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BACKGROUND:Antimicrobial resistance is an emerging global health issue. Data on the epidemiology of multidrug-resistant organisms are scarce for Africa, especially in HIV-infected individuals who often have frequent contact with healthcare. We investigated the prevalence of extended-spectrum beta-lactamase-producing Enterobacteriaceae (ESBL-E) carriage in stool among HIV-infected children attending an HIV outpatient department in Harare, Zimbabwe. METHODS:We recruited children who were stable on antiretroviral therapy (ART) attending a HIV clinic from August 2014 to June 2015. Information was collected on antibiotic use and hospitalization. Stool was tested for ESBL-E through combination disc diffusion. API20E identification and antimicrobial susceptibility was performed on the positive samples followed by whole genome sequencing. RESULTS:Stool was collected from 175/202 (86.6 %) children. Median age was 11 [inter-quartile range (IQR) 9-12] years. Median time on ART was 4.6 years (IQR 2.4-6.4). ESBL-Es were found in 24/175 samples (13.7 %); 50 % of all ESBL-Es were resistant to amoxicillin-clavulanate, 100 % to co-trimoxazole, 45.8 % to chloramphenicol, 91.6 % to ceftriaxone, 20.8 % to gentamicin and 62.5 % to ciprofloxacin. ESBL-Es variously encoded CTX-M, OXA, TEM and SHV enzymes. The odds of ESBL-E carriage were 8.5 times (95 % CI 2.2-32.3) higher in those on ART for less than one year (versus longer) and 8.5 times (95 % CI 1.1-32.3) higher in those recently hospitalized for a chest infection. CONCLUSION:We found a 13.7 % prevalence of ESBL-E carriage in a population where ESBL-E carriage has not been described previously. Antimicrobial resistance (AMR) in Africa merits further study, particularly given the high HIV prevalence and limited diagnostic and therapeutic options available.

Vitamin D dysregulation can occur in people living with HIV, disrupting calcium homeostasis and bone turnover. We aimed to investigate the potential mechanisms by which vitamin D regulates bone turnover in adolescents living with perinatally-acquired HIV (ALWH) in southern Africa. A pre-planned secondary analysis was performed of baseline data from the VITALITY trial [PACTR20200989766029] which enrolled ALWH (11-19 years) taking antiretroviral therapy for ≥6 months, and recorded socio-demographic, clinical and dietary data. After over-night fasting, vitamin D metabolites [25(OH)D, 1,25(OH)2D, 24,25(OH)2D], intact parathyroid hormone (PTH) and bone turnover markers (BTMs) [CTX and P1NP] were measured. Tandem Mass Spectrometry measured vitamin D metabolites, whilst intact PTH and BTMs were analysed by electrochemiluminescence immunoassay. Stratified by 25(OH)D [<75 vs ≥75 nmol/L], associations between standardized concentrations (β = standard deviations) of vitamin D metabolites, intact PTH and BTMs were assessed using structural equations modelling (SEM) adjusted for age, sex and country (Zimbabwe/Zambia). Among the 842 ALWH enrolled, the median dietary calcium intake was 100 mg [IQR:55-145]. The SEM showed PTH was positively associated [β 0.21, 95%CI: 0.1,0.32] with 1,25(OH)2D, only when 25(OH)D was <75 nmol/L vs ≥75 nmol/L [β 0.23, 95%CI: -0.13,0.59], with evidence of an interaction [β -0.11, 95%CI: -0.20,-0.02]. A positive relationship between 25(OH)D and 24,25(OH)2D was seen irrespective of 25(OH)D concentration. 24,25(OH)2D was inversely related to BTMs, particularly when 25(OH)D was <75 nmol/L [CTX: β -0.15, 95%CI: -0.24,-0.06, and P1NP: β -0.14, 95%CI: -0.22,-0.06]. There was interaction between dietary calcium and 25(OH)D on PTH [β -0.15, 95% CI: -0.22,-0.07] suggesting an interaction between low 25(OH)D and low dietary calcium which increases PTH. In conclusion, associations between 25(OH)D, PTH, 1,25(OH)2D and BTMs in ALWH appear dependent upon 25(OH)D concentrations <75 nmol/L and calcium intake. A novel, potentially causal pathway between 25(OH)D, 24,25(OH)2D and BTMs was seen. Findings enhance understanding of vitamin D metabolism in people living with HIV., (© The Author(s) 2024. Published by Oxford University Press on behalf of the American Society for Bone and Mineral Research.)

Objectives: Youth are at high risk of sexually transmitted infections (STIs) in Africa. We aimed to determine the risk factors for curable STIs in youth in Zimbabwe., Methods: A population-based survey was conducted among randomly selected 18-24 year-olds in 16 communities across two provinces in Zimbabwe to ascertain outcomes for a cluster randomised trial investigating the impact of community-based STI screening for youth on population prevalence of STIs. Participants underwent an interviewer-administered questionnaire, HIV testing and screening for Chlamydia trachomatis (CT), Neisseria gonorrhoeae (NG) and Trichomonas vaginalis (TV). Risk factors for curable STIs were explored through multivariable logistic regression., Results: Of the 5601 participants, 62.5% (n=3500) were female, and the median age was 20 (IQR 19-22) years. HIV prevalence was 6.3% (351/5556), and 55.4% (1939/3501) reported condomless sex at last intercourse. Only 7.2% (401/5599) reported STI symptoms, but CT/NG/TV prevalence was 19.8% (1107/5601). On multivariable analysis, factors associated with STI diagnosis included being aged 21-24 years (adjusted OR (aOR) 1.37, 95% CI 1.17 to 1.61); female sex (aOR 2.11, 95% CI 1.76 to 2.53); being unemployed/informally employed (compared with in education/formal employment) (aOR 1.35, 95% CI 1.13 to 1.61); increasing number of sexual partners in the preceding 12 months (one partner: aOR 2.23, 95% CI 1.73 to 2.88; two partners: aOR 2.39, 95% CI 1.69 to 3.39); living with HIV (aOR 1.44, 95% CI 1.07 to 1.94); and previous attempted suicide (aOR 1.58, 95% CI 1.08 to 2.32)., Conclusions: The prevalence of STIs among youth in Zimbabwe is high, particularly among those with HIV. In addition to moving away from syndromic STI management and strengthening implementation of existing prevention tools, there is a need for a more holistic focus on broader risk factors such as mental health and employment opportunities, and of integration of HIV and STI programming., Trial Registration Number: ISRCTN15013425, NCT03719521., Competing Interests: Competing interests: KM is a current editorial fellow at the Sexually Transmitted Infections journal., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY. Published by BMJ.)

