Cardiovascular toxicity of contemporary antiretroviral therapy

PURPOSE OF REVIEW: HIV treatment has evolved since the introduction of antiretroviral therapy (ART) in the 1990s. Earlier treatment strategies, and the introduction of integrase inhibitors in preferred first-line ART have fundamentally changed cardiovascular side effects due to HIV infection and ART. This review provides an update on cardiovascular toxicity of contemporary ART. RECENT FINDINGS: Cardiovascular disease (CVD) risk, including heart failure, is still increased in people living with HIV (PLWH). Exposure to older antiretrovirals, including stavudine and zidovudine, still impact on CVD risk through persistent changes in body fat distribution years after discontinuation. Protease inhibitors (PI) and efavirenz have associated metabolic disturbances and increased risk of CVD, although use is decreasing worldwide. Integrase inhibitors and CCR5 antagonists seem to have negligible immediate CVD toxicity. Weight gain on newer antiretrovirals including integrase inhibitors is a reason for concern. SUMMARY: CVD risk should be monitored carefully in PLWH who were exposed to first generation ART, efavirenz or to PIs. Registries should capture ART use and CVD events to stay informed on actual clinical risk in the current era of rapid initiation on integrase inhibitor-based ART

Epidemiology and Control of diabetes - tuberculosis comorbidity in Eswatini: protocol for the prospective study of tuberculosis patients on predictive factors, treatment outcomes and patient management practices

INTRODUCTION: Previous studies indicate people with diabetes mellitus (DM) may have varying treatment outcomes when receiving treatment for tuberculosis (TB) and that TB infection or its treatment may predispose them to develop an abnormal blood glucose or type 2 DM. This has implications for Eswatini which is a high TB burden country and with increasing cases of non-communicable diseases including DM. This study will describe the epidemiology of DM-TB comorbidity in a prospective cohort of patients receiving TB treatment and identify best practices for integration of care for non-communicable diseases into TB services in Eswatini. METHODS AND ANALYSIS: This study will employ a mixed-methods approach. Data from a prospective cohort of newly enrolled patients with TB at 12 health facilities from 1 June 2022 to 30 September 2022, and followed up to 30 April 2023, will be used. For the qualitative, key informants who provide TB services at the health facilities will be interviewed. Quantitative data from patients will be analysed descriptively and by tests of association and multivariate modelling. Key informant interviews from healthcare workers will be analysed using content analysis. ETHICS AND DISSEMINATION: This research has been approved by the Eswatini Health and Human Research Review Board and participant confidentiality will be maintained. COVID-19 safety measures to reduce the risk of infection or transmission by researchers and participants have been instituted. Key programmatic findings and how they can impact healthcare delivery and access will be presented to the specific programme in the Eswatini Ministry of Health and other relevant stakeholders

Patterns of Immune Activation in HIV and Non HIV Subjects and Its Relation to Cardiovascular Disease Risk

Introduction: Insight into inflammation patterns is needed to understand the pathophysiology of HIV and related cardiovascular disease (CVD). We assessed patterns of inflammation related to HIV infection and CVD risk assessed with carotid intima media thickness (CIMT). Methods: A cross-sectional study was performed in Johannesburg, South Africa, including participants with HIV who were virally suppressed on anti-retroviral therapy (ART) as well as HIV-negative participants who were family members or friends to the HIV-positive participants. Information was collected on CVD risk factors and CIMT. Inflammation was measured with the Olink panel ‘inflammation’, allowing to simultaneously assess 92 inflammation markers. Differences in inflammation patterns between HIV-positive and HIV-negative participants were explored using a principal component analysis (PCA) and ANCOVA. The impact of differentiating immune markers, as identified by ANCOVA, on CIMT was assessed using linear regression while adjusting for classic CVD risk factors. Results: In total, 185 HIV-positive and 104 HIV negative participants, 63% females, median age 40.7 years (IQR 35.4 – 47.7) were included. HIV-positive individuals were older (+6 years, p <0.01) and had a higher CIMT (p <0.01). No clear patterns of inflammation were identified by use of PCA. Following ANCOVA, nine immune markers differed significantly between HIV-positive and HIV-negative participants, including PDL1. PDL1 was independently associated with CIMT, but upon stratification this effect remained for HIV-negative individuals only. Conclusion: HIV positive patients on stable ART and HIV negative controls had similar immune activation patterns. CVD risk in HIV-positive participants was mediated by inflammation markers included in this study

Tuberculosis treatment and resulting abnormal blood glucose: a scoping review of studies from 1981 - 2021

