Associations of HIV and prevalent type 2 diabetes mellitus in the context of obesity in South Africa.

It is unclear how rising obesity among people with HIV (PWH) in sub-Saharan Africa (SSA) impacts their risk of type 2 diabetes mellitus (diabetes). Using a South African national cross-sectional sample of adult PWH and their peers without HIV (PWOH), we examined the associations between HIV and prevalent diabetes across the spectrum of body mass index (BMI), waist circumference (WC) and waist-to-height ratio (WtHR). Analyses were sex stratified, and adjusted for age, sociodemographic and behavioral factors. The prevalence of diabetes among males was similar between PWH and PWOH, overall and at all levels of adiposity. In contrast, overall diabetes prevalence was higher among female PWOH than female PWH. However, there were differences according to adiposity such that, compared to female PWOH, relative diabetes prevalence in female PWH was reduced with obesity but accentuated with leanness. These differences in the relationship between adiposity and diabetes by HIV serostatus call for better mechanistic understanding of sex-specific adipose tissue biology in HIV in South Africa, and possibly in other HIV endemic settings in SSA.

Insulin resistance, and not ß-cell impairment, mediates association between Mycobacterium tuberculosis sensitization and type II diabetes mellitus among US adults.

Type 2 diabetes mellitus (T2DM) may be a long-term sequela of infection with Mycobacterium tuberculosis (M.tb) by mechanisms that remain to be fully explained. We evaluated association between M.tb sensitization and T2DM among U.S adults and, via formal mediation analysis, the extent to which this association is mediated by insulin resistance and/or ß-cell failure. These evaluations accounted for demographic, socio-economic, behavioral and clinical characteristics. T2DM was assessed by fasting plasma glucose, 2-hour oral glucose tolerance testing and HbA1c; homoeostasis model assessment 2 (HOMA2) was used to estimate ß-cell dysfunction (HOMA2-B) and insulin resistance (HOMA2-IR); while M.tb sensitization status was ascertained by tuberculin skin testing (TST). Exposure to M.tb was associated with increased risk for T2DM, likely driven by an increase in insulin resistance. Definitive prospective studies examining incident T2DM following tuberculosis are warranted. Research in Context: What is already known about this subject?: Accumulating evidence suggests that pre-diabetes and new-onset type 2 diabetes mellitus (T2DM) may be a long-term complication of exposure to Mycobacterium tuberculosis ( M.tb ) via mechanisms that remain to be unraveled What is the key question?: To what extent do insulin resistance and ß-cell failure mediate the association between M.tb sensitization with T2DM among US adults? What are the new findings?: M.tb sensitization is characterized by distinct glucose metabolic disturbances manifesting as increased risk of T2DM and isolated impaired fasting glucose (IFG) Insulin resistance, and not ß-cell impairment, likely independently mediate the observed diabetogenic effects of M.tb sensitization How might this impact on clinical and/or public health practice in the foreseeable future?: If corroborated by prospective studies, both TB programs and individual clinical care must incorporate monitoring of serum glucose and long-term metabolic outcomesThis will be particularly urgent in sub-Saharan Africa and South-East Asia where scarce health resources coincide with overlapping endemic TB and epidemic T2DM.

Characteristics and efficacy of physical activity interventions to improve cardiometabolic and psychosocial outcomes in people living with HIV in sub-Saharan Africa: a protocol for a systematic review.

