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

Reply to Gautret et al

To the Editor—We thank Gautret et al for their comments and interest in our work. We found it compelling to see the Web of Science data that illustrated the ac-celeration of scholarly publications at the intersection of climate change and vec-tor-borne disease. This trend is perhaps unsurprising, considering that each of the last 3 decades has been successively warm-er at the Earth’s surface than any preced-ing decade since 1850, and well-accepted science has demonstrated the devastating ecologic effects of these changes [1]

Implementation of HIV Self-Testing to Reach Men in Rural uMkhanyakude, KwaZulu-Natal, South Africa. a DO-ART Trial Sub Study

Background: KwaZulu–Natal, South Africa has one of the highest HIV prevalence rates globally. Persons <35 years and men have lower rates of HIV testing. HIV self-testing (HIVST) may overcome many barriers of facility-based HIV testing in order to identify HIV positive young persons and men and link them to care. We investigated whether HIVST distribution was a feasible approach to reach men and assessed the proportion of participants who reported their HIVST results, tested positive and linked to care. / Methods: Teams comprised of a nurse, clinic research assistant, and recruiters distributed HIVST kits in rural uMkhanyakude, KwaZulu-Natal from August—November 2018 with a focus on testing men. Workplaces (farms), social venues, taxi ranks, and homesteads were used as HIVST kit distribution points following community sensitisation through community advisory boards and community leaders. HIVST kits, demonstration of use, and small incentives to report testing outcomes were provided. The Department of Health provided confirmatory testing and HIV care at clinics. / Results: Over 11 weeks in late 2018, we distributed 2,634 HIVST kits of which 2,113 (80%) were distributed to persons aged <35 years, 2,591 (98%) to men and 356 (14%) to first time testers. Of the HIVST distributed, 2,107 (80%) reported their results to the study team, and 157 (7%) tested positive. Of persons who tested positive, 107/130 (82%) reported having a confirmatory test of which 102/107 (95%) were positive and initiated on ART. No emergencies or social harms were reported. / Conclusion: Large scale distribution of HIVST kits targeting men in rural KwaZulu-Natal is feasible and highly effective in reaching men, including those who had not previously tested for HIV. While two-thirds of persons who tested HIV positive initiated ART, additional linkage strategies are needed for those who do not link after HIVST. HIVST should be used as a tool to reach men in order to achieve 95% coverage in the UNAIDS testing and care cascade in KwaZulu-Natal

Frailty and physical performance in the context of extreme poverty: a population-based study of older adults in rural Burkina Faso [version 1; peer review: 2 approved]

Background: Little is known about the prevalence of frailty and about normal values for physical performance among older individuals in low-income countries, in particular those in sub-Saharan Africa. We describe the prevalence of phenotypic frailty, and values and correlates of several physical performance measures in a cohort of middle-aged and older people living in rural Burkina Faso, one of the world’s poorest communities. Methods: We analysed data collected from participants aged over 40 in Nouna district, Burkina Faso. We measured handgrip strength, four metre walk speed, chair rise time, and derived the Fried frailty score based on grip strength, gait speed, body mass index, self-reported exhaustion, and physical activity. Frailty and physical performance indicators were then correlated with health and sociodemographic variables including comorbid disease, marital status, age, sex, wealth and activity impairment. Results: Our sample included 2973 individuals (1503 women), mean age 54 years. 1207 (43%) were categorised as non-frail, 1324 (44%) as prefrail, 212 (7%) as frail, and 167 (6%) were unable to complete all five frailty score components. Lower grip strength, longer chair stand time, lower walk speed and prevalence of frailty rose with age. Frailty was more common in women than men (8% vs 6%, p=0.01) except in those aged 80 and over. Frailty was strongly associated with impairment of activities of daily living and with lower wealth, being widowed, diabetes mellitus, hypertension, and self-reported diagnoses of tuberculosis or heart disease. With the exception of grip strength, which was higher in women than prior international normative values, women had greater deficits than men in physical performance. Conclusions: Phenotypic frailty and impaired physical performance were associated as expected with female sex, co-morbidities, increasing age and impaired activities of daily living. These results support the use of frailty measurements for classification of ageing related syndromes in this setting

