Browsing by Author "Cohen, Karen"
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- ItemOpen AccessA comparison of self-report and antiretroviral detection to inform estimates of antiretroviral therapy coverage, viral load suppression and HIV incidence in Kwazulu-Natal, South Africa(BioMed Central, 2017-09-29) Huerga, Helena; Shiferie, Fisseha; Grebe, Eduard; Giuliani, Ruggero; Farhat, Jihane B; Van-Cutsem, Gilles; Cohen, KarenBackground: Accurately identifying individuals who are on antiretroviral therapy (ART) is important to determine ART coverage and proportion on ART who are virally suppressed. ART is also included in recent infection testing algorithms used to estimate incidence. We compared estimates of ART coverage, viral load suppression rates and HIV incidence using ART self-report and detection of antiretroviral (ARV) drugs and we identified factors associated with discordance between the methods. Methods: Cross-sectional population-based survey in KwaZulu-Natal, South Africa. Individuals 15–59 years were eligible. Interviews included questions about ARV use. Rapid HIV testing was performed at the participants’ home. Blood specimens were collected for ARV detection, LAg-Avidity HIV incidence testing and viral load quantification in HIV-positive individuals. Multivariate logistic regression models were used to identify socio-demographic covariates associated with discordance between self-reported ART and ARV detection. Results: Of the 5649 individuals surveyed, 1423 were HIV-positive. Median age was 34 years and 76.3% were women. ART coverage was estimated at 51.4% (95%CI:48.5–54.3), 53.1% (95%CI:50.2–55.9) and 56.1% (95%CI:53.5–58.8) using self-reported ART, ARV detection and both methods combined (classified as ART exposed if ARV detected and/or ART reported) respectively. ART coverage estimates using the 3 methods were fairly similar within sex and age categories except in individuals aged 15–19 years: 33.3% (95%CI:23.3–45.2), 33.8% (95%CI:23.9–45.4%) and 44.3% (95%CI:39.3–46.7) using self-reported ART, ARV detection and both methods combined. Viral suppression below 1000cp/mL in individuals on ART was estimated at 89.8% (95%CI:87.3–91.9), 93.1% (95%CI:91.0–94.8) and 88.7% (95%CI:86.2–90.7) using self-reported ART, ARV detection and both methods combined respectively. HIV incidence was estimated at 1.4 (95%CI:0.8–2.0) new cases/100 person-years when employing no measure of ARV use, 1.1/100PY (95%CI:0.6–1.7) using self-reported ART, and 1.2/100PY (95%CI:0.7–1.7) using ARV detection. In multivariate analyses, individuals aged 15–19 years had a higher risk of discordance on measures of ARV exposure (aOR:9.4; 95%CI:3.9–22.8), while migrants had a lower risk (aOR:0.3; 95%CI:0.1–0.6). Conclusions: In KwaZulu-Natal, the method of identifying ARV use had little impact on estimates of ART coverage, viral suppression rate and HIV incidence. However, discordant results were more common in younger individuals. This may skew estimates of ART coverage and viral suppression, particularly in adolescent surveys.
- ItemOpen AccessA randomised controlled trial of N-acetylcysteine in the management of anti-tuberculosis drug-induced liver injury(2023) Moosa, Muhammed; Cohen, Karen; Maartens GaryBackground: Liver injury is the most common severe adverse effect of first-line anti-tuberculosis therapy (ATT). Nacetylcysteine (NAC) has efficacy in patients with paracetamol toxicity, and may be of benefit in liver injury due to other causes, such as ATT-induced liver injury (AT-DILI). Rechallenge of first line ATT after liver injury is usually attempted and may result in recurrence of liver injury. Alanine transaminase (ALT) is the biomarker currently used in AT-DILI diagnosis. MicroRNA-122 (miR-122) is a sensitive biomarker for liver injury due to paracetamol, but data on utility as a biomarker for ATDILI are limited. Methods: We conducted a randomized double-blind placebo-controlled trial of intravenous NAC in adult hospitalized participants with AT-DILI. Primary endpoint was time to ALT < 100 U/L; secondary endpoints included length of hospital stay and 8-week mortality. We described outcomes of ATT rechallenge following AT-DILI. We quantified miR-122 and ALT concentrations before and after infusion of NAC/placebo, and explored the effect of NAC on miR-122. Results We enrolled 102 participants with AT-DILI, 53 randomized to NAC and 49 to placebo. Mean age was 38 (SD±10) years, 58 (57%) were female and 89 (87%) were HIV positive. Median time to ALT
