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1.
AIDS Res Ther ; 17(1): 46, 2020 07 23.
Artigo em Inglês | MEDLINE | ID: mdl-32703286

RESUMO

BACKGROUND: The COVID-19 has been a severe pandemic all around the world. Nowadays the patient with co-infection of HIV and SARS-CoV-2 was rarely reported. Here we reported a special case with HIV and SARS-CoV-2 co-infection, which showed a prolonged viral shedding duration. CASE PRESENTATION: The patient was infected with HIV 8 years ago through sexual transmission and had the normal CD4+T cell count. She was found SARS-CoV-2 positive using real-time Polymerase Chain Reaction (RT-PCR) during the epidemic. Most importantly, the patient had a prolonged viral shedding duration of SARS-CoV-2 about 28 days. CONCLUSION: The viral shedding duration may be prolonged in people living with HIV. The 14 days isolation strategy might not be long enough for them. The isolation or discharge of these patients needs further confirmation for preventing epidemics.


Assuntos
Antirretrovirais/uso terapêutico , Betacoronavirus/isolamento & purificação , Infecções por Coronavirus/diagnóstico , Infecções por HIV/complicações , Pneumonia Viral/diagnóstico , Eliminação de Partículas Virais , Benzoxazinas/administração & dosagem , Betacoronavirus/genética , Betacoronavirus/imunologia , Proteína C-Reativa/análise , Contagem de Linfócito CD4 , Calafrios , Infecções por Coronavirus/diagnóstico por imagem , Infecções por Coronavirus/tratamento farmacológico , Fadiga , Feminino , Febre , HIV/crescimento & desenvolvimento , Infecções por HIV/tratamento farmacológico , Infecções por HIV/imunologia , Humanos , Hospedeiro Imunocomprometido , Imunoglobulina M/sangue , Lamivudina/administração & dosagem , Pessoa de Meia-Idade , Pandemias , Faringite , Pneumonia Viral/diagnóstico por imagem , Pneumonia Viral/tratamento farmacológico , Reação em Cadeia da Polimerase em Tempo Real , Escarro/virologia , Fatores de Tempo , Tomografia Computadorizada por Raios X , Eliminação de Partículas Virais/imunologia , Zidovudina/administração & dosagem
2.
Medicine (Baltimore) ; 99(22): e20487, 2020 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-32481459

RESUMO

Simultaneous therapeutic drug monitoring (TDM) of combination antiretroviral therapy (cART) is critical during pregnancy in order to improve clinical follow-up, monitor viral load, and patient adherence to treatment.A modified simple and fast ultra-high performance liquid chromatography coupled with tandem mass spectrometry and electrospray ionization (UPLC-ESI-MS/MS) method was developed and validated according to national and international guidelines for the simultaneous determination of lamivudine (LMV), zidovudine (ZDV), lopinavir (LPV), and ritonavir (RTV) concentrations in 100-µL plasma sample of Human Immunodeficiency Virus (HIV)-positive pregnant women. Protein precipitation using 0.1% formic acid in cold acetonitrile was used for sample preparation. The chromatographic separation was achieved with a run-time of 3.0 minutes and 3-µL injection on an ethylene bridged hybrid C18 column (2.1 µm × 50 mm, 1.7 µm), under gradient conditions using acetonitrile and formic acid (0.1%).The chromatographic method was used to analyze 10 plasma samples from 8 HIV pregnant women as a clinical patient routinely follow-up by applying TDM criteria.The protonated precursor/product ion transitions for LMV (230.18/112.08), ZDV (268.22/127.10), LPV (629.55/447.35), and RTV (721.50/296.20) were recorded in multiple-reaction-monitoring (MRM) mode. The calibration curve was linear in the range of 50-3,000, 75-4,500, 250-15,000, and 25-1,500-ng/mL for LMV, ZDV, LPV, and RTV, respectively. The range of accuracy was 97.2% to 100.1% and precision 3.4% to 12.7%. The method showed specificity and matrix effect values of < 15%. Minimum absolute recovery percentages (%CV) were 90.5 (5.4), 90.8 (5.0), 95.4 (3.5), and 93.7 (6.9), for LMV, ZDV, LPV, and RTV, respectively. Drug concentrations in patient samples had high inter-individual variability with %CV of 91.98%, 77.54%, 53.80%, and 92.16% for ZDV, LMV, LPV, and RTV, respectively. Two of the 8 patients showed no adherence due to the absence of Protease Inhibitors (PIs) levels in plasma.This technique demonstrated to be effective in therapeutic drug monitoring and is intended to be used in population pharmacokinetics specifically for HIV-positive pregnant women.