BACKGROUND: Hyperglycaemia is a risk factor for tuberculosis. Evidence of changes in blood glucose levels during and after tuberculosis treatment is unclear. OBJECTIVE: To compile evidence of changes in blood glucose during and after tuberculosis treatment and the effects of elevated blood glucose changes on treatment outcomes in previously normoglycaemic patients. METHODS: Original research studies (1980 to 2021) were identified in PubMed, Web of Science, CINAHL and Embase databases. RESULTS: Of the 1,277 articles extracted, 14 were included in the final review. All the studies were observational and 50% were prospective. Fasting blood sugar was the most common clinical test (64%), followed by the glycated haemoglobin test and the oral glucose tolerance test (each 50%). Most tests were conducted at baseline and in the third month of treatment. Twelve studies showed that the prevalence of hyperglycaemia in previously normoglycaemic patients decreased from baseline to follow-up and end of treatment. Three studies showed successful treatment outcomes of 64%, 75% and 95%. Patients with hyperglycaemia at baseline were more likely to develop cavitary lung lesions and poor treatment outcomes and had higher post-treatment mortality. There was no difference in outcomes by human immunodeficiency virus (HIV) status. CONCLUSION: Elevated blood glucose in normoglycaemic patients receiving treatment for tuberculosis decreased by the end of treatment. Positive HIV status did not affect glucose changes during treatment. Further research is needed to investigate post-treatment morbidity in patients with baseline hyperglycaemia and the effects of HIV on the association between blood glucose and tuberculosis

Influence of shift work on cardiovascular disease risk in Southern African long-distance truck drivers: a cross-sectional study

OBJECTIVES: Cardiovascular disease (CVD) is a major problem globally. Truck drivers have an increased risk of CVD due to a sedentary lifestyle, irregular working hours and behavioural choices. We aimed to get insight into the contribution of night shift work to CVD risk in long-distance truck drivers in South Africa. DESIGN: A cross-sectional study. SETTING: Enrolment took place at three South African truck stop locations in two provinces; Bloemfontein (Free State), Pomona Road (Gauteng) and Soweto (Gauteng). PARTICIPANTS: 607 males aged ≥18 years with full-time employment as a long-distance truck driver were included. The criteria for inclusion were willingness and being able to provide informed consent and to complete the study procedures. PRIMARY AND SECONDARY OUTCOME MEASURES: Information was collected on sociodemographics, occupational and health characteristics. Physical measurements, an ECG and carotid intima-media thickness (CIMT) measurements were taken. A night shift was defined as working at least 3 hours between 22:00 and 6:00 hours once a week. CVD risk was defined with the Framingham Risk Score (FRS), the Atherosclerotic Cardiovascular Disease (ASCVD) risk algorithm, left ventricular hypertrophy (LVH) and CIMT. RESULTS: In total, 607 truck drivers were included of which 305 (50.2%) worked in day shifts only and 302 (49.8%) worked day and night shifts. There was a high prevalence of CVD risk factors in both groups as 33% were hypertensive, 28% obese and 37% had abnormal lipid levels. Working day and night shifts compared with working only day shifts did not result in differences in FRS, ASCVD risk or LVH. No difference was found in CIMT measurements, except for the maximum bulb thickness which was higher in day shift workers. CONCLUSIONS: CVD risk factors are considerably present in male truck drivers in South Africa. CVD risk does not differ between dayshift and day-night shift workers in this cross-sectional analysis

Trends in body mass index in the pre-dolutegravir period in South Africa

Background: Antiretroviral therapy (ART) is associated with weight gain, but this has been shown to be more marked with dolutegravir and other integrase strand transfer inhibitors. Objectives: We studied weight gain in people living with HIV (PLWH) on ART compared to the general population in the period before dolutegravir was introduced in a rural South African cohort. Method: Longitudinal analysis of the Ndlovu Cohort Study including 36–48 months’ followup data. From 2014 to 2019, data were collected annually in Limpopo, rural South Africa. Linear mixed models using HIV status, demographics, ART use and cardiovascular risk factors were used to estimate trends in body mass index (BMI) over time. Results: In total, 1518 adult, non-pregnant participants were included, of whom 518 were PLWH on ART (79.8%), 135 PLWH not yet on ART (20.2%) and 865 HIV-negative. HIV-negative participants had significantly higher BMIs than PLWH on ART at all study visits. There was a significant increase in BMI in all subgroups after 36 months (PLWH on ART, BMI +1.2 kg/m2, P < 0.001; PLWH not on ART, BMI +1.8 kg/m2, P < 0.001 and HIV-negative, BMI +1.3 kg/m2, P < 0.001). Conclusion: The increase in BMI in PLWH and HIV-negative participants is a serious warning signal as obesity results in morbidity and mortality