- ItemOpen AccessAdverse drug reactions in South African patients receiving bedaquiline-containing tuberculosis treatment: an evaluation of spontaneously reported cases(2019-06-20) Jones, Jackie; Mudaly, Vanessa; Voget, Jacqueline; Naledi, Tracey; Maartens, Gary; Cohen, KarenBackground Bedaquiline was recently introduced into World Health Organization (WHO)-recommended regimens for treatment of drug resistant tuberculosis. There is limited data on the long-term safety of bedaquiline. Because bedaquiline prolongs the QT interval, there are concerns regarding cardiovascular safety. The Western Cape Province in South Africa has an established pharmacovigilance programme: a targeted spontaneous reporting system which solicits reports of suspected adverse drug reactions (ADRs) in patients with HIV-1 and/or tuberculosis infection. Since 2015, bedaquiline has been included in the treatment regimens recommended for resistant tuberculosis in South Africa. We describe ADRs in patients on bedaquiline-containing tuberculosis treatment that were reported to the Western Cape Pharmacovigilance programme. Methods We reviewed reports of suspected ADRs and deaths received between March 2015 and June 2016 involving patients receiving bedaquiline-containing tuberculosis treatment. A multidisciplinary panel assessed causality, and categorised suspected ADRs using World Health Organisation-Uppsala Monitoring Centre system categories. “Confirmed ADRs” included all ADRs categorised as definite, probable or possible. Preventability was assessed using Schumock and Thornton criteria. Where a confirmed ADR occurred in a patient who died, the panel categorised the extent to which the ADR contributed to the patient’s death as follows: major contributor, contributor or non-contributor. Results Thirty-five suspected ADRs were reported in 32 patients, including 13 deaths. There were 30 confirmed ADRs, of which 23 were classified as “possible” and seven as “probable”. Bedaquiline was implicated in 22 confirmed ADRs in 22 patients. The most common confirmed ADR in patients receiving bedaquiline was QT prolongation (8 cases, 7 of which were severe). A fatal arrhythmia was suspected in 4 sudden deaths. These 4 patients were all taking bedaquiline together with other QT-prolonging drugs. There were 8 non-bedaquiline-associated ADRs, of which 7 contributed to deaths. Conclusions Confirmed ADRs in patients receiving bedaquiline reflect the known safety profile of bedaquiline. Quantifying the incidence and clinical consequences of severe QT-prolongation in patients receiving bedaquiline-containing regimens is a research priority to inform recommendations for patient monitoring in treatment programmes for drug resistant tuberculosis. Pharmacovigilance systems within tuberculosis treatment programmes should be supported and encouraged, to provide ongoing monitoring of treatment-limiting drug toxicity.
- ItemOpen AccessAGREE to disagree: critical appraisal and the publication of practice guidelines(2014) Wiseman, Roger; Cohen, Karen; Gray, Andy; Jamaloodien, Khadija; Kredo, Tamara; Miot, Jacqui; Parrish, Andy; Taylor, Bettina; Blockman, MarcFaced by an explosion in available evidence for multiple new treatments, busy clinicians value guidelines that are clear, reliable, unbiased and locally applicable. Finding them can be difficult, however. The science of guideline development has moved rapidly in the past decade, resulting in a more robust and systematic process. However, just as the language of evidence-based medicine can be subverted to sound convincing while hiding errors and biases, so too guidelines may look convincing but lack many of the elements needed to ensure quality of care. In particular, the pharmaceutical and health technology industries are intensely aware of the marketing potential offered by widely disseminated and ostensibly neutral documents that ultimately influence medical practice.