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

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 &lt;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

Improving the Specificity of Plasmodium falciparum Malaria Diagnosis in High-Transmission Settings with a Two-Step Rapid Diagnostic Test and Microscopy Algorithm

ABSTRACT Poor specificity may negatively impact rapid diagnostic test (RDT)-based diagnostic strategies for malaria. We performed real-time PCR on a subset of subjects who had undergone diagnostic testing with a multiple-antigen (histidine-rich protein 2 and pan -lactate dehydrogenase pLDH [HRP2/pLDH]) RDT and microscopy. We determined the sensitivity and specificity of the RDT in comparison to results of PCR for the detection of Plasmodium falciparum malaria. We developed and evaluated a two-step algorithm utilizing the multiple-antigen RDT to screen patients, followed by confirmatory microscopy for those individuals with HRP2-positive (HRP2 + )/pLDH-negative (pLDH − ) results. In total, dried blood spots (DBS) were collected from 276 individuals. There were 124 (44.9%) individuals with an HRP2 + /pLDH + result, 94 (34.1%) with an HRP2 + /pLDH − result, and 58 (21%) with a negative RDT result. The sensitivity and specificity of the RDT compared to results with real-time PCR were 99.4% (95% confidence interval [CI], 95.9 to 100.0%) and 46.7% (95% CI, 37.7 to 55.9%), respectively. Of the 94 HRP2 + /pLDH − results, only 32 (34.0%) and 35 (37.2%) were positive by microscopy and PCR, respectively. The sensitivity and specificity of the two-step algorithm compared to results with real-time PCR were 95.5% (95% CI, 90.5 to 98.0%) and 91.0% (95% CI, 84.1 to 95.2), respectively. HRP2 antigen bands demonstrated poor specificity for the diagnosis of malaria compared to that of real-time PCR in a high-transmission setting. The most likely explanation for this finding is the persistence of HRP2 antigenemia following treatment of an acute infection. The two-step diagnostic algorithm utilizing microscopy as a confirmatory test for indeterminate HRP2 + /pLDH − results showed significantly improved specificity with little loss of sensitivity in a high-transmission setting

Impairment in Activities of Daily Living and unmet need for care among older adults: A population-based study from Burkina Faso

OBJECTIVES: The importance of impairment in performing Activities of Daily Living (ADL) is likely to increase in sub-Saharan Africa since few care options for affected people exist. This study investigated the prevalence of ADL impairment, the extent to which care-need was met and described characteristics of people with ADL impairment and unmet need in Burkina Faso. METHODS: This study used data from the CRSN Heidelberg Aging Study, a population-based study among 3,026 adults aged over 40 years conducted in rural Burkina Faso. Information on six basic ADL items was sought, with a follow-up question asking whether care-needs were not met, partially met or met. Bivariable correlations and multivariable logistic regression were used to determine sociodemographic and health characteristics associated with ADL impairment and unmet need. RESULTS: ADL impairment of any kind was reported by 1,202 (39.7%) respondents and was associated with older age (Adjusted Odds Ratio: 1.05 [95% CI: 1.04-1.06]), being a woman (1.33 [1.06-1.60]) and reporting depressive symptoms (1.90 [1.65-2.18]). Among those with ADL impairment, 67.8% had at least one unmet need. Severe ADL impairment was found in 202 (6.7%) respondents, who reported lower prevalence of unmet need (43.1%). Severe ADL impairment was associated with depressive symptoms (2.55 [2.11-3.07]) to a stronger degree than any ADL impairment. DISCUSSION: Prevalence of ADL impairment and unmet need was high in this setting. Variation in impairment across the population highlighted key groups for future interventions. Unmet need for care was highest in middle-aged adults, indicating a gap in care provision

