SUNScholar - Browsing by Author "Decloedt, Eric H."

Browsing by Author "Decloedt, Eric H."

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The 12-month period prevalence and cardiac manifestations of HIV in patients with acute coronary syndrome at a tertiary hospital in Cape Town, South Africa : a retrospective cross-sectional study
(BMC (part of Springer Nature), 2021) Pennefather, Camilla; Esterhuizen, Tonya; Doubell, Anton; Decloedt, Eric H.
Background: HIV-positive patients are increasingly being affected by non-communicable diseases such as coronary artery disease (CAD). Data from high-income countries (HICs) indicate that HIV-positive patients have different riskfactor profiles for acute coronary syndrome (ACS) as well as different cardiac manifestations of this syndrome compared to HIV-negative patients. There is limited data from Sub-Saharan Africa (SSA), and particularly from South Africa with the biggest HIV epidemic in the world. The objective of this study was to determine the 12-month period prevalence of HIV in patients with ACS and to compare the risk-factor profile, ACS presentation and management between HIV-positive and HIV-negative adults. Methods: We included all patients hospitalised with ACS from 01 January to 31 December 2018 in a tertiary hospital, Tygerberg Hospital, in Cape Town, South Africa. The HIV-status of all patients was determined using routine clinical records. We performed multiple conditional logistic regression on HIV-positive and HIV-negative patients (1:3 ratio) to compare the risk factor profile, ACS presentation and management between the groups. Results: Among 889 patients, 30 (3.4%) were HIV-positive (95% confidence interval (CI): 2.3–4.8). HIV-positive patients were younger, more frequently men, and had a lower prevalence of medical comorbidities and a family history of CAD. They were more likely to present with ST-elevation myocardial infarction (STEMI) [odd’s ratio (OR) (95% CI): 3.12 (1.2–8.4)], and have single-vessel disease [OR (95% CI): 3.03 (1.2–8.0)]. Angiographic and echocardiographic data, as well as management, did not differ between the groups. Among HIV-positive patients, 17 (65%) were virally suppressed (HIV viral load < 200 copies/mL) with a median CD4+ count of 271 cells/mm3. The majority (20, 67%) of HIV-positive patients were receiving antiretroviral therapy at the time of the ACS. Conclusions: We found an HIV-prevalence of 3.4% (95% CI 2.3–4.8) in adults with ACS in a high endemic HIV region. HIV-positive patients were younger and more likely to present with STEMIs and single-vessel disease, but had fewer CAD risk factors, suggesting additional mechanisms for the development of ACS.
Accelerating clinical evaluation of repurposed combination therapies for COVID-19
(American Society of Tropical Medicine and Hygiene, 2020-08-21) Rayner, Craig R.; Dron, Louis; Park, Jay J. H.; Decloedt, Eric H.; Cotton, Mark F.; Niranjan, Vis; Smith, Patrick F.; Dodds, Michael G.; Brown, Fran; Reis, Gilmar; Wesche, David; Mills, Edward J.
As the global COVID-19 pandemic continues, unabated and clinical trials demonstrate limited effective pharmaceutical interventions, there is a pressing need to accelerate treatment evaluations. Among options for accelerated development is the evaluation of drug combinations in the absence of prior monotherapy data. This approach is appealing for a number of reasons. First, combining two or more drugs with related or complementary therapeutic effects permits a multipronged approach addressing the variable pathways of the disease. Second, if an individual component of a combination offers a therapeutic effect, then in the absence of antagonism, a trial of combination therapy should still detect individual efficacy. Third, this strategy is time saving. Rather than taking a stepwise approach to evaluating monotherapies, this strategy begins with testing all relevant therapeutic options. Finally, given the severity of the current pandemic and the absence of treatment options, the likelihood of detecting a treatment effect with combination therapy maintains scientific enthusiasm for evaluating repurposed treatments. Antiviral combination selection can be facilitated by insights regarding SARS-CoV-2 pathophysiology and cell cycle dynamics, supported by infectious disease and clinical pharmacology expert advice. We describe a clinical evaluation strategy using adaptive combination platform trials to rapidly test combination therapies to treat COVID-19.