- ItemOpen AccessAntiretroviral therapy in a community clinic - early lessons from a pilot project(Health and Medical Publishing Group, 2003) Bekker, Linda-Gail; Orrell, Catherine; Reader, Larissa; Matoti, Larissa; Cohen, Karen; Martell, Rob; Abdullah, Fareed; Wood, RobinObjectives. To report on operational and clinical problems encountered during the first 6 months of a community-based antiretroviral therapy (ART) programme. Methods. ART was implemented in a primary care setting utilising an easily replicable service-delivery model based on a medical officer and nurse. Therapeutic counsellors, themselves HIV-infected, provided counselling and adherence support. Drug and monitoring costs were charitably funded and provincial health authorities supplied the medical infrastructure. The HIV Research Unit, University of Cape Town, supplied training and additional clinical support. Local HIV primary care clinics provided patient referrals. Standardised ART regimens were used with strict entry criteria (AIDS or CD4 count < 200 cells/µl). Results. Demand for the service was high. Referred patients had advanced disease (AIDS 57%, median CD4 count 96/µl) and high pre-treatment mortality (83/100 person-years). Mycobacterial disease was a major contributor to this mortality (40%). Scheduled clinic visit hours were six times higher during recruitment than maintenance. Attributable costs were: drugs 61%, staff 27%, viral load and CD4 cell counts 10% and safety monitoring 2%. Viral load after 16 weeks of therapy was < 400 copies/ml in the first 16 patients. Conclusions. ART can be successfully implemented within a primary care setting. Drug purchases and staff salaries drive programme costing. The service model is capable of managing 250 - 300 patients on chronic ART, but staffing needs to be increased during recruitment. Attention must be given to the diagnosis of tuberculosis during screening and early ART. Incorporating therapeutic counsellors into the programme increased community involvement and utilised a valuable and previously untapped resource.
- ItemOpen AccessAntiretroviral therapy, especially Efavirenz, is associated with low bone mineral density in HIV-infected South Africans(Public Library of Science, 2015) Dave, Joel A; Cohen, Karen; Micklesfield, Lisa K; Maartens, Gary; Levitt, Naomi SPurpose We determined the prevalence and correlates of low bone mineral density (BMD) in HIV-infected South Africans as there is a paucity of such data from Africa. METHODS: BMD and serum 25-hydroxyvitamin D were measured in HIV-positive participants on antiretroviral therapy (ART) and in those not yet on ART (ART-naïve). RESULTS: We enrolled 444 participants [median age 35(IQR: 30, 40) years; 77% women]. BMD was low (z score <-2SD) in 17% and 5% of participants at the lumbar spine and total hip, respectively. Total hip [0.909 (SD 0.123) vs 0.956 (SD 0.124) g/cm 2 , p = 0.0001] and neck of femur BMD [0.796 (SD 0.130) vs 0.844 (SD 0.120) g/cm 2 , p = 0.0001] were lower in the ART, compared to the ART-naïve group. Vitamin D deficiency was present in 15% of participants and was associated with efavirenz use [adjusted OR 2.04 (95% CI 1.01 to 4.13)]. In a multivariate linear regression, exposure to efavirenz or lopinavir-based ART was associated with lower total hip BMD, whereas higher weight, being male and higher vitamin D concentration were associated with higher total hip BMD (adjusted R 2 = 0.28). Age, weight, sex, and the use of efavirenz-based ART were independently associated with lumbar spine BMD (adjusted R 2 = 0.13). CONCLUSIONS: Vitamin D status, use of efavirenz or lopinavir/ritonavir, weight, age and sex are significantly associated with lower BMD in this young cohort of HIV-infected South Africans.
- ItemOpen AccessCases of antiretroviral-associated gynaecomastia reported to the National HIV & Tuberculosis Health Care Worker Hotline in South Africa(BioMed Central, 2016-11-16) Njuguna, Christine; Swart, Annoesjka; Blockman, Marc; Maartens, Gary; Chisholm, Briony; Stewart, Annemie; Uys, Anri; Cohen, KarenBackground: Gynaecomastia is associated with exposure to antiretroviral therapy (ART), in particular efavirenz. There is limited data on clinical characteristics of patients with ART-associated gynaecomastia in resource-limited settings and little guidance on the optimal management of this adverse drug reaction (ADR). We describe the clinical characteristics, management and outcomes of gynaecomastia cases reported to the National HIV & Tuberculosis Health Care Worker Hotline in South Africa. Methods: We identified all gynaecomastia cases in adolescent boys and men on ART reported to the hotline between June 2013 and July 2014. We collected follow up data telephonically at monthly intervals to document clinical management and outcomes. Results: We received 51 reports of gynaecomastia between June 2013 and July 2014; 11% of the 475 patient-specific ADR queries to the hotline. All patients were on efavirenz-based ART. Mean age was 34 years (standard deviation 12) and seven were adolescents. The median onset of gynaecomastia was 15 months after efavirenz initiation (interquartile range 6–42). Gynaecomastia was bilateral in 29 patients (57%) and unilateral in 16 (31%). Serum testosterone was quantified in 25 of 35 patients with follow up data, and was low in 2 (8%). Efavirenz was replaced with an alternative antiretroviral in 29/35 patients (83%) and gynaecomastia improved in 20/29 (69%). Conclusions: Gynaecomastia was a frequently reported ADR in our setting, occurring with prolonged efavirenz exposure. Testosterone was low in the minority of tested cases. Most clinicians elected to switch patients off efavirenz, and gynaecomastia improved in the majority.