Assuntos
Fármacos Anti-HIV/sangue , Monitoramento de Medicamentos , Soropositividade para HIV/tratamento farmacológico , Lamivudina/sangue , Lopinavir/sangue , Ritonavir/sangue , Zidovudina/sangue , Adulto , Cromatografia Líquida de Alta Pressão , Feminino , Humanos , Segurança do Paciente , Gravidez , Espectrometria de Massas em Tandem , Carga Viral
4.
PLoS One ; 15(4): e0232104, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32324800

RESUMO

BACKGROUND: While the scale-up of HIV services has improved national health management information systems (HMIS), there remain challenges in using routine data to guide the introduction of optimized antiretroviral (ARV) drugs. METHODS: Building on the recent enhancements to the HMIS in Kenya and coinciding with the introduction of a new ARV regimen, tenofovir+lamivudine+dolutegravir (TLD), we developed and implemented an enhanced data system (EDS) to improve availability of safety and efficacy data among people living with HIV (PLHIV) in Kenya. Using data from one health facility, we showcase how the EDS can be used to monitor ARV transition and identify missed opportunities to transition eligible patients to optimized regimes. RESULTS: The EDS was designed to create a comprehensive PLHIV database by triangulating patient-level data from the EMR, the pharmacy ARV dispensing tool (ADT) and HIV viral load (VL) databases. On a monthly basis, the database is de-identified and uploaded into a national data warehouse, with interactive dashboards. Using the EDS, we determined that of the 5,500 PLHIV ≥15 years on first-line ART at one facility, 4,233 (77%) had transitioned to optimized ARVs. Of the 1,267 still on legacy regimens, 459 (36%) were determined to be eligible and prioritized to switch. CONCLUSIONS: This project illustrates how enhancements to the national HMIS can facilitate the use of routine patient-level data to monitor the transition to new ARVs and inform the national HIV response.


Assuntos
Fármacos Anti-HIV/uso terapêutico , Sistemas de Dados , Infecções por HIV/tratamento farmacológico , Fármacos Anti-HIV/farmacologia , Sistemas de Gerenciamento de Base de Dados , Monitoramento de Medicamentos , Infecções por HIV/virologia , Compostos Heterocíclicos com 3 Anéis/uso terapêutico , Humanos , Quênia , Lamivudina/uso terapêutico , Tenofovir/uso terapêutico , Resultado do Tratamento , Carga Viral/métodos
5.
BMC Infect Dis ; 20(1): 230, 2020 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-32188424

RESUMO

BACKGROUND: Hepatitis B virus (HBV) infection is a major public health problem worldwide. More than 2 billion people have been exposed to HBV, and about 257 million individuals are chronic carriers of HBV. HBV reactivation has been increasingly reported in HBV carriers who have undergone immunosuppression or chemotherapy, resulting in mortality. Treatment of hypothalamic/pituitary tumors in HBV carriers requires extensive care to avoid HBV reactivation as steroid therapy is required after surgery for hypothalamic/pituitary tumors. CASE PRESENTATION: This retrospective review identified 5 patients, who were HBV carriers positive for hepatitis B surface antigen among 1352 patients with surgically treated hypothalamic/pituitary tumor in Kohnan Hospital between February 2007 and April 2017. Transsphenoidal surgery was performed with particular attention to prevent damage to the pituitary gland, with delicate manipulation to minimize postoperative steroid coverage. All patients received nucleot(s)ide analogue to control HBV-DNA levels before the surgery. As a result, all patients had a good clinical course. Blood examinations found a transient increase of liver enzymes and HBV-DNA levels in all patients, which started to decrease within 2 weeks after surgery. No specific treatment other than nucleot(s)ide analogues was needed to maintain liver function, and all patients returned to their previous activities including reinstatement. CONCLUSION: Initiation of nucleot(s)ide analogues administration prior to the surgery for hypothalamic/pituitary tumors can be an effective strategy for preventing reactivation in HBV carriers. Appropriate screening of the patient's HBV phase, optimal timing of nucleot(s)ide analogues -administration, and administration period of nucleot(s)ide analogues need to be established.


Assuntos
Antivirais/uso terapêutico , Hepatite B/tratamento farmacológico , Neoplasias Hipotalâmicas/cirurgia , Neoplasias Hipofisárias/cirurgia , Idoso , DNA Viral/sangue , Feminino , Guanina/análogos & derivados , Guanina/uso terapêutico , Hepatite B/virologia , Antígenos de Superfície da Hepatite B/sangue , Vírus da Hepatite B/patogenicidade , Vírus da Hepatite B/fisiologia , Humanos , Neoplasias Hipotalâmicas/virologia , Imunossupressão , Lamivudina/uso terapêutico , Masculino , Pessoa de Meia-Idade , Neoplasias Hipofisárias/virologia , Estudos Retrospectivos , Esteroides/uso terapêutico , Ativação Viral/efeitos dos fármacos
6.
Sud Med Ekspert ; 63(1): 42-46, 2020.
Artigo em Russo | MEDLINE | ID: mdl-32040087

