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2.
BMC Infect Dis ; 20(1): 68, 2020 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-31964348

RESUMO

BACKGROUND: Cryptococcal meningitis (CCM) is a common and deadly disease among HIV-infected patients. Notable about CCM is its association with the immune reconstitution inflammatory syndrome (IRIS). Though it has been posited a switch from first to second-line antiretroviral therapy (ART) can induce CCM IRIS, a case presentation of CCM IRIS has not been published. CASE PRESENTATION: A 10-year-old, HIV-infected girl who initially presented with severe headache and new-onset seizures, with cerebrospinal fluid that returned antigen, India Ink, and culture positive for Cryptococcus neoformans. Notably, 8 weeks prior to seizures, she had switched from first line to second-line ART (abacavir-lamivudine-efavirenz to zidovudine-lamivudine-lopinavir/ritonavir) due to virologic failure, with a viral load of 224,000 copies/milliliter. At time of seizures and 8 weeks on second-line ART, her viral load had reduced to 262 copies/milliliter. Her hospital course was prolonged, as she had ongoing headaches and developed bilateral cranial nerve VI palsies despite clearance of Cryptococcus from cerebrospinal fluid on antifungal therapy and therapeutic lumbar punctures. However, symptoms stabilized, and she was discharged with oral fluconazole. Cranial nerve palsies resolved 10 weeks post discharge and she has remained disease free. CONCLUSIONS: We describe a case of CCM IRIS in a 10-year-old HIV infected child after changing to second-line ART. This case provides evidence that screening for cryptococcal antigenaemia prior to switch from first-line to second-line ART could be an important measure to prevent cryptococcal disease.


Assuntos
Infecções Oportunistas Relacionadas com a AIDS/tratamento farmacológico , Fármacos Anti-HIV/uso terapêutico , Cryptococcus neoformans/isolamento & purificação , HIV/efeitos dos fármacos , Síndrome Inflamatória da Reconstituição Imune/diagnóstico , Lamivudina/uso terapêutico , Lopinavir/uso terapêutico , Meningite Criptocócica/diagnóstico , Ritonavir/uso terapêutico , Zidovudina/uso terapêutico , Infecções Oportunistas Relacionadas com a AIDS/complicações , Antifúngicos/uso terapêutico , Antígenos de Fungos/sangue , Benzoxazinas/uso terapêutico , Criança , Didesoxinucleosídeos/uso terapêutico , Combinação de Medicamentos , Feminino , Fluconazol/uso terapêutico , HIV/isolamento & purificação , Humanos , Síndrome Inflamatória da Reconstituição Imune/etiologia , Lamivudina/efeitos adversos , Meningite Criptocócica/tratamento farmacológico , Meningite Criptocócica/etiologia , Ritonavir/efeitos adversos , Resultado do Tratamento , Carga Viral , Zidovudina/efeitos adversos
3.
Xenobiotica ; 50(5): 570-579, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-31403353

RESUMO

HIV replication in the brain is unopposed due to reduced antiretroviral drug penetration into the central nervous system (CNS). Prevalence of HIV-associated neurocognitive disorder (HAND) has increased severely in patients living with HIV despite current treatments. The aims of this study were to evaluate the brain bio-distribution of alternative nucleoside reverse transcriptase inhibitors, abacavir, stavudine and didanosine in the CNS and to determine their localization patterns in the brain.Sprague-Dawley rats received 50 mg kg-1 single i.p dose of each drug. Mass spectrometric techniques were then used to investigate the pharmacokinetics and localization patterns of these drugs in the brain using LC-MS/MS and mass spectrometric imaging (MSI), respectively.Abacavir, stavudine and didanosine reached the Brain Cmax with concentration of 831.2, 1300 and 43.37 ngmL-1, respectively. Based on MSI analysis Abacavir and Stavudine were located in brain regions that are strongly implicated in the progression of HAND.Abacavir and Stavudine penetrated into CNS, reaching a Cmax that was above the IC50 for HIV (457.6 and 112.0 ngmL-1, respectively), however, it was noted ddI showed poor entry within the brain, therefore, it is recommended that this drug cannot be considered for treating CNS-HIV.