- ItemOpen AccessThe clinical role of therapeutic drug monitoring of antiretrovirals : a Cochrane systematic review(2008) Kredo, Tamara; Cohen, KarenThe objective of this study is to evaluate whether ARV TDM reduces mortality and morbidity of adult patients on cART.
- ItemOpen AccessCommon infections - local and systematic(Health and Medical Publishing Group, 2004) Wilson, Douglas; Cohen, KarenThe 6th edition of Price’s A Textbook of the Practice of Medicine was published in 1941, a few years before penicillin came into general clinical use. Common infectious diseases are meticulously described and the characteristics of the infecting organisms are discussed in detail. The only group of antibiotic agents available, however, were the sulphonamides. Sulphanilamide had revolutionised the treatment of bacterial meningitis and infections due to Streptococcus pyogenes, and sulphapyridine had been found to be invaluable in the treatment of pneumococcal pneumonia, pyelonephritis and gonorrhoea. However, tuberculosis, typhoid and systemic infections due to Staphylococcus aureus carried a grave prognosis, and infective endocarditis was invariably fatal. The treatment of syphilis was prolonged, painful and unpredictable. The only agent available for the treatment of malaria was quinine. More than 60 years later we have a plethora of highly effective antibiotics, and tuberculosis is routinely cured by a standardised course of potent antituberculous drugs. Even the almost invariably lethal human immunodeficiency virus (isolated only 20 years ago) can be tamed by highly active antiretroviral therapy (HAART).
- ItemOpen AccessComparison of six methods to estimate adherence in an ART-naïve cohort in a resource-poor setting: which best predicts virological and resistance outcomes?(BioMed Central, 2017-04-04) Orrell, Catherine; Cohen, Karen; Leisegang, Rory; Bangsberg, David R; Wood, Robin; Maartens, GaryBackground: Incomplete adherence to antiretroviral therapy (ART) results in virologic failure and resistance. It remains unclear which adherence measure best predicts these outcomes. We compared six patient-reported and objective adherence measures in one ART-naïve cohort in South Africa. Methods: We recruited 230 participants from a community ART clinic and prospectively collected demographic data, CD4 count and HIV-RNA at weeks 0, 16 and 48. We quantified adherence using 3-day self-report (SR), clinicbased pill count (CPC), average adherence by pharmacy refill (PR-average), calculation of medication-free days (PR-gaps), efavirenz therapeutic drug monitoring (TDM) and an electronic adherence monitoring device (EAMD). Associations between adherence measures and virologic and genotypic outcomes were modelled using logistic regression, with the area under the curve (AUC) from the receiver operator characteristic (ROC) analyses derived to assess performance of adherence measures in predicting outcomes. Results: At week 48 median (IQR) adherence was: SR 100% (100–100), CPC 100% (95–107), PR-average 103% (95– 105), PR-gaps 100% (95–100) and EAMD 86% (59–94), and efavirenz concentrations were therapeutic (>1 mg/L) in 92%. EAMD, PR-average, PR-gaps and CPC best predicted virological outcome at week 48 with AUC ROC of 0.73 (95% CI 0.61–0.83), 0.73 (95% CI 0.61–0.85), 0.72 (95% CI 0.59–0.84) and 0.64 (95% CI 0.52–0.76) respectively. EAMD, PR-gaps and PR-average were highly predictive of detection of resistance mutations at week 48, with AUC ROC of 0.92 (95% CI 0.87–0.97), 0.86 (0.67–1.0) and 0.83 (95% CI 0.65–1.0) respectively. SR and TDM were poorly predictive of outcomes at week 48. Conclusion: EAMD and both PR measures predicted resistance and virological failure similarly. Pharmacy refill data is a pragmatic adherence measure in resource-limited settings where electronic monitoring is unavailable. Trial registration The trial was retrospectively registered in the Pan African Clinical Trials Registry, number PACTR201311000641402, on the 13 Sep 2013 (www.pactr.org). The first participant was enrolled on the 12th July 2012. The last patient last visit (week 48) was 15 April 2014
