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

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

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

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’ follow-up 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

Predictors of impaired pulmonary function in people living with HIV in an urban African setting

Background: Studies have associated HIV with an increased risk of obstructive lung disease (OLD). Objectives: We aimed to identify the predictive factors for impaired lung function in an urban, African, HIV-positive population. Method: A cross-sectional study was performed in Johannesburg, South Africa, from July 2016 to November 2017. A questionnaire was administered and pre- and post-bronchodilator spirometry conducted. The predictors investigated included age, sex, antiretroviral treatment (ART) duration, body mass index, history of tuberculosis (TB) or pneumonia, occupational exposure, environmental exposure, smoking and symptoms of OLD (cough, wheeze, mucus and dyspnoea). Impaired lung function was defined as a forced expiratory volume in 1 second/forced vital capacity (FEV1/FVC) ratio of < 0.70, or below the 20th percentile of normal. Results: The 98 ART-naïve participants (mean age = 34.0, standard deviation [s.d.] = 8.2), 85 participants on first-line ART (mean age = 36.9, s.d. = 6.6) and 189 participants on second-line ART (mean age = 43.5, s.d. = 7.9) were predominantly female (65.6%). Of the participants, 64 (17.2%) had impaired lung function and 308 had normal lung function. Linear regression identified age (β = -0.003, P < 0.01), male sex (β = -0.016, P = 0.03) and history of TB or pneumonia (β = -0.024, P < 0.01) as independent predictors of a lower FEV1/FVC ratio. Following logistic regression, only a history of TB or pneumonia (odds ratio = 2.58, 95% confidence interval = 1.47-4.52) was significantly related to impaired lung function (area under the receiver operating characteristic curve = 0.64). Conclusion: Our data show that a history of TB or pneumonia predicts impaired lung function. In order to improve timely access to spirometry, clinicians should be alert to the possibility of impaired lung function in people with a history of TB or pneumonia

The influence of HIV infection and antiretroviral treatment on pulmonary function in individuals in an urban setting in sub-Saharan Africa

Background: With the roll-out of antiretroviral treatment (ART), the life expectancy of people with HIV and, hence, morbidity from non-communicable diseases, including pulmonary diseases, have increased.Objectives: This research study aims to investigate whether HIV infection and ART use are associated with pulmonary function, given the high frequency of pulmonary infections, including tuberculosis (TB), associated with HIV.Method: Adults living with HIV (ART-naïve, on first- or second-line ART), and age and sex matched HIV-negative controls were included in a cross-sectional study in Johannesburg, South Africa. Spirometry was performed to determine lung function, measuring the forced expiratory volume in one second (FEV1), the forced vital capacity (FVC) and the FEV1/FVC ratio before (pre), and after (post), short-acting bronchodilator. The association of HIV infection and ART use with pulmonary function was analysed using linear regression models, adjusting for age, gender, body surface area (BSA), employment, education, smoking and TB.Results: Overall, 548 participants (62% women) were included with a mean age of 38 (standard deviation [s.d.] 9.5) years. No effect of HIV or ART on post-FEV1 was observed in adjusted analysis. Additional adjustment for TB resulted in a higher post-FEV1 in participants on ART compared with HIV-negative participants, whereas TB was associated with a lower FEV1. No effect of HIV and ART on post-FEV1/FVC was observed.Conclusion: HIV infection and ART use were not associated with reduced pulmonary function in this urban African population. Tuberculosis showed a mediating effect on the association between HIV, ART and pulmonary function

No Evidence for an Association of HIV and Antiviral Treatment With Changes in Framingham Cardiovascular Risk Score in the Ndlovu Cohort Study

BACKGROUND: HIV and antiretroviral therapy (ART) have been associated with increased cardiovascular disease (CVD) risk in high-income countries. The authors studied the longitudinal association between HIV and ART and nonlaboratory Framingham Risk Score (FRS) in a middle-income country. METHODS AND RESULTS: This longitudinal analysis of the NCS (Ndlovu Cohort Study), South Africa used baseline to 36-month follow-up data. Demographics, HIV, ART status, and cardiometabolic measures were obtained. FRS was used as a CVD risk measure. Through linear mixed models, FRS trends over time and the association with HIV were studied. Analysis included 1136 participants, with 609 (54%) having HIV, and 495 (81%) taking ART. At baseline, 9.8% of participants had a high FRS. People living with HIV (PLHIV) had a 3.2% lower FRS than HIV-negative participants (P<0.001). FRS increased similarly for both groups over time. Other factors associated with FRS were secondary and higher education (ß value: -0.075, P<0.001; ß value: -0.084, P<0.001) and alcohol consumption (ß value: 0.011, P<0.001). CONCLUSIONS: CVD risk increased for all participants over 36 months, suggesting classic risk factors rather than HIV status or ART to be drivers of CVD risk. People living with HIV had a significantly lower FRS than their HIV-negative counterparts, possibly related to HIV itself or a more frequent interaction with healthcare services. No association of HIV and ART with changes in FRS over 36 months was observed, suggesting the need for research using clinical endpoints to elucidate the effects of HIV and ART on CVD risk. Population-based prevention of CVD risk factors in sub-Saharan Africa is warranted, regardless of HIV status