Eligibility for co-trimoxazole prophylaxis among adult HIV-infected patients in South Africa

Co-trimoxazole (fixed-dose trimethoprim-sulfamethoxazole) is a broad-spectrum antibiotic used to prevent opportunistic infections in patients with HIV infection. Primary prophylaxis with co-trimoxazole has been shown to decrease hospitalisation, morbidity and mortality among people living with HIV, primarily by decreasing rates of malaria, pneumonia, diarrhoea, Pneumocystis pneumonia, toxoplasmosis and severe bacterial infections.[1-4] Co-trimoxazole is inexpensive and widely available. In standard adult treatment guidelines and essential medicine lists in South Africa (SA), the current recommendation is that co-trimoxazole should be provided for HIV-infected patients with a CD4+ count ˂200 cells/μL, HIV/tuberculosis (TB) co-infection and/or advanced HIV disease (World Health Organization (WHO) stage 3 or 4). Because of expanded access and progression towards initiation of antiretroviral treatment (ART), the WHO issued updated guidelines for co-trimoxazole prophylaxis in 2014.[5] These guidelines recommend co-trimoxazole prophylaxis for adults (including pregnant women) with severe or advanced HIV clinical disease (WHO stage 3 or 4) and/or with a CD4+ count ≤350 cells/μL. In settings with a high prevalence of malaria and/or severe bacterial infections, prophylaxis is recommended for all patients regardless of WHO clinical stage or CD4+ cell count. However, the timing of discontinuation of co-trimoxazole prophylaxis may vary and is dependent on the malarial/ bacterial infection burden in different settings.[5] Therefore, the current WHO guidance should be adapted in the context of a country-specific epidemiological profile and priorities. The impact and benefit of co-trimoxazole prophylaxis on morbidity and mortality among HIV-infected patients with a CD4+ count ≤350 cells/μL in regions with high infectious disease burdens (irrespective of CD4+ count) have been shown in a good-quality systematic review and meta-analysis that included both randomised controlled trials (RCTs) and observational cohort studies.[6] This extensive systematic review by Suthar et al.[6] showed that co-trimoxazole prophylaxis reduced the rate of death when initiated at CD4+ counts ≤350 cells/μL with ART in populations in Africa and Asia. Co-trimoxazole prophylaxis in ART-naive patients with CD4+ counts >350 cells/μL reduced the rate of death and malaria, and continuation of prophylaxis after ART-induced recovery with CD4+ counts >350 cells/μL reduced hospital admission, pneumonia, malaria and diarrhoea in African populations (SA, Zimbabwe, Uganda, Malawi, Mozambique and Ethiopia).[6] While this review largely informed the 2014 WHO guideline update, the findings need to be interpreted in the context of studies included and the varied epidemiological profile across middle- and low-income countries. There were only 2 relatively small RCTs with very few events of key endpoints; therefore, the finding of non-significance was likely (e.g. total of ~5 deaths in both arms from both trials).[7,8] One of the 2 studies was unblinded, and the follow-up in the other study was only 4 months. Ongoing co-trimoxazole prophylaxis was better than discontinuation of the drug at CD4+ counts >200 cells/μL for 3 endpoints with an adequate number of events (pneumonia, diarrhoea and malaria). Furthermore, 8 of 9 studies were conducted in countries with a high burden of malaria and bacterial and parasitic diseases, which is generalisable to the SA context.[9] Although seasonal malaria occurs in the north-eastern parts of SA, the incidence of malaria mortality and morbidity has declined remarkably over time (˂10 000 cases annually for the past 10 years).[10] In contrast, in Uganda, >9 million confirmed cases of malaria were reported in the public health sector in 2015.[9] In this review, further stratification of the impact of co-trimoxazole prophylaxis at CD4+ counts ˂200 cells/μL v. 200 - 350 cells/μL was not available. Lower bacterial resistance to co-trimoxazole is possible among populations included in this review, while resistance to co-trimoxazole in SA is common in patients with community-acquired bacterial infections.[11-13] This potential risk of resistance compounded by the lack of long-term toxicity data needs to be weighed against recommending prophylaxis in populations where benefit has not been established. Local observational studies suggest no benefit of co-trimoxazole prophylaxis with a CD4+ count >200 cells/μL or in patients who were not WHO clinical stage 3 or 4.[14,15] In an observational cohort of patients attending the adult HIV clinics at the University of Cape Town, SA, the effect of prophylactic low-dose co-trimoxazole on survival and morbidity was examined over a 5-year follow-up period. Co-trimoxazole reduced the hazards of mortality by ~44% and the incidence of severe HIV-related illnesses by ~48% in patients with evidence of advanced immunosuppression (WHO stage 3 or 4) or laboratory measurement of total lymphocyte count ˂1 250 × 106/L or CD4+ count ˂200 cells/μL. However, no beneficial effect was seen in patients with WHO clinical stage 2 or CD4+ count 200 - 500 cells/μL. A potential limitation of this study was that the sample size of patients with a CD4+ count 200 - 500 cells/μL receiving co-trimoxazole was small and may have been underpowered to observe a significant benefit. In this study, patients on ART were excluded.[14] In another SA cohort study by Hoffmann et al.,[15] examining co-trimoxazole effectiveness in reducing mortality risk during ART among persons with a CD4+ count >200 cells/μL and varying WHO clinical stages, overall co-trimoxazole prophylaxis reduced mortality by 36% across all CD4+ count strata. Analysis stratified by baseline CD4+ count showed a similar reduction in mortality risk among persons with a CD4+ count ˂200 cells/μL, but no statistically significant association was found between co-trimoxazole prophylaxis and survival in the subgroup of persons with a CD4+ count >200 - 350 cells/μL, CD4+ count >350 cells/μL and WHO stage 1 or 2 disease. However, the findings of this study need to be interpreted cautiously for the following reasons: the group with a CD4+ count >350 cells/μL was small (n=917) and might not have had enough events to draw inferences; the study population was a cohort of miners and might not have been potentially representative of the SA population; and, being a non-randomised study, residual confounding might have been a potential limitation. An earlier Cochrane review established the benefit of initiating prophylaxis at a CD4+ count ˂200 cells/μL in those with stage 2, 3 or 4 HIV disease (including TB), and discontinuation once the CD4+ count was >200 cells/μL for >6 months.[16] There was a reduction of ~31% in mortality, 27% in morbid events and 55% in hospitalisation. Significant reductions were also detected for bacterial and parasitic infections and for Pneumocystis jirovecii pneumonia. Considering the above-mentioned evidence gaps and lack of generalisability of studies to SA, the current National Essential Medicines List Committee and Adult Hospital-Level Technical Sub-committee do not support the implementation of the updated guidance by the WHO for co-trimoxazole prophylaxis among adult HIV-infected patients. Efforts should be directed towards exploring several research gaps. The impact of co-trimoxazole prophylaxis on morbidity and mortality at higher CD4+ counts in low-malariaburden areas needs to be investigated further. More data are needed on timing of co-trimoxazole cessation in HIV and TB co-infection in our context

