Transfers between health facilities of people living with diabetes attending primary health care services in the Western Cape Province of South Africa: A retrospective cohort study.

OBJECTIVES: Transfers between health facilities of people living with HIV attending primary health care (PHC) including hospital to PHC facility, PHC facility to hospital and PHC facility to PHC facility transfers occur frequently, affect health service planning, and are associated with disengagement from care and viraemia. Data on transfers among people living with diabetes attending PHC, particularly transfers between PHC facilities, are few. We assessed the transfer incidence rate of people living with diabetes attending PHC, and the association between transfers between PHC facilities and subsequent HbA1c values. METHODS: We analysed data on HbA1c tests at public sector facilities in the Western Cape Province (2016-March 2020). Individuals with an HbA1c in 2016-2017 were followed-up for 27 months and included in the analysis if ≥18 years at first included HbA1c, ≥2 HbA1cs during follow-up and ≥1 HbA1c at a PHC facility. A visit interval was the duration between two consecutive HbA1cs. Successive HbA1cs at different facilities of any type indicated any transfer, and HbA1cs at different PHC facilities indicated a transfer between PHC facilities. Mixed effects logistic regression adjusted for sex, age, rural/urban facility attended at the start of the visit interval, disengagement (visit interval >14 months) and a hospital visit during follow-up assessed the association between transfers between PHC facilities and HbA1c >8%. RESULTS: Among 102,813 participants, 22.6% had ≥1 transfer of any type. Including repeat transfers, there were 29,994 transfers (14.4 transfers per 100 person-years, 95% confidence interval [CI] 14.3-14.6). A total of 6996 (30.1%) of those who transferred had a transfer between PHC facilities. Visit intervals with a transfer between PHC facilities were longer (349 days, interquartile range [IQR] 211-503) than those without any transfer (330 days, IQR 182-422). The adjusted relative odds of an HbA1c ≥8% after a transfer between PHC facilities versus no transfer were 1.20 (95% CI 1.05-1.37). CONCLUSION: The volume of transfers involving PHC facilities requires consideration when planning services. Individuals who transfer between PHC facilities require additional monitoring and support.

Phenotype and predictors of insulin independence in adults presenting with diabetic ketoacidosis: a prospective cohort study.

AIMS/HYPOTHESIS: The aim of this work was to describe the phenotype of adults presenting with a first episode of diabetic ketoacidosis (DKA) in Cape Town, South Africa, and identify predictors of insulin independence at 12 and 60 months after presentation. METHODS: A prospective, descriptive cohort study of all individuals, 18 years or older, presenting for the first time with DKA to four public-sector hospitals of the Groote Schuur Academic Health Complex was performed. Clinical, biochemical and laboratory data including GAD antibody and C-peptide status were collected at baseline. Insulin was systematically weaned and stopped in individuals who achieved normoglycaemia within the months after DKA. Individuals were followed for 12 months and then annually until 5 years after initial presentation with ketoacidosis. RESULTS: Eighty-eight individuals newly diagnosed with diabetes when presenting with DKA were included and followed for 5 years. The mean ± SD age was 35±10 years and the median (IQR) BMI at diagnosis was 28.5 (23.3-33.4) kg/m2. Overall, 46% were insulin independent 12 months after diagnosis and 26% remained insulin independent 5 years after presentation. Forty-one participants (47%) tested negative for anti-GAD and anti-IA-2 antibodies and had C-peptide levels >0.3 nmol/l; in this group, 68% were insulin independent at 12 months and 37% at 5 years after diagnosis. The presence of acanthosis nigricans was strongly associated with insulin independence (OR 27.1 [95% CI 7.2, 102.2]; p<0.001); a positive antibody status was associated with a lower likelihood of insulin independence at 12 months (OR 0.10 [95% CI 0.03, 0.36]; p<0.001). On multivariable analysis only acanthosis (OR 11.5 [95% CI 2.5, 53.2]; p=0.004) was predictive of insulin independence 5 years after diagnosis. CONCLUSIONS/INTERPRETATION: The predominant phenotype of adults presenting with a first episode of DKA in Cape Town, South Africa, was that of ketosis-prone type 2 diabetes. These individuals presented with obesity, acanthosis nigricans, negative antibodies and normal C-peptide and could potentially be weaned off insulin at follow-up. Classic type 1 diabetes (lower weight, antibody positivity, low or unrecordable C-peptide levels and long-term insulin dependence) was less common. The simple clinical sign of acanthosis nigricans is a strong predictor of insulin independence at 12 months and 5 years after initial presentation.