Background: Young people are at particularly high risk of acquiring sexually transmitted infections (STIs). We conducted a trial to investigate the effect of a community-based intervention that included STI screening among youth on population-level prevalence of STIs in Zimbabwe., Methods: STICH was a parallel-arm, cluster-randomised controlled trial nested within CHIEDZA, a trial of community-based integrated HIV and sexual and reproductive health services for youth in Zimbabwe. STICH was conducted in Harare and Bulawayo provinces with eight clusters in each province, randomised 1:1 to control (existing health services) or to the intervention: community-based screening and treatment for Chlamydia trachomatis and Neisseria gonorrhoeae (males and females) and Trichomonas vaginalis (females only) offered over 12 months to intervention cluster residents aged 16-24 years who were attending CHIEDZA. Outcomes were ascertained through a population-level survey immediately after the intervention period, which included young people aged 18-24 years who lived in randomly selected households in each of the 16 clusters. The primary outcome was population prevalence of any (one or more) of the three STIs; secondary outcomes were prevalence of each of the three STIs. The STICH trial is registered with ISRCTN registry, ISRCTN15013425, and the CHIEDZA trial is registered with ClinicalTrials.gov, NCT03719521., Findings: From Oct 6, 2021, to March 8, 2022, 6361 randomly sampled young people were recruited into the outcome survey (median age 20 years [IQR 19-22], 3500 female and 2101 male, 3066 in intervention clusters and 3295 in control clusters). 5601 participants were included in the primary outcome analysis (2756 in intervention clusters and 2845 in control clusters). In the intervention clusters, 612 (22·2%) of 2756 participants reported that they had attended CHIEDZA and 298 (10·8%) had been tested for C trachomatis and N gonorrhoeae. In the control clusters, 113 (4·0%) of 2845 participants had attended CHIEDZA and 40 (1·4%) had been tested for C trachomatis and N gonorrhoeae. In the outcome survey, the cluster-level geometric mean prevalence of the primary outcome (any of C trachomatis, N gonorrhoeae, and T vaginalis) was 19·07% (geometric standard deviation [GSD] 1·20) in the intervention arm versus 19·95% (GSD 1·10) in the control arm (risk ratio [RR] 0·93 [95% CI 0·78-1·10]; p=0·35). There was no difference between arms in geometric mean prevalence of C trachomatis (12·86% [GSD 1·14] in the intervention arm vs 12·94% [GSD 1·15] in the control arm, RR 0·97 [95% CI 0·84-1·11]; p=0·60) or T vaginalis (7·06% [GSD 1·48] vs 6·20% [1·38], RR 1·09 [95% CI 0·74-1·60]; p=0·66). N gonorrhoeae prevalence was significantly lower in the intervention arm, with a 43% risk reduction (geometric mean 1·65% [GSD 1·77] vs 2·87% [1·43], RR 0·57 [95% CI 0·34-0·96]; p=0·036)., Interpretation: Our study showed high population prevalence of curable STIs. Community-based STI screening appeared to reduce population-level prevalence of N gonorrhoeae, but not of C trachomatis or T vaginalis, probably due to low intervention coverage. Future research is needed on the effects of screening interventions on morbidity, antimicrobial resistance, and re-infection rates., Funding: Medical Research Council, Economic and Social Research Council, Department for International Development, National Institute for Health and Care Research, and the Wellcome Trust., Competing Interests: Declaration of interests KM has received funding from FIND to validate a novel lateral flow assay for gonorrhoea and a loan of a GeneXpert Machine. KM is also the recipient of a Wellcome Trust grant for a clinical PhD fellowship assessing point-of-care testing for STIs (Grant number 225468/Z/22/Z). All other authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Purpose of Review: HIV-associated cardiac disease was well recognized in the preantiretroviral (ART) era among children with perinatally-acquired HIV infection (PHIV). While ART has dramatically improved survival, it has become increasingly apparent that individuals with PHIV continue to experience multisystem co-morbidities. We review the cardiac and vascular manifestations in people growing up with PHIV in the ART era., Recent Findings: ART has resulted in a drop in incidence of serious cardiac morbidity. However, there is a substantial body of evidence that demonstrates that cardiac and vascular structural and functional abnormalities, mostly subclinical, are common in people with PHIV taking ART. Studies have considerable heterogeneity with respect to types of cardiovascular assessments used. HIV-mediated chronic inflammation and potentially effects of ART contribute to these abnormalities. The long-term clinical significance of these abnormalities remains unknown as studies have mainly been cross-sectional, but it is likely that the burden of cardiovascular disease will grow as individuals with PHIV age and the prevalence of traditional risk factors increases., Summary: Understanding the pathogenesis of cardiovascular disease in PHIV, is critical to inform screening and interventional strategies. Longitudinal studies are also needed to understand the natural history of cardiovascular abnormalities and incidence of clinical outcomes., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Understanding bone accrual in adolescents may inform approaches to improve skeletal health and reduce adult fracture risk. We investigated the effect of HIV on bone mineral accrual assessed by peripheral Quantitative Computed tomography (pQCT). Children with HIV (CWH) on ART for ≥2 years, and children without HIV (CWOH), aged 8-16 years (n = 609), had tibial pQCT scans at 0 and 12 months. Linear regression estimated sex stratified differences in change (∆) and mean pQCT bone density (trabecular and cortical), size (total cross-sectional area [CSA]) and strength (SSI) between CWH and CWOH, adjusting for socio-economic status (SES) and orphanhood and incorporating an interaction term for baseline pubertal status (Tanner 1-2[pre/early] vs 3-5[mid/late]). Structural equation modelling tested whether baseline height-for-age-Z-scores (HAZ) mediate the effect of HIV on ∆bone outcomes. CWH were more likely than CWOH to be orphans (44% vs 7%), of lower SES (43% vs 27%) and be stunted (30% vs 8%); but similar in age. At baseline and follow up, CWH had lower trabecular density, CSA and SSI than CWOH. After adjustment, bone density and strength increased similarly in CWH and CWOH. CWH in mid/late puberty at baseline had greater 12 months increases in CSA than CWOH, particularly males (mean difference [31.3(95%CI:-3.1, 65.6) mm2 in mid/late puberty vs. -2.04(-23.8, 19.7) mm2 in pre/early puberty; interaction P-value = 0.013]. HAZ mediated the effect of HIV on ∆bone outcomes only in females as follows: indirect pathways from HIV to ∆trabecular density [-1.85(-3.5, -0.2) mg/cm3], ∆cortical density [-2.01(-3.9, -0.01) mg/cm3], ∆CSA [-2.59(-4.7, -0.5) mm] and ∆SSI [-18.36(-29.6, -7.2) mm3]. In conclusion, CWH show bone deficits at follow up. Investigations of bone mineral accrual earlier in life and post-puberty to peak bone mass are needed., (© The Author(s) 2024. Published by Oxford University Press on behalf of the American Society for Bone and Mineral Research.)