Benefit v. risk when using chloroquine in patients with severe COVID-19 disease
(Health & Medical Publishing Group, 2020-04-02) Decloedt, Eric H.; Allwood, Brian W.; Parker, Arifa; Koegelenberg, Coenraad F. N.; Blockman, Marc; Taljaard, Jantjie; Reuter, Helmuth
ENGLISH ABSTRACT: Chloroquine (CQ) is widely advocated as treatment for coronavirus disease 2019 (COVID-19), including the president of the USA publicly supporting the use of hydroxychloroquine (HCQ) as a ‘game-changer’ on the social media platform Twitter. CQ and HCQ are structurally similar, with HCQ having an N-hydroxyl-ethyl side-chain in place of the N-diethyl group.[1] Currently only CQ is being marketed in South Africa. We encourage the development of curative directed therapy against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) using appropriate designed trials and regulatory oversight, and caution against the indiscriminate use of CQ or HCQ. Careful patient selection is essential, including assessing prognosis, anticipated benefit and potential harms prior to initiating CQ/HCQ therapy.
Chloroquine and hydroxychloroquine for the prevention or treatment of Novel Coronavirus Disease (COVID-19) in Africa : caution for inappropriate off-label use in healthcare settings
(American Society of Tropical Medicine and Hygiene, 2020) Abena, Pascale M.; Decloedt, Eric H.; Bottieau, Emmanuel; Suleman, Fatima; Adejumo, Prisca; Sam-Agudu, Nadia A.; TamFum, Jean-Jacques Muyembe; Seydi, Moussa; Eholie, Serge P.; Mills, Edward J.; Kallay, Oscar; Zumla, Alimuddin; Nachega, Jean B.
ENGLISH ABSTRACT: The novel severe acute respiratory syndrome-coronavirus-2 pandemic has spread to Africa, where nearly all countries have reported laboratory-confirmed cases of novel coronavirus disease (COVID-19). Although there are ongoing clinical trials of repurposed and investigational antiviral and immune-based therapies, there are as yet no scientifically proven, clinically effective pharmacological treatments for COVID-19. Among the repurposed drugs, the commonly used antimalarials chloroquine (CQ) and hydroxychloroquine (HCQ) havebecome the focus of global scientific, media, and political attention despite a lack of randomized clinical trials supporting their efficacy. Chloroquine has been used worldwide for about 75 years and is listed by theWHOas an essential medicine to treat malaria. Hydroxychloroquine is mainly used as a therapy for autoimmune diseases. However, the efficacy and safety of CQ/HCQ for the treatment of COVID-19 remains to be defined. Indiscriminate promotion and widespread use of CQ/HCQ have led to extensive shortages, self-treatment, and fatal overdoses. Shortages and increased market prices leave all countries vulnerable to substandard and falsified medical products, and safety issues are especially concerning for Africa because of its healthcare system limitations. Much needed in Africa is a cross-continental collaborative network for coordinated production, distribution, and post-marketing surveillance aligned to low-cost distribution of any approved COVID-19 drug; this would ideally be piggybacked on existing global aid efforts. Meanwhile, African countries should strongly consider implementing prescription monitoring schemes to ensure that any off-label CQ/HCQ use is appropriate and beneficial during this pandemic.
Clinical trials of disease stages in COVID 19 : complicated and often misinterpreted
(Elsevier, 2020-08-20) Park, Jay J. H.; Decloedt, Eric H.; Rayner, Craig R.; Cotton, Mark; Mills, Edward J.
As of July 28, 2020, 1840 clinical trials were registered globally, with 1001 clinical trials recruiting patients for COVID-19 management.1 Despite this large number, only 30 trials have been published as peer-reviewed or preprint publications.2 Media reports and prepublications on medRxiv and bioRxiv represent the most frequent mechanism for data sharing, with wide public reach and usually with little detail. However, with inadequate details on the trials and only superficial scrutiny by the public and scientific decision makers, the consequences have had disastrous effects on other clinical trial funding, permissions, recruitment, and interpretation.