BACKGROUND: Antiretroviral therapy (ART) has led to an increased lifespan for people living with HIV (PWH). This increased lifespan, coupled with the effects of HIV and adverse effects of ART have resulted in an increasing burden of cardiometabolic disease (CMD) among PWH. Physical activity (PA) has been proposed as an effective strategy to reduce the risk of developing cardiometabolic disease and other health complications in PWH. The aim of this paper is to review the characteristics and efficacy of PA interventions to improve cardiometabolic and psychosocial outcomes among PWH in sub-Saharan Africa. METHODS: The review will follow the preferred reporting items for systematic review and meta-analysis protocols (PRISMA-P). Literature searches will be conducted in PubMed, Web of Science (WoS), African Index Medicus, Cumulative Index to Nursing and Allied Health Literature (CINAHL), and Embase. Peer-reviewed publications will be included if they include adults (age 18 or older), PWH in sub-Saharan Africa, and a PA intervention to improve cardiometabolic outcomes and/or psychosocial outcomes. We will include randomized controlled trials and quasi-experimental study designs. Two independent reviewers will screen all abstracts and full-text articles. The study methodological quality (or bias) will be appraised using the Revised tool to assess risk of bias in randomized trials and the Downs and Black checklist. Certainty of evidence will be evaluated using the Grading of Recommendations Assessment, Development and Evaluation guidelines. Meta-analyses will be conducted if our results are adequate for meta-analysis. Outcomes will be analyzed as continuous or dichotomous and meta-analyses will be conducted using random effects models with Stata computer software. DISCUSSION: This review will identify and synthesize the current evidence regarding the characteristics and efficacy of PA interventions to improve cardiometabolic and psychosocial outcomes among PWH in sub-Saharan Africa. We also plan to identify the strengths and weaknesses of evaluated interventions. Based on the evidence, recommendations will be made to promote the design and further evaluate the most promising strategies to maximize the efficacy of PA interventions in improving cardiometabolic and psychosocial outcomes in PWH in sub-Saharan Africa. SYSTEMATIC REVIEW REGISTRATION: PROSPERO registration ID: CRD42021271937.

A nurse-led intervention to improve management of virological failure in public sector HIV clinics in Durban, South Africa: A pre- and post-implementation evaluation.

BACKGROUND: Identification of patients on antiretroviral therapy (ART) with virological failure (VF) and the response in the public health sector remain significant challenges. We previously reported improvement in routine viral load (VL) monitoring after ART commencement through a health system-strengthening, nurse-led 'VL champion' programme as part of a multidisciplinary team in three public sector clinics in Durban, South Africa. OBJECTIVES: To report on the impact of the VL champion model adapted to identify, support and co-ordinate the management of individuals with VF on first-line ART in a setting with limited electronic-based record capacity. METHODS: We evaluated the VL champion model using a controlled before-after study design. A paper-based tool, the 'high VL register', was piloted under the supervision of the VL champion to improve data management, monitoring of counselling support, and enacting of clinical decisions. We abstracted chart and electronic data (TIER.net) for eligible individuals with VF in the year before and after implementation of the programme, and compared outcomes for individuals during these periods. Our primary outcome was successful completion of the VF pathway, defined as a repeat VL <1 000 copies/mL or a change to second-line ART within 6 months of VF. In a secondary analysis, we assessed the completion of each step in the pathway. RESULTS: We identified 60 and 56 individuals in the pre-intervention and post-intervention periods, respectively, with VF who met the inclusion criteria. Sociodemographic and clinical characteristics were similar between the periods. Repeat VL testing was completed in 61.7% and 57.8% of individuals in these two groups, respectively. We found no difference in the proportion achieving our primary outcome in the pre- and post-intervention periods: 11/60 (18.3%; 95% confidence interval (CI) 9 - 28) and 15/56 (22.8%; 95% CI 15 - 38), respectively (p=0.28). In multivariable logistic regression models adjusted for potential confounding factors, individuals in the post-intervention period had a non-significant doubling of the odds of achieving the primary outcome (adjusted odds ratio 2.07; 95% CI 0.75 - 5.72). However, there was no difference in the rates of completion of each step along the first-line VF cascade of care. CONCLUSIONS: This enhanced intervention to improve VF in the public sector using a paper-based data management system failed to achieve significant improvements in first-line VF management over the standard of care. In addition to interventions that better address patient-centred factors that contribute to VF, we believe that there are substantial limitations to and staffing requirements involved in the ongoing utilisation of a paper-based tool. A prioritisation is needed to further expand and upgrade the electronic medical record system with capabilities for prompting staff regarding patients with missed visits and critical laboratory results demonstrating VF.

Clinical outcomes after first-line HIV treatment failure in South Africa: the next cascade of care.