Antiretroviral therapy roll-out has dramatically reduced HIV-related mortality; more women are living to reach menopause. Menopausal estrogen loss causes bone loss, as does HIV and some of its treatments. However, data describing HIV's impact on osteoporosis prevalence and fracture risk are scarce in southern Africa. A cross-sectional study of women aged 40-60 years (49% women with HIV [WLH]) was conducted in Harare, Zimbabwe. Menopause, fracture, and HIV history were collected, and anthropometry and BMD (by DXA) measured, and FRAX 10-year fracture probabilities quantified. The FRAX probability of a major osteoporotic fracture (MOF) included HIV as a risk factor for secondary osteoporosis. Linear and Poisson regression determined the relationships between clinical risk factors and both femoral neck (FN) BMD and the 10-year FRAX probability of MOF respectively. The 393 participants had a mean (SD) age of 49.6 (5.8) years and mean (SD) BMI of 29.1 (6.0) kg/m2. 95% of WLH were antiretroviral therapy (ART) established (85% tenofovir disoproxil fumarate) and 81% had a viral load <50 copies/mL. A BMD T-score ≤ -2.5 was more common in WLH than those without, at both FN and lumbar spine (LS) (FN, 22 [11.4%] vs 5 [2.5%]; LS, 40 [20.8%] vs 9 [4.5%], respectively). Prior fracture was more prevalent in WLH: any fracture type (27 [14%] vs 14 [7%]); MOF (14 [7.3%] vs 5 [2.5%]). WLH had a higher 10-year MOF probability (median, 1.2%; IQR, 0.9-1.8) compared with those without HIV (1.0%; IQR, 0.9-1.5) (p < .001), although probabilities were low. Older age, low weight, and HIV infection were strongly associated with lower FN BMD. Higher probability of MOF was associated with older age, HIV infection, parental hip fracture and prior fracture, although adjustment attenuated the association with HIV. No woman reported anti-osteoporosis medication use. While osteoporosis and previous fractures were common and untreated in this relatively young population, particularly in WLH, the FRAX-predicted 10-year MOF risk was low. Clinical risk factors considered in fracture risk prediction tools in Zimbabwe may need contextual modification., (© The Author(s) 2024. Published by Oxford University Press on behalf of the American Society for Bone and Mineral Research.)

Background: Youth in Southern Africa face a high burden of HIV and sexually transmitted infections, yet they exhibit low uptake of health care services., Objective: The Zvatinoda! intervention, co-designed with youth, aims to increase the demand for and utilization of health services among 18-24-year-olds in Chitungwiza, Zimbabwe., Methods: The intervention utilized mobile phone-based discussion groups, complemented by "ask the expert" sessions. Peer facilitators, supported by an "Auntie," led youth in anonymous online chats on health topics prioritized by the participants. Feedback on youth needs was compiled and shared with health care providers. The intervention was tested in a 12-week feasibility study involving 4 groups of 7 youth each, totaling 28 participants (n=14, 50%, female participants), to evaluate feasibility and acceptability. Mixed methods process evaluation data included pre- and postintervention questionnaires (n=28), in-depth interviews with participants (n=15) and peer facilitators (n=4), content from discussion group chats and expert guest sessions (n=24), facilitators' debrief meetings (n=12), and a log of technical challenges. Descriptive quantitative analysis and thematic qualitative analysis were conducted. The RE-AIM (Reach, Effectiveness, Adoption, Implementation, and Maintenance) framework was adapted to analyze and present findings on (1) reach, (2) potential efficacy, (3) adoption, (4) implementation, and (5) maintenance., Results: Mobile delivery facilitated engagement with diverse groups, even during COVID-19 lockdowns (reach). Health knowledge scores improved from pre- to postintervention across 9 measures. Preintervention scores varied from 14% (4/28) for contraception to 86% (24/28) for HIV knowledge. After the intervention, all knowledge scores reached 100% (28/28). Improvements were observed across 10 sexual and reproductive health (SRH) self-efficacy measures. The most notable changes were in the ability to start a conversation about SRH with older adults in the family, which increased from 50% (14/28) preintervention to 86% (24/28) postintervention. Similarly, the ability to use SRH services even if a partner does not agree rose from 57% (16/28) preintervention to 89% (25/28) postintervention. Self-reported attendance at a health center in the past 3 months improved from 32% (9/28) preintervention to 86% (24/28) postintervention (potential efficacy). Chat participation varied, largely due to network challenges and school/work commitments. The key factors facilitating peer learning were interaction with other youth, the support of an older, knowledgeable "Auntie," and the anonymity of the platform. As a result of COVID-19 restrictions, regular feedback to providers was not feasible. Instead, youth conveyed their needs to stakeholders through summaries of key themes from chat groups and a music video presented at a final in-person workshop (adoption and implementation). Participation in discussions decreased over time. To maintain engagement, introducing an in-person element was suggested (maintenance)., Conclusions: The Zvatinoda! intervention proved both acceptable and feasible, showing promise for enhancing young people's knowledge and health-seeking behavior. Potential improvements include introducing in-person discussions once the virtual group has established rapport and enhancing feedback and dialog with service providers., (©Constance Ruth Sina Mackworth-Young, Privillage Charashika, Zvatinoda Youth Advisory Group, Leyla Larsson, Olivia Jane Wilding-Davies, Nikita Simpson, Anna Sorrel Kydd, Theonevus Tinashe Chinyanga, Rashida Abbas Ferrand, Aveneni Mangombe, Karen Webb, Aoife Margaret Doyle. Originally published in JMIR Formative Research (https://formative.jmir.org), 24.09.2024.)