Incident tuberculosis disease in patients receiving biologic therapies in the Western Cape, South Africa from 2007 to 2018
(BMC (part of Springer Nature), 2019) Du Toit, Tessa; Esterhuizen, Tonya M.; Tiffin, Nicki; Abulfathi, Ahmed A.; Reuter, Helmuth; Decloedt, Eric H.
Background: South Africa has one of the highest tuberculosis incidence rates. Biologic disease-modifying antirheumatic drugs are associated with an increased risk of tuberculosis. The objective of this study was to describe the tuberculosis disease incidence rate among public sector patients receiving biologic therapies in the Western Cape Province. Methods: A retrospective, descriptive analysis was undertaken using routine health data collated by the Provincial Health Data Centre from January 2007 (first use of biologic therapy in the Western Cape) to September 2018. Results: We identified 609 patients treated with tumour necrosis factor-alpha (TNF-α) or non-TNF-α biologic therapies. Thirty-seven (37) patients developed tuberculosis after biologic therapy exposure, of whom the majority (78%) had an immune mediated inflammatory disease and the remainder (22%) a haematologic malignancy. The incidence rate of tuberculosis per 100,000 person-years was 2227 overall [95% confidence interval (CI): 1591, 3037]. Patients treated with TNF-α inhibitors and non-TNF-α inhibitors had estimated incidence rates of 2819 [95% CI: 1669, 4480] and 1825 [95% CI: 1131, 2797], respectively (p = 0.10). Conclusion: Patients exposed to both TNF-α and non-TNF-α biologic therapies may have a higher incidence of tuberculosis disease compared to the background risk of 681 cases per 100,000 per year in the Western Cape.
Ivermectin for COVID-19 : promising but not yet conclusive
(Health & Medical Publishing Group, 2021-03) Van Rensburg, Roland; Decloedt, Eric H.; Reuter, Helmuth; Parker, Arifa; Schrueder, Neshaad; Lahri, Sa'ad
Ivermectin has been proposed as a potential definitive and prophylactic treatment for COVID-19.[1] Ivermectin is an anthelmintic drug that is usually indicated for filarial and resistant scabies infections, but has been shown to have antiviral activity and anti-inflammatory activity in vitro.[2,3] Ivermectin has the potential to be a promising directed therapy in the drug armamentarium against COVID-19, as it has been shown to have in vitro activity against SARS-CoV-2.[4] Several randomised controlled trials (RCTs) and observational studies have reported on the effectiveness and safety outcomes of ivermectin in COVID-19.[1,5] These data are very promising, showing large treatment effects and acceptable adverse effect profiles for ivermectin against COVID-19, especially when combined in metaanalyses.
Moderate to severe HIV-associated neurocognitive impairment : a randomized placebo-controlled trial of lithium
(Wolters Kluwer Health, 2016-11) Decloedt, Eric H.; Freeman, Carla; Howells, Fleur; Casson-Crook, Martine; Lesosky, Maia; Koutsilieri, Eleni; Lovestone, Simon; Maartens, Gary; Joska, John A.
