Research Articles (Immunology)

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Triple-negative breast cancer at Helen Joseph Hospital : prevalence, age and imaging features
Zondi, Tsholofelo; Rubin, Grace; Benn, Carol-Ann; Gounden, Sharadini K. (AOSIS, 2025-10)
BACKGROUND : Triple-negative breast cancer (TNBC) is considered an aggressive subtype, defined by the absence of oestrogen, progesterone and HER2 receptors. It typically presents earlier and more aggressively. Limited data exist on its prevalence, age of onset and imaging features in South Africa. OBJECTIVES : This study aimed to assess the prevalence of TNBC at Helen Joseph Tertiary Hospital (HJTH), describe its histopathological features and explore trends in age at diagnosis and imaging patterns-including early-onset disease. METHOD : A retrospective review of 280 female patients with histologically confirmed breast cancer, diagnosed between January 2021 and December 2023, was conducted. Demographic, imaging and histopathology data were analysed using descriptive statistics and chi-square tests. RESULTS : The diagnosis of TNBC accounted for 17% (48/280) of all breast cancer cases in the cohort. The TNBC lesions typically measured 1-5 cm and showed nodal involvement in 73% of cases. Despite their aggressive biology, many TNBC lesions appeared circumscribed or only mildly irregular on imaging, mimicking benign masses. Among all the 280 breast cancer cases, 61% were high-grade. The mean Ki-67 index for TNBC was the highest at 52%, followed by HER2+ (39%), Luminal B (33%) and Luminal A (21%). Notably, some HER2+ and TNBC cases exhibited lower Ki-67 indices, highlighting heterogeneity within these subtypes. CONCLUSION : This study highlights the complexity of breast cancer presentation in a South African setting, particularly the discordance between tumour biology and imaging. CONTRIBUTION : These findings contribute local data on TNBC in an urban public healthcare context, supporting improved imaging awareness and clinical vigilance in resource-limited settings.
Heritable human genome editing in South Africa - time for a reality check
Ramsay, Michele; Pepper, Michael Sean; De Vries, Jantina; Mahomed, Safia; Flack-Davison, Eleni (South african Medical Association, 2025-02)
Referring to the third edition of the South African Ethics in Health Research Guidelines: Principles, Processes and Structures (the guidelines) dated May 2024, Baylis and Hasson assert that the guidelines support heritable human genome editing (HHGE), which allows for children conceived from ‘gene-edited’ cells to be born. On 7 November 2024, a news item appeared in Nature titled ‘Will South Africa become first country to accept controversial form of human genome editing?’ As South African (SA) scholars in the fields of genetics, biology, law and ethics, we wish to express our dismay that national and international audiences should be misled to believe that SA law accommodates or should be changed to allow for the clinical application of HHGE. What is at stake is not whether HHGE is permissible for research purposes in SA, but whether it is permissible to create live births.
Progress in advanced cellular and gene therapies in South Africa and barriers to patient access : a National Consortium paper on behalf of the BloodSA Cell and Gene Therapy working party
Hendricks, Candice Laverne; Viljoen, I.; Botes, M.; Brittain, D.; Mahlangu, J.; Verburgh, E.; Gerdener, T.; Herd, C.; Logan, M.G.; Marais, A.L.; Glatt, T.N.; Cockeran, R.; Poole, C.; Du Toit, J.; Pepper, Michael Sean (South african Medical Association, 2025-06)
The fields of molecular and cellular medicine have, in recent years, witnessed a great deal of progress globally, particularly in understanding disease pathogenesis and through the development of advanced cellular therapy products and gene therapies. Despite the transformative potential of these new therapies, low- and middle-income countries face significant barriers to their access. Advanced cellular therapy legislation in South Africa (SA) has not kept up with this fast-advancing field, and requires a fast-tracked renewal. Furthermore, the prohibitive cost of commercial therapies, including chimeric antigen receptor (CAR) T-cell products, and the lack of infrastructure, manufacturing and research capacity, must be addressed to make equitable patient access an achievable goal in our setting. To this end, a national cell and gene therapy consortium, comprising clinicians, clinician-scientists, scientists, legal experts, postgraduate students and representatives from industry, the national blood service and the pharmaceutical industry, was initiated. The mandate of this group is to aid the progression of advanced cellular therapies in SA, and the purpose of this article is to outline the progress that has been made. We will highlight the gaps in each core field of practice within this space, and provide a proposal for making these therapies more accessible in SA.
