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Introduction: When protease inhibitor (PI)-based second-line ART fails, guidelines recommend drug resistance testing and individualized third-line treatment. However, PI-resistant viral strains are rare and drug resistance testing is costly. We investigated whether less costly PI-exposure testing can be used to select those patients who would benefit most from drug resistance testing. Methods: We performed a retrospective analysis of South African adults living with HIV experiencing failure of ritonavir-boosted-lopinavi (LPV/r)-based second-line ART for whom drug resistance testing results were available. We included patients who received plasma-based drug resistance testing at a central South African reference laboratory in 2017 and patients who received dried blood spots (DBS)-based drug resistance testing at a rural South African clinic between 2009 and 2017. PI-exposure testing was performed on remnant plasma or DBS using liquid chromatography mass spectrometry (LCMS). Additionally, a low-cost immunoassay was used on plasma. Population genotypic drug resistance testing of the pol region was performed on plasma and DBS using standard clinical protocols. Results: Samples from 544 patients (494 plasma samples and 50 DBS) were included. Median age was 41.0 years (IQR: 33.3 to 48.5) and 58.6% were women. Median HIV-RNA load was 4.9 log10 copies/mL (4.3 to 5.4). Prevalence of resistance to the NRTI-backbone was 70.6% (349/494) in plasma samples and 56.0% (28/50) in DBS. Major PI-resistance mutations conferring high-level resistance to LPV/r were observed in 26.7% (132/494) of plasma samples and 12% (6/50) of DBS. PI-exposure testing revealed undetectable LPV levels in 47.0% (232/494) of plasma samples and in 60.0% (30/50) of DBS. In pooled analysis of plasma and DBS samples, detectable LPV levels had a sensitivity of 90% (84% to 94%) and a negative predictive failure of 95% (91% to 97%) for the presence of major LPV/r resistance. Conclusions: PI-exposure testing revealed non-adherence in half of patients experiencing failure on second-line ART and accurately predicted the presence or absence of clinically relevant PI resistance. PI-exposure testing constitutes a novel screening strategy in patients with virological failure of ART that can differentiate between different underlying causes of therapy failure and may allow for more effective use of limited resources available for drug resistance testing. Keywords: antiretroviral treatment; treatment failure; HIV drug resistance; adherence; drug level testing; low- and middle-income countries, 1 | INTRODUCTION Antiretroviral treatment (ART) programmes are expanding rapidly to people living with HIV in low- and middle-income countries (LMIC) in an effort to control the HIV epidemic. First-line [...]

Introduction: To date, very little programmatic data has been published regarding serial antiretroviral (ARV) levels in infants exposed to maternal treatment and/or infant prophylaxis during the first months of life. Such data provide the opportunity to describe the proportion of infants exposed to virologically suppressive levels of ARVs and to gauge adherence to the prevention of mother-to-child transmission of HIV (PMTCT) programme. Methods: From August 2014 to January 2016, HIV-exposed infants born at Kalafong Provincial Tertiary Hospital in Pretoria, South Africa were enrolled as part of an observational cohort study. Plasma samples from HIV-exposed uninfected infants were obtained at birth, 6-weeks, 10-weeks and 14-weeks of age and quantitative efavirenz (EFV) and nevirapine (NVP) drug eve testing performed using liquid chromatography-mass spectrometry, irrespective of maternal ARV regimen. Descriptive analysis of EFV and NVP levels in relation to self-reported maternal and infant ARV exposure was performed. EFV levels >500 ng/mL and NVP levels >100 ng/mL were reported based on studies suggesting that trough levels above these thresholds are associated with virological suppression and PMTCT respectively. Results: Among 66 infants exposed to maternal EFV in utero, 29 (44%) had virologically suppressive plasma EFV levels at birth, with a median level of 1665 ng/mL (IQR: 1094 to 3673). Among infants who were exclusively breastfed at 6-, 10- and 14 weeks, 13/48 (27%), 5/25 (25%) and 0/21 (0%) had virologically suppressive EFV levels. Among 64 infants whose mothers reported administering daily infant NVP at time of their 6-week HIV PCR test, only 45 (70%) had NVP levels above the minimum prophylactic trough level. Conclusions: During the first 10-weeks after delivery, a quarter of breastfed infants born to women on an EFV-containing treatment regimen maintained virologically suppressive EFV plasma levels. This finding highlights the importance of both careful monitoring of ARV side effects and repeat HIV PCR after the first few months of life among HIV-exposed uninfected infants. As 30% of infants had inadequate NVP plasma levels at 6-weeks of age, adherence counselling to caregivers regarding infant prophylaxis needs to be enhanced to further reduce mother-to-child transmission of HIV. Keywords: PMTCT; option B+; antiretrovirals; efavirenz; nevirapine; toxicity; adherence; early infant diagnosis, 1 INTRODUCTION As combination antiretroviral therapy (cART) becomes more readily available in resource-limited settings, a rapid rise in the number of foetal antiretroviral (ARV) drug exposures is expected [1]. Current [...]