Routine health data describe adherence and persistence patterns for oral diabetes medication for a virtual cohort in the Khayelitsha sub-district of Cape Town, South Africa.

Type 2 diabetes mellitus (T2DM) is managed with combined lifestyle modifications and antidiabetic drugs, but people on treatment often fail to reach glycaemic control. Adherence is important for achieving optimal glycaemic control, and management of diabetes with drugs is a lifelong process, so understanding adherence through analysis of longitudinal medications data is important. Using retrospective routine health data and metformin dispensing records as a proxy for medication use, we describe longitudinal persistence and adherence to oral diabetes medication in a virtual cohort of 10541 people with diabetes (PLWD) in Khayelitsha subdistrict, Cape Town. Adherence was measured in 120-day sliding windows over two years and used to estimate metformin adherence trajectories. Multinomial logistic regression identified factors influencing these trajectories. Analysis of pharmacy dispensing records showed varying medication refill patterns: while some PLWD refilled prescriptions consistently, others had treatment gaps with periods of non-persistence and multiple treatment episodes-from one to five per individual across two years. There was a general trend of decreasing adherence over time across all sliding windows in the two-year period, with only 25% of the study population achieved medication adherence (> = 80% adherence) after two years. Four adherence trajectories; 'low adherence gradual decline (A), 'high adherence rapid decline' (B), 'low adherence gradual increase (C) and 'adherent' (D) were identified. Only trajectory D represented participants who were adherent at treatment start and remained adherent after two years. Taking HIV antiretroviral treatment before or concurrently with diabetes treatment and taking metformin in combination with sulphonylurea and/or insulin were associated with the long-term adherence (trajectory D). Routine data shows real life medication implementation patterns which might not be seen under controlled study conditions. This study illustrates the utility of these data in describing longitudinal adherence patterns at both an individual and population level.

Management of Type 2 Diabetes Mellitus and Kidney Failure in People with HIV-Infection in Africa: Current Status and a Call to Action.

There is an increasing global burden of diabetes mellitus (DM) and chronic kidney disease (CKD), coupled with a high burden of people with HIV (PWH). Due to an increased lifespan on ART, PWH are now at risk of developing non-communicable diseases, including DM. Africa has the greatest burden of HIV infection and will experience the greatest increase in prevalence of DM over the next two decades. In addition, there is a rising number of people with CKD and progression to kidney failure. Therefore, there is an urgent need for the early identification and management of all 3 diseases to prevent disease progression and complications. This is particularly important in Africa for people with CKD where there is restricted or no access to dialysis and/or transplantation. This review focuses on the epidemiology and pathophysiology of the interaction between HIV infection and DM and the impact that these diseases have on the development and progression of CKD. Finally, it also aims to review the data on the management, which stems from the growing burden of all three diseases.

Clinical features and outcomes of COVID-19 admissions in a population with a high prevalence of HIV and tuberculosis: a multicentre cohort study.