Addressing the limitations of the regulatory landscape in South Africa regarding advanced cell and gene therapies and related sectors involving human cells, tissues and organs
Viljoen, Ignatius M.; Pepper, Michael Sean (South african Medical Association, 2025-02)
Advanced cell-based and gene therapy products emerged during the 1990s as new health product categories for treating and curing previously untreatable or incurable conditions. These products are complex, diverse and therapeutically specific, requiring specialised regulatory frameworks. During the last three decades, several jurisdictions have constructed specific regulatory frameworks to ensure these products’ safety, clinical efficacy and quality. As these are new and disruptive products, these frameworks are continuously evolving. However, South Africa (SA)’s regulatory frameworks for medicines, human biological materials and genetically modified organisms have not kept pace with scientific and technological developments, leaving regulatory gaps. We briefly describe these novel products and their regulatory frameworks, and propose a way forward in SA.
Section on heritable human genome editing withdrawn from the National Health Research Ethics Council guidelines
Mahomed, Safia; Ramsay, Michèle; Pepper, Michael Sean; De Vries, Jantina; Flack-Davison, Eleni (South african Medical Association, 2025-08)
No abstract available.
Response to : In defence of South Africa’s National Health Research Ethics Council guidelines on heritable human genome editing
Ramsay, Michèle; Pepper, Michael Sean; De Vries, Jantina; Mahomed, Safia; Flack-Davison, Eleni (South african Medical Association, 2025-02)
No abstract available.
RSV : an overview of infection in adults
Feldman, Charles; Anderson, Ronald (BioMed Central, 2025-06-28)
BACKGROUND : Respiratory syncytial virus (RSV) infection was originally considered to be simply a disease of childhood. However, it has increasingly been recognized that the virus may also cause infection in adults. Furthermore, great strides have been made in understanding the clinical manifestations, as well as aspects of its management and prevention, requiring the need for greater awareness of the various aspects of this infection in adults. MAIN BODY : There are several potential reasons that RSV may have been overlooked in adults. Firstly, it was due to a lack of knowledge that this infection could occur in this age group. Secondly, there was infrequent testing for RSV infection in adults, both for this reason and because RSV antigen testing in adults is less sensitive than in children. Thirdly, RSV diagnosis, therefore, required the performance of polymerase chain reaction (PCR) testing, which is both expensive and underutilized. Finally, there was also the belief at that time that if the infection was due to RSV, there was little one could do to about it in terms of treatment and/or prevention. More recently, however, enormous advances have been made particularly in the management and prevention of this infection. This manuscript, which is an extensive literature review, describes the modern understanding of the burden of infection, the clinical presentation, risk factors, immunopathogenesis, management, and prevention of RSV infections in adults. CONCLUSION : RSV virus is a common cause of respiratory tract infections in adults and advances in recent research have not only enhanced our knowledge of this infection but have led to the development of effective treatment and prevention of the infection.
Guest editorial
Van Niekerk, Andre (Allergy Society of South Africa, 2025-03)
Many short courses (bursts) of oral corticosteroids (OCS) are commonly prescribed for indicated and non-indicated conditions. These bursts are perceived to be safe and are usually given by prescription for less than 14 days at a time. The global corticosteroid market was USD 5.7 billion in 2023, and with a projected annual growth rate of 4.6% across all regions, reflects its widespread use. Published data of OCS use in South Africa are difficult to find, yet parents of children attending a clinic for immune deficiencies frequently report repetitive prescriptions.