The influence of smoking and HIV infection on pulmonary function

Background: Prevalence of HIV, smoking, and pulmonary infections in South Africa are high.Objectives: We investigated the role of smoking and HIV status on lung function.Methods: This is a secondary analysis of a cross-sectional study conducted in South Africa. Data included demographics, pulmonary risk factors and a spirometry test to obtain the forced expiratory volume in one second (FEV1) and the ratio of FEV1/forced vital capacity (FVC). In the initial multivariable regression analysis, the effect of smoking on pulmonary function in HIV-positive adults was assessed. The analysis was repeated, assessing the influence of HIV status on lung function in both HIV-negative and HIV-positive smokers. The models were adjusted for age, sex, body mass index (BMI), time since HIV diagnosis, antiretroviral treatment (ART) use, occupational hazards, history of tuberculosis or pneumonia, indoor smoking and the presence of an indoor fireplace during childhood.Results: This study included 524 people living with HIV (PLWH, 66.7% female, mean age 40.9 years [s.d.; 9.4]) and 79 HIV-negative smokers (77.2% male, mean age 34.4 years [s.d.: 12.1]). Of the PLWH, 118 (22.5%) were past or current smokers and 406 (77.5%) were non-smokers. Smoking was not associated with changes in the FEV1 or FEV1/FVC ratio in multivariable regression analysis. In the second analysis, HIV status was also not associated with reduced pulmonary function following adjustment for confounders.Conclusion: Neither smoking nor being HIV-positive was associated with decreased pulmonary function in this relatively young population. These findings should be confirmed in a longitudinal study, including an older population

Corrigendum: Diabetes—Tuberculosis Care in Eswatini: A Qualitative Study of Opportunities and Recommendations for Effective Services Integration

[This corrects the article DOI: 10.3389/ijph.2023.1605551.]

Tuberculosis services during the COVID-19 pandemic: A qualitative study on the impact of COVID-19 and practices for continued services delivery in Eswatini

Objectives To describe the impact of the COVID-19 pandemic on tuberculosis services and the different approaches healthcare workers adopted to ensure continued tuberculosis service delivery in Eswatini. Study design This is a qualitative study with a cross-sectional design. Methods Thirteen nurses and 9 doctors who provide tuberculosis care from 10 health facilities participated in an in-depth interview to describe how the COVID-19 pandemic affected tuberculosis services and the approaches adopted to ensure continued patient care. Twenty in-person and 2 telephone interviews were conducted. The participating facilities were selected based on a ranking criterion of the number of patients seen. Data were analyzed using thematic content analysis. NVivo 12 software was used for qualitative analysis, and the Consolidated Criteria guided the study for Reporting Qualitative research (COREQ). Results Two major themes emerged: COVID-19 impacted services delivery and access; and best practices that ensured healthcare services delivery. Six sub-themes describe how COVID-19 impacted services: all attention focused on COVID-19; COVID worsened the health system challenges; COVID hindered patients from accessing care; patients defaulted due to the lockdown; COVID impacted the quality of care and increased the risk of infection among healthcare workers. Five sub-themes describe best practices that ensure continued service delivery: Home-based care, Patient support, Patient Education, Integrated Services, and Staff rotation. Conclusion While various strategies were adopted globally to mitigate the impact of the COVID-19 pandemic, these strategies need contextualization to be effective and sustainably incorporated into routine care to ensure continuity of and access to TB and other healthcare services

Diabetes—Tuberculosis Care in Eswatini: A Qualitative Study of Opportunities and Recommendations for Effective Services Integration

Objective: This study describes the availability of basic services, equipment, and commodities for integrated DM–TB services, best practices by healthcare workers, and opportunities for better integration of DM–TB care in Eswatini.Methods: A qualitative design was used. Twenty-three healthcare workers participated in a survey and key informant interview.Results: Most respondents indicated DM and TB care are integrated and clients access blood pressure and fasting/random blood glucose assessment. Few respondents indicated they provide visual assessment, hearing assessment, and HbA1c testing. Respondents experienced stockouts of urinalysis strips, antihypertensive drugs, insulin, glucometer strips, and DM drugs in the previous 6 months before the interview. Four main themes emerged from the qualitative interviews—quality and current standards of care, best practices, opportunities, and recommendations to improve integrated services delivery.Conclusion: While DM care is provided for TB patients, the implementation of integrated DM–TB services is suboptimal as the quality and current standards of care vary across health facilities due to different patient-level and health system challenges. Some identified opportunities must be utilized for a successful DM–TB integration