BACKGROUND: There is still a paucity of evidence on the outcomes of coronavirus disease 2019 (COVID-19) among people living with human immunodeficiency virus (PWH) and those co-infected with tuberculosis (TB), particularly in areas where these conditions are common. We describe the clinical features, laboratory findings and outcome of hospitalised PWH and human immunodeficiency virus (HIV)-uninfected COVID-19 patients as well as those co-infected with tuberculosis (TB). METHODS: We conducted a multicentre cohort study across three hospitals in Cape Town, South Africa. All adults requiring hospitalisation with confirmed COVID-19 pneumonia from March to July 2020 were analysed. RESULTS: PWH comprised 270 (19%) of 1434 admissions. There were 47 patients with active tuberculosis (3.3%), of whom 29 (62%) were PWH. Three-hundred and seventy-three patients (26%) died. The mortality in PWH (n = 71, 26%) and HIV-uninfected patients (n = 296, 25%) was comparable. In patients with TB, PWH had a higher mortality than HIV-uninfected patients (n = 11, 38% vs n = 3, 20%; p = 0.001). In multivariable survival analysis a higher risk of death was associated with older age (Adjusted Hazard Ratio (AHR) 1.03 95%CI 1.02-1.03, p < 0.001), male sex (AHR1.38 (95%CI 1.12-1.72, p = 0.003) and being "overweight or obese" (AHR 1.30 95%CI 1.03-1.61 p = 0.024). HIV (AHR 1.28 95%CI 0.95-1.72, p 0.11) and active TB (AHR 1.50 95%CI 0.84-2.67, p = 0.17) were not independently associated with increased risk of COVID-19 death. Risk factors for inpatient mortality in PWH included CD4 cell count < 200 cells/mm3, higher admission oxygen requirements, absolute white cell counts, neutrophil/lymphocyte ratios, C-reactive protein, and creatinine levels. CONCLUSION: In a population with high prevalence of HIV and TB, being overweight/obese was associated with increased risk of mortality in COVID-19 hospital admissions, emphasising the need for public health interventions in this patient population.

Reference intervals for biochemical analytes in transgender individuals on hormone therapy.

BACKGROUND: Hormone therapy in transgender individuals may impact processes that lead to changes in biochemical analytes, and therefore reference intervals. Currently, few reference interval studies are available for the transgender population. We determined biochemical reference intervals for transgender individuals receiving hormone therapy. METHODS: Our retrospective, laboratory-based, observational study included healthy transgender males (N = 24) and transgender females (N = 84) on hormone therapy. Various biochemical reference intervals were established for each cohort and compared to their cisgender counterparts. RESULTS: We detected significant differences in reference intervals for sodium, 139-142 mmol/L vs. 136-145 mmol/L when comparing transgender males (TM) with cisgender males (CM). The following significant changes in upper reference limits (URL) for TM versus CM were detected, ALP (URL: 96 U/L vs. 128 U/L), GGT (URL: 27 U/L vs. 67 U/L) and testosterone (URL: 46.7 nmol/L vs. 29.0 nmol/L), respectively. Moreover, when comparing transgender female (TF) to cisgender female (CF), significant differences in creatinine (URL: 117 µmol/L vs. 90 µmol/L), albumin (lower reference limit: 41 g/L, vs. 35 g/L), AST (URL: 50 U/L vs. 35 U/L), ALP (URL: 118 U/L vs. 98 U/L) and oestradiol (URL: 934 pmol/L vs. 213 pmol/L) were noted, respectively. Significantly higher LDL-C was observed for TM on hormone treatment, compared to baseline (2.9 mmol/L vs. 2.2 mmol/L, p <0.01). CONCLUSIONS: Biochemical results for TM and TF receiving hormone therapy can be evaluated against our transgender-specific reference intervals for some analytes, while others can be compared to their identified gender reference intervals.

Tumor-induced osteomalacia: a case report.

