Adverse drug reactions in South African patients receiving bedaquiline-containing tuberculosis treatment: an evaluation of spontaneously reported cases

Background 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

Risk factors for Coronavirus disease 2019 (Covid-19) death in a population cohort study from the Western Cape province, South Africa

Risk factors for coronavirus disease 2019 (COVID-19) death in sub-Saharan Africa and the effects of human immunodeficiency virus (HIV) and tuberculosis on COVID-19 outcomes are unknown. We conducted a population cohort study using linked data from adults attending public-sector health facilities in the Western Cape, South Africa. We used Cox proportional hazards models, adjusted for age, sex, location, and comorbidities, to examine the associations between HIV, tuberculosis, and COVID-19 death from 1 March to 9 June 2020 among (1) public-sector “active patients” (≥1 visit in the 3 years before March 2020); (2) laboratory-diagnosed COVID-19 cases; and (3) hospitalized COVID-19 cases. We calculated the standardized mortality ratio (SMR) for COVID-19, comparing adults living with and without HIV using modeled population estimates.Among 3 460 932 patients (16% living with HIV), 22 308 were diagnosed with COVID-19, of whom 625 died. COVID19 death was associated with male sex, increasing age, diabetes, hypertension, and chronic kidney disease. HIV was associated with COVID-19 mortality (adjusted hazard ratio [aHR], 2.14; 95% confidence interval [CI], 1.70–2.70), with similar risks across strata of viral loads and immunosuppression. Current and previous diagnoses of tuberculosis were associated with COVID-19 death (aHR, 2.70 [95% CI, 1.81–4.04] and 1.51 [95% CI, 1.18–1.93], respectively). The SMR for COVID-19 death associated with HIV was 2.39 (95% CI, 1.96–2.86); population attributable fraction 8.5% (95% CI, 6.1–11.1)

Self-reported strategies for maintaining adherence to antiretroviral therapy in men aged 21 - 49

Thesis (MPhil (Industrial Psychology. Africa Centre for HIV/AIDS Management))--University of Stellenbosch, 2010.ENGLISH ABSTRACT:Adherence to antiretroviral therapy (ART) is essential to maintain long term health benefits and avoid development of drug resistance. It is not possible for health care providers to reliably predict which individuals will ultimately be adherent to their treatment plan. The reason being that adherence does not correlate with gender, cultural background, socio-economic status or level of education. Studies showed that adherence in resource-limited settings are equal or superior to that in resource-rich settings. HIV positive patients‟ adherence to ART is relatively high in African nations compared to developed world countries. Adherence is a multidimensional phenomenon determined by five sets of factors as set out by the World Health Organisation (WHO). The predictors of adherence are related to factors pertaining to the patient, their condition, socio-economic status, the health care system and the ART they receive. Semi-structured interviews were conducted with twelve men at a government clinic that provides ART services. The ages range from 25 to 44 years. The mean CD4 count was 294 (range 68 – 622) and all the participants had undetectable viral loads within the last six months. They were on ART for a mean 27.8 months (range 9 – 41 months). Some self-strategies emerged from this study to explain the good virological response that is linked to good adherence. Participants experienced remarkable improvement in their health and physical condition and maintained good health whilst taking ART. This led to increased confidence in the ART and motivated them to stay adherent. Participants were fearful of falling ill again and of dying. Feedback regarding their CD4 counts recovering and viral loads decreasing provided them with positive reinforcement. Monthly pill counts are a strategy that gave them a sense of achievement and motivated them to maintain adherence. The participants developed specific strategies to remember to take ART. They made use of watches and cell phone alarms. Pill-taking was incorporated into their daily activities such as mealtimes, listening to radio and watching television. All the participants had an open relationship with the clinic staff. Patients at this particular clinic were well prepared by the clinic staff before starting ART. They trust the advice and instructions from the doctor and other clinic staff. The findings support the recommendations made by the National Antiretroviral Treatment Guidelines pertaining to adherence. This study emphasises the fact that patients devise their own strategies to stay adherent to ART. Each community is different and each clinic should further investigate the unique strategies that patients employ to stay adherent and build it into their treatment plan.AFRIKAANSE OPSOMMING: Die nakoming van ART is noodsaaklik om langtermyn gesondheid te onderhou en om middelverwante weerstandigheid te voorkom. Dit is nie moontlik vir gesondheidsdiens beamptes om te voorspel watter individue nakomend gaan wees aan hulle behandeling nie. Die rede vir dit is omdat nakoming nie verband hou met geslag, kultuur, sosio-ekonomiese status of die vlak van onderrig nie. Studies het bewys dat nakoming in swak bediende areas net so goed of selfs beter is as in beter bediende areas. Die menslike immuniteitsgebreksvirus (MIV) positiewe pasiënte se nakoming aan ART is relatief hoog in Afrika nasies in vergelyking met die ontwikkelde nasies. Nakoming van ART is „n fenomeen met verskeie fasette en vyf faktore word geïdentifiseer deur die Wêreld Gesondheid Organisasie (WHO). Die voorspellers van nakoming is verbind aan faktore wat verwant is aan die pasiënt, sy kondisie, sosio-ekonomiese status, die gesondheidsisteem en die ART wat geneem word. Onderhoude was gevoer met 12 mans wat ART ontvang by „n staats fasiliteit. Hulle ouderdomme wissel van 25 tot 44 jaar. Die gemiddelde CD4 telling is 294 (wissel van 68 tot 622) en al die deelnemers het onderdrukte virale ladings gehad in die afgelope ses maande. Die deelnemers was op ART vir gemiddeld 27,8 maande (wissel 9 tot 41 maande). Daar het sekere self-strategieë na vore gekom wat die goeie virologiese reaksie wat gekoppel is aan nakoming kon verduidelik. Die deelnemers se gesondheid het merkwaardig verbeter en dit het so gebly terwyl hulle ART ontvang het. Dit het beteken dat deelnemers baie vertroue gehad het in die middels en hulle was gemotiveerd om nakomend te bly. Die deelnemers was bang dat hulle weer sou siek raak of doodgaan as hulle die ART sou stop. Die terugvoering wat hulle ontvang het aangaande hulle hoë CD4 tellings en lae virale ladings het hulle as positiewe terugvoering beskou. Die strategie van maandelikse pil telling het bygedra tot hulle gevoel van sukses en het ook gedien as motivering om nakomend te bly. Die deelnemers het spesifieke strategieë ontwikkel wat gedien het as „n herinnering om hulle ART gereeld te neem. Hulle het gebruik gemaak van horlosies en selfoon alarms. Dit was ook geinkorporeer in hulle daaglikse roetine soos maaltye, om radio te luister en televisie te kyk. Al die deelnemers het „n goeie verhouding met die personeel van die kliniek gehad. Die pasiënte word baie goed voorberei deur die personeel voordat hulle ART begin. Die pasiënte vertrou die instruksies wat die personeel vir hulle gee. My bevindings ondersteun die aanbevelings wat gestel word deur die Nasionale Antiretrovirale Riglyne aangaande nakoming aan ART. v Elke gemeenskap is verskillend en elke kliniek moet verder ondersoek instel in die unieke strategieë wat hulle pasiente gebuik om nakomend te bly