: 53%-93%) and breadth (median and range: 3 [1-4]) of reactivity across the assays compared with those treated within 3 months (N = 43):16%-61% and breadth (1 [0-4]). The 4thG IA showed significantly reduced reactivity relative to the 2ndG IA at one (P = 0.016) and 3 (P = 0.004) years of ART. Western blot profiles following 3 years of ART showed the highest frequency of reactivity to HIV Gag p24 (76%) and lowest reactivity to Env gp120 and gp41, with only 24% of children confirmed positive by the assay. CONCLUSIONS: These results suggest that the use of 4thG IA and RDT test combination algorithms with limited HIV antigen breadth may not be adequate for diagnosis of HIV-infected children following early treatment.


Assuntos
Fármacos Anti-HIV/uso terapêutico , Infecções por HIV/tratamento farmacológico , Testes Sorológicos/métodos , Adulto , Envelhecimento , Pré-Escolar , Esquema de Medicação , Feminino , Anticorpos Anti-HIV/sangue , Antígenos HIV , Humanos , Lactente , Recém-Nascido , Transmissão Vertical de Doença Infecciosa , Masculino , Gravidez , Complicações Infecciosas na Gravidez
17.
J Int AIDS Soc ; 23(1): e25432, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31916420

RESUMO

INTRODUCTION: High levels of HIV seroconcordance at the population level reduce the potential for effective HIV transmission. However, the level of HIV seroconcordance is largely unknown among heterosexual couples in sub-Saharan Africa. We aimed to quantify the population level HIV seroconcordance in stable heterosexual couples in rural South Africa. METHODS: We followed adults (≥15 years old) using a population-based, longitudinal and open surveillance system in KwaZulu-Natal, South Africa, from 2003 to 2016. Sexual partnerships and HIV status were confirmed via household surveys and annual HIV surveillance. We calculated the proportions of HIV seroconcordance and serodiscordance in stable sexual partnerships and compared them to the expected proportions under the assumption of random mixing using individual-based microsimulation models. Among unpartnered individuals, we estimated the incidence rates and hazard of sexual partnership formation with HIV-positive or HIV-negative partners by participants' own time-varying HIV status. Competing risks survival regressions were fitted adjusting for sociodemographic and clinical factors. We also calculated Newman's assortativity coefficients. RESULTS: A total of 18,341 HIV-negative and 11,361 HIV-positive individuals contributed 154,469 person-years (PY) of follow-up. Overall, 28% of the participants were in stable sexual partnerships. Of the 677 newly formed stable sexual partnerships, 7.7% (95% CI: 5.8 to 10.0) were HIV-positive seroconcordant (i.e. both individuals in the partnership were HIV-positive), which was three times higher than the expected proportion (2.3%) in microsimulation models based on random mixing. The incidence rates of sexual partnership formation were 0.54/1000PY with HIV-positive, 1.12/1000PY with HIV-negative and 2.65/1000PY with unknown serostatus partners. HIV-positive individuals had 2.39 (95% CI: 1.43 to 3.99) times higher hazard of forming a sexual partnership with an HIV-positive partner than did HIV-negative individuals after adjusting for age, opposite-sex HIV prevalence (by 5-years age groups), HIV prevalence in the surrounding community, ART coverage and other sociodemographic factors. Similarly, forming a sexual partnership with an HIV-negative partner was 1.47 (95% CI: 1.01 to 2.14) times higher in HIV-negative individuals in the adjusted model. Newman's coefficient also showed that assortativity by participant and partner HIV status was moderate (r = 0.35). CONCLUSIONS: A high degree of population level HIV seroconcordance (both positive and negative) was observed at the time of forming new sexual partnerships. Understanding factors driving these patterns may help the development of strategies to bring the HIV epidemic under control.


Assuntos
Infecções por HIV/sangue , Heterossexualidade/estatística & dados numéricos , Adolescente , Adulto , Feminino , Anticorpos Anti-HIV/sangue , Infecções por HIV/diagnóstico , Infecções por HIV/epidemiologia , Infecções por HIV/psicologia , Soropositividade para HIV/sangue , Soropositividade para HIV/diagnóstico , Humanos , Masculino , População Rural/estatística & dados numéricos , Parceiros Sexuais , África do Sul/epidemiologia , Adulto Jovem
18.
BMC Infect Dis ; 20(1): 9, 2020 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-31906866

RESUMO

BACKGROUND: An individual is considered HIV positive when a confirmatory HIV-1/HIV-2 differentiation test returns positive following an initial reactive antigen/antibody combination screen. Falsely reactive HIV screens have been reported in patients with various concomitant infectious and autoimmune conditions. Falsely positive confirmatory HIV differentiation assays are seen less frequently, but have been observed in cases of pregnancy, pulmonary embolism, and malaria. CASE PRESENTATION: A healthy 27 year-old man was referred after a reactive ADVIA Centaur® HIV Ag/Ab screen and positive Bio-Rad Geenius™ HIV 1/2 Confirmatory assay, suggesting HIV-1 infection. The patient's HIV viral load was undetectable prior to initiation of antiretroviral therapy, and remained undetectable on subsequent testing after initiation of antiretroviral therapy. Both Centaur® and Geenius™ tests were repeated and returned reactive. As this patient was believed to be at low risk of acquiring HIV infection, samples were additionally run on Genscreen™ HIV-1 Ag assay and Fujirebio Inno-LIA™ HIV-1/2 score, with both returning non-reactive. For confirmation, the patient's proviral HIV DNA testing was negative, confirming the initial results as being falsely positive. The patient disclosed that he had been using a variety of anabolic steroids before and during the time of HIV testing. DISCUSSION AND CONCLUSIONS: The erroneous diagnosis of HIV can result in decreased quality of life and adverse effects of antiretroviral therapy if initiated, hence the importance of interpreting the results of HIV testing in the context of an individual patient. This reports suggests a potential association between the use of anabolic steroids and falsely-reactive HIV testing.