Abstract Background The 516G > T polymorphism in exon 4 of the CYP2B6 gene has been associated with increased plasma Efavirenz (EFV) concentrations. EFV concentrations greater than the recommended therapeutic range have been associated with the increased likelihood of developing adverse CNS effects. The aims of this study were to a) determine the presence of the 516G > T and other CYP2B6 exon 4 polymorphisms in a South African group of HIV-infected individuals b) investigate the relationship between the EFV plasma concentrations, the CYP2B6 516G > T polymorphism and the occurrence of CNS related side effects in this group of patients and c) develop and validate a rapid method for determination of EFV in plasma. Method Data from 80 patients is presented. Genetic polymorphisms in exon 4 of the CYP2B6 gene were identified using PCR amplification of this region followed by sequencing of the amplification products. EFV concentrations were analysed by UPLC-MS/MS. Assessment of the presence of CNS related side effects following EFV initiation were elicited with the use of a questionnaire together with physical examination. Results Plasma EFV concentrations displayed high inter-individual variability amongst subjects with concentrations ranging from 94 μg/l to 23227 μg/l at 2 weeks post initiation of treatment. For the 516G > T polymorphism the following frequencies were observed 23% of patients were TT homozygous, 36% GG and 41% GT. The TT homozygous patients had significantly higher EFV concentrations vs. those with the wild (GG) genotype (p < 0.05). Patients who experienced no side effects had significantly lower EFV plasma concentrations vs. the group of patients which experienced the most severe side effects (p < 0.05). Conclusion The significant association between the 516G > T polymorphism and plasma EFV concentrations has been demonstrated in this study. A rapid and sensitive method for the measurement of plasma EFV concentration was developed and validated.

The COVID-19 pandemic has highlighted resource constraints in respiratory support. The oxygen transfer characteristics of a specific hollow fiber membrane dialyser was investigated with a view to repurposing the device as a low-cost, readily available blood oxygenator. Oxygen transfer in a low-flux hollow fiber dialyser with a polysulfone membrane was studied by passing first water and then blood through the dialyser in countercurrent to high-purity oxygen. Oxygen transfer rates of about 15% of the nominal 250 ml (STP)/min of a typical adult oxygen consumption rate were achieved for blood flow rates of 500 ml/min. Using two such dialysis devices in parallel could provide up to 30% of the nominal oxygen consumption. Specific hollow fiber dialysis devices operating with suitable pumps in a veno-venous access configuration could provide a cost-effective and readily available supplementation of respiratory support in the face of severe resource constraints. [ABSTRACT FROM AUTHOR]

As part of a larger cross-sectional, case-control study on cardiometabolic diseases in psoriasis this study investigated the association of visceral fat and serum adipokines with psoriasis and cardiometabolic diseases. A total of 103 patients with psoriasis and 98 controls, matched for body mass index, ethnicity and sex, were recruited over 15 months. Abdominal visceral fat was measured by computerized tomography. Logistic regression analysis revealed that visceral fat was associated with psoriasis (odds ratio (95% confidence interval): 1.56 (1.15, 2.11)), hypertriglyceridaemia (1.67 (1.22, 2.28)), low high-density lipoprotein (1.63 (1.19, 2.22)) and type 2 diabetes (1.77 (1.24, 2.54)), (p < 0.005 for all). These respective associations were linked to serum interleukin-6, adiponectin, tumour necrosis factor and insulin resistance. Psoriasis was associated with type 2 diabetes (7.94 (2.64, 23.9)), independent of visceral fat. These data suggest that visceral fat and its mediators play a key role in psoriasis-associated cardiometabolic diseases. Psoriasis itself is associated with an increased risk of type 2 diabetes. [ABSTRACT FROM AUTHOR]