- ItemOpen AccessDetectable HIV-1 in semen in individuals with very low blood viral loads(2020-03-05) Kariuki, Samuel M; Selhorst, Philippe; Norman, Jennifer; Cohen, Karen; Rebe, Kevin; Williamson, Carolyn; Dorfman, Jeffrey RAbstract Background Several reports indicate that a portion (5–10%) of men living with HIV-1 intermittently shed HIV-1 RNA into seminal plasma while on long term effective antiretroviral therapy (ART). This is highly suggestive of an HIV-1 reservoir in the male genital tract. However, the status of this reservoir in men living with HIV-1 who are not under treatment is underexplored and has implications for understanding the origins and evolution of the reservoir. Finding Forty-three HIV-1 positive, antiretroviral therapy naïve study participants attending a men’s health clinic were studied. Semen viral loads and blood viral loads were generally correlated, with semen viral loads generally detected in individuals with blood viral loads > 10,000 cp/ml. However, we found 1 individual with undetectable viral loads (<20cp/ml) and 2 individuals with very low blood viral load (97 and 333cp/ml), but with detectable HIV-1 in semen (485–1157 copies/semen sample). Blood viral loads in the first individual were undetectable when tested three times over the prior 5 years. Conclusions Semen HIV-1 viral loads are usually related to blood viral loads, as we confirm. Nonetheless, this was not true in a substantial minority of individuals suggesting unexpectedly high levels of replication in the male genital tract in a few individuals, despite otherwise effective immune control. This may reflect establishment of a local reservoir of HIV-1 populations.
- ItemOpen AccessEffect of rifampicin-based antitubercular therapy on nevirapine plasma concentrations in South African adults with HIV-associated tuberculosis(2013) Cohen, Karen; Maartens, Gary; McIlleron, HelenSub-Saharan Africa is overwhelmed by dual epidemics of human immunodeficiency virus (HIV) and tuberculosis (TB) infection. Non-nucleoside reverse-transcriptase inhibitor (NNRTI)-based antiretroviral therapy (ART) is recommended for first-line treatment in adult HIV treatment programmes in resource-limited settings [1]. Many South African HIV-infected patients initiate ART while on TB treatment, 38 percent in one local study [2]. In addition, although ART reduces the incidence of TB, incidence in patients on ART is higher than in the HIV uninfected population [3], therefore incident TB on ART requiring concomitant treatment is very common. Efavirenz is regarded as the NNRTI of choice for TB co-infected patients [1] as outcomes are superior compared to those achieved with nevirapine-based ART [4] and concomitant TB treatment does not significantly reduce efavirenz concentrations [5]. However nevirapine is cheaper than efavirenz and is used extensively used in lower income countries with limited access to efavirenz [1]. Data characterising the extent to which concomitant rifampicin-based TB treatment decreases nevirapine plasma concentration therefore remain important.
- ItemOpen AccessThe impact of the National HIV Health Care Worker Hotline on patient care in South Africa(BioMed Central Ltd, 2011) Chisholm, Briony; Cohen, Karen; Blockman, Marc; Kinkel, Hans-Friedemann; Kredo, Tamara; Swart, AnnoesjkaBACKGROUND:South Africa has a huge burden of illness due to HIV infection. Many health care workers managing HIV infected patients, particularly those in rural areas and primary care health facilities, have minimal access to information resources and to advice and support from experienced clinicians. The Medicines Information Centre, based in the Division of Clinical Pharmacology at the University of Cape Town, has been running the National HIV Health Care Worker (HCW) Hotline since 2008, providing free information for HIV treatment-related queries via telephone, fax and e-mail. RESULTS: A questionnaire-based study showed that 224 (44%) of the 511 calls that were received by the hotline during the 2-month study period were patient-specific. Ninety-four completed questionnaires were included in the analysis. Of these, 72 (77%) were from doctors, 13 (14%) from pharmacists and 9 (10%) from nurses. 96% of the callers surveyed took an action based on the advice received from the National HIV HCW Hotline. The majority of actions concerned the start, dose adaption, change, or discontinuation of medicines. Less frequent actions taken were adherence and lifestyle counselling, further investigations, referring or admission of patients. CONCLUSIONS: The information provided by the National HIV HCW Hotline on patient-specific requests has a direct impact on the management of patients.