BACKGROUND: Tumor-induced osteomalacia is a rare, acquired paraneoplastic syndrome, including hypophosphatemia, high serum alkaline phosphatase, reduced active vitamin D, suboptimal bone mineral density, bone pain, fragility fractures, and muscle weakness. CASE PRESENTATION: We report a case of 74-year-old male of mixed ancestry with hypophosphatemia resistant to treatment despite optimal compliance, associated with profound reduction of bone mineral density and multiple nontraumatic fractures, including bilateral rib fractures, lower-thoracic (T11, T12) vertebrae, and two fractures involving the surgical and anatomical neck of the right humerus. We discuss an approach to identifying the underlying cause of hypophosphatemia associated with fragility fractures, and options for management of this rare condition. CONCLUSION: Although rare, tumor-induced osteomalacia can be diagnosed if a logical stepwise approach is implemented. Surgery could be curative if the tumor is properly located and is resectable.

Erratum: Demographic and socio-economic predictors of physical activity among people living with HIV of low socio-economic status.

[This corrects the article DOI: 10.4102/hsag.v24i0.1127.].

Factors Associated with Bone Mineral Density and Bone Resorption Markers in Postmenopausal HIV-Infected Women on Antiretroviral Therapy: A Prospective Cohort Study.

The study aimed to determine factors associated with changes in bone mineral density (BMD) and bone resorption markers over two years in black postmenopausal women living with human immunodeficiency virus (HIV) on antiretroviral therapy (ART). Women (n = 120) aged > 45 years were recruited from Potchefstroom, South Africa. Total lumbar spine and left femoral neck (LFN) BMD were measured with dual energy X-ray absorptiometry. Fasting serum C-Telopeptide of Type I collagen (CTx), vitamin D and parathyroid hormone were measured. Vitamin D insufficiency levels increased from 23% at baseline to 39% at follow up. In mixed linear models serum CTx showed no change from baseline to end (p = 0.363, effect size = 0.09). Total and LFN BMD increased significantly over two years, but effect sizes were small. No significant change in spine BMD over time was detected (p = 0.19, effect size = 0.02). Age was significantly positively associated with CTx over time, and negatively with total and LFN BMD. Physical activity (PA) was positively associated with LFN BMD (p = 0.008). Despite a decrease in serum vitamin D, BMD and CTx showed small or no changes over 2 years. Future studies should investigate PA interventions to maintain BMD in women living with HIV.

Risk factors for COVID-19 hospitalisation and death in people living with diabetes: A virtual cohort study from the Western Cape Province, South Africa.

BACKGROUND: COVID-19 outcomes and risk factors, including comorbidities and medication regimens, in people living with diabetes (PLWD) are poorly defined for low- and middle-income countries. METHODS: The Provincial Health Data Centre (Western Cape, South Africa) is a health information exchange collating patient-level routine health data for approximately 4 million public sector health care seekers. Data from COVID-19 patients diagnosed between March and July 2020, including PLWD, were analysed to describe risk factors, including dispensed diabetes medications and comorbidities, and their association with COVID-19 outcomes in this population. FINDINGS: There were 64,476 COVID-19 patients diagnosed. Of 9305 PLWD, 44.9% were hospitalised, 4.0% admitted to ICU, 0.6% received ventilation and 15.4% died. In contrast, proportions of COVID-19 patients without diabetes were: 12.2% hospitalised, 1.0% admitted, 0.1% ventilated and 4.6% died. PLWD were significantly more likely to be admitted (OR:3.73, 95 %CI: 3.53, 3.94) and to die (OR:3.01, 95 %CI: 2.76,3.28). Significant hospitalised risk factors included HIV infection, chronic kidney disease, current TB, male sex and increasing age. Significant risk factors for mortality were CKD, male sex, HIV infection, previous TB and increasing age. Pre-infection use of insulin was associated with a significant increased risk for hospitalisation (OR:1·39, 95 %CI:1·24,1·57) and mortality (OR1·49, 95 %CI:1·27; 1·74) and metformin was associated with a reduced risk for hospitalisation (OR:0·62,95 %CI:0·55, 0·71) and mortality (OR 0·77, 95 %CI:0·64; 0·92). INTERPRETATION: Using routine health data from this large virtual cohort, we have described the association of infectious and noncommunicable comorbidities as well as pre-infection diabetes medications with COVID-19 outcomes in PLWD in the Western Cape, South Africa. FUNDING: This research was funded in part, by the Wellcome Trust 203135/Z/16/Z, through support of NT. For the purpose of open access, the author has applied a CC BY public copyright licence to any Author Accepted Manuscript version arising from this submission. The Wellcome Centre for Infectious Diseases Research in Africa is supported by core funding from the Wellcome Trust [203135/Z/16/Z]. NT receives funding from the CIDRI-Africa Wellcome Trust grant (203135/Z/16/Z), and NT and TT receive funding from the NIH H3ABioNET award (U24HG006941). NT receives funding from the UKRI/MRC (MC_PC_MR/T037733/1).