Selection of psychotropic medications for the primary health care essential medicine list: Rationale and process

Introduction: Equitable access to essential psychotropic medicines at primary level is fundamental to universal health coverage for mental health. It relies upon rational selection, affordable pricing, financial protection and consistent supply systems. Which medicines are selected as essential impacts patient care and the economic sustainability of the health system. Rational selection uses the best available evidence for efficacy, safety and acceptability, and requires the assurance of affordability, obtainability and appropriate usage of the medicines. The process should be reliable, transparent and consultative. Aim: The aim of this study is to describe the process of rational selection of essential psychotropic medicines at primary health care (PHC) level, using SSRIs as an example. Methods: Population, intervention, comparison and outcome (PICO) questions were developed for a rapid review of SSRIs for depression and anxiety. PubMed, Trip Database and Cochrane Library were searched for evidence, which was critically appraised (graded as per SORT criteria) and synthesised. Good governance principles were maintained using a consensus decision-making process within the constraints of the PHC Expert Review Committee’s terms of reference, confidentiality and conflict of interest policies. Evidence-based medicine principles were used, considering social values of equity, acceptability, comparative cost and relative budget impact analysis. Results: The PubMed search for meta-analyses yielded 588 articles, of which 13 met inclusion criteria. An additional 4 meta-analyses were retrieved from the Cochrane Library and 4 from additional reference lists. A second search specifying an HIV population retrieved 43 articles, of which 3 were included. The evidence for efficacy and harm of 24 papers was critically appraised by the committee. Conflicts of interest were declared, and there was appropriate recusal from the final decision-making, which took place in July 2018. Conclusion: Rapid reviews using an evidence-based medicine framework contributed to the selection of SSRIs for the PHC essential medicine list. This approach is intensive in terms of resources and capacity, requiring adaptation to the South African setting. Important limitations include time pressure and the use of a single reviewer, with possible incomplete database searches and reviewer bias. Nevertheless, the process allows for thorough, consistent and transparent decision-making, and improved capacity is recommended