- ItemOpen AccessLiver Injury in HIV-positive Patients on Antituberculosis and/or Antiretroviral Therapy – Assessing Causality(2022) Gunter, Hannah May; Cohen, KarenBackground We compared performance of the Roussel Uclaf Causality Assessment Method (RUCAM) with multidisciplinary expert panel review in identifying a drug-induced liver injury (DILI) due to antituberculosis therapy (ATT) and/or antiretroviral therapy (ART). Methods Cases were drawn from a prospective registry of hospitalised adults with suspected DILI due to ATT and/or ART in Cape Town, South Africa. Participants had to fulfil American Thoracic Society criteria for ATT interruption (alanine transaminase [ALT]≥5 times upper limit of normal [ULN]/ALT≥3 times [ULN] and symptomatic). Causality assessment by expert panel review served as reference standard. The panel ranked potentially implicated drugs as certain, probable, possible, or unlikely causes guided by World Health Organization Uppsala Monitoring Centre criteria. The RUCAM was performed for each potentially implicated drug. We calculated sensitivity and specificity of the RUCAM in identifying a probable/certain drug cause for liver injury. Results We included 48 participants. All were HIV-positive. Twenty-seven were on concomitant ART and ATT, with a median of 6 potentially hepatotoxic drugs per case. Sensitivity and specificity of the RUCAM in identifying a probable/certain drug cause of liver injury compared with expert panel review was 11% and 85% respectively. Implicated drugs (times ranked probable/certain by panel) were isoniazid (18/0), pyrazinamide (17/0), rifampicin (15/1), efavirenz (6/4), lopinavir/ritonavir (1/0). Conclusions HIV-positive patients with liver injury received multiple potentially implicated drugs, which may increase liver injury risk and complicates causality assessment. Compared with expert panel review, the RUCAM had low sensitivity in detecting probable or certain drug causes of liver injury.
- ItemOpen AccessMorbidity from antiretroviral metabolic effects in Africa: The Mama Study(2017) Karamchand, Sumanth; Cohen, Karen; Maartens, GaryIntroduction: Combination antiretroviral therapy (ART) has considerably reduced both the morbidity and mortality of Human Immunodeficiency Virus (HIV) infection and its associated complications, thus effectively transforming a fatal disease into a manageable chronic condition. However, the chronic use of ART has been accompanied by the emergence of adverse metabolic abnormalities in HIV-infected patients, including dysglycaemia. There is, however, a paucity of data from sub-Saharan Africa on the incidence and risk factors associated with new onset diabetes mellitus in the HIV-infected population. Furthermore, efavirenz is the preferred nonnucleoside reverse transcriptase inhibitor (NNRTI) in first-line antiretroviral therapy (ART) regimens in low- and middle-income countries, where the prevalence of diabetes is increasing. Randomized control trials have shown mild increases in plasma glucose in participants in the efavirenz arms, but no association has been reported with overt diabetes. This study explores the risk factors and incidence of diabetes, and in particular the association between efavirenz exposure and diabetes, in a large Southern African cohort commencing NNRTI-based first-line ART. Subjects and Methods: The study cohort included HIV-infected adults commencing NNRTI-based ART in a private sector HIV disease management programme from January 2002 to December 2011. Incident diabetes was identified by the initiation of diabetes treatment. Patients with prevalent diabetes were excluded. The incidence of diabetes in patients receiving efavirenz versus nevirapine containing regimens was compared with a Kaplan-Meier plot and a log-rank test. The association of efavirenz exposure with the hazard of developing diabetes was modelled using a multivariate Cox-proportional hazards model. The following variables were adjusted for in the regression model: age, sex, baseline BMI, baseline CD4, baseline viral load, exposure to diabetogenic drugs, and nucleoside reverse transcriptase inhibitor (NRTI) exposure. Results: Between January 2002 and June 2011, 62,467 patients commenced ART in the AfA program, of whom 56,298 patients met the inclusion and exclusion criteria and were included in the analysis. Median follow-up was 1.56 years (interquartile range (IQR): 0.71- 2.79 years), 21.7% of patients were followed up for 3 or more years. New onset diabetes was identified in 1500 (2.66%) patients over 113,297 patient-years of follow-up (PYFU), giving a crude incidence of 13.24 cases per 1000 PYFU. In the multivariate analysis treatment with efavirenz rather than nevirapine was associated with increased risk of developing diabetes (hazard ratio 1.27 (95% confidence interval: 1.10 - 1.46). Zidovudine and stavudine exposure, older baseline age, elevated baseline BMI, and exposure to diabetogenic medication were also associated with increased risk of diabetes. No association was found between baseline CD4 and an increased risk of diabetes. There was an association between the lowest stratum of baseline viral load and an increased relative risk for developing diabetes, but no association with higher viral load strata. Conclusion: Treatment with efavirenz, as well as stavudine and zidovudine, increased the risk of incident diabetes. Interventions to detect and prevent diabetes should be implemented in ART programmes, and use of antiretrovirals with lower risk of metabolic complications should be encouraged.
