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1.
J Interprof Care ; 33(3): 298-307, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-30777493

RESUMEN

The need for interprofessional education (IPE) in health science disciplines is a current global trend. However, despite international support and demand, IPE is still new to many health professions curricula in South Africa. Furthermore, while ample existing academic literature addresses commonly encountered barriers to IPE, there is still a need to investigate the dynamics and challenges associated with the process of implementing IPE at universities. IPE is not yet part of the formal curriculum at a faculty of health sciences at a South African Higher Education Institute, so a pilot project was conducted to investigate the experiences of an IPE process by students from different health professions toward informing the planning and implementation of IPE in the formal curriculum. To this effect, a multi-layered IPE project was piloted across pharmacy, nursing, social work, psychology, dietetics, and human movement sciences within this Faculty of Health Sciences. The aim of this research was to determine the dynamics between the different health professions by exploring and describing the students' experiences of the IPE process. Theoretical case studies were presented to third-year students, who were grouped into interprofessional teams from the six different health professions at the Higher Education Institute's health sciences faculty. Data were gathered from reflective journals over a five-week period and a questionnaire was administered at the end of the project. Data were analysed and evaluated based on the interprofessional learning domains listed in the IPE framework of the World Health Organization. All participating health professions students felt positive about the project and agreed that it provided them with valuable IPE experiences. However, their long-term participation and commitment presented difficulty in an already demanding curriculum. The interprofessional dynamics were influenced by the relevance of the scenarios presented in the case studies to the different professions, the students' personalities and their previous experiences. Although the nursing students took initial leadership, contributions from the other professions became more prominent as the case studies unfolded. The findings indicated that the inclusion of different health professions in an interprofessional team should be guided by the specific scenarios incorporated to simulate interprofessional cooperation. The availability of the students and their scope of practice at third-year level should also be taken into account.


Asunto(s)
Empleos en Salud/educación , Relaciones Interprofesionales , Curriculum , Proyectos Piloto , Estudiantes del Área de la Salud , Encuestas y Cuestionarios
2.
South Afr J HIV Med ; 19(1): 766, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-30167336

RESUMEN

Background: Hypertriglyceridaemia (HTG) is an important risk factor for pancreatitis and cardiovascular disease (CVD), depending on severity. Hypertriglyceridaemia is common in human immunodeficiency virus (HIV) infection and is also a common complication of lopinavir/ritonavir (LPV/r). Objectives: To evaluate the risk of pancreatitis associated with HTG in patients six months post initiation of LPV/r-based therapy in a regional public hospital. Methods: Triglyceride (TG), serum amylase (s-amylase) and CD4+ count values were retrospectively investigated six months post LPV/r-based initiation. Age, gender, previous antiretroviral regimen and period since HIV diagnosis were also recorded. Results: The final sample consisted of 194 patients, 50 males and 144 females; mean (± standard deviation [s.d.]) age was 39.52 (± 9.98) years, and the mean (± s.d.) period since HIV diagnosis was 91.32 (± 25.18) months. Normal TG levels (< 1.70 mmol/L) were detected in only 55% of patients and the rest presented with some degree of HTG. The mean (± s.d.) TG for the entire sample was elevated at 1.94 (± 1.30) mmol/L with the mean (± s.d.) of the males at 2.36 (± 1.74) - statistically higher compared to the females at 1.79 (± 1.08) mmol/L (p = 0.034). No cases of pancreatitis were recorded and the time since HIV diagnosis did not indicate any statistically significant differences in the means of the TG, serum amylase or CD4 count values. Conclusion: Triglyceride levels were not substantially elevated to induce pancreatitis at six months post initiation of LPV/r, but were elevated above the accepted upper normal limit of 1.70 mmol/L which may have implications for cardiovascular risk.