RESUMO

The purpose of the study is to develop a method for detecting, isolating and quantifying lamivudine in biological substances. Lamivudine was isolated by liquid-liquid and solid phase extraction. The conditions for isolating lamivudine (extractant, pH of the medium, electrolyte, time and frequency of extraction) from aqueous solutions were selected and methods were developed for isolating it from biological substances, including urine, saliva and liver, using liquid-liquid and solid phase extraction methods. Qualitative and quantitative analysis of lamivudine in extracts from urine, saliva and liver was performed by thin layer chromatography, UV spectrophotometry and high-performance liquid chromatography. A validation assessment of the developed techniques indicates their suitability for chemical and toxicological analysis of lamivudine.


Assuntos
Lamivudina/análise , Fígado/química , Saliva/química , Urinálise , Cromatografia Líquida de Alta Pressão , Cromatografia em Camada Delgada , Humanos , Extração em Fase Sólida , Espectrofotometria
7.
AAPS PharmSciTech ; 21(3): 91, 2020 Feb 13.
Artigo em Inglês | MEDLINE | ID: mdl-32060665

RESUMO

Doravirine is a non-nucleoside reverse transcriptase inhibitor indicated for the treatment of human immunodeficiency virus-1 infection, available as a single tablet in combination with other antiretroviral agents or as a fixed-dose regimen with lamivudine and tenofovir disoproxil fumarate (TDF). Alternative formulations of these drugs are being developed for individuals who have difficulty swallowing tablets. Two phase 1 trials were conducted, both in 24 healthy adults, to assess the pharmacokinetics of uncoated and coated oral granule formulations of doravirine, lamivudine, and TDF administered alone and with vanilla pudding or apple sauce. The pharmacokinetics for all uncoated granules, and of coated lamivudine and TDF granules, were similar to those of currently marketed tablets (geometric mean ratios [GMRs] 0.92-1.04). Coated doravirine granules had decreased AUC0-∞ (11%) and Cmax (23%) values versus the tablet. The pharmacokinetics were similar for uncoated and coated doravirine granules administered with or without pudding (GMRs 0.96-1.10); administration with apple sauce increased doravirine AUC0-∞ (26-29%), Cmax (56-59%), and C24 (20-21%) versus administration of granules alone. Lamivudine granules administered with pudding or apple sauce decreased AUC0-∞ and Cmax (14-25%) versus granules alone. Tenofovir AUC0-∞, Cmax, and C24 increased for TDF granules administered with pudding or apple sauce versus alone (11-23%). Pharmacokinetic differences when administering doravirine, lamivudine, or TDF as uncoated or coated granules versus tablets, or when granules were administered with (versus without) pudding or apple sauce, are not considered clinically meaningful, supporting further development of these granule formulations.


Assuntos
Fármacos Anti-HIV/farmacocinética , Antirretrovirais/farmacocinética , Lamivudina/farmacocinética , Piridonas/farmacocinética , Inibidores da Transcriptase Reversa/farmacocinética , Tenofovir/farmacocinética , Triazóis/farmacocinética , Adulto , Fármacos Anti-HIV/administração & dosagem , Antirretrovirais/administração & dosagem , Disponibilidade Biológica , Estudos Cross-Over , Feminino , Infecções por HIV/tratamento farmacológico , Infecções por HIV/metabolismo , Humanos , Lamivudina/administração & dosagem , Masculino , Pessoa de Meia-Idade , Piridonas/administração & dosagem , Inibidores da Transcriptase Reversa/administração & dosagem , Comprimidos , Tenofovir/administração & dosagem , Triazóis/administração & dosagem , Adulto Jovem
8.
BMC Infect Dis ; 20(1): 123, 2020 Feb 11.
Artigo em Inglês | MEDLINE | ID: mdl-32046664