Assuntos
Sorodiagnóstico da AIDS/normas , Reações Falso-Positivas , Infecções por HIV/diagnóstico , HIV/imunologia , Congêneres da Testosterona/efeitos adversos , Adulto , Anticorpos Anti-HIV/sangue , Infecções por HIV/sangue , Infecções por HIV/virologia , Humanos , Masculino , Autoadministração , Congêneres da Testosterona/administração & dosagem , Congêneres da Testosterona/imunologia
19.
mSphere ; 5(1)2020 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-31996422

RESUMO

Analysis of breakthrough HIV-1 infections could elucidate whether prior vaccination primes relevant immune responses. Here, we measured HIV-specific antibody responses in 14 South African volunteers who acquired HIV infection after participating in phase 1/2 trials of envelope-containing immunogens. Serum samples were collected annually following HIV-1 infection from participants in trials HVTN 073 (subtype C, DNA/MVA, phase 1 trial, n = 1), HVTN 086 (subtype C, DNA/MVA/gp140 protein, phase 1 trial, n = 2), and HVTN 204 (multisubtype, DNA/adenovirus serotype 5 [Ad5], phase 2 trial, n = 7) and 4 placebo recipients. Binding and neutralizing antibody responses to Env proteins and peptides were determined pre- and post-HIV infection using an enzyme-linked immunosorbent assay and the TZM-bl cell neutralization assay, respectively. HIV-infected South African individuals served as unvaccinated controls. Binding antibodies to gp41, V3, V2, the membrane-proximal external region (MPER), and the CD4 binding site were detected from the first year of HIV-1 subtype C infection, and the levels were similar in vaccinated and placebo recipients. Neutralizing antibody responses against tier 1A viruses were detected in all participants, with the highest titers being to a subtype C virus, MW965.26. No responses were observed just prior to infection, indicating that vaccine-primed HIV-specific antibodies had waned. Sporadic neutralization activity against tier 2 isolates was observed after 2 to 3 years of HIV infection, but these responses were similar in the vaccinated and placebo groups as well as the unvaccinated controls. Our data suggest that prior vaccination with these immunogens did not alter the antibody responses to HIV-1 infection, nor did it accelerate the development of HIV neutralization breadth.IMPORTANCE There is a wealth of information on HIV-specific vaccine-induced immune responses among HIV-uninfected participants; however, data on immune responses among participants who acquire HIV after vaccination are limited. Here we show that HIV-specific binding antibody responses in individuals with breakthrough HIV infections were not affected by prior vaccination with HIV envelope-containing immunogens. We also found that these vectored vaccines did not prime tier 2 virus-neutralizing antibody responses, which are thought to be required for prevention against HIV acquisition, or accelerate the development of neutralization breadth. Although this study is limited, such studies can provide insights into whether vaccine-elicited antibody responses are boosted by HIV infection to acquire broader neutralizing activity, which may help to identify antigens relevant to the design of more effective vaccines.


Assuntos
Vacinas contra a AIDS/imunologia , Infecções por HIV/prevenção & controle , Produtos do Gene env do Vírus da Imunodeficiência Humana/imunologia , Adulto , Anticorpos Neutralizantes/sangue , Formação de Anticorpos , Ensaio de Imunoadsorção Enzimática , Feminino , Anticorpos Anti-HIV/sangue , Proteína gp41 do Envelope de HIV/imunologia , Infecções por HIV/imunologia , HIV-1 , Humanos , Masculino , Pessoa de Meia-Idade , Testes de Neutralização , Carga Viral , Adulto Jovem
20.
J Infect Dis ; 221(2): 232-237, 2020 01 02.
Artigo em Inglês | MEDLINE | ID: mdl-31504656

RESUMO

Mother-to-child transmission of human immunodeficiency virus (HIV) occurs in the setting of maternal and passively acquired antibodies, providing a unique window into immune correlates of HIV risk. We compared plasma antibody binding to HIV antigens between 51 nontransmitting mother-infant pairs and 21 transmitting mother-infant pairs. Plasma antibody binding to a variety of gp41 ectodomain-containing antigens was associated with increased odds of transmission. Understanding the reasons why gp41 ectodomain-targeting antibodies are associated with transmission risk will be important in determining whether they can directly enhance infection or whether their presence reflects a redirecting of the humoral response away from targeting more protective epitopes.


Assuntos
Proteína gp41 do Envelope de HIV/imunologia , Infecções por HIV/transmissão , HIV-1/imunologia , Transmissão Vertical de Doença Infecciosa , Aleitamento Materno/efeitos adversos , Estudos de Casos e Controles , Epitopos/imunologia , Feminino , Anticorpos Anti-HIV/sangue , Anticorpos Anti-HIV/imunologia , Infecções por HIV/virologia , Humanos , Lactente , Gravidez , Complicações Infecciosas na Gravidez/imunologia
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