Assuntos
Encéfalo/metabolismo , Inibidores da Transcriptase Reversa/metabolismo , Animais , Didanosina/metabolismo , Didesoxinucleosídeos/metabolismo , Infecções por HIV , Ratos , Estavudina/metabolismo , Espectrometria de Massas em Tandem
4.
Br J Radiol ; 93(1106): 20180781, 2020 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-31860336

RESUMO

OBJECTIVE: The aim of the study was to assess the feasibility of multitracer positron emission tomography (PET) imaging before and during chemoradiation and to evaluate the predictive value of image-based factors for outcome in locally advanced head and neck cancers treated with chemoradiation. METHODS: In the week prior to the treatment [18F]-2-flu-2-deoxy-D-glucose (FDG), [18F]-3'-flu-3'deoxythymidine (FLT) and [18F]-flumisonidazole (FMISO) imaging was performed. FLT scans were repeated at 14 and 28 Gy and FMISO at 36 Gy. Overall survival, disease-free survival and local control were correlated with subvolume parameters, and with tumour-to-muscle ratio for FMISO. For every tracer, total metabolic tumour volume was calculated. RESULTS: 33 patients were included. No correlation was found between pre-treatment maximum standardised uptake value for FDG, FLT, FMISO and outcomes. Tumour volume measured on initial CT scans and initial FLT volume correlated with disease-free survivall (p = 0.007 and 0.04 respectively). FDG and FLT metabolic tumour volumes correlated significantly with local control (p = 0.005 and 0.02 respectively). In multivariate Cox analysis only individual initial TMRmax correlated with overall survival. CONCLUSION: PET/CT imaging is a promising tool. However, various aspects of image analysis need further clinical validation in larger multicentre study employing uniform imaging protocol and standardisation, especially for hypoxia tracer. ADVANCES IN KNOWLEDGE: Monitoring of biological features of the tumour using multitracer PET modality seems to be a feasible option in daily clinical practice.Evaluation of hypoxic subvolumes is more patient dependent; thus, exploration of individual parameters of hypoxia is needed. tumour-to-muscle ratio seems to be the most promising so far.


Assuntos
Quimiorradioterapia/métodos , Neoplasias de Cabeça e Pescoço/terapia , Idoso , Antineoplásicos/administração & dosagem , Biomarcadores Tumorais/metabolismo , Cisplatino/administração & dosagem , Didesoxinucleosídeos/metabolismo , Intervalo Livre de Doença , Esquema de Medicação , Estudos de Viabilidade , Feminino , Fluordesoxiglucose F18/metabolismo , Neoplasias de Cabeça e Pescoço/diagnóstico por imagem , Neoplasias de Cabeça e Pescoço/mortalidade , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Misonidazol/análogos & derivados , Misonidazol/metabolismo , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons/métodos , Estudos Prospectivos , Radiossensibilizantes/metabolismo , Resultado do Tratamento , Hipóxia Tumoral/efeitos dos fármacos
5.
Infez Med ; 27(4): 410-414, 2019 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-31846991

RESUMO

We investigated the effectiveness and safety of a dual therapy (DT) with lamivudine plus dolutegravir versus a single tablet regimen (STR) with abacavir/lamivudine/dolutegravir. We performed a retrospective analysis in a cohort of virologically suppressed HIV+ patients switching to lamivudine-dolutegravir or abacavir/lamivudine/dolutegravir. We evaluated the incidence of virological failure and treatment discontinuation, as well as their predictors. Non-parametric tests were applied to assess changes in immunological and metabolic parameters. In all, 616 patients were analyzed: 380 began STR and 236 DT. In the STR group three patients experienced VF; in the DT group seven patients experienced VF. No differences in cause of treatment discontinuation were found. The estimated probability of continuing therapy at 48 weeks were 88.5 % in DT and 90.3% in STR, without a statistically significant difference (Log-rank 0.338). Regarding the metabolic profile, in the STR group there was a reduction in LDL cholesterol levels at week 48 (p=0.008), whereas in the lamivudine group there was a significant reduction in total cholesterol level at week 48 (p=0.044). Regarding the renal function, in both groups we registered a reduction in estimated glomerular filtration rate (eGFR), with a median reduction of 8.4 ml/min in the STR group (p<0.001) and 10.2 mL/min in DT (p<0.001). We found a difference in strategy option: in a context of side effect and comorbidities, dual therapy strategy was preferred. Conversely, simplification and compliance improvement more frequently translated into a DTG-STR strategy.