Eligibility for co-trimoxazole prophylaxis among adult HIV-infected patients in South Africa

Co-trimoxazole (fixed-dose trimethoprim-sulfamethoxazole) is a broad-spectrum antibiotic used to prevent opportunistic infections in patients with HIV infection. Primary prophylaxis with co-trimoxazole has been shown to decrease hospitalisation, morbidity and mortality among people living with HIV, primarily by decreasing rates of malaria, pneumonia, diarrhoea, Pneumocystis pneumonia, toxoplasmosis and severe bacterial infections.[1-4] Co-trimoxazole is inexpensive and widely available. In standard adult treatment guidelines and essential medicine lists in South Africa (SA), the current recommendation is that co-trimoxazole should be provided for HIV-infected patients with a CD4+ count ˂200 cells/μL, HIV/tuberculosis (TB) co-infection and/or advanced HIV disease (World Health Organization (WHO) stage 3 or 4). Because of expanded access and progression towards initiation of antiretroviral treatment (ART), the WHO issued updated guidelines for co-trimoxazole prophylaxis in 2014.[5] These guidelines recommend co-trimoxazole prophylaxis for adults (including pregnant women) with severe or advanced HIV clinical disease (WHO stage 3 or 4) and/or with a CD4+ count ≤350 cells/μL. In settings with a high prevalence of malaria and/or severe bacterial infections, prophylaxis is recommended for all patients regardless of WHO clinical stage or CD4+ cell count. However, the timing of discontinuation of co-trimoxazole prophylaxis may vary and is dependent on the malarial/ bacterial infection burden in different settings.[5] Therefore, the current WHO guidance should be adapted in the context of a country-specific epidemiological profile and priorities. The impact and benefit of co-trimoxazole prophylaxis on morbidity and mortality among HIV-infected patients with a CD4+ count ≤350 cells/μL in regions with high infectious disease burdens (irrespective of CD4+ count) have been shown in a good-quality systematic review and meta-analysis that included both randomised controlled trials (RCTs) and observational cohort studies.[6] This extensive systematic review by Suthar et al.[6] showed that co-trimoxazole prophylaxis reduced the rate of death when initiated at CD4+ counts ≤350 cells/μL with ART in populations in Africa and Asia. Co-trimoxazole prophylaxis in ART-naive patients with CD4+ counts >350 cells/μL reduced the rate of death and malaria, and continuation of prophylaxis after ART-induced recovery with CD4+ counts >350 cells/μL reduced hospital admission, pneumonia, malaria and diarrhoea in African populations (SA, Zimbabwe, Uganda, Malawi, Mozambique and Ethiopia).[6] While this review largely informed the 2014 WHO guideline update, the findings need to be interpreted in the context of studies included and the varied epidemiological profile across middle- and low-income countries. There were only 2 relatively small RCTs with very few events of key endpoints; therefore, the finding of non-significance was likely (e.g. total of ~5 deaths in both arms from both trials).[7,8] One of the 2 studies was unblinded, and the follow-up in the other study was only 4 months. Ongoing co-trimoxazole prophylaxis was better than discontinuation of the drug at CD4+ counts >200 cells/μL for 3 endpoints with an adequate number of events (pneumonia, diarrhoea and malaria). Furthermore, 8 of 9 studies were conducted in countries with a high burden of malaria and bacterial and parasitic diseases, which is generalisable to the SA context.[9] Although seasonal malaria occurs in the north-eastern parts of SA, the incidence of malaria mortality and morbidity has declined remarkably over time (˂10 000 cases annually for the past 10 years).[10] In contrast, in Uganda, >9 million confirmed cases of malaria were reported in the public health sector in 2015.