The mechanism of action of oral corticosteroids in relation to short- and long-term-burst therapy
Cordier, Werner; Rossouw, Theresa M. (Allergy Society of South Africa, 2025-03)
Corticosteroids, potent anti-inflammatory agents, are broadly used in various inflammatory and immune-dependent pathologies, which include asthma. Through non-genomic and genomic mechanisms of action, corticosteroids reduce pro-inflammatory mediators while promoting anti-inflammatory molecule expression. Furthermore, in the context of asthma treatment, they also promote the expression of β2 adrenergic receptors which increase the therapeutic potential of β2-receptor agonists to promote bronchodilation. However, corticosteroids also precipitate a variety of adverse events which reduce the quality of life of patients and predispose them to further pathological alterations. Given the ubiquitous expression of the glucocorticoid receptor, alongside the non-genomic and genomic mechanisms of corticosteroids, a myriad interconnecting physiological processes are altered upon receptor modulation. Both long- and short-course treatment has been linked to immune suppression, metabolic and cardiovascular disease, cerebrovascular accidents, osteoporosis, ophthalmic disorders, pneumonia and mood disorders. Consequently, clinical decision-making should consider the potential risks involved in short- and long-term use of corticosteroids because pathophysiological changes may be precipitated in both.
Effect of adipose-derived mesenchymal stromal/stem cells on mouse mammary tumour growth and formation of lung metastases
Peta, Kimberly Thando; Durandt, Chrisna; Van Heerden, Marlene B.; Pepper, Michael Sean; Ambele, Melvin (Elsevier, 2025-12)
The role of mesenchymal stromal/stem cells (MSCs) in tumour development and progression remains a subject of debate. Previous studies have reported contradictory outcomes, possibly due to variations in experimental design and the use of xenograft models. Xenograft models limit interpretation and translation due to cross-species variability. To address these limitations, we employed an isogenic mouse model of spontaneous breast cancer (BC) to investigate the impact of murine MSCs on BC development and progression. Methods: MSCs isolated from FVB/N mouse adipose tissue (mASCs) were administered to female mice with palpable mammary tumours. Tumour volume and mass were assessed, and analysis of histopathological necrosis and gene expression was conducted on mammary (MT) and lung metastatic tumours (LT). Results: No change in MT mass and volume was observed between mASC-treated and control mice. However, mASC treatment led to increased necrosis in LT but not in MT. Immunohistochemistry revealed that mASC-treated mice had fewer CD163+ anti-inflammatory macrophages in the LT but not in the MT. Tgf-β3, vegfr1, and cd105 were observed and downregulated in both MT and LT in mASC-treated mice. The downregulation of cd36 and tgf-β3 contributes to pro-tumourigenic activities, whereas the downregulation of vegfr1 and cd105 is associated with an anti-tumour effect. In the mASC treatment group, all cytokines tested for, except IL-27, were elevated. Conclusion: This study suggests that mASCs are anti-tumourigenic in pulmonary metastatic BC. Our findings emphasize the importance of considering the tumour microenvironment and employing relevant animal models when investigating the impact of MSCs on tumour progression.
Sustained activation of myeloperoxidase is associated with oxidative stress and inflammation in people living with the human immunodeficiency virus at risk of cardiovascular disease
Mokoena, Haskly; Choshi, Joel; Hanser, Sidney; Mabhida, Sihle E.; Steel, Helen Carolyn; Mokgalaboni, Kabelo; Phoswa, Wendy N.; Maarman, Gerald; Nkambule, Bongani B.; Dludla, Phiwayinkosi V. (MDPI, 2025-11)
People living with the human immunodeficiency virus (PLWH) are continually subjected to challenges involving the development of non-acquired immunodeficiency syndrome (AIDS)-related comorbidities despite the effectiveness of highly active antiretroviral therapy (HAART). Exacerbated oxidative stress, which is intrinsically linked to chronic inflammation, is implicated in non-AIDS comorbidities, including the increased risk of cardiovascular disease (CVD) observed in PLWH. Here, we review evidence on the potential pathological implications of myeloperoxidase (MPO), a leukocyte-derived enzyme and a key mediator of oxidative stress and inflammation, in driving CVD-related complications in PLWH. A systematic review approach was taken to identify relevant clinical studies through searches of Cochrane Libraries, PubMed, Web of Science, ScienceDirect, and Google Scholar, up to the 30 June 2025. The summarized data appraised clinical studies (n = 14) on adults (n = 1445) with a mean age of 45 years reporting on the association between MPO and enhanced lipid peroxidation marked by elevated concentrations of oxidized low-density lipoprotein cholesterol (oxLDL-C) in PLWH. Such results were consistent with elevated inflammatory markers, including high sensitivity C-reactive protein (hsCRP), which was also linked with endothelial dysfunction. There is a lack of evidence linking the duration of HAART to MPO levels or an increased risk of CVD. However, there is room to explore whether enhanced levels of oxLDL-C, in association with sustained MPO activation, could drive CVD risk in PLWH. The present review provides essential information on the pathological relevance of MPO in endothelial dysfunction and CVD risk in PLWH.