Assuntos
Fármacos Anti-HIV/administração & dosagem , Didesoxinucleosídeos/administração & dosagem , Infecções por HIV/tratamento farmacológico , Compostos Heterocíclicos com 3 Anéis/administração & dosagem , Lamivudina/administração & dosagem , Adulto , Estudos de Coortes , Combinação de Medicamentos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Comprimidos , Resultado do Tratamento
6.
Niger Postgrad Med J ; 26(4): 195-198, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31621657

RESUMO

Background: The presence of human leukocyte antigen (HLA) B*57:01 allele predicts hypersensitivity reaction (HSR) to abacavir (ABC), a nucleoside reverse-transcriptase inhibitor used for human immunodeficiency virus (HIV) treatment. However, the prevalence of this allele amongst Nigerians with HIV is yet to be established. We aimed to determine the prevalence of HLA-B*57:01 allele amongst Nigerians with HIV infection. Methods: We conducted a multicentre cross-sectional epidemiologic survey. Between April 2016 and April 2017, patients were enrolled across five HIV treatment facilities in Nigeria. Participants' demographic information and their history of ABC exposure were obtained, and venous blood was obtained for HLA typing. Results: One thousand five hundred and four (1504) adults were enrolled, with a mean age of 44.6 ± 10.7 years, 1078 (71.7%) were female. 1463 (97.3%) were on antiretroviral therapy. ABC use was reported by 12 (0.8%) participants and none reported HSR. Of 1500 blood samples that were processed, 1458 (97.2%) were successfully typed. Of these, 132 (9.1%) were HLA-B*57 positive using non-specific low-resolution HLA-B*5701 primer mix. On further analysis, none of the 132 samples (0%) had the HLA-B*5701 allele. Conclusion: HLA-B*5701allele is rare amongst Nigerians.


Assuntos
Fármacos Anti-HIV/uso terapêutico , Didesoxinucleosídeos/uso terapêutico , Hipersensibilidade a Drogas/imunologia , Infecções por HIV/tratamento farmacológico , Infecções por HIV/imunologia , Antígenos HLA-B/genética , Inibidores da Transcriptase Reversa/uso terapêutico , Adulto , Grupo com Ancestrais do Continente Africano/genética , Idoso , Estudos Transversais , Didesoxinucleosídeos/efeitos adversos , Hipersensibilidade a Drogas/epidemiologia , Hipersensibilidade a Drogas/genética , Feminino , Infecções por HIV/epidemiologia , Infecções por HIV/genética , Antígenos HLA-B/sangue , Antígenos HLA-B/imunologia , Humanos , Masculino , Pessoa de Meia-Idade , Nigéria/epidemiologia , Prevalência , Inibidores da Transcriptase Reversa/efeitos adversos
7.
Top Antivir Med ; 27(3): 123-127, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31634859

RESUMO

Antiretroviral therapy (ART) should be started as soon as possible after HIV diagnosis. Recommended starting ART regimens in patients with any baseline viral load include ictegravir plus tenofovir alafenamide (TAF)/emtricitabine (FTC), dolutegravir (DTG) plus abacavir/lamivudine, DTG plus TAF (or TDF)/FTC, or DTG plus 3TC. Initial laboratory evaluation includes CD4+ cell count, plasma HIV-1 RNA, and testing for HIV reverse transcriptase and protease resistance mutations. ART regimens do not need to be altered for virologic blips due to release of virus from chronically latently infected cells in patients otherwise exhibiting viral suppression. Patients with continuously undetectable viral load on ART pose virtually no risk of transmitting infection through sexual contact. This article is based on a case-based presentation by Michael S. Saag, MD, at the 2018 Clinical Conference at the National Ryan White Conference on HIV Care & Treatment in December 2018 and intended for clinicians who are new to HIV disease management.


Assuntos
Fármacos Anti-HIV/uso terapêutico , Antirretrovirais/uso terapêutico , Infecções por HIV/tratamento farmacológico , HIV-1/efeitos dos fármacos , Adenina/análogos & derivados , Adenina/uso terapêutico , Adulto , Terapia Antirretroviral de Alta Atividade/métodos , Contagem de Linfócito CD4 , Didesoxinucleosídeos/uso terapêutico , Combinação de Medicamentos , Quimioterapia Combinada , Emtricitabina/uso terapêutico , Feminino , Infecções por HIV/transmissão , Transcriptase Reversa do HIV/efeitos dos fármacos , HIV-1/genética , Compostos Heterocíclicos com 3 Anéis/uso terapêutico , Humanos , Inibidores de Integrase/uso terapêutico , Lamivudina/uso terapêutico , Estágios do Ciclo de Vida/efeitos dos fármacos , Masculino , Pessoa de Meia-Idade , Mutação , RNA Viral/sangue , Tenofovir/uso terapêutico , Carga Viral
8.
Ultrastruct Pathol ; 43(4-5): 220-223, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31578116

RESUMO

Combined antiretroviral therapy (cART) consisting of two nucleoside reverse transcriptase inhibitors (NRTIs) and one non-nucleoside reverse transcriptase inhibitor (NNRTI), such as efavirenz, is still the first-line treatment in resource-limited settings. However, efavirenz has shown strong prominence of disadvantages with variance in plasma concentration and central nervous side effects. Our study presents HIV infected, drug naïve, female patient with relatively low BMI, CYP2B6 516G>T (rs3745274) genotype with high efavirenz plasma concentration. In this case report, the patient was admitted at the hospital 6 months after cART initiation with drug-induced severe hepatotoxicity. Furthermore, pathophysiological findings proved confluent parenchymal necrosis after aspiration liver biopsy, with mild to moderate inflammation in portal tracts with focal interface hepatitis. All other possible causes were excluded. Thus, we conclude that efavirenz has a potential harmful effect in patients with low BMI, specific genotyping and interindividual pharmacokinetics affecting high plasma concentration.