Background: Globally, the increasing use of digital technologies such as mobile phones and the internet has allowed for the development of innovative mobile health interventions, particularly for reaching and engaging with youth. However, there is a risk that using such technologies may exclude those who lack access to them., Objective: In this study, we investigated the sociodemographic factors associated with mobile phone ownership, internet use, and social media use among youth in Zimbabwe., Methods: A population-based prevalence survey was conducted in 24 urban and periurban communities across 3 provinces of Zimbabwe (Harare, Mashonaland East, and Bulawayo). Youths aged 18 to 24 years resident in randomly selected households in the study communities completed an interviewer-administered questionnaire. The primary outcomes were mobile phone ownership and current internet and social media use. A household wealth indicator was developed using principal components analysis, based on household asset ownership. Multivariable logistic regression was used to investigate the factors associated with each primary outcome. Age, sex, and province were considered a priori confounders. Household wealth, marital status, education level, employment status, time lived at current address, and HIV status were included in the final multivariable model if there was an age-, sex-, and province-adjusted association with a primary outcome on univariable analysis at a significance level of P<.10., Results: Of the 17,636 participants assessed for the primary outcome, 16,370 (92.82%) had access to a mobile phone, and 15,454 (87.63%) owned a mobile phone. Among participants with access to a mobile phone, 58.61% (9594/16,370) and 57.79% (9460/16,370), respectively, used internet and social media at least weekly. Older age (adjusted odds ratio [aOR] 1.76, 95% CI 1.55-2.00), increasing wealth (ranging from aOR 1.85, 95% CI 1.58-2.16, for wealth quintile 2 to aOR 3.80, 95% CI 3.00-4.80, for wealth quintile 5, with quintile 1 as reference), and higher education level (secondary: aOR 1.96, 95% CI 1.60-2.39; tertiary: aOR 8.36, 95% CI 5.29-13.20) were associated with mobile phone ownership. Older age, male sex, increasing wealth, having never been married, higher education level, being in education or formal employment, and having lived at the same address for ≥2 years were associated with higher levels of internet and social media use., Conclusions: While mobile phone ownership was near-universal, over one-third of youths in urban and periurban settings did not have access to the internet and social media. Access to the internet and social media use were strongly associated with household wealth and education level. Mobile health interventions must ensure that they do not amplify existing inequalities in access to health care. Such interventions must be accompanied by alternative strategies to engage and enroll individuals without internet or social media access to prevent the exclusion of young people by sex and socioeconomic status., (©Kevin Martin, Rachel Wei Chun Peh, Mandikudza Tembo, Constancia Vimbayi Mavodza, Aoife M Doyle, Chido Dziva Chikwari, Ethel Dauya, Tsitsi Bandason, Steven Azizi, Victoria Simms, Rashida A Ferrand. Originally published in the Journal of Medical Internet Research (https://www.jmir.org), 23.09.2024.)

Objectives: We investigated associations between HIV, frailty and health-related quality of life (HRQoL)., Methods: This cross-sectional study recruited men and women aged ≥40 years in Zimbabwe. A researcher collected clinical and HRQoL data, and performed physical assessments and HIV testing. Frailty was defined using five criteria: unintentional weight loss, exhaustion, low physical activity, low gait speed, low handgrip strength. The presence of three or more criteria defined frailty, one to two pre-frailty, and zero non-frail. Data analysis used adjusted regression modelling., Results: Of 1034 adults (mean ± SD, 62.0 ± 14.0 years), 21.6% (n = 223) were living with HIV: 93.3% knew their status, of whom 96.2% were on antiretroviral therapy (ART) and 89.7% of these had a viral load <50 copies/mL. Mean age at HIV diagnosis was 44.6 ± 10.4 years (only 8.1% were ≥70 years), people had been living with HIV for 9.8 ± 5.0 years and had been on ART for 9.4 ± 5.2 years. Overall, HIV was not associated with frailty: adjusted odds ratio (aOR) was 0.99 [95% confidence interval (CI): 0.42-2.33] for frailty versus non-frailty. However, each 5 years lived with HIV was associated with twice the odds of frailty/pre-frailty (aOR = 2.03, 95% CI: 1.03-4.13), independent of age and ART duration. Furthermore, each 5 years of ART use was associated with 60% lower odds of frailty/pre-frailty (aOR = 0.39, 95% CI: 0.19-0.78), independent of age and years lived with HIV. Older age, minimal education and poverty were associated with frailty. Frailty was associated with lower HRQoL in people both with and without HIV., Conclusion: Reduced survival and good viral suppression may explain the lack of association between HIV and frailty. Early ART initiation could reduce future risk of frailty., (© 2024 The Author(s). HIV Medicine published by John Wiley & Sons Ltd on behalf of British HIV Association.)