Comprehensive chemoanatomical mapping, and the gonadal regulation, of seven kisspeptin neuronal populations in the mouse brain
Hernandez, Vito S.; Zetter, Mario A.; Hernandez-Perez, Oscar R.; Hernandez-Gonzalez, Rafael; Camacho-Arroyo, Ignacio; Millar, Robert P.; Eiden, Lee E.; Zhang, Limei (Wiley, 2025-05)
Kisspeptinergic signaling is well-established as crucial for the regulation of reproduction, but its potential broader role in brain function is less understood. This study investigates the distribution and chemotyping of kisspeptin-expressing neurons within the mouse brain. RNAscope single, dual, and multiplex in situ hybridization methods were used to assess kisspeptin mRNA (Kiss1) expression and its co-expression with other neuropeptides, excitatory and inhibitory neurotransmitter markers, and sex steroid receptors in wild-type intact and gonadectomized young adult mice. Seven distinct kisspeptin neuronal chemotypes were characterized, including two novel kisspeptin-expressing groups described for the first time, that is, the Kiss1 population in the ventral premammillary nucleus and the nucleus of the solitary tract. Kiss1 mRNA was also observed to localize in both somatic and dendritic compartments of hypothalamic neurons. High androgen receptor expression and changes in medial amygdala and septo-hypothalamic Kiss1 expression following GDX in males, but not in females, suggest a role for androgen receptors in regulating kisspeptin signaling. This study provides a detailed chemoanatomical map of kisspeptin-expressing neurons, highlighting their potential functional diversity. The discovery of a new kisspeptin-expressing group and gonadectomy-induced changes in Kiss1 expression patterns suggest broader roles for kisspeptin in brain functions beyond those of reproduction.
Synthesis and characterisation of DOTA-kisspeptin-10 as a potential gallium-68/lutetium-177 pan-tumour radiopharmaceutical
Kleynhans, Janke; Reeve, Robert; Driver, Cathryn Helena Stanford; Marjanovic-Painter, Biljana; Sathekge, Mike Machaba; Zeevaart, Jan Rijn; Ebenhan, Thomas; Millar, Robert P. (Wiley, 2025-03)
Kisspeptin (KISS1) and its cognate receptor (KISS1R) are implicated in the progression of various cancers. A gallium-68 labelled kisspeptin-10 (KP10), the minimal biologically active structure, has potential as a pan-tumour radiopharmaceutical for the detection of cancers. Furthermore, a lutetium-177 labelled KP10 could find therapeutic application in treating oncological diseases. DOTA (1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid) was attached to the NH2-terminus of KP10 as we posited from our previous publications that this modification would not impair biological activity. Here, we showed that the biological activity, as monitored by stimulation of inositol phosphate accumulation in HEK293 transfected with the KISS1R gene, was indeed similar for KP10 and DOTA-KP10. The optimisation of radiolabelling with gallium-68 and lutetium-177 is described. Stability in serum, plasma and whole blood was also investigated. Pharmacokinetics and biodistribution were established with micro-PET/CT (positron emission tomography/computerised tomography) and ex vivo measurements. Dynamic studies with micro-PET/CT demonstrated that background clearance for the radiopharmaceutical was rapid with a blood half-life of 18 ± 3 min. DOTA-KP10 demonstrated preserved functionality at KISS1R and good blood clearance. These results lay the foundation for the further development of DOTA-KP10 analogues that have high binding affinity along with proteolytic resistance.