RESUMO

BACKGROUND: The rate of S68G mutation in human immunodeficiency virus type 1 (HIV-1) reverse transcriptase has increased and is closely related to the K65R mutation among CRF01_AE-infected patients who failed treatment. We aimed to explore the temporal association of S68G and K65R mutations and disclose the role of the former on susceptibility to nucleotide/nucleoside reverse transcriptase inhibitor (NRTI) and viral replication with the K65R double mutations among CRF01_AE-infected patients who failed treatment. METHODS: The occurrence of S68G and K65R mutations was evaluated among HIV-1 of various subtypes in the global HIV Drug Resistance Database. The temporal association of S68G and K65R mutations was analyzed through next-generation sequencing in four CRF01_AE-infected patients who failed treatment with tenofovir/lamivudine/efavirenz. The impact of the S68G mutation on susceptibility to NRTI and replication fitness was analyzed using pseudovirus phenotypic resistance assays and growth competition assays, respectively. RESULTS: The frequency of the S68G mutation increased by 1.4-9.7% in almost all HIV subtypes and circulating recombinant forms in treatment-experienced patients, except subtype F. The S68G mutation often occurred in conjunction with the K65R mutation among RTI-treated patients, with frequencies ranging 21.1-61.7% in various subtypes. Next-generation sequencing revealed that the S68G mutation occurred following the K65R mutation in three of the four CRF01_AE-infected patients. In these three patients, there was no significant change detected in the half maximal inhibitory concentration for zidovudine, tenofovir, or lamivudine between the K65R and K65R/S68G mutations, as demonstrated by the phenotypic resistance assays. Virus stocks of the K65R and K65R/S68G mutations were mixed with 4:6, 1:1, and 9:1 and cultured for 13 days, the K65R/S68G mutants outgrew those of the K65R mutants irrespective of the input ratio. CONCLUSIONS: S68G may be a natural polymorphism and compensatory mutation of K65R selected by NRTIs in the CRF01_AE strain of HIV-1. This mutation does not affect susceptibility to NRTI; however, it improves the replication fitness of K65R mutants. This study deciphers the role of the S68G mutation in the HIV reverse transcriptase of the CRF01_AE strain and provides new evidence for the interpretation of drug-resistant mutations in non-B subtypes of HIV-1.


Assuntos
Farmacorresistência Viral/genética , Infecções por HIV/tratamento farmacológico , Infecções por HIV/virologia , Transcriptase Reversa do HIV/genética , HIV-1/genética , Mutação , Fármacos Anti-HIV/uso terapêutico , HIV-1/efeitos dos fármacos , Humanos , Lamivudina/uso terapêutico , Taxa de Mutação , Polimorfismo Genético , Inibidores da Transcriptase Reversa/uso terapêutico , Tenofovir/uso terapêutico , Falha de Tratamento , Replicação Viral/efeitos dos fármacos , Zidovudina/uso terapêutico
9.
BMC Infect Dis ; 20(1): 158, 2020 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-32075584

RESUMO

BACKGROUND: Although the global human immunodeficiency virus (HIV) epidemic has improved significantly due to antiretroviral treatment (ART), ART-related adverse events (AEs) remain an issue. Therefore, investigating the factors associated with ART-related AEs may provide vital information for monitoring risks. METHODS: A prospective cohort study was conducted among adult patients (aged 18 years or older) with HIV who received Tenofovir (TDF) + Lamivudine (3TC) + Efavirenz (EFV) as first-line ART regimens. All AEs during the first 12 months of therapy were recorded. Logistic regression analysis was used to identify variables associated with AEs. RESULTS: Four hundred seventy-four patients receiving TDF+ 3TC+ EFV ART regimens between March 2017 and October 2017 were included in the study analysis. Among them, 472 (99.6%) experienced at least one AE, 436 (92.0%) patients experienced at least one AE within 1 month of treatment, 33 (7.0%) between one and 3 months of treatment, and three (0.6%) patients after 3 months of treatment. The most commonly reported AE was nervous system (95.6%) related, followed by dyslipidemia (79.3%), and impaired liver function (48.1%). Patients with baseline body mass index (BMI) greater than 24 kg/m2 (adjusted OR 1.77, 95%CI 1.03-3.02), pre-existing multiple AEs (adjusted OR 2.72, 95%CI 1.59-4.64), and pre-existing severe AEs (adjusted OR 5.58, 95%CI 2.65-11.73) were at increased odds of developing a severe AE. Patients with baseline BMI greater than 24 kg/m2 (adjusted OR 2.72, 95%CI 1.25-5.89) were more likely to develop multiple AEs. CONCLUSION: The incidence of ART-related adverse events over a 12-month period in China was high. Baseline BMI greater than 24 kg/m2, pre-existing multiple AEs, and pre-existing severe AEs were shown to be independent risk factors for developing a severe AE.


