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Mass Spectrometry Imaging Demonstrates the Regional Brain Distribution Patterns of Three First-Line Antiretroviral Drugs.

ABSTRACT: HIV in the central nervous system (CNS) contributes to the development of HIV-associated neurological disorders (HAND), even with chronic antiretroviral therapy. In order for antiretroviral therapy to be effective in protecting the CNS, these drugs should have the ability to localize in brain areas known to be affected by HIV. Consequently, this study aimed to investigate the localization patterns of three first-line antiretroviral drugs, namely, efavirenz, tenofovir, and emtricitabine, in the rat brain. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) and matrix-assisted laser desorption ionization mass spectrometry imaging (MALDI-MSI) were utilized to assess the pharmacokinetics and brain spatial distribution of the three drugs. Each drug was administered (50 mg/kg) to healthy female Sprague-Dawley rats via intraperitoneal administration. LC-MS/MS results showed that all three drugs could be delivered into the brain, although they varied in blood-brain barrier permeability. MALDI-MSI showed a high degree of efavirenz localization across the entire brain, while tenofovir localized mainly in the cortex. Emtricitabine distributed heterogeneously mainly in the thalamus, corpus callosum, and hypothalamus. This study showed that efavirenz, tenofovir, and emtricitabine might be a potential drug combination antiretroviral therapy for CNS protection against HAND.

SUBMITTER: Ntshangase S

PROVIDER: S-EPMC6921606 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature

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Mass Spectrometry Imaging Demonstrates the Regional Brain Distribution Patterns of Three First-Line Antiretroviral Drugs.

Ntshangase Sphamandla S Mdanda Sipho S Singh Sanil D SD Naicker Tricia T Kruger Hendrik G HG Baijnath Sooraj S Govender Thavendran T

ACS omega 20191205 25

HIV in the central nervous system (CNS) contributes to the development of HIV-associated neurological disorders (HAND), even with chronic antiretroviral therapy. In order for antiretroviral therapy to be effective in protecting the CNS, these drugs should have the ability to localize in brain areas known to be affected by HIV. Consequently, this study aimed to investigate the localization patterns of three first-line antiretroviral drugs, namely, efavirenz, tenofovir, and emtricitabine, in the r ...[more]

PMID: 31867510

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Project description:IntroductionThere are a limited number of paediatric antiretroviral drug options. Characterising the long term safety and durability of different antiretrovirals in children is important to optimise management of HIV infected children and to determine the estimated need for alternative drugs in paediatric regimens. We describe first-line antiretroviral therapy (ART) durability and reasons for discontinuations in children at two South African ART programmes, where lopinavir/ritonavir has been recommended for children <3 years old since 2004, and abacavir replaced stavudine as the preferred nucleoside reverse transcriptase inhibitor in 2010.MethodsWe included children (<16 years at ART initiation) who initiated ?3 antiretrovirals between 2004-2014 with ?1 follow-up visit on ART. We estimated the incidence of first antiretroviral discontinuation using Kaplan-Meier analysis. We determined the reasons for antiretroviral discontinuations using competing risks analysis. We used Cox regression to identify factors associated with treatment-limiting toxicity.ResultsWe included 3579 children with median follow-up duration of 41 months (IQR 14-72). At ART initiation, median age was 44 months (IQR 13-89) and median CD4 percent was 15% (IQR 9-21%). At three and five years on ART, 72% and 26% of children respectively remained on their initial regimen. By five years on ART, the most common reasons for discontinuations were toxicity (32%), treatment failure (18%), treatment simplification (5%), drug interactions (3%), and other or unspecified reasons (18%). The incidences of treatment limiting toxicity were 50.6 (95% CI 46.2-55.4), 1.6 (0.5-4.8), 2.0 (1.2-3.3), and 1.3 (0.6-2.8) per 1000 patient years for stavudine, abacavir, efavirenz and lopinavir/ritonavir respectively.ConclusionsWhile stavudine was associated with a high risk of treatment-limiting toxicity, abacavir, lopinavir/ritonavir and efavirenz were well-tolerated. This supports the World Health Organization recommendation to replace stavudine with abacavir or zidovudine in paediatric first-line ART regimens in order to improve paediatric first-line ART durability.

Project description:BackgroundIn Ethiopia, nearly one-third of people living with human immunodeficiency viruses do not adhere to antiretroviral therapy. Moreover, information regarding non-adherence and its associated factors among adults on first-line antiretroviral therapy in Northeast Ethiopia is limited. Therefore, this study aimed to assess the level of non-adherence and its associated factors among adults on first-line antiretroviral therapy in North Shewa Zone, Amhara Regional State, Ethiopia.MethodsA facility-based cross-sectional study was conducted on 326 participants selected by systematic random sampling technique from the five randomly selected public health facilities. Data were collected using the questionnaire adapted from the studies conducted previously and the collected data were entered into Epi data version 3.1 and exported to Stata version 14 for further analysis. Multivariable logistic regression analysis was done and an adjusted odds ratio with its corresponding 95% confidence interval was used to declare a statistical significance.ResultsThe overall prevalence of non-adherence was 17.4% [95% CI: (12.8%, 21.2%)]. Patients with no formal education [AOR (95% CI) = 5.57 (1.97, 15.88)], those who did not use memory aids to take their medications [AOR (95% CI) = 3.01 (1.27, 7.11)], travel more than 10 kilometers to visit the nearby antiretroviral therapy clinics [AOR (95% CI) = 2.42 (1.22, 25.86)], those who used substance [AOR (95% CI) = 3.57 (1.86, 28.69)], and patients whose medication time interfered with their daily routine activities [AOR (95% CI) = 15.46 (4.41, 54.28) had higher odds of having non-adherence to first-line antiretroviral therapy compared to their counter groups.ConclusionThe level of non-adherence to first-line antiretroviral therapy was 17.4%, higher compared to WHO's recommendation. Hence, patients counseling focused on avoiding substance use, use memory aids, and adjusting working time with medication schedule are very crucial. Furthermore, the ministry of health and the regional health bureau with other stakeholders should expand antiretroviral therapy service delivery at health facilities that are close to the community to address distance barriers.

Dataset Information

Mass Spectrometry Imaging Demonstrates the Regional Brain Distribution Patterns of Three First-Line Antiretroviral Drugs.

Publications

Mass Spectrometry Imaging Demonstrates the Regional Brain Distribution Patterns of Three First-Line Antiretroviral Drugs.

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