Assuntos
Benzoxazinas/efeitos adversos , Índice de Massa Corporal , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Infecções por HIV/tratamento farmacológico , Inibidores da Transcriptase Reversa/efeitos adversos , Adulto , Doença Hepática Induzida por Substâncias e Drogas/patologia , Didesoxinucleosídeos/uso terapêutico , Quimioterapia Combinada , Feminino , Humanos , Lamivudina/uso terapêutico
9.
Clin Nucl Med ; 44(11): e624-e626, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31584492

RESUMO

F-Fluorothymidine-positron emission tomography with CT fusion ([F]FLT-PET/CT) offers a unique and non-invasive method for three-dimensional localization and quantification of functional bone marrow. [F]FLT-PET/CT has potential application in radiotherapy planning when risk of marrow toxicity is a significant clinical concern. In this patient with chemo-refractory, transformed lymphoma and treatment-induced cytopenias, [F]FLT-PET/CT was a novel and useful adjunct to (1) image the distribution of functional bone marrow reserve, (2) guide "marrow-sparing" radiotherapy planning, and (3) quantify the effects of radiotherapy-induced bone marrow suppression both in-field and out-of-field.


Assuntos
Células Sanguíneas/efeitos da radiação , Medula Óssea/fisiopatologia , Medula Óssea/efeitos da radiação , Didesoxinucleosídeos , Tratamentos com Preservação do Órgão , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons , Idoso , Células Sanguíneas/patologia , Medula Óssea/diagnóstico por imagem , Contagem de Células , Feminino , Humanos , Linfoma/radioterapia
10.
PLoS One ; 14(9): e0222650, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31560700

RESUMO

BACKGROUND: Very few data are available on treatment in HIV Late presenter population that still represents a clinical challenge. METHODS: Prospective, multicenter, randomized open-label, 2 arm, phase-3 trial comparing the 48-week virological response of two different regimens: abacavir/lamivudine + darunavir/r vs abacavir/lamivudine + raltegravir in antiretroviral naive with CD4+ counts < 200/mm3 and a viral load (VL)<500,000 copies/mL. The primary Endpoint was the proportion of patients with undetectable viremia (VL<50 copies/mL) after 48 weeks. The planned sample size for this trial was 350 patients. RESULTS: In 3 years, 53 patients were screened and 46 enrolled: 22 randomized to raltegravir and 24 to darunavir/r; 7 patients were excluded, 4 because of a VL >500,000 copies/mL and 3 for HLAB5701 positivity. The snapshot analysis at 48 weeks showed a virologic success of 77.3% in raltegravir and 66.7% in darunavir/r. Time to starting treatment was 34.5 days in raltegravir and 53 days in darunavir/r. At the as treated analysis, the median CD4 counts at 48 weeks was 297 cells/µL in raltegravir and 239 cells/µL in darunavir/r. No difference in total cholesterol, while triglycerides were higher in the darunavir/r arm. No statistical analyses were performed due to the low number of patients enrolled. CONCLUSIONS: Late presenter patients are frequent but very difficult to enroll in clinical trials, especially in western countries. These regimens and the conditions of many patients could not allow the test and treat strategy. The rate of virologic success was higher than 65% in both arms with a median CD4 cell count >200/µL at week 48. TRIAL REGISTRATION: EUDRACT number: 2011-005973-21.


Assuntos
Fármacos Anti-HIV/uso terapêutico , Darunavir/uso terapêutico , Didesoxinucleosídeos/uso terapêutico , Infecções por HIV/tratamento farmacológico , Lamivudina/uso terapêutico , Raltegravir Potássico/uso terapêutico , Ritonavir/uso terapêutico , Adulto , Fármacos Anti-HIV/administração & dosagem , Contagem de Linfócito CD4 , Darunavir/administração & dosagem , Diagnóstico Tardio , Didesoxinucleosídeos/administração & dosagem , Feminino , Humanos , Lamivudina/administração & dosagem , Masculino , Pessoa de Meia-Idade , Raltegravir Potássico/administração & dosagem , Ritonavir/administração & dosagem
11.
Infect Dis (Lond) ; 51(11-12): 838-846, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31556765