3.
Pharmacol Rev ; 70(3): 684-711, 2018 07.
Artículo en Inglés | MEDLINE | ID: mdl-29945900

RESUMEN

Efavirenz is a highly effective HIV-1 antiretroviral; however, it is also frequently associated with neuropsychiatric adverse events (NPAE) that include abnormal dreams, sleep disturbances, nervousness, anxiety, depression, and dizziness. The incidence of NPAEs upon initiation of treatment with efavirenz-containing medications is high, exceeding 50% in most studies. Although the NPAEs tend to decrease after the first month in many patients, they persist for long periods of time in others. Efavirenz-based treatment is generally well-tolerated in children, although some experience persistent concentration problems, as well as sleep disturbances, psychotic reactions, and seizures. In an effort to link basic with clinical research, parameters associated with efavirenz brain exposure are discussed, and factors that increase efavirenz levels are explored in depth as they are expected to contribute to NPAE risk. These include the role of modifiable and nonmodifiable risk factors such as diet, weight, and drug-drug interactions and sex, age, and ethnicity/pharmacogenetics. In addition to NPAEs, this review explores what is known about antiretroviral (ARV) drugs being used for recreational purposes. Although multiple ARV drugs are covered, special attention is devoted to efavirenz given that the majority of reports of NPAEs and illicit use of ARV drugs concern efavirenz. The evolving molecular mechanistic basis of NPAEs and abuse of efavirenz point to a complex and polymodal receptor pharmacology. Animal studies to date primarily point to a serotonergic mechanism of action. Recently emerging associations between HIV-associated neurocognitive disorder and efavirenz use, and possible contributions of the mitochondrial-immune-inflammatory-redox cascade are explored in the context of the signaling mechanisms that appear to be involved.


Asunto(s)
Fármacos Anti-VIH/efectos adversos , Benzoxazinas/efectos adversos , Síndromes de Neurotoxicidad , Inhibidores de la Transcriptasa Inversa/efectos adversos , Animales , Fármacos Anti-VIH/sangre , Fármacos Anti-VIH/farmacocinética , Benzoxazinas/sangre , Benzoxazinas/farmacocinética , Infecciones por VIH/tratamiento farmacológico , Humanos , Inhibidores de la Transcriptasa Inversa/sangre , Inhibidores de la Transcriptasa Inversa/farmacocinética
4.
OMICS ; 21(8): 465-473, 2017 08.
Artículo en Inglés | MEDLINE | ID: mdl-28816644

RESUMEN

South Africa has the highest burden of the human immunodeficiency virus (HIV) infection globally. Efavirenz (EFV), a frequently used drug against HIV infection, displays a relationship between drug concentration and pharmacodynamics effects clinically. However, haplotype-based genetic variation in drug metabolism in a pediatric sample has been little considered in a longitudinal long-term context. CYP2B6 plays a key role in variation of EFV plasma concentration through altered drug metabolism. We report here on a prospective clinical pharmacogenomics/pharmacokinetic study of Bantu-speaking children, importantly, over a period of 24 months post-initiation of EFV-based treatment in South Africa. We characterized the HIV-1-infected children (n = 60) for the CYP2B6 c.516G>T, c.785A>G, c.983T>C, and c.1459C>T single nucleotide polymorphisms (SNPs). These SNPs were determined using polymerase chain reaction/restricted fragment length polymorphism and SNaPshot genotyping. Longitudinal mid-dose EFV plasma concentrations were determined by LC-MS/MS and association analyses with genotypes and haplotypes at 1, 3, and 24 months were performed. The CYP2B6 c.516T/T genotype showed significantly higher EFV plasma concentrations (p < 0.001) compared to non 516T-allele carriers at all three time points. The minor allele frequencies (MAF) for CYP2B6 c.516T, c.785G, c.983C, and c.1459T were 0.410, 0.408, 0.110, and 0.000 respectively. Haplotypes were constructed using CYP2B6 c.516G>T,-c.785A>G and c.983T>C. The haplotype T-G-T presented with significantly increased EFV plasma concentrations compared to the reference G-A-T haplotype at 1, 3, and 24 months (p = 0.009; p = 0.003; p = 0.001), suggesting that the T-G-T haplotype predisposes a risk of EFV plasma concentrations >4 µg/mL. The clinical implications of these pharmacogenomics observations for EFV toxicity and treatment resistance warrant further future research.