Assuntos
Fármacos Anti-HIV/efeitos adversos , Terapia Antirretroviral de Alta Atividade/efeitos adversos , Infecções por HIV/tratamento farmacológico , Adolescente , Adulto , Fármacos Anti-HIV/uso terapêutico , Benzoxazinas/efeitos adversos , Benzoxazinas/uso terapêutico , Índice de Massa Corporal , China/epidemiologia , Dislipidemias/induzido quimicamente , Dislipidemias/epidemiologia , Feminino , Humanos , Incidência , Lamivudina/efeitos adversos , Lamivudina/uso terapêutico , Masculino , Pessoa de Meia-Idade , Cobertura de Condição Pré-Existente , Estudos Prospectivos , Tenofovir/efeitos adversos , Tenofovir/uso terapêutico , Adulto Jovem
12.
Artigo em Inglês | MEDLINE | ID: mdl-31967210

RESUMO

A 37-year-old male patient, Fitzpatrick skin phototype IV, a student living in Belem, Amazon region, in 2015 had a confirmed diagnosis of acquired immunodeficiency virus (HIV) infection, but did not initiate antiretroviral treatment at his own option. Three years after the diagnosis, erythematous maculae appeared on the dorsum of the nose with rapid progression to the entire face, with posterior diffuse infiltration and appearance of nodules on the chin and shoulder. In December 2018, the patient presented with exacerbation of the condition with an increase in infiltrated violaceous plaques and disseminated violaceous nodules. A histopathological biopsy of the skin was performed, confirming the diagnosis of angiomatoid proliferation suggestive of Kaposi's sarcoma (KS), with an important dissemination of this disease to the noble organs. In addition, it is important to note that he only started antiretroviral therapy (ART) after the exacerbation of Kaposi (December 2018). In such cases, chemotherapy associated with ART is crucial for the treatment and follow-up of the patient, since Kaposi's sarcoma develops relatively low in patients who do not have immunodeficiency.


Assuntos
Fármacos Anti-HIV/administração & dosagem , Infecções por HIV/complicações , Sarcoma de Kaposi/etiologia , Neoplasias Cutâneas/etiologia , Adulto , Infecções por HIV/tratamento farmacológico , Compostos Heterocíclicos com 3 Anéis/administração & dosagem , Humanos , Lamivudina/administração & dosagem , Masculino , Sarcoma de Kaposi/diagnóstico , Tenofovir/administração & dosagem
13.
Int J Antimicrob Agents ; 55(3): 105893, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31926287

RESUMO

This was a retrospective study on the efficacy and drug resistance mutations selected at virological failure (VF) in prospectively-followed HIV-infected patients switched to dolutegravir plus rilpivirine (DTG+RPV) or lamivudine (DTG+3TC) while virologically suppressed (HIV-RNA <50 copies/mL). VF was defined as HIV-RNA >50 copies/mL in two consecutive determinations or in a single determination if followed by treatment modification, or >1000 copies/mL in a single determination. Totally, 374 patients were analysed (307 switched to DTG+3TC and 67 to DTG+RPV); 220 had documented historical resistance. The median (IQR) time with HIV-RNA <50 copies/mL before switch was 4.52 (1.93-8.14) years. VF occurred in 17 patients after a median of 1.74 (0.90-2.46) years of follow-up in the 3TC group [incidence rate (95% CI) 3.34 (2.08-5.37) per 100-PYFU] and in 2 patients after a median of 1.78 (1.10-2.99) years of follow-up in the RPV group [incidence rate (95% CI) 1.57 (0.4-6.28) per 100-PYFU]. The 48-week estimated probabilities to maintain virological suppression during treatment with a two-drug regimen were 97.8% (95% CI 95.1-99.0%) vs. 98.3% (95% CI 88.6-99.8%) in the 3TC versus RPV group (P = 0.311). At switch, patients with VF had undetectable HIV-RNA since 0.71 (0.23-1.07) years versus 1.49 (0.64-2.2) years in those without VF (P = 0.001). In the 3TC group, VF was not associated with the presence of historical resistance to nucleoside analogues, and DTG-resistant variants were not selected at VF. One VF to DTG+RPV occurred because of historical resistance to RPV, accompanied by newly selected G140A and Q148R mutations. VF was infrequent with these regimens and was negatively associated with duration of viral undetectability. Drug resistance mutations selected at failure of these regimens were those expected in case of failure of any regimen including DTG, 3TC or RPV, but the impact of resistance to NRTIs on efficacy of DTG+3TC seems lower than expected.


Assuntos
Fármacos Anti-HIV/uso terapêutico , Infecções por HIV/tratamento farmacológico , Compostos Heterocíclicos com 3 Anéis/uso terapêutico , Lamivudina/uso terapêutico , Inibidores da Transcriptase Reversa/uso terapêutico , Rilpivirina/uso terapêutico , Fármacos Anti-HIV/administração & dosagem , Farmacorresistência Viral , Compostos Heterocíclicos com 3 Anéis/administração & dosagem , Humanos , Lamivudina/administração & dosagem , Estudos Retrospectivos , Rilpivirina/administração & dosagem , Resultado do Tratamento
14.
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
15.
PLoS One ; 15(1): e0227473, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31978137