Background: Stunting and pubertal delay are common among children growing up with human immunodeficiency virus (HIV) and are associated with bone and muscle impairments. We investigated factors associated with bone density and muscle function in adolescents living with HIV (ALWH)., Methods: The VITALITY trial (PACTR202009897660297) investigated whether vitamin D and calcium supplementation improves musculoskeletal health among ALWH. A total of 842 ALWH aged 11-19 years, established on antiretroviral therapy (ART) for ≥6 months, were enrolled from HIV clinics in Zambia and Zimbabwe. Clinical history and examination were undertaken, and serum 25-hydroxyvitamin D 3 (25[OH]D 3 ) was measured. Dual-energy X-ray absorptiometry measured total-body-less-head bone mineral density adjusted for height (TBLH-BMD HT ), and lumbar spine bone mineral apparent density (LS-BMAD) z scores. The association between a priori-defined covariates and musculoskeletal outcomes were investigated using baseline enrollment data and multivariable logistic regression., Results: TBLH-BMD HT   z scores were impaired (mean, -1.42 for male and -0.63 female participants), as were LS-BMAD z scores (mean -1.15 for male and -0.47 for female participants). In bivariate analysis, early pubertal stage, less physical activity, and older age at ART initiation were associated with lower TBLH-BMD HT   z scores. Younger age, early pubertal stage, and low socioeconomic status were associated with lower LS-BMAD z scores. Grip-strength-for-height and jump-power-for-height z scores were associated with lower TBLH-BMD HT and LS-BMAD z scores. Low dietary vitamin D and calcium were associated with lower adjusted TBLH-BMD HT   z scores. Lower 25(OH)D 3 was associated with lower adjusted TBLH-BMD HT and LS-BMAD z scores., Conclusions: Deficits in bone density are common in ALWH. Vitamin D and calcium supplementation and promotion of exercise may improve musculoskeletal health among perinatally infected ALWH., Competing Interests: Potential conflicts of interest. All authors: No reported conflicts., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Objective: Cluster randomised trials (CRTs) are used for evaluating health-related interventions in low-income and middle-income countries (LMICs) but raise complex ethical issues. To inform the development of future ethics guidance, we aim to characterise CRTs conducted exclusively in LMICs by examining the types of clusters, settings, author affiliations and primary clinical focus and to evaluate adherence to trial registration and ethics reporting requirements over time., Design: A systematic scoping review using the Preferred Reporting Items for Systematic Review and Meta-Analyses Extension for Scoping Reviews., Data Sources: We searched MEDLINE between 1 January 2017 and 17 August 2022., Eligibility Criteria for Selecting Studies: We included primary reports of CRTs evaluating health-related interventions, conducted exclusively in LMICs and published in English between 2017 and 2022., Data Extraction and Synthesis: Data were extracted by one reviewer; a second reviewer verified accuracy by extracting data from 10% of the reports. Results were summarised overall and categorised by country's economic level or publication year., Results: Among 800 identified CRTs, 400 (50.0%) randomised geographical areas and 373 (46.6%) were conducted in Africa. 30 (3.7%) had no authors with an LMIC affiliation, and 246 (30.8%) had neither first nor last author with an LMIC affiliation. The relative frequency of first or last authors holding an LMIC affiliation increases as a country's economic level increases. Most CRTs focused on reducing maternal and neonatal disorders (106, 13.3%). 670 (83.8%) CRTs reported trial registration, 786 (98.2%) reported research ethics committee review and 757 (94.6%) reported consent statements. Among the 757 CRTs, 46 (6.1%) reported a waiver or no consent and, among these, 10 (21.7%) did not provide a rationale. Gatekeepers were identified in 403 (50.4%) CRTs. No meaningful trends were observed in adherence to trial registration or ethics reporting requirements over time., Conclusion: Our findings suggest existing inequity in authorship practices. There is high adherence to trial registration and ethics reporting requirements, although greater attention to reporting a justification for using a waiver of consent is needed., Competing Interests: Competing interests: CW receives consulting income from Cardialen and Eli Lilly & Company. Other authors declare no competing interests., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: To systematically review literature from randomised controlled trials (RCTs) investigating the effectiveness of electronic monitoring device informed interventions on adherence and clinical outcomes in children and adolescents with chronic conditions., Study Design: A systematic review was conducted. An electronic literature search covering studies, with no pre-specified starting date up to June 2024, was performed in Medline, EMBASE, Web of Science, Cochrane and Trials databases was conducted., Participants: RCTs of electronic monitoring device informed interventions in individuals aged 0 to 18 years with chronic conditions, were identified, with no restriction on geography or publication date., Methods: Extracted data was synthesised. As a result of differences in definitions and analysis of adherence and clinical outcomes across the studies a pooled meta-analysis was not possible therefore, a descriptive analysis was conducted. Risk of bias across all studies was assessed using the Cochrane Collaboration risk of bias tool., Results: 11 RCTs, with 1485 children and adolescents were included. Studies were all from high- and middle-income countries, conducted among children and adolescents with asthma, and one each among children and adolescents with kidney transplant, multiple sclerosis, and epilepsy. Eight of the 11 studies reported a positive effect on adherence. Only four studies reported a positive effect on clinical outcomes and seven studies found no effect on clinical outcomes., Conclusions: Electronic monitoring device interventions show promise in improving adherence in children and adolescents with chronic conditions, in a limited number of chronic conditions, mostly asthma. Evidence for the efficacy of electronic monitoring device informed interventions on clinical outcomes and from low-income settings is lacking., Systematic Review Registration: PROSPERO, CRD42022312057, registered in March 2022., Tweetable Abstract: Electronic monitoring device informed interventions may improve treatment adherence in children and adolescents with chronic conditions but evidence from low-income settings is lacking @nyasha&#95;dzavakwa @KatharinaKranz4 @dopapus @hilda&#95;mujuru @rashida&#95;abbferr @vickysimms&#95;epi., Competing Interests: Declaration of Competing Interest All authors declare no conflict of interest., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Pakistan is one of the five highest tuberculosis burden countries globally. We estimated prevalence of adult bacteriologically confirmed pulmonary tuberculosis and annual risk of Mycobacterium tuberculosis (M. tuberculosis) infection in children aged 2-4 years in Karachi, Pakistan. The survey design enabled exploration of tuberculosis burden by whether the population had previously been exposed to widespread tuberculosis active case-finding (ACF) activities or not. We conducted a concurrent adult pulmonary tuberculosis prevalence survey and a child M. tuberculosis infection survey using interferon gamma release assays in four districts (Korangi, South, West and Central). A cluster-based unequal probability random sampling method was employed with the a priori plan to oversample Korangi district which had been the focus of tuberculosis ACF activities since 2011. We defined Korangi district as the 'prior ACF' zone and remaining districts as the 'no prior ACF' zone. Between March 2018 and May 2019, 34,962 adults (78·5% of those eligible) and 1,505 children (59·9%) participated. Overall estimated prevalence of bacteriologically confirmed pulmonary tuberculosis was 387 cases per 100,000 population (95% CI 276-498) with a prevalence of 421 cases [95% CI 276-567] per 100,000 in the 'no prior ACF' and 279 cases [95% CI 155-403] per 100,000 in the 'prior ACF' zone. We estimated the annual risk of M. tuberculosis infection in children to be 1·1% (95% CI 0·7-1·5) in the 'no prior ACF' zone and 0·6% (95% CI 0·3-1·1) in the 'prior ACF' zone. We observed consistent differences in the population distribution of tuberculosis between the 'prior ACF' and 'no prior' ACF zones with a trend towards lower estimates of burden and M. tuberculosis transmission in the 'prior ACF' zone. A plausible explanation is that intensive ACF activities that have been ongoing in Korangi district for the preceding years have noticeably reduced the burden of tuberculosis and transmission., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Khan et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Multimorbidity is an emerging challenge for health systems globally. It is commonly defined as the co-occurrence of two or more chronic conditions in one person, but its meaning remains a lively area of academic debate, and the utility of the concept beyond high-income settings is uncertain. This article presents the findings from an interdisciplinary research initiative that drew together 60 academic and applied partners working in 10 African countries to answer the questions: how useful is the concept of multimorbidity within Africa? Can the concept be adapted to context to optimise its transformative potentials? During a three-day concept-building workshop, we investigated how the definition of multimorbidity was understood across diverse disciplinary and regional perspectives, evaluated the utility and limitations of existing concepts and definitions, and considered how to build a more context-sensitive, cross-cutting description of multimorbidity. This iterative process was guided by the principles of grounded theory and involved focus- and whole-group discussions during the workshop, thematic coding of workshop discussions, and further post-workshop development and refinement. Three thematic domains emerged from workshop discussions: the current focus of multimorbidity on constituent diseases; the potential for revised concepts to centre the priorities, needs, and social context of people living with multimorbidity (PLWMM); and the need for revised concepts to respond to varied conceptual priorities amongst stakeholders. These themes fed into the development of an expanded conceptual model that centres the catastrophic impacts multimorbidity can have for PLWMM, families and support structures, service providers, and health systems., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Dixon et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Introduction: HIV infection and its treatment compromises skeletal development (growth and maturation). Skeletal maturity is assessed as bone age (BA) on hand and wrist radiographs. BA younger than chronological age (CA) indicates delayed development. We conducted a cross-sectional study to determine differences between BA and CA (i.e., skeletal maturity deviation [SMD]), and risk factors associated with SMD in peripubertal children with and without HIV established on antiretroviral therapy (ART) including use of tenofovir disoproxil fumarate (TDF)., Methods: Children with HIV taking ART for at least two years and a comparison group of HIV-negative children, aged 8-16 years and frequency-matched by age and sex, were recruited from HIV clinics and local schools in the same catchment area, in Harare, Zimbabwe. BA was assessed from non-dominant hand-wrist radiographs using the Tanner Whitehouse 3 method. Negative SMD values correspond to delayed development, i.e., BA younger than CA. Multivariable linear regression models determined factors associated with SMD overall, and in children with HIV., Results: In total, 534 participants (54% males) were included; by design CA was similar in males and females, whether living with or without HIV. Mean (SD) SMD was more negative in CWH than in HIV-negative children in both males [-1.4(1.4) vs. -0.4(1.1) years] and females [-1.1(1.3) vs. -0.0(1.2) years]. HIV infection and weight-for-age Z-score<-2 were associated with more negative SMD in both males and females after adjusting for socio-economic status, orphanhood, pubertal stage, and calcium intake. Age at ART initiation was associated with SMD in both males and females with those starting ART later more delayed: starting ART aged 4-8 years 1.14 (-1.84, -0.43), or over 8 years 1.47 (-2.30, -0.65) (p-value for trend < 0.001). Similar non-significant trends were seen in males. TDF exposure TDF exposure whether < 4years or ≥ 4 years was not associated with delayed development., Conclusion: Perinatally-acquired HIV infection and being underweight were independently associated with delayed skeletal maturation in both males and females. Starting ART later was independently associated with skeletal maturation delay in CWH. Given the known effects of delayed development on later health, it is important to find interventions to ensure healthy weight gain through early years and in CWH to initiate ART as early as possible., (© 2024. The Author(s).)