INTRODUCTION: There is limited literature on the appropriateness of viral load (VL) monitoring and management of detectable VL in public health settings in rural South Africa. METHODS: We analysed data captured in the electronic patient register from HIV-positive patients ≥ 15 years old initiating antiretroviral therapy (ART) in 17 public sector clinics in rural KwaZulu-Natal, during 2010-2016. We estimated the completion rate for VL monitoring at 6, 12, and 24 months. We described the cascade of care for those with any VL measurement ≥ 1000 HIV-1 RNA copies/mL after ≥ 20 weeks on ART, including the following proportions: (1) repeat VL within 6 months; (2) re-suppressed; (3) switched to second-line regimen. RESULTS: There were 29 384 individuals who initiated ART during the period [69% female, median age 31 years (interquartile range 25-39)]. Of those in care at 6, 12, and 24 months, 40.7% (9861/24 199), 34% (7765/22 807), and 25.5% (4334/16 965) had a VL test at each recommended time-point, respectively. The VL results were documented at all recommended time-points for 12% (2730/22 807) and 6.2% (1054/16 965) of ART-treated patients for 12 and 24 months, respectively. Only 391 (18.3%) of 2135 individuals with VL ≥ 1000 copies/mL on first-line ART had a repeat VL documenting re-suppression or were appropriately changed to second-line with persistent failure. Completion of the treatment failure cascade occurred a median of 338 days after failure was detected. CONCLUSION: We found suboptimal VL monitoring and poor responses to virologic failure in public-sector ART clinics in rural South Arica. Implications include increased likelihood of morbidity and transmission of drug-resistant HIV.

Urgent need to improve programmatic management of patients with HIV failing first-line antiretroviral therapy.

INTRODUCTION: Delayed identification and response to virologic failure in case of first-line antiretroviral therapy (ART) in resource-limited settings is a threat to the health of HIV-infected patients. There is a need for the implementation of an effective, standardized response pathway in the public sector. DISCUSSION: We evaluated published cohorts describing virologic failure on first-line ART. We focused on gaps in the detection and management of treatment failure, and posited ways to close these gaps, keeping in mind scalability and standardization. Specific shortcomings repeatedly recorded included early loss to follow-up (>20%) after recognized first-line ART virologic failure; frequent delays in confirmatory viral load testing; and excessive time between the confirmation of first-line ART failure and initiation of second-line ART, which exceeded 1 year in some cases. Strategies emphasizing patient tracing, resistance testing, drug concentration monitoring, adherence interventions, and streamlined response pathways for those failing therapy are further discussed. CONCLUSION: Comprehensive, evidence-based, clinical operational plans must be devised based on findings from existing research and further tested through implementation science research. Until this standard of evidence is available and implemented, high rates of losses from delays in appropriate switch to second-line ART will remain unacceptably common and a threat to the success of global HIV treatment programs.

Comparative analyses of published cost effectiveness models highlight critical considerations which are useful to inform development of new models.

Background: Comparative analyses of published cost effectiveness models provide useful insights into critical issues to inform the development of new cost effectiveness models in the same disease area.Objective: The purpose of this study was to describe a comparative analysis of cost-effectiveness models and highlight the importance of such work in informing development of new models. This research uses genotypic antiretroviral resistance testing after first line treatment failure for Human Immunodeficiency Virus (HIV) as an example.Method: A literature search was performed, and published cost effectiveness models were selected according to predetermined eligibility criteria. A comprehensive comparative analysis was undertaken for all aspects of the models.Results: Five published models were compared, and several critical issues were identified for consideration when developing a new model. These include the comparator, time horizon and scope of the model. In addition, the composite effect of drug resistance prevalence, antiretroviral therapy efficacy, test performance and the proportion of patients switching to second-line ART potentially have a measurable effect on model results. When considering CD4 count and viral load, dichotomizing patients according to higher cost and lower quality of life (AIDS) versus lower cost and higher quality of life (non-AIDS) status will potentially capture differences between resistance testing and other strategies, which could be confirmed by cross-validation/convergent validation. A quality adjusted life year is an essential outcome which should be explicitly explored in probabilistic sensitivity analysis, where possible.Conclusions: Using an example of GART for HIV, this study demonstrates comparative analysis of previously published cost effectiveness models yields critical information which can be used to inform the structure and specifications of new models.

Findings from home-based HIV testing and facilitated linkage after scale-up of test and treat in rural South Africa: young people still missing.