RESUMO

Background: Despite suppressive antiretroviral therapy (ART), many HIV-infected individuals have low-level persistent immune activation in the central nervous system (CNS). There have been concerns regarding the CNS efficacy of tenofovir alafenamide fumarate (TAF) because of its low cerebrospinal fluid (CSF) concentrations and because it is a substrate of the active efflux transporter P-glycoprotein. Our aim was to investigate whether switching from emtricitabine (FTC)/tenofovir disoproxil fumarate (TDF) or abacavir (ABC)/lamivudine (3TC) to FTC/TAF would lead to changes in residual intrathecal immune activation, viral load, or neurocognitive function. Methods: Twenty HIV-1-infected neuro-asymptomatic adults (11 on ABC/3TC and 9 on FTC/TDF) were included in this prospective study. At baseline, all participants changed their nucleoside analogues to FTC/TAF without any other changes in their ART regimen. We performed lumbar punctures, venipunctures, and neurocognitive testing at baseline and after three and 12 months. Results: During follow-up, there were no significant changes in CSF or plasma HIV RNA, CSF neopterin, CSF ß2-microglobulin, IgG index, albumin ratio, CSF NFL, or neurocognitive function in assessed by Cogstate in any of the groups. Conclusion: This small pilot study indicates that switching to FTC/TAF from ABC/3TC or FTC/TDF has neither a positive, nor a negative effect on the HIV infection in the CNS.


Assuntos
Fármacos Anti-HIV/uso terapêutico , Sistema Nervoso Central/efeitos dos fármacos , Sistema Nervoso Central/virologia , Substituição de Medicamentos , Infecções por HIV/tratamento farmacológico , Adenina/análogos & derivados , Adenina/uso terapêutico , Adulto , Idoso , Didesoxinucleosídeos/uso terapêutico , Combinação de Medicamentos , Emtricitabina/uso terapêutico , Feminino , Humanos , Lamivudina/uso terapêutico , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Estudos Prospectivos , Tenofovir/uso terapêutico , Carga Viral
13.
Biotechnol Appl Biochem ; 66(6): 977-989, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31486095

RESUMO

Newcastle disease virus (NDV) causes huge economic loss to the poultry industry due to high mortality and morbidity. The present study aimed to assess the protective role of novel phosphorylated analogue ABC-1 in vivo in NDV-infected chickens through the inhibition of fusion protein. Both NDV-induced oxidative damage and protective role of novel phosphorylated ABC-1 were evaluated in vital organs such as the liver and lung of chickens. Enzyme linked immunosorbent assay (ELISA) results showed that protein oxidation and nitration levels were significantly raised in NDV-infected tissues compared to healthy controls, whereas these levels were reduced significantly (P < 0.05) in birds treated with phosphorylated compounds compared to the NDV-infected group alone. Additional investigation with double immunofluorescence showed that the large amount of immuno colocalization and Western blot analysis also confirmed this observation through its band pattern in NDV-infected birds compared to healthy birds, whereas these alterations were reduced in treatment with novel phosphorylated ABC-1. The expression of fusion glycoprotein was studied by immuno colocalization, PCR, and flow cytometry, and results demonstrated that the novel phosphorylated analogues reduced the expression of fusion glycoprotein. These results put forth that novel phosphorylated ABC-1 protects chickens from NDV-induced pathogenesis, protein oxidation/nitration, and exerts potent antiviral activity.


Assuntos
Fármacos Anti-HIV/farmacologia , Didesoxinucleosídeos/farmacologia , Vírus da Doença de Newcastle/efeitos dos fármacos , Animais , Galinhas , Testes de Sensibilidade Microbiana , Fosforilação
14.
Indian Pediatr ; 56(8): 685-686, 2019 08 15.
Artigo em Inglês | MEDLINE | ID: mdl-31477651

RESUMO

We studied 48 children receiving abacavir-based HAART regimen, over a period of one-year for side effects and failure rates. None of the children developed hypersensitivity reaction. The CD4 count significantly improved from the time of enrolment till 12 months of therapy while the failure rate was 14.5%.