- ItemOpen AccessN-Acetylcysteine for non-paracetamol drug-induced liver injury: A systemic review(2016) Chughlay, Mohamed Farouk; Cohen, KarenAims: There are limited therapeutic options for drug-induced liver injury (DILI). N-acetylcysteine (NAC ) is known to be of benefit in management of DILI due to paracetamol overdose and may also be useful in the management of non-paracetamol DILI. Our objective was to systematically review evidence for the use of NAC as a therapeutic option for non-paracetamol DILI. Methods: We conducted a systematic review of the benefit and harm of NAC in non-paracetamol DILI. We searched for randomized controlled trials (RCTs) and prospective cohort studies. We searched several bibliographic databases (including PubMed, Scopus, CINAHL, CENTRAL), grey literature sources, conference proceedings and ongoing trials. Our pre-specified primary outcomes were all cause and DILI related mortality, time to normalisation of liver biochemistry and adverse events. Secondary outcomes were proportion receiving liver transplant, time to transplantation, transplant-free survival and hospitalization duration. Two reviewers independently assessed studies for inclusion and quality and extracted data. Results: We identified one RCT of NAC versus placebo in patients with non-paracetamol acute liver failure. There was no difference in the primary outcomes of overall survival at 3-weeks between NAC [70%, 95% Confidence Interval (CI)= 60% to 81%, n=81 ] and placebo (66%, 95% C I= 56% to 77%, n=92 ). NAC significantly improved the secondary outcomes of transplant-free survival compared with placebo : 40% NAC ( 95% CI= 28% to 51%) versus 27% placebo ( 95% CI= 18% to 37%). A subgroup analysis according to aetiology found improved transplant-free survival in patients with non-paracetamol DILI; NAC (58%, n=19 ) versus placebo (27%, n=26 ); odds ratio (OR) 0.27 (95% CI= 0.076 to 0.942 ). O verall survival was similar NAC ( 79% ) v ersus placebo ( 65% ); OR 0.5 0 ( 95% CI= 0.13 to 1.98 ). Conclusion : Current available evidence is limited and does not allow for any firm conclusions to be made regarding the role of NAC in non-paracetamol DILI. We therefore highlight the need for further research in this area.
- ItemOpen AccessN-acetylcysteine for non-paracetamol drug-induced liver injury: a systematic review protocol(BioMed Central Ltd, 2015) Chughlay, Mohamed; Kramer, Nicole; Werfalli, Mahmoud; Spearman, Wendy; Engel, Mark E; Cohen, KarenBACKGROUND: Drug-induced liver injury (DILI) refers to acute or chronic liver injury that may occur as a consequence of using drugs and herbal or dietary supplements. Specific therapies for DILI are limited. There is considerable evidence for efficacy and safety of N-acetylcysteine (NAC) in management of paracetamol-induced liver injury. More recently, research has explored the use of NAC in non-paracetamol drug-induced liver injury. It is important to summarise the evidence of NAC for non-paracetamol DILI to determine if NAC may be considered a therapeutic option in this condition.METHODS/DESIGN:We will conduct a systematic review of the benefit and harm of NAC in non-paracetamol drug-induced liver injury. Primary and secondary outcomes of interest are pre-specified. Primary outcomes include all-cause mortality, mortality due to DILI, time to normalisation of liver biochemistry (e.g. return of alanine transaminase to <100 U/l and/or international normalized ratio (INR) <1.5) and adverse events. Secondary outcomes include transplantation rate, time to transplantation, transplant-free survival and duration of hospitalisation. We will include randomized controlled trials (RCTs) and prospective cohort studies. RCTs will contribute to the evaluation of safety and efficacy of NAC, whereas, the cohort studies will contribute exclusively to the evaluation of safety. We will search several bibliographic databases (including PubMed, Scopus, CINAHL, CENTRAL), grey literature sources, conference proceedings and ongoing trials. Following data extraction and assessment of the risk of bias, we will conduct a meta-analysis if feasible, as well as subgroup analyses. We will assess and explore clinical and statistical heterogeneity.DISCUSSION:The aim of this review is to provide evidence on the effectiveness and safety of NAC in non-paracetamol DILI. We anticipate that the results could aid health care practitioners, researchers and policymakers in the decision-making regarding the use of NAC in patients with non-paracetamol DILI.SYSTEMATIC REVIEW REGISTRATION:PROSPERO CRD42014008771