Background: Of the 2 million children living with HIV globally, 90% live in sub-Saharan Africa. Despite antiretroviral therapy, longstanding HIV infection is associated with several chronic complications in children including growth failure, particularly stunting and delayed puberty. Vitamin D deficiency, which is highly prevalent among children living with HIV in sub-Saharan Africa, has further adverse impact on bone health. This trial aims to establish whether supplementation with vitamin D 3 and calcium carbonate improves musculoskeletal health among peripubertal children living with HIV. This paper is an update to an already existing protocol that was previously published in Trials in 2022 and details changes in the trial outcomes., Methods/design: We will conduct an individually randomised, double-blinded, placebo-controlled trial of weekly high-dose vitamin D 3 (20,000 IU) plus daily calcium carbonate (500 mg) supplementation for 48 weeks. Eight hundred and forty children living with HIV aged 11-19 years taking ART for ≥ 6 months will be enrolled and followed up for 96 weeks. The primary outcome is DXA-measured total body less-head bone mineral density Z-score (TBLH-BMD) at 48 weeks and is an update to the previous primary outcome total body less-head bone mineral content adjusted for lean mass (TBLH-BMC LBM ) Z-score. The primary outcome was updated to address the substantial differences in distributions of TBLH-BMC LBM Z-score between the two sites as a result of software differences of the DXA machines. Secondary outcomes are DXA-measured TBLH-BMD Z-score adjusted for height at 48 weeks a new secondary outcome, lumbar spine bone mineral apparent density Z-score, number of respiratory infections, lean muscle mass and grip-strength at 48 and 96 weeks, and TBLH-BMD Z-score at 96 weeks. Sub-studies will investigate the effect of the intervention on vitamin D 3 pathway metabolites and markers of bone turnover, intestinal microbiota, and innate and acquired immune function., Discussion: This is the largest trial to date of vitamin D supplementation in children living with HIV. Intervening to address deficits in bone accrual through childhood is critical for optimising adolescent and early adult bone health, and prevention of later adult osteoporotic fractures. Trial results will draw attention to the need to screen for and treat long-term comorbidities in children living with HIV in resource-limited settings., Trial Registration: Pan African Clinical Trials Registry PACTR20200989766029. Registered on September 3, 2020. URL of trial registry record: https://pactr.samrc.ac.za TRIAL STATUS: Participant follow-up completed; data analysis ongoing., (© 2024. The Author(s).)

Background: Chronic lung disease (CLD) is common among children with HIV (CWH) including in those taking antiretroviral therapy (ART). Azithromycin has both antimicrobial and anti-inflammatory effects and has been effective in improving lung function in a variety of lung diseases. We investigated lung function trajectories among CWH with CLD on ART enrolled in a randomized controlled trial of adjuvant azithromycin. We also investigated factors that modified the effect of azithromycin on lung function., Methods: The study used data from a double-blinded placebo-controlled trial conducted in Malawi and Zimbabwe of 48 weeks on azithromycin (BREATHE: ClinicalTrials.gov NCT02426112) among CWH aged 6 to 19 years taking ART for at least six months who had a forced expiratory volume in one second (FEV 1 ) z-score <-1.0. Participants had a further follow-up period of 24 weeks after intervention cessation. FEV 1 , forced vital capacity (FVC) and FEV 1 /FVC were measured at baseline, 24, 48 and 72-weeks and z-scores values calculated. Generalized estimating equations (GEE) models were used to determine the mean effect of azithromycin on lung-function z-scores at each follow-up time point., Results: Overall, 347 adolescents (51% male, median age 15 years) were randomized to azithromycin or placebo. The median duration on ART was 6.2 (interquartile range: 3.8-8.6) years and 56.2% had an HIV viral load < 1000copies/ml at baseline. At baseline, the mean FEV 1 z-score was - 2.0 (0.7) with 44.7% (n = 155) having an FEV 1 z-score <-2, and 10.1% had microbiological evidence of azithromycin resistance. In both trial arms, FEV 1 and FVC z-scores improved by 24 weeks but appeared to decline thereafter. The adjusted overall mean difference in FEV 1 z-score between the azithromycin and placebo arms was 0.004 [-0.08, 0.09] suggesting no azithromycin effect and this was similar for other lung function parameters. There was no evidence of interaction between azithromycin effect and baseline age, lung function, azithromycin resistance or HIV viral load., Conclusion: There was no observed azithromycin effect on lung function z-scores at any time point suggesting no therapeutic effect on lung function., Trial Registration: ClinicalTrials.gov NCT02426112. First registered on 24/04/2015., (© 2024. The Author(s).)