Background: HIV-associated neurocognitive disorder (HAND) remains highly prevalent despite effective anti-retroviral therapy (ART). A number of adjunctive pharmacotherapies for HAND have been studied with disappointing results, but preliminary data suggest that lithium may provide clinical benefit. In addition, the low cost of lithium would facilitate access in low- and middle-income countries which carry the greatest burden of HIV. Methods: Our objective was to evaluate the 24-week efficacy and safety of lithium in patients with moderate to severe HAND. Our primary efficacy endpoint was the change in Global Deficit Score (GDS) from baseline to 24 weeks, whereas our secondary endpoint was the change in proton magnetic resonance spectroscopy (1H-MRS) brain metabolite concentrations. We conducted a 24-week randomized placebo-controlled trial of lithium as adjunctive pharmacotherapy. We enrolled participants with moderate to severe HAND, on ART for at least 6 months, with suppressed viral loads and attending public sector primary care clinics in Cape Town, South Africa. We randomized 66 participants to lithium (n = 32) or placebo (n = 34). Lithium or placebo was dosed 12-hourly and titrated to achieve the maintenance target plasma concentration of 0.6 to 1.0 mmol/L. Sham lithium concentrations were generated for participants receiving placebo. Results: Totally 61 participants completed the study (lithium arm = 30; placebo arm = 31). Participants at enrolment had a mean age of 40 years and a median CD4+ T-cell count of 500 cells/μL. The median change in GDS between baseline and week 24 for the lithium and placebo arms were –0.57 (95% confidence interval [CI] –0.77, –0.32) and –0.56 (–0.69, –0.34) respectively, with a mean difference of –0.054 (95% CI –0.26, 0.15); P = 0.716. The improvement remained similar when analyzed according to age, severity of impairment, CD4+ count, time on ART, and ART regimen. Standard 1H-MRS metabolite concentrations were similar between the treatment arms. The study drug was well tolerated in both study arms. Six serious adverse events occurred, but none were considered related to the study drug. Conclusion: Adjunctive lithium pharmacotherapy in patients on ART with HAND was well tolerated but had no additional benefit on neurocognitive impairment.
Renal safety of lithium in HIV-infected patients established on tenofovir disoproxil fumarate containing antiretroviral therapy : analysis from a randomized placebo-controlled trial
(BioMed Central, 2017-02-04) Decloedt, Eric H.; Lesosky, Maia; Maartens, Gary; Joska, John A.
Background: The prevalence of bipolar disorder in HIV-infected patients is higher than the general population. Lithium is the most effective mood stabiliser, while tenofovir disoproxil fumarate (TDF) is frequently used as part of combination antiretroviral therapy (ART). Both TDF and lithium are associated with renal tubular toxicity, which could be additive, or a pharmacokinetic interaction may occur at renal transporters with a decrease in TDF elimination. Objective: We report on the change in estimated glomerular filtration rate (eGFR) using the modification of diet in renal disease formula in participants who received ART including TDF and were enrolled in a 24 week randomised trial of lithium versus placebo in patients with HIV-associated neurocognitive impairment. Methods: We included HIV-infected adults with cognitive impairment established on ART for at least 6 months with a suppressed viral load attending public sector ART clinics in Cape Town, South Africa. We excluded participants with an eGFR <60 mL/min and treated with medications predisposing to lithium toxicity. We reviewed participants weekly for the first month for adverse events followed by 4 weekly visits for renal function assessment, adverse event monitoring and adherence. Lithium dose was titrated to achieve the maintenance target plasma concentration of between 0.6 and 1.0 mmol/L. Sham lithium concentrations were generated for participants receiving placebo. Results: We included 23 participants allocated to the lithium arm and 30 participants allocated to the placebo arm. Baseline characteristics were not statistically different with a mean age of 37.7 and 40.8 years, a median time on ART of 33 and 40 months and an eGFR of 139.3 and 131.0 mL/min in the lithium and placebo arms respectively. There was no statistical significant difference in the reduction in eGFR or increase in potassium between the two arms during the 24 weeks. Conclusions: We found that 24-week treatment of HIV-infected patients with lithium and TDF did not result in increased nephrotoxicity.
Single dose abacavir pharmacokinetics and safety in neonates exposed to human immunodeficiency virus (HIV)
(Oxford University Press, 2021-06) Bekker, Adrie; Decloedt, Eric H.; Slade, Gretchen; Cotton, Mark F.; Rabie, Helena; Cressey, Tim R.
Abacavir is a potential option for prophylaxis and early treatment of human immunodeficiency virus (HIV), but no data are available in neonates. Ten neonates administered a single abacavir dose of 8 mg/kg before 15 days of life had substantially higher exposures than those reported in infants and children, with no reported adverse events.

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