[9] In this review, further stratification of the impact of co-trimoxazole prophylaxis at CD4+ counts ˂200 cells/μL v. 200 - 350 cells/μL was not available. Lower bacterial resistance to co-trimoxazole is possible among populations included in this review, while resistance to co-trimoxazole in SA is common in patients with community-acquired bacterial infections.[11-13] This potential risk of resistance compounded by the lack of long-term toxicity data needs to be weighed against recommending prophylaxis in populations where benefit has not been established. Local observational studies suggest no benefit of co-trimoxazole prophylaxis with a CD4+ count >200 cells/μL or in patients who were not WHO clinical stage 3 or 4.[14,15] In an observational cohort of patients attending the adult HIV clinics at the University of Cape Town, SA, the effect of prophylactic low-dose co-trimoxazole on survival and morbidity was examined over a 5-year follow-up period. Co-trimoxazole reduced the hazards of mortality by ~44% and the incidence of severe HIV-related illnesses by ~48% in patients with evidence of advanced immunosuppression (WHO stage 3 or 4) or laboratory measurement of total lymphocyte count ˂1 250 × 106/L or CD4+ count ˂200 cells/μL. However, no beneficial effect was seen in patients with WHO clinical stage 2 or CD4+ count 200 - 500 cells/μL. A potential limitation of this study was that the sample size of patients with a CD4+ count 200 - 500 cells/μL receiving co-trimoxazole was small and may have been underpowered to observe a significant benefit. In this study, patients on ART were excluded.[14] In another SA cohort study by Hoffmann et al.,[15] examining co-trimoxazole effectiveness in reducing mortality risk during ART among persons with a CD4+ count >200 cells/μL and varying WHO clinical stages, overall co-trimoxazole prophylaxis reduced mortality by 36% across all CD4+ count strata. Analysis stratified by baseline CD4+ count showed a similar reduction in mortality risk among persons with a CD4+ count ˂200 cells/μL, but no statistically significant association was found between co-trimoxazole prophylaxis and survival in the subgroup of persons with a CD4+ count >200 - 350 cells/μL, CD4+ count >350 cells/μL and WHO stage 1 or 2 disease. However, the findings of this study need to be interpreted cautiously for the following reasons: the group with a CD4+ count >350 cells/μL was small (n=917) and might not have had enough events to draw inferences; the study population was a cohort of miners and might not have been potentially representative of the SA population; and, being a non-randomised study, residual confounding might have been a potential limitation. An earlier Cochrane review established the benefit of initiating prophylaxis at a CD4+ count ˂200 cells/μL in those with stage 2, 3 or 4 HIV disease (including TB), and discontinuation once the CD4+ count was >200 cells/μL for >6 months.[16] There was a reduction of ~31% in mortality, 27% in morbid events and 55% in hospitalisation. Significant reductions were also detected for bacterial and parasitic infections and for Pneumocystis jirovecii pneumonia. Considering the above-mentioned evidence gaps and lack of generalisability of studies to SA, the current National Essential Medicines List Committee and Adult Hospital-Level Technical Sub-committee do not support the implementation of the updated guidance by the WHO for co-trimoxazole prophylaxis among adult HIV-infected patients. Efforts should be directed towards exploring several research gaps. The impact of co-trimoxazole prophylaxis on morbidity and mortality at higher CD4+ counts in low-malariaburden areas needs to be investigated further. More data are needed on timing of co-trimoxazole cessation in HIV and TB co-infection in our context

Fixed dose drug combinations - are they pharmacoeconomically sound? Findings and implications especially for lower- and middle-income countries.