Asunto(s)
Fármacos Anti-VIH/sangre , Benzoxazinas/sangre , Citocromo P-450 CYP2B6/genética , Infecciones por VIH/tratamiento farmacológico , Haplotipos , Polimorfismo de Nucleótido Simple , Adolescente , Grupo de Ascendencia Continental Africana , Alelos , Fármacos Anti-VIH/farmacocinética , Fármacos Anti-VIH/uso terapéutico , Benzoxazinas/farmacocinética , Benzoxazinas/uso terapéutico , Niño , Preescolar , Cálculo de Dosificación de Drogas , Femenino , Expresión Génica , Frecuencia de los Genes , Infecciones por VIH/etnología , Infecciones por VIH/virología , VIH-1/efectos de los fármacos , VIH-1/fisiología , Humanos , Masculino , Farmacogenética , Estudios Prospectivos , Sudáfrica
5.
South Afr J HIV Med ; 17(1): 458, 2016.
Artículo en Inglés | MEDLINE | ID: mdl-29568614

RESUMEN

Background: Tenofovir disoproxil fumarate (TDF) has been associated with kidney tubular dysfunction and reduced renal function. Limited studies were performed in Europe and Asia that related plasma tenofovir (TFV) concentration with renal function; no such studies to date have been performed on Africans. Objective: To investigate the correlation between plasma tenofovir (TFV) concentration and certain renal function markers in HIV-infected women on TDF antiretroviral therapy (ART). These markers were also compared to a HIV-uninfected control group. Methods: HIV-infected women (n = 30) on TDF-based ART were matched with 30 controls for age and body mass index. Renal markers analysed were estimated glomerular filtration rate (eGFR), creatinine clearance (CrCl), serum creatinine, albuminuria, glucosuria, serum urea, serum uric acid, urine sodium and maximum tubular reabsorption of phosphate. Baseline eGFR and CrCl data were obtained retrospectively for the HIV-infected women. Plasma TFV was assayed using a validated HPLC-MS/MS method. Stepwise regression, Mann-Whitney test, unpaired and paired t-tests were applied in the statistical analyses. Results: TFV concentration was independently associated with albuminuria (adjusted r2 = 0.339; p = 0.001) in HIV-infected women. In the adjusted (weight) analysis, eGFR (p = 0.038), CrCl (p = 0.032) and albuminuria (p = 0.048) were significantly higher in HIV-infected compared to the uninfected women, but eGFR was abnormally high in HIV-infected women. Both eGFR (p < 0.001) and CrCl (p = 0.008) increased from baseline to follow-up in HIV-infected women. Conclusion: Plasma TFV concentration was associated with increased albuminuria in HIV-infected women in this sub-study. Both eGFR and CrCl were increased in HIV-infected women from baseline. These findings should be confirmed in larger studies, and hyperfiltration in HIV-infected women warrants further investigation.

6.
Nutr Res ; 33(1): 50-8, 2013 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-23351410

RESUMEN

Anemia is a common complication of pediatric HIV infection and is associated with suboptimal cognitive performance and growth failure. Routine iron supplementation is not provided to South African HIV-infected children. We hypothesized that dietary iron intake without supplementation is sufficient to protect against iron deficiency (ID) in HIV-infected children receiving highly active antiretroviral therapy. In this prospective study, the difference between dietary intakes of iron-deficient children (soluble transferrin receptor >9.4 mg/L) and iron-sufficient children after 18 months on highly active antiretroviral therapy was examined. The association between iron intake and hemoglobin (Hb) concentration was also assessed. Longitudinal data collected for 18 months from 58 HIV-infected African children were assessed by generalized estimation equations, with adjustment for demographic information, dietary intakes, growth parameters, and CD4%. After adjustment for covariates, the longitudinal association between dietary iron intake and Hb concentration remained significant. This association shows that for every 1-mg increase in iron intake per day, Hb increases by 1.1 g/L (P < .001). Mean Hb increased significantly after 18 months of follow-up (106 ± 14 to 129 ± 14 g/L, P < .01), but soluble transferrin receptor also increased (7.7 ± 2.7 to 8.9 ± 3.0 mg/L, P < .01). The incidence of ID increased from 15.2% at baseline to 37.2% after 18 months. Children with animal protein intakes greater than >20 g/d had significantly lower odds for ID at 18 months than did children with lower intakes (odds ratio, 0.40; 95% confidence interval, 0.21-0.77). Dietary iron intake was insufficient to protect against ID, pointing to a need for low-dose iron supplementation for iron-deficient HIV-infected children and interventions to increase the consumption of animal protein.