OBJECTIVES: The aim of the study was to estimate rates of linkage to HIV care and antiretroviral treatment (ART) initiation after the introduction of home-based HIV counselling and testing (HBHCT) and telephone-facilitated support for linkage in rural South Africa. METHODS: A population-based prospective cohort study was carried out in KwaZulu Natal, South Africa. All residents aged ≥ 15 years were eligible for HBHCT. Those who tested positive and were not in care were referred for ART at one of 11 public-sector clinics. Individuals who did not attend the clinic within 2 weeks were sent a short message service (SMS) reminder; those who had not attended after a further 2 weeks were telephoned by a nurse counsellor, to discuss concerns and encourage linkage. Kaplan-Meier methods were used to estimate the proportion of newly diagnosed individuals linking to care and initiating ART. RESULTS: Among 38 827 individuals visited, 26% accepted HBHCT. Uptake was higher in women than in men (30% versus 20%, respectively), but similar in people aged < 30 years and ≥ 30 years (28% versus 26%, respectively). A total of 784 (8%) tested HIV positive, of whom 427 (54%) were newly diagnosed. Within 6 months, 31% of women and 18% of men < 30 years old had linked to care, and 29% and 16%, respectively, had started ART. Among those ≥ 30 years, 41% of women and 38% of men had linked to care within 6 months, and 41% and 35%, respectively, had started ART. CONCLUSIONS: Despite facilitated linkage, rates of timely linkage to care and ART initiation after HBHCT were very low, particularly among young men. Innovations are needed to provide effective HIV care and prevention interventions to young people, and thus maximize the benefits of universal test and treat.

Comparative assessment of methicillin resistant Staphylococcus aureus diagnostic assays for use in resource-limited settings.

BACKGROUND: The rise of methicillin-resistant Staphylococcus aureus (MRSA) is a global health concern. Paucity of data on MRSA carriage prevalence and diagnostic methods in resource-limited settings hampers efforts to define the problem and plan an appropriate response. Additionally, high variability in cost and logistical characteristics of MRSA screening methods may impede infection control efforts. We compared the performance of locally-available chromogenic agar BD CHROMagar MRSA II and two PCR-based assays (Hain GenoQuick MRSA and Cepheid Xpert SA Complete) for the detection of asymptomatic MRSA carriage in nasal swabs. RESULTS: During 2015, we enrolled 500 patients from five hospital wards at a Ugandan regional referral hospital. We found 30% prevalence of methicillin-sensitive Staphylococcus aureus (MSSA) nasal carriage, and 5.4% MRSA nasal carriage prevalence. Compared to a composite reference standard defined as a positive test result on any one of the three assays, Hain GenoQuick MRSA demonstrated the highest sensitivity (96%) followed by direct plating on CHROMagar at (70%), with the lowest sensitivity observed with Xpert SA Complete (52%). Cepheid Xpert provided the most rapid results (< 1 h) but was the most expensive (US $45-50/test). Substantially more labor was required for the Hain GenoQuick MRSA compared to Xpert SA Complete or CHROMagar tests. CONCLUSION: MRSA nasal carriage prevalence rates were low, and high diagnostic sensitivity was achieved using Hain GenoQuick MRSA. Chromogenic media had significantly lower sensitivity, but may represent a viable local option given its lower cost compared to PCR-based assays.

Targeting the third '90': introducing the viral load champion.

Objective: To move closer to achieving the third target of the UNAIDS 90-90-90 goals, we prospectively implemented a viral load (VL) champion (VLC) program aimed at enhancing VL monitoring and recognition of treatment failure. Design: Three clinics in eThekwini, Kwa-Zulu Natal (low-, medium- and high-volume, encompassing 9184 patients overall) were each assigned a VLC. We employed a descriptive analysis (chart audit) to compare the pre-intervention period to a 1-year post-intervention period. The number of patients with a VL test performed 6 and 12 months after the intervention was calculated as a proportion of VL tests due at those time points (VL completion rate). Results: The pre-implementation VL completion rate at the three sites was respectively 68% (140/205 patients), 54% (84/155 patients) and 64% (323/504 patients), and the 6-month post-implementation completion rate increased to 83% (995/1194 patients), 90% (793/878 patients) and 99% (3101/3124 patients) (P < 0.0001 for each site). VL completion rates remained significantly higher at 12 months post-implementation, with an average cumulative VL completion rate of >90% across all facilities. Conclusion: We demonstrate a successful, multifaceted, quality-improvement intervention centered on a clinic-level VLC which, taken to scale, has important implications for attaining the third UNAIDS 90-90-90 target.