Predicting cerebral palsy and 18-month neurodevelopmental outcome in infants with presumed hypoxic ischaemic encephalopathy : role of general movements assessment and early neurological examination
Kali, Gugulabatembunamahlubi T.J.; Du Preez, Jacomina C.F.; Van Zyl, Jeanetta I.; Burger, Marlette; Katsabola, Hillary; Pepper, Michael Sean (Frontiers Media, 2025-10-03)
INTRODUCTION : General movements assessment (GMA), including the Motor Optimality Score—Revised (MOS-R) and the Hammersmith Infant Neurological Examination (HINE), has been shown in different settings to predict cerebral palsy (CP) and delayed neurodevelopment with high accuracy. However, their combined predictive ability has not been fully evaluated in infants with presumed hypoxic–ischaemic encephalopathy (HIE). OBJECTIVE : This study aimed to assess the predictive ability of combined GMA, MOS-R, and HINE at 3 months in term or near-term infants diagnosed with presumed HIE, for neurodevelopmental outcome at 18 months. METHODS : A cohort of presumed HIE infants treated with therapeutic hypothermia (TH) underwent GMA, MOS-R, and HINE at 12–15 weeks, and neurodevelopmental assessments using the Bayley Scales of Infant and Toddler Development Third Edition (BSID-III) at 9–12 and at 18–24 months of age. Combined early assessments were analysed for their predictive ability across different domains on the BSID-III. RESULTS : Twenty-four infants were included; 7 (29%) had both 12-month and 18-month BSID-III assessments, 12 (50%) were seen only at 12 months, and 5 (21%) only at 18 months. Two infants with absent fidgety movements (FMs) and poor motor repertoire were later diagnosed with CP or showed delays in two domains on the BSID-III assessment at 18 months. While most infants had some abnormality in the MOS-R categories, only absent FMs and abnormal finger variability showed some association with the 18-month BSID-III assessment on univariate analysis. Of the four infants classified as at risk for CP on the HINE at 3 months, two had some motor abnormalities at 18 months. Combining the GMA, MOS-R, and HINE had high sensitivity and negative predictive value (100%), but low specificity (0–17.6%) and positive predictive value (6.2%–25%) for the BSID-III outcome. CONCLUSION : Combining GMA, MOS-R, and HINE was highly sensitive in this cohort, but had low specificity. This may lead to overdiagnosis, but it may be a useful screening tool for identifying typically developing infants who do not need intensive follow-up.
Minimal impact of feed intolerance during therapeutic hypothermia for hypoxic ischaemic encephalopathy in a South African cohort with a standardised feeding regimen
Samaai, Ilhaam; Pepper, Michael Sean; Pillay, Shakti; Horn, Alan R. (Frontiers Media, 2025-07-30)
INTRODUCTION : Enteral feeding during therapeutic hypothermia (TH) for neonatal hypoxic ischaemic encephalopathy (HIE), is beneficial, but there is insufficient evidence to guide timing and feed advancement strategies. The aim of this study was to describe feed tolerance and outcomes after TH with a standardized progressive early enteral feeding regimen. METHODS : Data were retrospectively reviewed from neonates with HIE who were treated with TH for HIE in the Groote Schuur Hospital (GSH) Neonatal intensive care unit (NICU), between 1 July 2019 and 31 October 2022. Enteral feeds were commenced at age 12–24 h and incremented daily if tolerated, at 12 ml/kg/day for the first 3 days and 24 ml/kg thereafter. Nutritional, morbidity and mortality outcomes were compared between neonates with and without early feed intolerance (EFI) by the fourth day of life. RESULTS : Thirty three percent (16/48) developed EFI. However, by day six the median (IQR) enteral volumes were, 120 (110–120) and 90 (90–99), in neonates without and with feed intolerance respectively. There were no differences in resuscitation characteristics. Neonates with EFI, had higher HIE grades, more amplitude integrated electro-encephalograph (aEEG) suppression at 48 h (p = 0.002), later attainment of full nutritive sucking or cup feeds (p < 0.001) and longer hospital stays (p = 0.038). There were no differences in other morbidities. Mortality was 6% and necrotising enterocolitis did not occur in either group. CONCLUSIONS : Early feeding was generally well tolerated. Feed intolerance was more frequent in neonates with severe HIE, but most neonates achieved independence from IV fluids by day six.