Diabetes in a TB and HIV-endemic South African population: Analysis of a virtual cohort using routine health data.

BACKGROUND: It is widely accepted that people living with diabetes (PLWD) are at increased risk of infectious disease, yet there is a paucity of epidemiology studies on the relationship between diabetes and infectious disease in SSA. In a region with a high burden of infectious disease, this has serious consequences for PLWD. METHODS AND FINDINGS: Using routinely collected longitudinal health data, we describe the epidemiology of diabetes in a large virtual cohort of PLWD who have a high burden of HIV and TB, from the Khayelitsha subdistrict in the Western Cape Province in South Africa. We described the relationship between previous TB, newly diagnosed TB disease and HIV infection on diabetes using HbA1c results as an outcome measure. The study population was predominately female (67%), 13% had a history of active TB disease and 18% were HIV positive. The HIV positive group had diabetes ascertained at a significantly younger age (46 years c.f. 53 years respectively, p<0.001) and in general had increased HbA1c values over time after their HIV diagnosis, when compared to the HIV-negative group. There was no evidence of TB disease influencing the trajectory of glycaemic control in the long term, but diabetes patients who developed active TB had higher mortality than those without TB (12.4% vs 6.7% p-value < 0.001). HIV and diabetes are both chronic diseases whose long-term management includes drug therapy, however, only 52.8% of the study population with an HIV-diabetes comorbidity had a record of diabetes treatment. In addition, the data suggest overall poor glycaemic control in the study population with only 24.5% of the participants having an HbA1c <7% at baseline despite 85% of the study population being on diabetes treatment. CONCLUSION: The epidemiologic findings in this exploratory study highlight the need for further research into diabetes outcomes in a high TB and HIV burden setting and demonstrate that routine health data are a valuable resource for understanding disease epidemiology in the general population.

The utility of high-flow nasal oxygen for severe COVID-19 pneumonia in a resource-constrained setting: A multi-centre prospective observational study.

BACKGROUND: The utility of heated and humidified high-flow nasal oxygen (HFNO) for severe COVID-19-related hypoxaemic respiratory failure (HRF), particularly in settings with limited access to intensive care unit (ICU) resources, remains unclear, and predictors of outcome have been poorly studied. METHODS: We included consecutive patients with COVID-19-related HRF treated with HFNO at two tertiary hospitals in Cape Town, South Africa. The primary outcome was the proportion of patients who were successfully weaned from HFNO, whilst failure comprised intubation or death on HFNO. FINDINGS: The median (IQR) arterial oxygen partial pressure to fraction inspired oxygen ratio (PaO2/FiO2) was 68 (54-92) in 293 enroled patients. Of these, 137/293 (47%) of patients [PaO2/FiO2 76 (63-93)] were successfully weaned from HFNO. The median duration of HFNO was 6 (3-9) in those successfully treated versus 2 (1-5) days in those who failed (p<0.001). A higher ratio of oxygen saturation/FiO2 to respiratory rate within 6 h (ROX-6 score) after HFNO commencement was associated with HFNO success (ROX-6; AHR 0.43, 0.31-0.60), as was use of steroids (AHR 0.35, 95%CI 0.19-0.64). A ROX-6 score of ≥3.7 was 80% predictive of successful weaning whilst ROX-6 ≤ 2.2 was 74% predictive of failure. In total, 139 patents (52%) survived to hospital discharge, whilst mortality amongst HFNO failures with outcomes was 129/140 (92%). INTERPRETATION: In a resource-constrained setting, HFNO for severe COVID-19 HRF is feasible and more almost half of those who receive it can be successfully weaned without the need for mechanical ventilation.