Introduction: There are positive aspects regarding the prescribing of fixed dose combinations (FDCs) versus prescribing the medicines separately. However, these have to be balanced against concerns including increased costs and their irrationality in some cases. Consequently, there is a need to review their value among lower- and middle-income countries (LMICs) which have the greatest prevalence of both infectious and noninfectious diseases and issues of affordability.Areas covered: Review of potential advantages, disadvantages, cost-effectiveness, and availability of FDCs in high priority disease areas in LMICs and possible initiatives to enhance the prescribing of valued FDCs and limit their use where there are concerns with their value.Expert commentary: FDCs are valued across LMICs. Advantages include potentially improved response rates, reduced adverse reactions, increased adherence rates, and reduced costs. Concerns include increased chances of drug:drug interactions, reduced effectiveness, potential for imprecise diagnoses and higher unjustified prices. Overall certain FDCs including those for malaria, tuberculosis, and hypertension are valued and listed in the country's essential medicine lists, with initiatives needed to enhance their prescribing where currently low prescribing rates. Proposed initiatives include robust clinical and economic data to address the current paucity of pharmacoeconomic data. Irrational FDCs persists in some countries which are being addressed

The current situation regarding long-acting insulin analogues including biosimilars among selected African, Asian, European and South American countries : findings and implications for the future

Background: Diabetes mellitus rates continue to rise, which coupled with increasing costs of associated complications has appreciably increased global expenditure in recent years. The risk of complications are enhanced by poor glycaemic control including hypoglycaemia. Long-acting insulin analogues were developed to reduce hypoglycaemia and improve adherence. Their considerably higher costs though have impacted their funding and use. Biosimilars can help reduce medicine costs. However, their introduction has been affected by a number of factors. These include the originator company dropping its price as well as promoting patented higher strength 300 IU/ml insulin glargine. There can also be concerns with different devices between the manufacturers. Objective: To assess current utilisation rates for insulins, especially long-acting insulin analogues, and the rationale for patterns seen, across multiple countries to inform strategies to enhance future utilisation of long-acting insulin analogue biosimilars to benefit all key stakeholders. Our approach: Multiple approaches including assessing the utilisation, expenditure and prices of insulins, including biosimilar insulin glargine, across multiple continents and countries. Results: There was considerable variation in the use of long-acting insulin analogues as a percentage of all insulins prescribed and dispensed across countries and continents. This ranged from limited use of long-acting insulin analogues among African countries compared to routine funding and use across Europe in view of their perceived benefits. Increasing use was also seen among Asian countries including Bangladesh and India for similar reasons. However, concerns with costs and value limited their use across Africa, Brazil and Pakistan. There was though limited use of biosimilar insulin glargine 100 IU/ml compared with other recent biosimilars especially among European countries and Korea. This was principally driven by small price differences in reality between the originator and biosimilars coupled with increasing use of the patented 300 IU/ml formulation. A number of activities were identified to enhance future biosimilar use. These included only reimbursing biosimilar long-acting insulin analogues, introducing prescribing targets and increasing competition among manufacturers including stimulating local production. Conclusions: There are concerns with the availability and use of insulin glargine biosimilars despite lower costs. This can be addressed by multiple activities

Grading of recommendations, assessment, development and evaluations concept 7: issues and insights linking guideline recommendations to trustworthy essential medicine lists

Objectives: Guidelines and essential medicine lists (EMLs) bear similarities and differences in the process that lead to decisions. Access to essential medicines is central to achieve universal health coverage. The World Health Organization (WHO) EML has guided prioritization of essential medicines globally for nearly 50 years, and national EMLs (NEMLs) exist in over 130 countries. Guideline and EML decisions, at WHO or national levels, are not always coordinated and aligned. We sought to explore challenges, and potential solutions, for decision-making to support trustworthy medicine selection for EMLs from a Grading of Recommendations, Assessment, Development and Evaluations (GRADE) Working Group perspective. We primarily focus on the WHO EML; however, our findings may be applicable to NEML decisions as well. Study Design and Setting: We identified key challenges in connecting the EML to health guidelines by involving a broad group of stakeholders and assessing case studies including real applications to the WHO EML, South Africa NEML, and a multiple sclerosis guideline connected to a WHO EML application for multiple sclerosis treatments. To address challenges, we utilized the results of a survey and feedback from the stakeholders, and iteratively met as a project group. We drafted a conceptual framework of challenges and potential solutions. We presented a summary of the results for feedback to all attendees of the GRADE Working Group meetings in November 2022 (approximately 120 people) and in May 2023 (approximately 100 people) before finalizing the framework. Results: We prioritized issues and insights/solutions that addressed the connections between the EML and health guidelines. Our suggested solutions include early planning alignment of guideline groups and EMLs, considering shared participation to strengthen linkage, further clarity on price/cost considerations, and using explicit shared criteria to make guideline and EML decisions. We also provide recommendations to strengthen the connection between WHO EML and NEMLs including through contextualization methods. Conclusion: This GRADE concept article, jointly developed by key stakeholders from the guidelines and EMLs field, identified key conceptual issues and potential solutions to support the continued advancement of trustworthy EMLs. Adopting structured decision criteria that can be linked to guideline recommendations bears the potential to advance health equity and gaps in availability of essential medicines within and between countries