Assuntos
Fármacos Anti-HIV/uso terapêutico , Didesoxinucleosídeos/uso terapêutico , Infecções por HIV/tratamento farmacológico , Adolescente , Terapia Antirretroviral de Alta Atividade , Criança , Pré-Escolar , Quimioterapia Combinada , Feminino , Humanos , Lactente , Masculino , Resultado do Tratamento
15.
Sensors (Basel) ; 19(16)2019 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-31416185

RESUMO

Pre-treatment screening of individuals for human leukocyte antigens (HLA) HLA-B*57:01 is recommended for the prevention of life-threatening hypersensitivity reactions to abacavir, a drug widely prescribed for HIV treatment. However, the implementation of screening in clinical practice is hindered by the slow turnaround time and high cost of conventional HLA genotyping methods. We have developed a biosensor platform using interdigitated electrode (IDE) functionalized with a monoclonal antibody to detect cells expressing HLA-B*57:01. This platform was evaluated using cell lines and peripheral blood mononuclear cells expressing different HLA-B alleles. The functionalized IDE sensor was able to specifically capture HLA-B*57:01 cells, resulting in a significant change in the impedance magnitude in 20 min. This IDE platform has the potential to be further developed to enable point-of-care HLA-B*57:01 screening.


Assuntos
Técnicas Biossensoriais/métodos , Didesoxinucleosídeos/efeitos adversos , Hipersensibilidade a Drogas/prevenção & controle , Antígenos HLA-B/análise , Leucócitos Mononucleares/metabolismo , Alelos , Anticorpos Imobilizados/química , Anticorpos Imobilizados/imunologia , Anticorpos Monoclonais/química , Anticorpos Monoclonais/imunologia , Didesoxinucleosídeos/uso terapêutico , Hipersensibilidade a Drogas/etiologia , Técnicas Eletroquímicas , Eletrodos , Infecções por HIV/tratamento farmacológico , Antígenos HLA-B/genética , Antígenos HLA-B/imunologia , Humanos
16.
Braz J Infect Dis ; 23(4): 268-270, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31374183

RESUMO

Abacavir can cause a multi-systemic hypersensitivity reaction (HSR) in 5-8% of the patients, which is related to HLA-B*57-01 allele. In Brazil, the HLA-B*57-01 screening test became available only in March 2018, several years after abacavir was in use. In this retrospective study we reviewed medical charts of all patients receiving an abacavir-containing regimen to evaluate the frequency of HSR in patients followed at a referral center in Salvador, Brazil. A total of 192 patients who received abacavir were identified, most male (67.1%), black or racially mixed (77.8%), and having diagnosis of a previous AIDS defining conditions (83.7%). Only one patient developed HSR (incidence: 0.52%). The main reasons for abacavir-containing antiretroviral therapy discontinuation were virological failure (28%), adverse effects to other components of the regimen (25%), and simplification of therapy (16%). The low incidence of HSR to abacavir does not support the use of HLA-B*57-01 screening test, in Salvador, Brazil.


Assuntos
Fármacos Anti-HIV/efeitos adversos , Didesoxinucleosídeos/efeitos adversos , Hipersensibilidade a Drogas/epidemiologia , Hipersensibilidade a Drogas/etiologia , Infecções por HIV/tratamento farmacológico , Adulto , Brasil/epidemiologia , Feminino , Humanos , Incidência , Masculino , Estudos Retrospectivos
17.
J Int AIDS Soc ; 22(8): e25386, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31441211

RESUMO

INTRODUCTION: Adolescents with perinatally acquired HIV (PHIV) are at risk of chronic disease due to long-standing immune suppression, HIV disease and antiretroviral therapy (ART) exposure. However, there are few data on multisystem disease in this population. We investigated the overlapping burden of neurocognitive, cardiovascular, respiratory and/or renal impairment among PHIV positive (PHIV+) adolescents. METHODS: In this cross-sectional analysis, participants aged 9 to 14 years on ART for >6 months were recruited from seven sites across Cape Town from July 2013 through March 2015, together with age-matched HIV-negative (HIV-) adolescents. Impairment at enrolment was assessed across neurocognitive functioning (using the youth-International HIV Dementia Scale); cardiac function (echocardiogram abnormality); respiratory function (abnormal spirometry) and renal function (abnormal glomerular filtration rate). RESULTS AND DISCUSSION: Overall, 384 PHIV+ and 95 HIV- adolescents were included (mean age, 11.9 years; 49% female). Median age of ART initiation was 4.2 years (IQR: 1.7 to 7.6) and median CD4 count was 709 (IQR: 556 to 944) with 302 (79%) of PHIV+ adolescents virologically suppressed. Abacavir and Zidovudine were the most commonly used nucleoside reverse transcriptase inhibitors (NRTIs) with 60% of adolescents on non-nucleoside reverse transcriptase inhibitors (NNRTI) and 38% on a protease inhibitor (PI). Among PHIV+ adolescents, 167 (43.5%) had single system impairment only, 110 (28.6%) had two systems involved, and 39 (10.2%) had three or four systems involved. PHIV+ participants had more 2-system and 3-system impairment than HIV-, 110 (28.6%) versus 17 (17.9%), p = 0.03 and 39 (10.2%) versus 3 (4.3%), p = 0.03. PHIV+ participants who had failed a year of school (73.8% vs. 46.4%, p = 0.00) and with a viral load >1000 copies/mL at enrolment (16.8% vs. 8.1%, p = 0.03) were more likely to have dual or multisystem impairment. Of those with cardiac impairment, 86.7% had an additional system impaired. Similarly, in those with neurocognitive impairment, almost 60% had additional systems impaired and of those with respiratory impairment, 74% had additional systems impaired. CONCLUSIONS: Despite relatively early ART initiation, there is a substantial burden of multisystem chronic impairment among PHIV+ adolescents. This phenomenon needs to be further explored as this population ages and begins to engage in adult lifestyle factors that may compound these impairments.