Factors that influence patient empowerment in inpatient chronic care: early thoughts on a diabetes care intervention in South Africa.

BACKGROUND: The burden of non-communicable diseases is growing rapidly in low- and middle-income countries. Research suggests that health interventions that aim to improve patient self-management and empower patients to care actively for their disease will improve health outcomes over the long-term. There is, however, a gap in the literature about the potential role of the inpatient setting in supporting chronic care. This is particularly important in low-and-middle income countries where hospitals may be a rare prolonged point of contact between patient and health provider. The aim of this small scale, exploratory study was to understand what factors within the inpatient setting may affect patients' feelings of empowerment in relation to their chronic disease care and provides recommendations for future inpatient-based interventions to support self-management of disease. METHODS: This study was based in a public, academic hospital in South Africa. Eighteen qualitative, semi-structured interviews were conducted with multiple participants with experience of diabetes care: inpatients and health professionals such as nurses, endocrinologists, and dieticians. Findings were analysed using a broad, exploratory, thematic approach, guided by self-management and chronic care literature. RESULTS: Interviews with both patients and providers suggest that patients living in low socio-economic contexts are likely to struggle to access appropriate healthcare information and services, and may often have financial and emotional priorities that take precedence over their chronic illness. Younger people may also be more dependent on their family and community, giving them less ability to take control of their disease care and lifestyle. In addition, hospital care remains bound by an acute care model; and the inpatient setting of focus is characterised by perceived staff shortages and ineffective communication that undermine the implementation of patient empowerment-focused interventions. CONCLUSIONS: Patient and provider contexts are likely to make supporting patient engagement in long-term chronic care difficult in lower income settings. However, knowledge of these factors can be harnessed to improve chronic care interventions in South Africa and other similar countries.

Demographic and socio-economic predictors of physical activity among people living with HIV of low socio-economic status.

BACKGROUND: Physical activity (PA) is beneficial for the health of people living with HIV and AIDS (PLWHA). AIM: The aim of this study was to determine if age, body weight, height, gender, waist-to-hip ratio (WHR), educational attainment, employment status, CD4+ cell count and body mass index (BMI) can predict overall PA among PLWHA of low socio-economic status (SES). SETTING: Participants in this study were HIV-infected patients on first-line antiretroviral therapy (ART) regimen offered by the South African National Department of Health, and those not on ART. Participants were conveniently sampled from a list at a community health care centre in Cape Town. METHODS: This study sample consisted of 978 HIV-infected South Africans. Physical activity data were collected using the Global Physical Activity Questionnaire. Backward multiple linear regression modelling was used to determine the relative influence of variables (age, body weight, height, gender, WHR, educational attainment, employment status, CD4+ count and BMI) on total moderate-to-vigorous PA. Alpha level was set at 0.05. RESULTS: The mean age of the participants was 38.2 (standard deviation [SD] = 8.76) years for men and 33.9 (SD = 8.53) years for women. Physical activity was significantly higher in men (480.2 [SD = 582.9] min/week) than among women (369.35 [SD = 222.53] min/week). The results of the multiple linear regression showed that educational attainment (ß = 0.127; p = 0.00), employment (ß = -0.087; p = 0.01) and gender (ß = 0.235; p = 0.00) significantly predicted total moderate-to-vigorous PA. Gender had the greatest effect, followed by educational attainment and employment status. CONCLUSION: There is a need for PA programmes that are designed to (1) target women, (2) strengthen programmes for education and promotion of PA and (3) engage the unemployed into PA for PLWHA. Physical activity interventions for this particular group should be tailored for persons of low SES.