Objectif : Dans le but de se rapprocher de l'atteinte de la troisième cible des objectifs 90-90-90 du Programme commun des Nations Unies sur le VIH/Sida (ONUSIDA), nous avons prospectivement mis en œuvre un programme « champion de la charge virale ¼ (VLC) visant à améliorer le suivi de la charge virale (VL) et la reconnaissance de l'échec du traitement.Schéma : Trois centres à eThekwini, Kwa-Zulu Natal (volume faible, moyen et élevé, soit 9184 patients au total), ont été chacun affectés au VLC. Nous employons une analyse descriptive (audit de dossiers) afin de comparer la période avant l'intervention à la période d'un an qui a suivi l'intervention. Le nombre de patients ayant eu un test VL 6 et 12 mois après l'intervention a été calculé comme une proportion de test VL exigibles à ces dates respectivement (taux d'achèvement du VL).Résultats : Le taux d'achèvement du VL avant la mise en route dans trois sites a été de 68% (140/205 patients), 54% (84/155 patients) et 64% (323/504 patients), respectivement, et le taux d'achèvement à 6 mois après la mise en œuvre a augmenté à 83% (995/1194 patients), 90% (793/878 patients) et 99% (3101/3124 patients), respectivement (P < 0,0001 pour chaque site). Les taux d'achèvement du VL sont restés significativement plus élevés à 12 mois après la mise en œuvre, avec un taux cumulé moyen du VL >90% dans toutes les structures.Conclusion : Nous avons montré la qualité d'une intervention d'amélioration réussie à multiples facettes, centrée sur le VLC au niveau des centres qui­à plus grande échelle­a des implications majeures pour l'atteinte de la troisième cible 90-90-90 de l'ONUSIDA.

Objetivo: Con el propósito de avanzar hacia el cumplimiento del tercer elemento del objetivo «90-90-90¼ del Programa Conjunto de las Naciones Unidas sobre el VIH/SIDA (ONUSIDA), se introdujo un programa con un promotor del seguimiento de la viremia, encaminado a reforzar la vigilancia de la concentración vírica y el reconocimiento del fracaso terapéutico.Método: En cada uno de tres consultorios de eThekwini, en Kwa-Zulu Natal (con una carga asistencial baja, intermedia y alta, que cubrían un total de 9184 pacientes) se nombró un promotor del seguimiento de la viremia. Mediante un análisis descriptivo, se comparó el período preintervención con un período posintervención de un año. El número de pacientes en quienes se practicó la viremia a los 6 y 12 meses después de la intervención se calculó como la proporción de las viremias previstas en estos puntos temporales (tasa de compleción de la viremia).Resultados: La tasa de compleción de la viremia en los tres centros fue como sigue: 68% (140/205 pacientes), 54% (84/155 pacientes) y 64% (323/504 pacientes) y a los 6 meses posintervención, esta tasa aumentó respectivamente a 83% (995/1194 pacientes), 90% (793/878 pacientes) y 99% (3101/3124 pacientes) (P < 0,0001 para cada centro). Las tasas de compleción de la viremia permanecieron significativamente más altas a los 12 meses posintervención con una tasa acumulada superior al 90% en todos los establecimientos.Conclusión: Se puso en evidencia una intervención polifacética eficaz de mejoramiento de la calidad centrada en un promotor clínico del seguimiento de la viremia en cada consultorio, cuya aplicación en una escala más amplia, tendría importantes repercusiones en favor del cumplimiento del tercer elemento del objetivo «90-90-90¼ del ONUSIDA.

High-output left ventricular failure after dextran use in an operative hysteroscopy.

High-output left ventricular failure occurred in a patient after a difficult case of hysteroscopic lysis of adhesions using dextran as a distension medium. The excessive dissection in the uterine wall, the long duration of the operation, and the large volumes of dextran probably caused intravasation of dextran into the systemic circulation inducing a significant shift of fluids from the third space. This was possibly assisted by the large volume of fluids given intravenously in a 45-kg patient initiating the reported sequence of events.