Background: Psoriasis is associated with cardiometabolic diseases (CMDs) in Caucasians, but no data is available from sub‐Saharan populations on either CMD prevalence or psoriasis risk factors. Our aim was to investigate the prevalence of CMDs in a predominantly non‐Caucasian cohort of South Africans with psoriasis and to determine the principal risk factors associated with psoriasis. Methods: This was a cross‐sectional case‐control study of adult psoriasis patients (n = 103) and controls (n = 98), comparing sociodemographic, anthropometric, clinical, and biochemical characteristics. The groups were matched for gender, ethnicity, and body mass index (BMI). Results: The prevalence of metabolic syndrome (MetS) (52.4% vs. 33.7%; P = 0.007), type 2 diabetes (T2D) (25.2% vs. 4.1%; P < 0.0001), and hypertension (70.9% vs. 46.6%; P = 0.001) were all higher in the psoriasis group. High‐sensitivity CRP was higher in psoriasis patients than controls (4.70 (2.00, 10.9) vs. 2.00 (1.10, 4.80) ng/ml; P < 0.0005). Multivariable logistic regression analysis showed that severe psoriasis was independently associated with MetS (odds ratio [95% CIs]: 4.42 [1.72, 11.4]; P = 0.002), T2D (11.3 [3.07, 41.3]; P = 0.0002), and hypertension (2.48 [0.97, 6.32]; P = 0.05), whilst for psoriasis the principal risk factors were smoking (3.87 [1.97, 7.63]; P < 0.0001) and hsCRP (1.05 [1.00, 1.10]; P = 0.029), with completion of high school (0.23 [0.11, 0.48]; P < 0.0001) being protective. Conclusions: In this population, psoriasis is characterized by a high burden of CMDs, particularly in those subjects with severe psoriasis. Inflammation plays a role in the etiology of psoriasis, whilst smoking and poor education further increase disease risk. [ABSTRACT FROM AUTHOR]

BACKGROUND Although groups of African descent are particularly sensitive to blood pressure (BP) effects of salt intake, the role of obesity and insulin resistance in mediating this effect is uncertain. We determined whether obesity or insulin resistance is independently associated with urinary Na+/K+–BP relationships in a community sample of African ancestry. METHODS We measured 24-hour urinary Na+/K+, homeostasis model assessment of insulin resistance (HOMA-IR), and nurse-derived conventional and 24-hour ambulatory BP in 331 participants from a South African community sample of black African descent not receiving treatment for hypertension. RESULTS With adjustments for diabetes mellitus and the individual terms, an interaction between waist circumference and urinary Na+/K+ was associated with day diastolic BP (P < 0.05) and an interaction between log HOMA-IR and urinary Na+/K+ was associated with 24-hour and day systolic (P < 0.05) and 24-hour, day, and night diastolic (P < 0.002; P < 0.001) BP. The multivariable-adjusted relationship between urinary Na+/K+ and night diastolic BP increased across tertiles of HOMA-IR (tertile 1: β-coefficient = −0.79±0.47; tertile 2: β-coefficient = 0.65±0.35; tertile 3: β-coefficient = 1.03±0.46; P < 0.05 tertiles 3 and 2 vs. 1). The partial correlation coefficients for relationships between urinary Na+/K+ and 24-hour (partial r = 0.19; P < 0.02), day (partial r = 0.17; P < 0.05), and night (partial r = 0.18; P < 0.02) diastolic BP in participants with log HOMA-IR greater than or equal to the median were greater than those for relationships between urinary Na+/K+ and 24-hour (partial r = −0.08; P = 0.29), day (partial r = −0.10; P < 0.22), and night (partial r = −0.06; P = 0.40) diastolic BP in participants with log HOMA-IR less than the median (comparisons of r values: P < 0.05). CONCLUSIONS Insulin resistance may modify the relationship between salt intake, indexed by urinary Na+/K+, and ambulatory BP in groups of African descent. [ABSTRACT FROM AUTHOR]

Several letters to the editor are presented in response to articles in previous issues including "Limitation of the Vitros™ dry-slide technique in measuring high concentrations of salicylate in plasma," and "Tomatoes and blood: changing dietary habits and faecal occult blood testing."