Management of HER2-low metastatic breast cancer : a comprehensive statement by an expert group from the Middle East and Africa region
Dawood, Shaheenah S.; Mokhtar, Mohsen; Alwbari, Ahmed M.; Rapoport, Bernardo Leon; Esin, Ece; Jaafar, Hassan N.; Zekri, Jamal M.; Berrada, Narjiss; Özyılkan, Özgür; El-Saghir, Nagi S. (Shiraz University of Medical Sciences, 2025-10)
Approximately 50 to 67% of breast cancers (BCs), traditionally categorized as human epidermal growth factor receptor 2 (HER2)-negative, but demonstrating low HER2 expression, are now being defined as a new HER2-low subset or HER2-low category of BC. For metastatic BC (mBC), standard therapy options include targeted approaches, such as cyclin-dependent kinase 4/6 inhibitors, phosphoinositide 3-kinase inhibitors, poly (adenosine diphosphate-ribose) polymerase inhibitors, and anti-programmed death-ligand 1 agents, depending on tumor type and its molecular profile. Recent clinical trials reported significant clinical benefits from novel anti‑HER2 antibody‑drug conjugates, such as trastuzumab deruxtecan in HER2‑low mBC. Novel treatment options have increased the complexity of the clinical decision‑making process, particularly for treatment sequencing for each clinical setting. A regional expert committee meeting was held to discuss the challenges, overcome limitations, and present recommendations to enhance HER2 reporting as well as treatment of patients with HER2‑low mBC in the Middle East and Africa region.
Genetic variants associated with suspected neonatal hypoxic ischaemic Encephalopathy : a study in a South African context
Foden, Caroline J.; Durant, Kevin; Mellet, Juanita; Joubert, Fourie; Van Rensburg, Jeanne; Masemola, Mogomane Yvonne Khomotso; Velaphi, Sithembiso C.; Nakwa, Firdose L.; Horn, Alan R.; Pillay, Shakti; Kali, Gugu; Coetzee, Melantha; Ballot, Daynia E.; Kalua, Thumbiko; Babbo, Carina; Pepper, Michael Sean; NESHIE Working Group (MDPI, 2025-03)
Neonatal encephalopathy suspected to be due to hypoxic ischaemic encephalopathy (NESHIE) carries the risk of death or severe disability (cognitive defects and cerebral palsy). Previous genetic studies on NESHIE have predominantly focused on exomes or targeted genes. The objective of this study was to identify genetic variants associated with moderate–severe NESHIE through whole-genome, unbiased analysis. Variant filtering and prioritization were performed, followed by association testing both on a case–control basis and to compare the grades of severity and/or progression. Association testing on neonates with NESHIE (N = 172) and ancestry-matched controls (N = 288) produced 71 significant genetic variants (false discovery rate corrected p-value < 6.2 × 10−4), all located in non-coding regions and not previously implicated in NESHIE. Disease-associated variants in non-coding regions are considered to affect regulatory functions, possibly by modifying gene expression, promoters, enhancers, or DNA structure. The most significant variant was at position 6:162010973 in the Parkin RBR E3 ubiquitin protein ligase (PRKN) intron. Intronic variants were also identified in genes involved in inflammatory processes (SLCO3A1), DNA repair (ZGRF1), synaptogenesis (CNTN5), haematopoiesis (ASXL2), and the transcriptional response to hypoxia (PADI4). Ten variants were associated with a higher severity or lack of improvement in NESHIE, including one in ADAMTS3, which encodes a procollagen amino protease with a role in angiogenesis and lymphangiogenesis. This analysis represents one of the first efforts to analyze whole-genome data to investigate the genetic complexity of NESHIE in diverse ethnolinguistic groups of African origin and provides direction for further study.