COVID-19 presented countries with unprecedented health policy challenges. For low-income countries in particular, policymakers had to contend with both the direct threats posed by COVID-19 as well as the social, educational, and economic harms associated with lockdown and other infection prevention and control measures. We present a holistic and contextualised case study of the direct and indirect impacts of COVID-19 on women and children, with some assessment of their uneven distribution across socio-economic, age and gender groups. We used different types of primary and secondary data from multiple sources to produce a holistic descriptive analysis. Primary data included: qualitative data obtained from 28 in-depth interviews of key informants, six focus group discussions; and 40 household interviews. We also extracted data from government reports and announcements, the District Health Information Software version 2 (DHIS2), newspaper articles and social media, as well as from published research articles. Our findings show that the direct and indirect adverse impacts of COVID-19 were compounded by many years of severe political economic challenges, and consequent deterioration of the healthcare system. The indirect effects of the pandemic had the most severe impacts on the poorest segment of society and widened age and gender inequalities. The pandemic and its accompanying infection prevention and control measures negatively affected health service delivery and uptake. The management of COVID-19 presented enormous challenges to policymakers and public health specialists. These included managing the greatest tension between direct and indirect harms; short-term and long-term effects; and the unequal distribution of harms across different segments of society., Competing Interests: Conflicts of interest SN was one of the health experts working on the ground who called for the lockdowns as he had first-hand information on the healthcare preparedness to face such a new novel coronavirus.

Background: There is increasing interest in utilising two-drug regimens for HIV treatment with the goal of reducing toxicity and improve acceptability. The D3 trial evaluates the efficacy and safety of DTG/3TC in children and adolescents and includes a nested pharmacokinetics(PK) substudy for paediatric drug licensing., Methods: D3 is an ongoing open-label, phase III, 96-week non-inferiority randomised controlled trial(RCT) conducted in South Africa, Spain, Thailand, Uganda and the United Kingdom. D3 has enrolled 386 children aged 2- < 15 years, virologically suppressed for ≥6 months, with no prior treatment failure. Participants were randomised 1:1 to receive DTG/3TC or DTG plus two nucleoside reverse transcriptase inhibitors(NRTIs), stratified by region, age (2- < 6, 6- < 12, 12- < 15 years) and DTG use at enrolment (participants permitted to start DTG at enrolment). The primary outcome is confirmed HIV-1 RNA viral rebound ≥50 copies/mL by 96-weeks. The trial employs the Smooth Away From Expected(SAFE) non-inferiority frontier, which specifies the non-inferiority margin and significance level based on the observed event risk in the control arm. The nested PK substudy evaluates WHO weight-band-aligned dosing in the DTG/3TC arm., Discussion: D3 is the first comparative trial evaluating DTG/3TC in children and adolescents. Implications of integrating a PK substudy and supplying data for prompt regulatory submission, were carefully considered to ensure the integrity of the ongoing trial. The trial uses an innovative non-inferiority frontier for the primary analysis to allow for a lower-than-expected confirmed viral rebound risk in the control arm, while ensuring interpretability of results and maintaining the planned sample size in an already funded trial., Trial Registration: International Standard Randomised Clinical Trial Number Register: ISRCTN17157458. European Clinical Trials Database: 2020-001426-57., Clinicaltrials: gov: NCT04337450., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier Inc.)

Introduction: Chronic lung disease is a major cause of morbidity in African children with HIV infection; however, the microbial determinants of HIV-associated chronic lung disease (HCLD) remain poorly understood. We conducted a case-control study to investigate the prevalence and densities of respiratory microbes among pneumococcal conjugate vaccine (PCV)-naive children with (HCLD +) and without HCLD (HCLD-) established on antiretroviral treatment (ART)., Methods: Nasopharyngeal swabs collected from HCLD + (defined as forced-expiratory-volume/second < -1.0 without reversibility postbronchodilation) and age-, site-, and duration-of-ART-matched HCLD- participants aged between 6-19 years enrolled in Zimbabwe and Malawi (BREATHE trial-NCT02426112) were tested for 94 pneumococcal serotypes together with twelve bacteria, including Streptococcus pneumoniae (SP), Staphylococcus aureus (SA), Haemophilus influenzae (HI), Moraxella catarrhalis (MC), and eight viruses, including human rhinovirus (HRV), respiratory syncytial virus A or B, and human metapneumovirus, using nanofluidic qPCR (Standard BioTools formerly known as Fluidigm). Fisher's exact test and logistic regression analysis were used for between-group comparisons and risk factors associated with common respiratory microbes, respectively., Results: A total of 345 participants (287 HCLD + , 58 HCLD-; median age, 15.5 years [IQR = 12.8-18], females, 52%) were included in the final analysis. The prevalence of SP (40%[116/287] vs. 21%[12/58], p = 0.005) and HRV (7%[21/287] vs. 0%[0/58], p = 0.032) were higher in HCLD + participants compared to HCLD- participants. Of the participants positive for SP (116 HCLD + & 12 HCLD-), 66% [85/128] had non-PCV-13 serotypes detected. Overall, PCV-13 serotypes (4, 19A, 19F: 16% [7/43] each) and NVT 13 and 21 (9% [8/85] each) predominated. The densities of HI (2 × 10 4 genomic equivalents [GE/ml] vs. 3 × 10 2 GE/ml, p = 0.006) and MC (1 × 10 4 GE/ml vs. 1 × 10 3 GE/ml, p = 0.031) were higher in HCLD + compared to HCLD-. Bacterial codetection (≥ any 2 bacteria) was higher in the HCLD + group (36% [114/287] vs. (19% [11/58]), (p = 0.014), with SP and HI codetection (HCLD + : 30% [86/287] vs. HCLD-: 12% [7/58], p = 0.005) predominating. Viruses (predominantly HRV) were detected only in HCLD + participants. Lastly, participants with a history of previous tuberculosis treatment were more likely to carry SP (adjusted odds ratio (aOR): 1.9 [1.1 -3.2], p = 0.021) or HI (aOR: 2.0 [1.2 - 3.3], p = 0.011), while those who used ART for ≥ 2 years were less likely to carry HI (aOR: 0.3 [0.1 - 0.8], p = 0.005) and MC (aOR: 0.4 [0.1 - 0.9], p = 0.039)., Conclusion: Children with HCLD + were more likely to be colonized by SP and HRV and had higher HI and MC bacterial loads in their nasopharynx. The role of SP, HI, and HRV in the pathogenesis of CLD, including how they influence the risk of acute exacerbations, should be studied further., Trial Registration: The BREATHE trial (ClinicalTrials.gov Identifier: NCT02426112 , registered date: 24 April 2015)., (© 2024. The Author(s).)