RESUMO

INTRODUCTION: Loss to follow up after the initiation of antiretroviral therapy (ART) is common in Africa, particularly in Ethiopia and it is a considerable obstacle for the effectiveness of the ART program. Mortality is a competing risk of loss to follow up but it is often overlooked and there is limited evidence about the incidence and predictors of loss to follow up in the presence of competing events. OBJECTIVE: To assess the Incidence and predictors of loss to follow up among adult HIV patients on ART in University of Gondar Comprehensive Specialized Hospital between January 1, 2015, and December 31, 2018. METHODS: Institution based retrospective follow up study was conducted in University of Gondar Comprehensive Specialized Hospital. A Gray's test and cumulative incidence curve were used to compare the cumulative incidence function of loss to follow up. Bivariable and multivariable competing risk regression models were fitted to identify the predictors of lost to follow up and those variables with p-value <0.05 in the multivariable analysis was considered as significant predictors of lost to follow up. RESULT: A total of 531 adult HIV patients on ART were included in the analysis. The incidence rate of loss to follow up in this study was 10.90 (95% CI: 8.9-13.2) per 100 person years. Being age group 15-30 years (aSHR = 2.01; 95%CI;1.11-3.63), being daily laborer(aSHR = 2.60; 95%CI;1.45-4.66), not receiving cotrimoxazole preventive therapy (aSHR = 2.66; 95%CI;1.68-4.21), not receiving isoniazid preventive therapy(aSHR = 4.57; 95% CI;1.60-13.08), ambulatory functional status (aSHR = 1.61; 95% CI; 1.02-2.51) and taking AZT-3TC-NVP medication at start of ART(aSHR = 2.01; 95% CI; 1.16-3.78) were significant predictors of lost to follow up. CONCLUSION: In this study the incidence of lost to follow up was high. Young people, daily laborer, ambulatory patients and those taking AZT-3TC-NVP as well as those who did not take opportunistic prophylaxis were at higher risk of loss to follow up. Therefore, giving special attention to the high-risk groups for lost to follow up highlighted in this study could decrease the rate of LTFU.


Assuntos
Antirretrovirais/uso terapêutico , Infecções por HIV/tratamento farmacológico , Perda de Seguimento , Adolescente , Adulto , Assistência Ambulatorial , Quimioterapia Combinada , Feminino , Seguimentos , Hospitais Especializados , Humanos , Incidência , Lamivudina/uso terapêutico , Masculino , Nevirapina/uso terapêutico , Análise de Regressão , Estudos Retrospectivos , Fatores de Risco , Adulto Jovem , Zidovudina/uso terapêutico
16.
Environ Pollut ; 258: 113700, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31838398

RESUMO

Dissolved organic matter (DOM) is the most important light absorber that may induce indirect photolytic transformation of organic pollutants in natural waters. In this study, effects of DOM derived from freshwater and seawater on the photodegradation of three antiviral drugs acyclovir, lamivudine and zidovudine were investigated. Results show that the photodegradation of acyclovir is promoted mainly by excited triplet states DOM (3DOM*), and the photodegradation of lamivudine is accelerated by 3DOM*, •OH and 1O2 together; however, the photodegradation of zidovudine is inhibited by DOM mainly via light screening. Compared with DOM from freshwater, promotion effect of DOM extracted from seawater (SDOM) on the photodegradation of acyclovir and lamivudine is weaker, which is attributed to lower productivity of reactive intermediates. On the other hand, inhibitory effect of SDOM on the photodegradation of zidovudine is also weaker, which is due to weaker light screening caused by lower light absorption. Photodegradation half-lives of the three antiviral drugs are predicted to be all more than 20 days in freshwater and seawater bodies of the Yellow River estuarine region. These findings are significant for understanding the phototransformation processes of antiviral drugs and other organic pollutants in estuarine and coastal regions.


Assuntos
Antivirais/química , Substâncias Húmicas , Fotólise , Poluentes Químicos da Água/química , Aciclovir , Água Doce/química , Lamivudina , Água do Mar/química , Zidovudina
17.
Braz J Infect Dis ; 24(1): 65-72, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31835018

RESUMO

Antiretroviral therapy (ART) has modified the outcome of patients with HIV infection, providing virological control and reducing mortality. However, there are several reasons as to why patients may discontinue their antiretroviral therapy, with adverse events being one of the main reasons reported in the literature. This is a case-control nested in a cohort of people living with HIV/AIDS, conducted to identify the incidence of ART modification due to adverse events and the associated factors, in two referral services in Recife, Brazil, between 2011 and 2014. Of the modifications occurred in the first year of ART, 25.7% were driven by adverse events. The median time elapsed between initiating ART and the first modification due to adverse events was 70.5 days (95% CI: 26-161 days). The main adverse events were dermatological, neuropsychiatric and gastrointestinal. Dermatological events were the earliest to appear after initiating ART. Efavirenz was the most prescribed and most modified drug during the study period. The group of participants who used zidovudine, lamivudine, and efavirenz had a 2-fold greater chance (adjusted OR: 2.16 95% CI: 1.28-3.65) of switching ART due to adverse events when compared to the group that used tenofovir with lamivudine and efavirenz.