Background: The burden of kidney disease in many African countries is unknown. Equations used to estimate kidney function from serum creatinine have limited regional validation. We sought to determine the most accurate way to measure kidney function and thus estimate the prevalence of impaired kidney function in African populations., Methods: We measured serum creatinine, cystatin C, and glomerular filtration rate (GFR) using the slope-intercept method for iohexol plasma clearance (mGFR) in population cohorts from Malawi, Uganda, and South Africa. We compared performance of creatinine and cystatin C-based estimating equations to mGFR, modelled and validated a new creatinine-based equation, and developed a multiple imputation model trained on the mGFR sample using age, sex, and creatinine as the variables to predict the population prevalence of impaired kidney function in west, east, and southern Africa., Findings: Of 3025 people who underwent measured GFR testing (Malawi n=1020, South Africa n=986, and Uganda n=1019), we analysed data for 2578 participants who had complete data and adequate quality measurements. Among 2578 included participants, creatinine-based equations overestimated kidney function compared with mGFR, worsened by use of ethnicity coefficients. The greatest bias occurred at low kidney function, such that the proportion with GFR of less than 60 mL/min per 1·73 m 2 either directly measured or estimated by cystatin C was more than double that estimated from creatinine. A new creatinine-based equation did not outperform existing equations, and no equation, including the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) 2021 race-neutral equation, estimated GFR within plus or minus 30% of mGFR for 75% or more of the participants. Using a model to impute kidney function based on mGFR, the estimated prevalence of impaired kidney function was more than two-times higher than creatinine-based estimates in populations across six countries in Africa., Interpretation: Estimating GFR using serum creatinine substantially underestimates the individual and population-level burden of impaired kidney function in Africa with implications for understanding disease progression and complications, clinical care, and service provision. Scalable and affordable ways to accurately identify impaired kidney function in Africa are urgently needed., Funding: The GSK Africa Non-Communicable Disease Open Lab., Translations: For the Luganda, Chichewa and Xitsonga translations of the abstract see Supplementary Materials section., Competing Interests: Declaration of interests The Ugandan and Malawian study was funded by a project grant from the GSK Africa Non-Communicable Disease Open Lab (project number 8111). CHH received funding from Medical Research Council (MRC) Grant Reference MR/R010161/1. The South African study was jointly funded by the South African MRC, MRC UK (via the Newton Fund), and GSK Africa Non-Communicable Disease Open Lab (via a supporting grant; project number 074). Additional sources of funding for the South African project were obtained from the International Society for Nephrology Clinical Research Program 15–2-015 (Validation of eGFR equations in South Africans; South Africa); the National Health Laboratory Services; and Faculty of Health Sciences Research Incentive Grant (number 0012838434203512110500000000000000004550), University of the Witwatersrand. Funding supported implementation, execution, and completion of the study in Malawi, South Africa, and Uganda., (Copyright © 2022 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Methods used for the detection of toxic components of Callilepis laureola and Senecio latifolius have ranged from the use of thin-layer chromatography, spectrophotometry, and immunoassay to gas chromatography with mass spectrometry. However, each of these techniques has a number of drawbacks. In this chapter, we will describe a solid-phase extraction technique, which allows for the detection and quantitation of the toxins atractyloside and retrorsine in each plant extract using ultra-performance liquid chromatography-mass spectrometry (UPLC-MS/MS). This methodology offers high specificity and sensitivity and the ability to identify a broad range of analytes., (© 2022. The Author(s), under exclusive license to Springer Science+Business Media, LLC, part of Springer Nature.)

As part of a larger cross-sectional, case-control study on cardiometabolic diseases in psoriasis this study investigated the association of visceral fat and serum adipokines with psoriasis and cardiometabolic diseases. A total of 103 patients with psoriasis and 98 controls, matched for body mass index, ethnicity and sex, were recruited over 15 months. Abdominal visceral fat was measured by computerized tomo-graphy. Logistic regression analysis revealed that visceral fat was associated with psoriasis (odds ratio (95% confidence interval): 1.56 (1.15, 2.11)), hyper-triglyceridaemia (1.67 (1.22, 2.28)), low high-density lipoprotein (1.63 (1.19, 2.22)) and type 2 diabetes (1.77 (1.24, 2.54)), (p < 0.005 for all). These respective associations were linked to serum interleukin-6, adiponectin, tumour necrosis factor and insulin resistance. Psoriasis was associated with type 2 diabetes (7.94 (2.64, 23.9)), independent of visceral fat. These data suggest that visceral fat and its mediators play a key role in psoriasis-associated cardiometabolic diseases. Psoriasis itself is associated with an increased risk of type 2 diabetes.

Introduction: The abuse of alcohol and drugs is a major public health problem and intoxication is one of the most important risk factors for violence and other causes of injury. The aim of the current study was to evaluate the prevalence of drug and alcohol use associated with injury in adult trauma patients in an inner city trauma unit in Johannesburg., Methods: A cohort of 105 adult trauma patients admitted to our university trauma unit and its allied medicolegal laboratory were studied in order to provide prospective data and enable us to correlate the prevalence and type of substance abuse with the demographics and injury patterns after major trauma., Results: Forty-five patients required resuscitation at the Johannesburg Hospital Trauma Unit (JHTU) and 60 patients were examined at the Johannesburg Medicolegal Laboratory (JMLL), giving a total of 105 patients. Blood alcohol concentration (BAC) was positive in 59% of the patients. The average BAC in the trauma unit patients was 37 mmol/l (0.17 g/dl), more than three times the legal limit for driving. Of the patients 43.7% were positive for urinary cannabis; women were statistically significantly more likely to have taken cannabis than men (p = 0.039). There was no difference in rates of exposure to cannabis or alcohol in patients who were the victims of interpersonal violence compared with the victims of accidents (p = 0.17). Only 3 patients had taken other drugs of abuse; 2 had taken Mandrax (methaqualone) and 1 amphetamine., Conclusion: Alcohol and cannabis are commonly misused by trauma patients in Johannesburg; the degree of misuse of other drugs appears to be low. Intoxication is a significant risk factor for violence and accidents and the resultant injuries are a massive burden on our society. Doctors have a responsibility to highlight the association between substance misuse and trauma and should also attempt to persuade individual trauma patients to reduce future alcohol consumption.