Availability and use of long-acting insulin analogues including their biosimilars across Africa; findings and implications

Background: Prevalence rates of diabetes mellitus are growing across Africa with an appreciable number likely to be on insulin to manage their condition. This has significant implications on future morbidity and mortality exacerbated by high complication rates. Complication rates in patients requiring insulins are enhanced by hypoglycaemia. Long-acting insulin analogues were developed to reduce hypoglycaemia and improve patient compliance. However, they are typically appreciably more expensive than human and other insulins in Africa, and continuing controversies surrounding their benefits limits their listing on national essential medicine lists (EMLs). Biosimilars can reduce the prices long-acting insulin analogues. This needs assessing. Methods: Mixed methods approach including documentation of insulin utilisation patterns and prices among a range of African countries. In addition, input from senior level government, academic, and healthcare professionals from across Africa on the current situation with long-acting insulin analogues as well as potential changes needed to enhance future funding of long-acting analogue biosimilars. Results: There is variable listing of long-acting insulin analogues on national EMLs across Africa due to their high prices and issues of affordability. Even when listed, utilisation of long-acting insulin analogues is limited by similar issues including affordability. Appreciably lowering the prices of long-acting insulin analogues via biosimilars should enhance future listing on EMLs and use accompanied by educational and other initiatives. However, this will require increased competition to lower prices. Conclusion: There are concerns with value and funding of long-acting insulin analogues across Africa including biosimilars. A number of activities have been identified to improve future funding and listing on EMLs

Genomic epidemiology of SARS-CoV-2 in a UK university identifies dynamics of transmission

AbstractUnderstanding SARS-CoV-2 transmission in higher education settings is important to limit spread between students, and into at-risk populations. In this study, we sequenced 482 SARS-CoV-2 isolates from the University of Cambridge from 5 October to 6 December 2020. We perform a detailed phylogenetic comparison with 972 isolates from the surrounding community, complemented with epidemiological and contact tracing data, to determine transmission dynamics. We observe limited viral introductions into the university; the majority of student cases were linked to a single genetic cluster, likely following social gatherings at a venue outside the university. We identify considerable onward transmission associated with student accommodation and courses; this was effectively contained using local infection control measures and following a national lockdown. Transmission clusters were largely segregated within the university or the community. Our study highlights key determinants of SARS-CoV-2 transmission and effective interventions in a higher education setting that will inform public health policy during pandemics.</jats:p

Cook County And Downstate Illinois An Analysis Of Strategies To Bridge The Chasm An Analysis Of Strategies To Bridge The Chasm

Downstate Illinois and Cook County share common problems. The pension crisis drains state revenue. Illinois cut funding to higher education with the 12 state public universities not receiving funding for two years. Instead of working together to address these issues that are the core for a better future for the state, downstate Illinois voters believe that Cook County has downstate Illinois at a disadvantage. They believe that Cook County spends more state revenue than it contributes. However, a 2017 Illinois Legislative Review Unit report completed for State Senator Tom Cullerton indicated that the opposite is true. Counties in and around Chicago contribute more revenue than they receive in funding from the state. DuPage County in particular contributes more than its fair share, but more research will be needed to determine whether DuPage pays more because of higher income levels and more property taxes from its higher property values. Legislators cannot adequately address this chasm between the different parts of the state because they dedicate their time to serving their constituents and legislating, which usually requires building consensus. Building consensus involves accepting the various stakeholders’ positions and finding compromise from there. As a result, the chasm between the Chicago area and downstate Illinois persists. The thesis ends with suggestions for bridging the chasm between the Chicago area and downstate Illinois

Rheumatologists' perceptions of the co-incidence of tuberculosis associated with TNF-a inhibitors used for the treatment of rheumatoid arthritis in South Africa.