Assuntos
Síndrome de Imunodeficiência Adquirida/tratamento farmacológico , Fármacos Anti-HIV/efeitos adversos , Síndrome de Imunodeficiência Adquirida/mortalidade , Adolescente , Adulto , Terapia Antirretroviral de Alta Atividade/efeitos adversos , Benzoxazinas/efeitos adversos , Brasil , Combinação de Medicamentos , Feminino , Humanos , Estimativa de Kaplan-Meier , Lamivudina/efeitos adversos , Modelos Logísticos , Lopinavir/efeitos adversos , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Ritonavir/efeitos adversos , Tenofovir/efeitos adversos , Fatores de Tempo , Adulto Jovem , Zidovudina/efeitos adversos
18.
Drugs ; 80(1): 61-72, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31865558

RESUMO

The oral once-daily, fixed-dose single-tablet regimen (STR) of dolutegravir/lamivudine (Dovato®), combining a second generation integrase single-strand transfer inhibitor (INSTI) and a nucleoside reverse transcriptase inhibitor (NRTI), is indicated as a complete regimen for the treatment of HIV-1 infection in adults and adolescents (> 12 years of age weighing at least 40 kg) with no known or suspected resistance to the INSTI class or lamivudine. In GEMINI trials in antiretroviral therapy (ART)-naïve HIV-1-infected adults, treatment with dolutegravir plus lamivudine provided rapid and sustained virological suppression and was noninferior to dolutegravir plus tenofovir disoproxil fumarate/emtricitabine at 48 weeks, irrespective of baseline patient or disease characteristics. Virological suppression was sustained at 96 weeks in these ongoing trials. In patients with HIV-1 with sustained virological suppression on their current tenofovir alafenamide (AF)-based ART regimen (≥ 3 drugs), switching to treatment with dolutegravir/lamivudine was noninferior to continuing on a tenofovir AF-based regimen at 48 weeks in the ongoing TANGO trial. No resistance mutations to dolutegravir or lamivudine were detected in patients who met criteria for confirmed virological withdrawal in GEMINI and TANGO trials. Hence, the dolutegravir/lamivudine STR is an effective, generally well tolerated and convenient initial and subsequent ART option for adolescents and adults with HIV-1 infection with no known or suspected resistance to the INSTI class or lamivudine.


Assuntos
Infecções por HIV/tratamento farmacológico , Compostos Heterocíclicos com 3 Anéis/administração & dosagem , Lamivudina/administração & dosagem , Adolescente , Adulto , Fármacos Anti-HIV/administração & dosagem , Fármacos Anti-HIV/efeitos adversos , Fármacos Anti-HIV/farmacologia , Criança , Combinação de Medicamentos , Farmacorresistência Viral , HIV-1/efeitos dos fármacos , Compostos Heterocíclicos com 3 Anéis/efeitos adversos , Compostos Heterocíclicos com 3 Anéis/farmacologia , Humanos , Lamivudina/efeitos adversos , Lamivudina/farmacologia , Comprimidos
19.
S Afr Med J ; 109(12): 919-926, 2019 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-31865953

RESUMO

BACKGROUND: World Health Organization guidelines recommend that HIV patients who do not achieve viral suppression on efavirenz-based first-line antiretroviral therapy (ART) should be changed to a protease inhibitor (PI)-based regimen. In South Africa (SA), ~200 000 people are on second-line treatment, but little is known about these patients. OBJECTIVES: To describe second-line black African patients in a large urban area. METHODS: A quantitative retrospective study of 825 second-line patients in central Johannesburg, SA (subdistrict F), was performed with data extracted from government databases. Demographic characteristics, treatment status and laboratory information were gathered, then analysed with CD4+ cell count, viral load (VL) and retention-in-care data as outcome variables. RESULTS: The average recorded time to VL measurement after the switch to a PI-based ART regimen was 20 months, and 83.1% (570/686) of patients with a recent VL achieved viral suppression while on second-line treatment. The most recent median CD4+ cell count for the cohort was 286 cells/µL (interquartile range 160 - 478), which represented a 177 cells/µL increase from the baseline count at the start of first-line ART. Slightly less than three-quarters (72.4%) of the population remained active in care in the study clinics from initiation on first-line ART. Demographic characteristics such as being <25 years of age, male sex and geographical transfer (started initial treatment in a different region) independently predicted low CD4+ cell counts and virological failure on second-line treatment. Patients with virological failure were most likely (odds ratio (OR) 3.13, 95% confidence interval (CI) 1.50 - 6.56) to be lost to follow-up after the switch, while patients from Hillbrow Community Health Centre (OR 0.27, 95% CI 0.16 - 0.44), South Rand Hospital (OR 0.24, 95% CI 0.12 - 0.47) and Jeppe Clinic (OR 0.38, 95% CI 0.16 - 0.88), three larger sites, were most likely to remain active in care. CONCLUSIONS: VL suppression was high in patients on second-line treatment, but one-fifth of patients were lost to follow-up. Younger age, male sex and transfer from other treatment sites predicted poor treatment outcomes, highlighting opportunities for prioritisation of adherence interventions.