HIV treatment is associated with a two-fold higher probability of raised triglycerides: Pooled Analyses in 21 023 individuals in sub-Saharan Africa.

BACKGROUND: Anti-retroviral therapy (ART) regimes for HIV are associated with raised levels of circulating triglycerides (TG) in western populations. However, there are limited data on the impact of ART on cardiometabolic risk in sub-Saharan African (SSA) populations. METHODS: Pooled analyses of 14 studies comprising 21 023 individuals, on whom relevant cardiometabolic risk factors (including TG), HIV and ART status were assessed between 2003 and 2014, in SSA. The association between ART and raised TG (>2.3 mmol/L) was analysed using regression models. FINDINGS: Among 10 615 individuals, ART was associated with a two-fold higher probability of raised TG (RR 2.05, 95% CI 1.51-2.77, I2=45.2%). The associations between ART and raised blood pressure, glucose, HbA1c, and other lipids were inconsistent across studies. INTERPRETATION: Evidence from this study confirms the association of ART with raised TG in SSA populations. Given the possible causal effect of raised TG on cardiovascular disease (CVD), the evidence highlights the need for prospective studies to clarify the impact of long term ART on CVD outcomes in SSA.

Evolution of sensory neuropathy after initiation of antiretroviral therapy.

INTRODUCTION: We studied the evolution of sensory neuropathy after antiretroviral therapy (ART) in human immunodeficiency virus-infected South Africans. METHODS: Enrolment commenced before ART with 6-monthly follow-ups for 24 months. Symptomatic distal sensory polyneuropathy (SDSP) was defined as one symptom and sign. Symptom/sign scores were compared between visits. RESULTS: We enrolled 184 participants. Pre-ART, 16% had SDSP. After 18 months of ART, pain prevalence decreased in those with pre-ART SDSP (odds ratio [OR], 0.09; 95% confidence interval [95%CI], 0.03-0.29). Symptoms improved in 50% ever experiencing pain (mean improvement = 4.5 on 11-point scale). Participants SDSP-free pre-ART developed SDSP at a rate of 18 per 100 person-years. After 24 months (n = 102), 18% had SDSP. Stavudine (60% of cohort) did not predict incident SDSP, but associated with increased prevalence of reduced/absent reflexes at 18 months (OR, 2.24; 95% CI, 1.08-4.65). DISCUSSION: Painful symptoms improved during ART. Evolving sensory neuropathy was due to increasing small and large fiber dysfunction. Muscle Nerve 57: 371-379, 2018.

Increased risk of dysglycaemia in South Africans with HIV; especially those on protease inhibitors.

AIMS: To compare dysglycaemia prevalence (impaired fasting glucose (IFG), impaired glucose tolerance (IGT), or diabetes) in HIV-infected persons, stratified by antiretroviral therapy (ART), with a community-based survey (CBS) in Cape Town, South Africa. METHODS: Three groups of HIV-infected adults without known diabetes were conveniently sampled from community healthcare centres; ART-naïve, first-line ART (non-nucleoside reverse transcriptase inhibitor (NNRTI) plus dual NRTIs), and second-line ART (lopinavir/ritonavir-boosted protease inhibitor plus dual NRTIs). The CBS recruited a representative cross-sectional sample from urban townships. Participants reporting ART use or known diabetes were excluded. All participants underwent oral glucose tolerance testing. Multiple logistic regression determined independent associations with dysglycaemia. RESULTS: The samples comprised ART-naïve, first-line ART, second-line ART and CBS participants (n=393, 439, 108 and 880, respectively). Mean age was 34-40years. Dysglycaemia prevalence was as follows: CBS 18.0%, ART-naïve 21.6%, first-line ART 26.0% and second-line ART 37.0%. Diabetes was similar across groups, but IGT was 3-4-fold higher in second-line ART and CBS compared with ART-naïve and first-line ART groups. In contrast, IFG was 14.3-21.2% across HIV groups but only 1.5% in the CBS. Increased risk of dysglycaemia was associated with older age, female gender, and HIV status (ART-naïve: OR 2.31, 95% CI 1.65-3.24; first-line ART: OR 2.47, 95% CI 1.80-3.38; second-line ART: OR 4.10, 95% CI 2.54-6.61). Diabetes family history and central obesity were not related to dysglycaemia. CONCLUSIONS: In view of the increased risk of dysglycaemia in HIV-infected participants, screening for diabetes should be instituted in ART programmes.