Assuntos
Antirretrovirais/uso terapêutico , Doenças Cardiovasculares/etiologia , Transtornos Cognitivos/etiologia , Infecções por HIV/complicações , Nefropatias/etiologia , Doenças Respiratórias/etiologia , Adolescente , Contagem de Linfócito CD4 , Criança , Estudos Transversais , Didesoxinucleosídeos/uso terapêutico , Feminino , Infecções por HIV/congênito , Infecções por HIV/tratamento farmacológico , Humanos , Transmissão Vertical de Doença Infecciosa , Masculino , África do Sul , Carga Viral , Zidovudina/uso terapêutico
18.
Nucl Med Commun ; 40(10): 1066-1071, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31469809

RESUMO

OBJECTIVE: 3'-Deoxy-3'-[18F] fluorothymidine (18F-FLT) is a marker of cell proliferation and displays a high tumor-to-background ratio in brain tumor lesions. We determined whether combining 18F-FLT PET and MRI study improves the detection of tumoral tissue compared to MRI alone and whether 18F-FLT uptake has a prognostic value by studying its association with histopathological features. METHODS: Thirteen patients with a supratentorial malignant glioma were recruited and scheduled for surgery. The tumor volume was defined in all patients on both 18F-FLT PET and MRI images. The images were coregistered and uploaded onto a neuronavigation system. During surgery, an average of 11 biopsies per patient were taken in regions of the brain that were positive to one or both imaging modalities, as well as from control peritumoral regions. The standardized uptake values (SUVs) of each biopsy region were correlated to histopathological data (i.e., proliferation index and number of mitoses) and the SUV values of high and low-grade samples were compared. RESULTS: Out of a total of 149 biopsies, 109 contained tumoral tissue at histopathological analysis. The positive predictive value was 93.1% for MRI alone and 78.3% for MRI and PET combined. In addition, 40% of the biopsy samples taken from areas of the brain that were negative at both PET and MRI had evidence of malignancy at pathology. The SUV values were not significantly correlated to either the proliferation index or the number of mitoses, and could not differentiate between high- and low-grade samples. CONCLUSION: In patients with newly diagnosed glioma, a combination of MRI and 18F-FLT-PET detects additional tumoral tissue and this may lead to a more complete surgical resection. Also, the addition of a negative PET to a negative MRI increases the negative predictive value. However, 18F-FLT still underestimated the margins of the lesion and did not correlate with histopathological features.


Assuntos
Didesoxinucleosídeos , Glioma/diagnóstico por imagem , Glioma/patologia , Imagem por Ressonância Magnética , Carga Tumoral , Adulto , Idoso , Transporte Biológico , Proliferação de Células , Didesoxinucleosídeos/metabolismo , Feminino , Glioma/metabolismo , Humanos , Processamento de Imagem Assistida por Computador , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Valor Preditivo dos Testes , Prognóstico , Sensibilidade e Especificidade
19.
J Int AIDS Soc ; 22(7): e25324, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31294931