Assuntos
Infecções por HIV/tratamento farmacológico , Inibidores da Protease de HIV/uso terapêutico , Adesão à Medicação/estatística & dados numéricos , Carga Viral , Adulto , Fatores Etários , Contagem de Linfócito CD4 , Bases de Dados Factuais , Quimioterapia Combinada , Feminino , Infecções por HIV/imunologia , Humanos , Lamivudina/uso terapêutico , Lopinavir/uso terapêutico , Perda de Seguimento , Masculino , Pessoa de Meia-Idade , Retratamento , Estudos Retrospectivos , Inibidores da Transcriptase Reversa/uso terapêutico , Ritonavir/uso terapêutico , Fatores Sexuais , Tenofovir/uso terapêutico , Falha de Tratamento , Organização Mundial da Saúde , Zidovudina/uso terapêutico
20.
Pol J Microbiol ; 68(3): 317-322, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31880877

RESUMO

Mutations associated with the pol and the S gene can emerge as a consequence of the high replication capacity and proofreading deficiencies of hepatitis B virus during replication. The current study was constructed to evaluate primary, partial, compensatory and the escape mutations in chronic hepatitis B patients in Northern Cyprus. The samples of HBsAg positive treatment naïve 100 patients were involved in this study. HBV pol gene region was sequenced, amplified and HBV pol/S gene mutations were determined. The samples of thirty-two patients were excluded because of their low viral load (HBV < 1000 iu/ml). Among the sequenced 68 samples, there was a partial mutation (1.5%) and 36.7% displayed a resistance profile to lamivudine, adevofir, and telbivudine. Immune response escape, vaccine escape, HBIg and diagnosis escape mutations were determined in 24%, 10%, 6%, and 4% samples of the patients, respectively. Additionally, there were six different combined mutations. These data underscored that there is no concern for primary mutations in Northern Cyprus, however, we have identified a compensatory mutation (rtV173M) that may have primary mutation characteristics by combining with other mutation patterns. Additionally, HBsAg escape mutants demonstrated that detection of the S gene together with the pol gene mutations might be beneficial and important to monitor the surveillance of S variants.Mutations associated with the pol and the S gene can emerge as a consequence of the high replication capacity and proofreading deficiencies of hepatitis B virus during replication. The current study was constructed to evaluate primary, partial, compensatory and the escape mutations in chronic hepatitis B patients in Northern Cyprus. The samples of HBsAg positive treatment naïve 100 patients were involved in this study. HBV pol gene region was sequenced, amplified and HBV pol/S gene mutations were determined. The samples of thirty-two patients were excluded because of their low viral load (HBV < 1000 iu/ml). Among the sequenced 68 samples, there was a partial mutation (1.5%) and 36.7% displayed a resistance profile to lamivudine, adevofir, and telbivudine. Immune response escape, vaccine escape, HBIg and diagnosis escape mutations were determined in 24%, 10%, 6%, and 4% samples of the patients, respectively. Additionally, there were six different combined mutations. These data underscored that there is no concern for primary mutations in Northern Cyprus, however, we have identified a compensatory mutation (rtV173M) that may have primary mutation characteristics by combining with other mutation patterns. Additionally, HBsAg escape mutants demonstrated that detection of the S gene together with the pol gene mutations might be beneficial and important to monitor the surveillance of S variants.


Assuntos
Evolução Molecular , Produtos do Gene pol/genética , Antígenos de Superfície da Hepatite B/genética , Vírus da Hepatite B/genética , Hepatite B Crônica/virologia , Adulto , Idoso , Antivirais/farmacologia , Chipre , Farmacorresistência Viral , Feminino , Vírus da Hepatite B/classificação , Vírus da Hepatite B/efeitos dos fármacos , Vírus da Hepatite B/isolamento & purificação , Hepatite B Crônica/tratamento farmacológico , Humanos , Lamivudina/farmacologia , Masculino , Pessoa de Meia-Idade , Mutação , Adulto Jovem
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