Asunto(s)
Anemia Ferropénica/tratamiento farmacológico , Anemia Ferropénica/epidemiología , Suplementos Dietéticos , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/epidemiología , Hierro en la Dieta/administración & dosificación , Terapia Antirretroviral Altamente Activa , Niño , Preescolar , Femenino , Hemoglobinas/análisis , Humanos , Incidencia , Hierro en la Dieta/sangre , Modelos Logísticos , Estudios Longitudinales , Masculino , Estado Nutricional , Oportunidad Relativa , Estudios Prospectivos , Sudáfrica/epidemiología , Encuestas y Cuestionarios
7.
Biol Pharm Bull ; 34(1): 66-70, 2011.
Artículo en Inglés | MEDLINE | ID: mdl-21212519

RESUMEN

The interaction between verapamil, a P-glycoprotein (P-gp) inhibitor, with ritonavir and lopinavir/ritonavir (LPV/r) after acute and chronic treatment was investigated in rats. Rats were divided into 4 groups, viz. Group 1: ritonavir, 20 mg/kg/d (n=18), group 2: ritonavir, 20 mg/kg/d plus verapamil 5 mg/kg/d (n=18), group 3: LPV/r, 80 and 20 mg/kg/d (n=17) and group 4: LPV/r, 80 and 20 mg/kg/d plus verapamil 5 mg/kg/d (n=18). Blood samples were collected after decapitation on days 1, 7 and 21. Lopinavir and ritonavir plasma levels were simultaneous determined by a validated LC/MS/MS method. The lower limit of quantification for both ritonavir and lopinavir was 0.078 µg/ml. Verapamil significantly increased ritonavir plasma levels, administered as monotherapy, following acute (p<0.005) and chronic treatment (day 21) (p<0.005). During acute (but not chronic) LPV/r treatment, verapamil also increased the lopinavir levels (p<0.05). A time or exposure dependent pharmacokinetic interaction was thus observed between verapamil and ritonavir whether administered alone or after the lopinavir-ritonavir combination (LPV/r). This interaction occurred most prominently after acute treatment, and became less pronounced over time. This study indicates the importance of a longer time frame to investigate enzyme based drug interactions in rat models.


Asunto(s)
Miembro 1 de la Subfamilia B de Casetes de Unión a ATP/antagonistas & inhibidores , Fármacos Anti-VIH/farmacología , Pirimidinonas/farmacología , Ritonavir/farmacología , Verapamilo/farmacología , Miembro 1 de la Subfamilia B de Casetes de Unión a ATP/metabolismo , Animales , Fármacos Anti-VIH/administración & dosificación , Fármacos Anti-VIH/sangre , Bloqueadores de los Canales de Calcio/farmacología , Esquema de Medicación , Lopinavir , Masculino , Pirimidinonas/administración & dosificación , Pirimidinonas/sangre , Ratas , Ratas Sprague-Dawley , Ritonavir/administración & dosificación , Ritonavir/sangre
8.
J Chromatogr B Analyt Technol Biomed Life Sci ; 878(28): 2886-90, 2010 Oct 15.
Artículo en Inglés | MEDLINE | ID: mdl-20869336