RESUMO

INTRODUCTION: Dolutegravir (DTG) is recommended as part of first-line antiretroviral therapy (ART) for people living with HIV(PLHIV). We sought to determine the rate of adverse events (AEs) and discontinuations among Thais treated during acute HIV infection (AHI) and switched to DTG-based regimens. METHODS: Thai participants in the SEARCH010/RV254 cohort who initiated ART during AHI and switched to DTG for at least 48 weeks were prospectively observed and included in the analysis. Rates and characteristics of DTG-related AEs and discontinuations were described. RESULTS: A total of 313 Thai participants were included in the analysis. The median age was 29 years, 96% were male, 64% had a Bachelor's degree or higher and 16% had a body mass index (BMI) <18.5 kg/m2 . Participants were on ART for a median of 124 weeks before switching to DTG. The median (IQR) body weight increased from 63 (56 to 70) kg before to 65 (58 to 73) kg (p < 0.0001) after 48 weeks of DTG. Forty-nine (16%) developed DTG-related AEs, corresponding to an incidence of 16.6 per 100 person-years. Neuropsychiatric symptoms were most frequently encountered (n = 25, 8%), followed by laboratory abnormalities (n = 16, 5%). Six (2%) discontinued DTG, corresponding to an incidence of 2.4 per 100 person-years. All discontinuations were due to increased liver enzymes in the presence of hepatitis C virus coinfection. In the multivariate analysis, incident hepatitis C virus infection was the only risk factor for discontinuing DTG (hazard ratio 59.4, 95% CI 8.5 to 297.9, p < 0.0001). Neither low BMI nor concurrent abacavir therapy was associated with discontinuation. CONCLUSIONS: DTG was well tolerated with few discontinuations in this cohort of young men. Incident hepatitis C virus infection was a driver of liver-related AEs leading to discontinuations. In populations at risk, regular testing for hepatitis C virus during ART is recommended to anticipate possible AEs, guide management and improve safety.


Assuntos
Fármacos Anti-HIV/uso terapêutico , Infecções por HIV/tratamento farmacológico , Infecções por HIV/epidemiologia , Compostos Heterocíclicos com 3 Anéis/uso terapêutico , Adulto , Fármacos Anti-HIV/administração & dosagem , Fármacos Anti-HIV/efeitos adversos , Estudos de Coortes , Didesoxinucleosídeos/administração & dosagem , Didesoxinucleosídeos/uso terapêutico , Feminino , HIV-1 , Hepatite C/tratamento farmacológico , Compostos Heterocíclicos com 3 Anéis/administração & dosagem , Compostos Heterocíclicos com 3 Anéis/efeitos adversos , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Tailândia/epidemiologia , Adulto Jovem
20.
Clin Exp Nephrol ; 23(11): 1272-1279, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31327092

RESUMO

BACKGROUND: Chronic kidney disease (CKD) has become one of the most frequent non-infectious comorbidities in the aging HIV-infected population on long-standing combination antiretroviral therapy (cART). METHODS: We conducted a retrospective, cross-sectional study including HIV-infected adult patients attending our HIV outpatient clinic during the years 2017 and 2018 to assess prevalence and associated risk factors of CKD. Estimated glomerular filtration rate (eGFR) was measured by Chronic Kidney Disease-Epidemiology Collaboration (CKD-EPI) equation. CKD was diagnosed and classified according to the National Kidney Foundation guidelines. Logistic regression was employed to identify factors associated with CKD. RESULTS: We enrolled 2339 HIV-infected patients (91% were Caucasian) with a mean age of 45.3 years and a mean current CD4 lymphocyte count of 531 cells/mm3. CKD was diagnosed in 311 subjects (13.3%). Overall, 294 (12.6%) patients had albuminuria, 108 (4.6%) had eGFR < 60 mL/min/1.73 m2, and 78 (3.3%) had albuminuria plus eGFR < 60 mL/min/1.73 m2. Stages 4-5 of CKD were documented in 23 (1%) cases. Age greater than 50 years, male gender, hypertension, diabetes mellitus, high triglycerides, nadir CD4 cell count < 200 cells/mm3, current use of tenofovir disoproxyl fumarate (TDF) and of TDF plus a ritonavir-boosted protease inhibitors were independently associated with CKD, while current use of abacavir plus one integrase inhibitor was associated with a reduced risk of CKD. CONCLUSION: There is a significant prevalence of CKD among HIV-infected persons in association with both traditional and HIV-specific risk factors, requiring a careful periodic monitoring of renal function in these patients.


Assuntos
Fármacos Anti-HIV/uso terapêutico , Infecções por HIV/tratamento farmacológico , HIV-1 , Insuficiência Renal Crônica/epidemiologia , Adulto , Fatores Etários , Albuminúria/etiologia , Contagem de Linfócito CD4 , Estudos Transversais , Diabetes Mellitus/epidemiologia , Didesoxinucleosídeos/uso terapêutico , Quimioterapia Combinada , Feminino , Taxa de Filtração Glomerular , Infecções por HIV/virologia , Humanos , Hipertensão/epidemiologia , Hipertrigliceridemia/epidemiologia , Inibidores de Integrase/uso terapêutico , Itália/epidemiologia , Masculino , Pessoa de Meia-Idade , Prevalência , Fatores de Proteção , Insuficiência Renal Crônica/fisiopatologia , Estudos Retrospectivos , Fatores de Risco , Ritonavir/uso terapêutico , Fatores Sexuais , Tenofovir/uso terapêutico
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