- ItemOpen AccessSafety and effectiveness of colistin compared with tobramycin for multi-drug resistant Acinetobacter baumannii infections(2009) Gounden, Ronald; Maartens, Gary; Cohen, KarenBackground: Nosocomial infections due to multi-drug resistant Acinetobacter baumannii are often treated with colistin, but there are few data comparing its safety and effectiveness with other antimicrobials, particularly the aminoglycosides. Metbods: A retrospective cohort study of patients treated with colistin or tobramycin for A. baumannii infections in intensive care units (ICUs) at Groote Schuur hospital was performed. Colistin was used for A baumannii isolates which were resistant to all other available antimicrobials. Tobramycin was used when the organism was susceptible to this antimicrobial. We assessed and compared ICU mortality, nephrotoxicity and time to the first negative culture in the colistin and tobramycin groups.
- ItemOpen AccessSerious adverse drug reactions at two children’s hospitals in South Africa(2020-01-04) Mouton, Johannes P; Fortuin-de Smidt, Melony C; Jobanputra, Nicole; Mehta, Ushma; Stewart, Annemie; de Waal, Reneé; Technau, Karl-Günter; Argent, Andrew; Kroon, Max; Scott, Christiaan; Cohen, KarenAbstract Background The high HIV prevalence in South Africa may potentially be shaping the local adverse drug reaction (ADR) burden. We aimed to describe the prevalence and characteristics of serious ADRs at admission, and during admission, to two South African children’s hospitals. Methods We reviewed the folders of children admitted over sequential 30-day periods in 2015 to the medical wards and intensive care units of each hospital. We identified potential ADRs using a trigger tool developed for this study. A multidisciplinary team assessed ADR causality, type, seriousness, and preventability through consensus discussion. We used multivariate logistic regression to explore associations with serious ADRs. Results Among 1050 patients (median age 11 months, 56% male, 2.8% HIV-infected) with 1106 admissions we found 40 serious ADRs (3.8 per 100 drug-exposed admissions), including 9/40 (23%) preventable serious ADRs, and 8/40 (20%) fatal or near-fatal serious ADRs. Antibacterials, corticosteroids, psycholeptics, immunosuppressants, and antivirals were the most commonly implicated drug classes. Preterm neonates and children in middle childhood (6 to 11 years) were at increased risk of serious ADRs compared to infants (under 1 year) and term neonates: adjusted odds ratio (aOR) 5.97 (95% confidence interval 1.30 to 27.3) and aOR 3.63 (1.24 to 10.6) respectively. Other risk factors for serious ADRs were HIV infection (aOR 3.87 (1.14 to 13.2) versus HIV-negative) and increasing drug count (aOR 1.08 (1.04 to 1.12) per additional drug). Conclusions Serious ADR prevalence in our survey was similar to the prevalence found elsewhere. In our setting, serious ADRs were associated with HIV-infection and the antiviral drug class was one of the most commonly implicated. Similar to other sub-Saharan African studies, a large proportion of serious ADRs were fatal or near-fatal. Many serious ADRs were preventable.
- ItemOpen AccessA survey of the availability of palliative care drugs to patients served by the public sector in the Knysna Health sub-district(2005) Stanford, Janet; Gwyther, Liz; Cohen, KarenThe research aimed to assess the availability of palliative care drugs to patients served by the public sector in the Knysna Health district. The population of approximately 50 000 is served by a Hospice organisation which offers home-based care (it has no residential component), 4 Municipal clinics, the 96 bed Knysna Provincial District Hospital and a regional referral centre 65km away, viz., the George Provincial Hospital. Tertiary referral is to Cape Town 600km away. The need for palliative care services has increased with the HIV/AIDS epidemic. Drugs on the hospital level EDLs are collected from the Knysna PRovincial Hospital by the Hospice staff and given to their patients.