Antiretroviral-induced toxicity in umbilical cord blood-derived haematopoietic stem/progenitor cells
Hendricks, Candice Laverne; Ellero, Andrea Antonio; Mellet, Juanita; Stivaktas, Voula; Pepper, Michael Sean (Wiley, 2025-04)
Improvements in administration and efficacy of antiretroviral therapy (ART) have reduced rates of mother-to-child transmission (MTCT) of human immunodeficiency virus (HIV) to < 2%. However, in utero exposure to antiretrovirals (ARVs) leads to abnormalities in HIV-exposed uninfected (HEU) infants. We determined the effect of five ARVs on human umbilical cord blood (UCB)-derived haematopoietic stem/progenitor cells (HSPC) with the aim of exploring a potential causal relationship with haematological abnormalities. Efavirenz (EFV) was cytotoxic to HSPCs alone and in combination with tenofovir disoproxil fumarate (TDF) and emtricitabine (FTC). Dolutegravir (DTG) had a biphasic effect on HSPC expansion. Immunophenotypic analysis showed increased erythroid and granulocyte precursors after 7-day culture with these drugs. Finally, using colony forming unit (CFU) assays, we observed impairment in the formation of CFU-GEMM and CFU/Burst forming unit (BFU) erythroid (E) in the presence of DTG, lamivudine (3TC) and TDF, both visually and immunophenotypically. We conclude that multiple potential HSPC toxicities exist with ARVs commonly used in pregnancy, prompting the need for further research to confirm the safety of these drugs in this vulnerable group.
Comparative effects of efavirenz and dolutegravir on metabolomic and inflammatory profiles, and platelet activation of people living with HIV
Roux, Crystal Gayle; Mason, Shayne; Du Toit, Louise; Nel, Jan-Gert; Rossouw, Theresa M.; Steel, Helen Carolyn (MDPI, 2024-09-14)
Antiretroviral therapy (ART) has reduced the mortality and morbidity associated with HIV. However, irrespective of treatment, people living with HIV remain at a higher risk of developing non-AIDS-associated diseases. In 2019, the World Health Organization recommended the transition from efavirenz (EFV)- to dolutegravir (DTG)-based ART. Data on the impact of this transition are still limited. The current study therefore investigated the metabolic profiles, cytokine inflammatory responses, and platelet activation before and after the treatment transition. Plasma samples from nine virally suppressed adults living with HIV and sixteen healthy, HIV-uninfected individuals residing in Gauteng, South Africa were compared. Metabolite and cytokine profiles, and markers associated with platelet activation, were investigated with untargeted proton magnetic resonance metabolomics, multiplex suspension bead array immunoassays, and sandwich enzyme-linked immunosorbent assays, respectively. In those individuals with normal C-reactive protein levels, the transition to a DTG-based ART regimen resulted in decreased concentrations of acetoacetic acid, creatinine, adenosine monophosphate, 1,7-dimethylxanthine, glycolic acid, 3-hydroxybutyric acid, urea, and lysine. Moreover, increased levels of formic acid, glucose, lactic acid, myo-inositol, valine, glycolic acid, and 3-hydroxybutyric acid were observed. Notably, levels of interleukin-6, platelet-derived growth factor-BB, granulocyte-macrophage colony-stimulating factor, tumor necrosis factor-alpha, soluble cluster of differentiation 40 ligand, as well as regulated on activation, normal T-cell expressed and secreted (RANTES) reached levels close to those observed in the healthy control participants. The elevated concentration of macrophage inflammatory protein-1 alpha was the only marker indicative of elevated levels of inflammation associated with DTG-based treatment. The transition from EFV- to DTG-based regimens therefore appears to be of potential benefit with metabolic and inflammatory markers, as well as those associated with cardiovascular disease and other chronic non-AIDS-related diseases, reaching levels similar to those observed in individuals not living with HIV.
Neonatal encephalopathy due to suspected hypoxic-ischaemic encephalopathy
Horn, Alan Richard; Pillay, Shakti; Velaphi, Sithembiso Christopher; Ballot, Daynia Elizabeth; Mellet, Juanita; Foden, Caroline J.; Van Rensburg, Jeanne; Babbo, Carina Corte-Real; Kali, Gugulabatembunahlubi Tenjiwe Jabulile; Coetzee, Melantha; Masemola, Mogomane Yvonne Khomotso; Nakwa, Firdose Lambey; Pepper, Michael Sean (Springer, 2025-09)
No abstract available.

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