RESUMEN

A novel and robust screening method for the determination of the non-nucleoside reverse transcriptase inhibitor, efavirenz (EFV), in human saliva has been developed and validated based on high performance liquid chromatography tandem mass spectrometry (LC-MS/MS). Sample preparation of the saliva involved solid-phase extraction (SPE) on C18 cartridges. The analytes were separated by high performance liquid chromatography (Phenomenex Kinetex C18, 150mm×3mm internal diameter, 2.6µm particle size) and detected with tandem mass spectrometry in electrospray positive ionization mode with multiple reaction monitoring. Gradient elution with increasing methanol (MeOH) concentration was used to elute the analytes, at a flow-rate of 0.4mL/min. The total run time was 8.4min and the retention times for the internal standard (reserpine) was 5.4min and for EFV was 6.5min. The calibration curves showed linearity (r(2), 0.989-0.992) over the concentration range of 3.125-100µg/L. Mean intra- and inter-assay relative standard deviation, accuracy, mean extraction recovery, limit of detection (LOD) and limit of quantification (LOQ) were 0.46-9.43%, 80-120%, 60% (±7.95), 1.84 and 6.11µg/L respectively. The working range was defined as 6.25-100µg/L. This novel LC-MS/MS assay is suitable for reliable detection of low EFV concentrations in saliva and can be used as a screening tool for monitoring EFV compliance.


Asunto(s)
Benzoxazinas/análisis , Cromatografía Líquida de Alta Presión/métodos , Saliva/química , Espectrometría de Masas en Tándem/métodos , Fármacos Anti-VIH/análisis , Niño , Estabilidad de Medicamentos , Infecciones por VIH , Humanos , Modelos Lineales , Reproducibilidad de los Resultados , Inhibidores de la Transcriptasa Inversa/análisis , Sensibilidad y Especificidad
9.
AIDS Res Hum Retroviruses ; 26(6): 613-9, 2010 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-20507205

RESUMEN

The aim of this study was to quantify the plasma efavirenz concentrations over 6 months in black HIV-1-infected South African children (3-14 years), from resource-limited households, attending an outpatient clinic. The children were antiretroviral treatment (ART) naive and received efavirenz in combination with two nucleoside reverse transcriptase inhibitors according to South African national guidelines. Two blood samples were taken between 12 and 20 h after the last efavirenz dose at 1 (n = 58), 3 (n = 54), and 6 (n = 54) months post-ART initiation. A total of 328 efavirenz mid-dose plasma samples from 58 patients was determined with a validated liquid chromatography tandem mass spectrometry method. Viral suppression (<25 copies/ml) was achieved in 95% of the children after 6 months on ART. The median (range) plasma concentration at time points 1 and 2 were 2.06 (0.10-11.14) and 1.80 (0.14-10.70) microg/ml with respective mean (+/-SD) blood sampling times of 15.24 (2.03) and 16.91 (2.03) h post-evening dose. Efavirenz plasma samples within the therapeutic range of 1-4 microg/ml accounted for 58%; 17% were <1 microg/ml and 25% were >4 microg/ml over the 6 months. Efavirenz levels persistently >4 microg/ml were recorded for 13 (23%) children and 3 (5%) children had persistent efavirenz levels <1 microg/ml. Possible reasons for efavirenz plasma levels outside the accepted therapeutic range include genetic variation in drug metabolism, incorrect dosing, drug-drug interactions, and nonadherence. However, these need to be further explored and the importance of sequential plasma levels has been highlighted in this study.


Asunto(s)
Fármacos Anti-VIH/farmacocinética , Benzoxazinas/farmacocinética , Infecciones por VIH/tratamiento farmacológico , Plasma/química , Adolescente , Atención Ambulatoria , Fármacos Anti-VIH/uso terapéutico , Terapia Antirretroviral Altamente Activa , Benzoxazinas/uso terapéutico , Niño , Preescolar , Cromatografía Liquida , Femenino , Infecciones por VIH/virología , VIH-1/aislamiento & purificación , Humanos , Masculino , Sudáfrica , Espectrometría de Masas en Tándem , Factores de Tiempo
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