Biological disease-modifying anti-rheumatic drugs (DMARDs) for the treatment of Rheumatoid Arthritis, particularly TNF-α inhibitors, have been shown to improve patient outcome by slowing or halting radiographic damage. However, similar to most immunemodulators, there is an increased risk of infections co-incident with Tumour necrosis factor (TNF)-α inhibitor use, particularly the risk of activated latent tuberculosis infection (LTBI). Therefore, local and international guidelines recommend pre-screening for tuberculosis (TB) prior to the initiation of TNF-α therapy in rheumatoid arthritis (RA) patients. Also of critical importance in South Africa is the need for clinicians to be aware of environmental risk factors such as TB being highly endemic. Thus, a qualitative analysis was performed to investigate rheumatologists’ perceptions of TB co-incident with TNF-α inhibitors. Method: Physicians (n=18) practising rheumatology in the private and public healthcare sectors in Gauteng were interviewed to obtain their perceptions and attitudes related to TB co-incident with TNF-α inhibitor use. Interviews were audio-recorded and the transcripts analysed using thematic content analysis. Results: The determinants of health equity: Affordability, accessibility and availability of medicines (specifically TNF-α inhibitors) was reported to be different for the public care versus the private care patient. The high cost of TNF-α inhibitors warranted funding predominantly by the private medical schemes. A higher occurrence of latent TB infection was reported by physicians practising in the public or combined practice compared to the occurrence of LTBI in the private sector (21.4%versus 1.5%). The majority of study participants advocated pre-screening of TB, prior to the initiation of TNF-α inhibitors, in RA. However, it was suggested that because of the high occurrence of LTBI in the public sector, Isoniazid preventative therapy (IPT) should be compulsory, irrespective of the patient’s TB status, for the duration of TNF-α therapy. Most study participants supported local South African Rheumatism and Arthritis Association (SARAA) guideline recommendation to re-screen for TB by chest x-ray (CXR), every 6 months. However, the value of re-screening using diagnostic tools, purified protein derivative (PPD) skin test or interferon-gamma release assays (IGRAs) was queried due to the possibility of false readings. The occurrence of associated active TB in RA patients on TNF-α inhibitors was reported to be 0.07% in the private or combined practice versus 3.00% in the public sector. Forty percent of TB cases were reported to be extra-pulmonary. Despite active vigilance, some physicians reported that active TB month occurred months after the cessation of TNF-α inhibitor therapy. [Similar findings were observed from the British Society for Rheumatology Biologics Register (BSRBR)]. The majority of patients that developed TB co-incident with TNF-α inhibitors were treated successfully with TB chemotherapy. Only 1 of 12 patients died of extra-pulmonary TB, following compassionate use of infliximab in public care. Conclusion: Physicians practising rheumatology in Gauteng were of the opinion that there is a TB risk associated with the use of TNF-α inhibitors for the management of rheumatoid arthritis, as South Africa is a TB endemic country. Most acknowledged that these biological DMARDs were efficacious in slowing or halting radiographic progression in rheumatoid arthritis, but emphasised the need to take steps to prevent TB reactivation in the immuno - compromised RA patients and to remain overtly vigilant for active TB. In clinical practice, physicians mentioned that the monitoring and management of TB associated with TNF-α inhibitors appears to follow the socio-economic status of the RA patient and that distinct recommendations should be made for the public healthcare as well as the private healthcare sectors. Different opinions emanated from different physicians relating to the adequacy of local SARAA guidelines for the prevention of TB associated with TNF-α inhibitors. Some physicians mentioned that local guidelines were sufficient, whilst other physicians mentioned that the diagnostic tools were inadequate in the South African setting and that additional precautions should be taken in the form of IPT for the full duration of TNF-α therapy for all candidates, irrespective of TB status determined during pre-screening. As the science of biological DMARDs evolves with the rapid development of new medicinal therapies, physicians showed a preference to consider alternative non TNF-α biological DMARDs that had a lower risk of associated TB, specifically in high-risk RA patients. Physicians’ overall perception of the management of RA with TNF-α inhibitor therapy was that the risk-benefit assessment of these interventions, as well as patient preference and economic considerations should be taken into account