Developing cardiac and skeletal muscle share fast-skeletal myosin heavy chain and cardiac troponin-I expression

Skeletal muscle derived stem cells (MDSCs) transplanted into injured myocardium can differentiate into fast skeletal muscle specific myosin heavy chain (sk-fMHC) and cardiac specific troponin-I (cTn-I) positive cells sustaining recipient myocardial function. We have recently found that MDSCs differentiate into a cardiomyocyte phenotype within a three-dimensional gel bioreactor. It is generally accepted that terminally differentiated myocardium or skeletal muscle only express cTn-I or sk-fMHC, respectively. Studies have shown the presence of non-cardiac muscle proteins in the developing myocardium or cardiac proteins in pathological skeletal muscle. In the current study, we tested the hypothesis that normal developing myocardium and skeletal muscle transiently share both sk-fMHC and cTn-I proteins. Immunohistochemistry, western blot, and RT-PCR analyses were carried out in embryonic day 13 (ED13) and 20 (ED20), neonatal day 0 (ND0) and 4 (ND4), postnatal day 10 (PND10), and 8 week-old adult female Lewis rat ventricular myocardium and gastrocnemius muscle. Confocal laser microscopy revealed that sk-fMHC was expressed as a typical striated muscle pattern within ED13 ventricular myocardium, and the striated sk-fMHC expression was lost by ND4 and became negative in adult myocardium. cTn-I was not expressed as a typical striated muscle pattern throughout the myocardium until PND10. Western blot and RT-PCR analyses revealed that gene and protein expression patterns of cardiac and skeletal muscle transcription factors and sk-fMHC within ventricular myocardium and skeletal muscle were similar at ED20, and the expression patterns became cardiac or skeletal muscle specific during postnatal development. These findings provide new insight into cardiac muscle development and highlight previously unknown common developmental features of cardiac and skeletal muscle. © 2012 Clause et al

Adverse Childhood Experiences and Adult Cardiometabolic Risk Factors and Disease Outcomes: Cross-Sectional, Populationbased Study of Adults in Rural Uganda

Background: Cardiovascular diseases (CVD) pose a major threat to public health in sub-Saharan African communities, where the burden of these classes of illnesses is expected to double by 2030. Growing research suggests that past developmental experiences and early life conditions may also elevate CVD risk throughout the life course. Greater childhood stress and adversity are consistently associated with a range of adult CVDs and associated risk factors, yet little research exists on the long-term effects of early life stress on adult physical health outcomes, especially CVD risk, in sub-Saharan African contexts. This study aims to evaluate the associations between adverse childhood experiences and adult cardiometabolic risk factors and health outcomes in a population-based study of adults living in Mbarara, a rural region of southwestern Uganda. Methods Data come from an ongoing, whole-population social network cohort study of adults living in the eight villages of Nyakabare Parish, Mbarara. A modified version of the Adverse Childhood Experiences-International Questionnaire (ACEs) assessed past exposure to physical, emotional, and sexual adversity. Participants also took part in a health fair where medical histories on cardiometabolic risk factors and cardiovascular diseases were gathered. Multiple logistic regression models estimated the associations between ACEs and cardiometabolic risk factors and health outcomes. Results Data were available on 545 adults. The average number of ACEs was 4.9 out of a possible 16. The cumulative number of ACEs were associated with having a history of heart attack and/or heart failure (adjusted odds ratio (AOR) = 1.11, 95% confidence interval (CI) = 0.999-1.234, P = 0.051), but the estimated association was not statistically significant. ACEs did not have statistically significant associations with any others measures of adult cardiometabolic risk and CVD. Conclusions: Adverse childhood experiences are not associated with a range of adult cardiometabolic risk factors and health outcomes in this sample of rural Ugandan adults. Further research in this sample is necessary to identify the pathways that may motivate these null relationship and possibly protect against adverse cardiometabolic and cardiovascular health outcomes