Risk Factors for Incident Diabetes in a Cohort Taking First-Line Nonnucleoside Reverse Transcriptase Inhibitor-Based Antiretroviral Therapy.

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. We explored the association between efavirenz exposure and incident diabetes in a large Southern African cohort commencing NNRTI-based first-line ART. Our cohort included HIV-infected adults starting NNRTI-based ART in a private sector HIV disease management program from January 2002 to December 2011. Incident diabetes was identified by the initiation of diabetes treatment. Patients with prevalent diabetes were excluded. We included 56,298 patients with 113,297 patient-years of follow-up (PYFU) on first-line ART. The crude incidence of diabetes was 13.24 per 1000 PYFU. Treatment with efavirenz rather than nevirapine was associated with increased risk of developing diabetes (hazard ratio 1.27 (95% confidence interval (CI): 1.10-1.46)) in a multivariate analysis adjusting for age, sex, body mass index, baseline CD4 count, viral load, NRTI backbone, and exposure to other diabetogenic medicines. Zidovudine and stavudine exposure were also associated with an increased risk of developing diabetes. We found that 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 programs, and use of antiretrovirals with lower risk of metabolic complications should be encouraged.

Anti-Retroviral Therapy Increases the Prevalence of Dyslipidemia in South African HIV-Infected Patients.

PURPOSE: Data on the prevalence of dyslipidaemia and associated risk factors in HIV-infected patients from sub-Saharan Africa is sparse. We performed a cross-sectional analysis in a cohort of HIV-infected South African adults. METHODS: We studied HIV-infected patients who were either antiretroviral therapy (ART)-naive or receiving non-nucleoside reverse transcriptase inhibitor (NNRTI)-based or protease inhibitor (PI)-based ART. Evaluation included fasting lipograms, oral glucose tolerance tests and clinical anthropometry. Dyslipidemia was defined using the NCEP ATPIII guidelines. RESULTS: The median age of the participants was 34 years (range 19-68 years) and 78% were women. The prevalence of dyslipidemia in 406 ART-naive and 551 participants on ART was 90.0% and 85%, respectively. Low HDL-cholesterol (HDLC) was the most common abnormality [290/406 (71%) ART-naïve and 237/551 (43%) ART- participants]. Participants on ART had higher triglycerides (TG), total cholesterol (TC), LDL-cholesterol (LDLC) and HDLC than the ART-naïve group. Severe dyslipidaemia, (LDLC> 4.9 mmol/L or TG >5.0 mmol/L) was present in <5% of participants. In multivariate analyses there were complex associations between age, gender, type and duration of ART and body composition and LDLC, HDLC and TG, which differed between ART-naïve and ART-participants. CONCLUSION: Participants on ART had higher TG, TC, LDLC and HDLC than those who were ART-naïve but severe lipid abnormalities requiring evaluation and treatment were uncommon.

Antiretroviral Therapy, Especially Efavirenz, Is Associated with Low Bone Mineral Density in HIV-Infected South Africans.

PURPOSE: 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/cm2, p = 0.0001] and neck of femur BMD [0.796 (SD 0.130) vs 0.844 (SD 0.120) g/cm2, 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 R2 = 0.28). Age, weight, sex, and the use of efavirenz-based ART were independently associated with lumbar spine BMD (adjusted R2 = 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.