Tuberculosis (TB) disproportionally affects poor people, leading to income and non-income losses. Measures of socioeconomic impact of TB, e.g. impoverishment and patient costs are inadequate to capture non-income losses. We applied impoverishment and a multidimensional measure on TB and non-TB affected households in Zimbabwe. We conducted a cross-sectional study in 270 households: 90 non-TB; 90 drug-susceptible TB (DS-TB), 90 drug-resistant TB (DR-TB) during the COVID-19 pandemic (2020-2021). Household data included ownership of assets, number of household members, income and indicators on five capital assets: financial, human, social, natural and physical. Households with incomes per capita below US$1.90/day were considered impoverished. We used principal component analysis on five capital asset indicators to create a binary outcome variable indicating loss of livelihood. Log-binomial regression was used to determine associations between loss of livelihood and type of household. TB-affected households were more likely to report episodes of TB and household members requiring care than non-TB households. The proportions of impoverished households were 81% (non-TB), 88% (DS-TB) and 94% (DR-TB) by the time of interview. Overall, 56% (152/270) of households sold assets: 44% (40/90) non-TB, 58% (52/90) DS-TB and 67% (60/90) DR-TB. Children's education was affected in 33% (55/168) of TB-affected compared to 14% (12/88) non-TB households. Overall, 133 (50%) households experienced loss of livelihood, with TB-affected households almost twice as likely to experience loss of livelihood; adjusted prevalence ratio (aPR = 1.78 [95%CI:1.09-2.89]). The effect of TB on livelihood was most pronounced in poorest households (aPR = 2.61, [95%CI:1.47-4.61]). TB-affected households experienced greater socioeconomic losses compared to non-TB households. Multisectoral social protection is crucial to mitigate impacts of TB and other shocks, especially targeting poorest households., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Timire et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

The study explored social and health system influences on young women's decision-making about family planning in a community setting with low uptake. Seventy-two semi-structured interviews were conducted between April 2020 and November 2021, with both young women accessing, and healthcare workers providing, a community-based integrated package of HIV and sexual and reproductive health services (CHIEDZA) in Zimbabwe. Data were thematically analysed. Although long-acting contraception was freely available as part of the CHIEDZA initiative, uptake was low. Young women's contraception choices were influenced by a desired reproductive sequence, which reflected prevailing social norms and was conveyed by peers and female relatives. Nulliparous young women preferred short-term contraception and avoided hormonal contraceptives prepartum to 'preserve' their fertility. Once fertility had been confirmed within marriage through the birth of a child, hormonal contraceptive use became socially permissible. Healthcare workers, cognisant of community discourse, sensitively proposed alternative approaches. Increasing the availability of correct and adequate information and commodities is critical to improving the uptake of contraceptives for young women, but it is insufficient alone. Recognising and responding to local contextual understandings which frame considerations of appropriateness is paramount. Successful implementation of family planning interventions requires engaging with social norms and the influential groups that perpetuate them.

Cardiac abnormalities were identified early in the epidemic of AIDS, predating the isolation and characterization of the etiologic agent, HIV. Several decades later, the causation and pathogenesis of cardiovascular disease (CVD) linked to HIV infection continue to be the focus of intense speculation. Before the widespread use of antiretroviral therapy, HIV-associated CVD was primarily characterized by HIV-associated cardiomyopathy linked to profound immunodeficiency. With increasing antiretroviral therapy use, viral load suppression, and establishment of immune competency, the effects of HIV on the cardiovascular system are more subtle. Yet, people living with HIV still face an increased incidence of cardiovascular pathology. Advances in cardiac imaging modalities and immunology have deepened our understanding of the pathogenesis of HIV-associated CVD. This review provides an overview of the pathogenesis of HIV-associated CVD integrating data from imaging and immunologic studies with particular relevance to the HIV population originating from high-endemic regions, such as sub-Saharan Africa. The review highlights key evidence gaps in the field and suggests future directions for research to better understand the complex HIV-CVD interactions., Competing Interests: Disclosures None.

Objectives: To determine how muscle strength, power, mass, and density (i.e. quality) differ between children living with HIV (CWH) and those uninfected, and whether antiretroviral therapy (ART) regime is associated with muscle quality., Design: A cross-sectional study in Harare, Zimbabwe., Methods: The study recruited CWH aged 8-16 years, taking ART for at least 2 years, from HIV clinics, and HIV-uninfected children from local schools. Muscle outcomes comprised grip strength measured by hand-held Jamar dynamometer, lower limb power measured by standing long-jump distance, lean mass measured by dual-energy X-ray absorptiometry, and muscle density (reflecting intramuscular fat) by peripheral quantitative computed tomography. Linear regression calculated adjusted mean differences (aMD) by HIV status., Results: Overall, 303 CWH and 306 without HIV, had mean (SD) age 12.5 (2.5) years, BMI 17.5 (2.8), with 50% girls. Height and fat mass were lower in CWH, mean differences (SE) 7.4 (1.1) cm and 2.7 (0.4)kgs, respectively. Male CWH had lower grip strength [aMD 2.5 (1.1-3.9) kg, P  < 0.001], long-jump distance [7.1 (1.8-12.5) cm, P  = 0.006], muscle density [0.58 (0.12-1.05) mg/cm 3 , P  = 0.018, but not lean mass 0.06 (-1.08 to 1.21) kg, P  = 0.891) versus boys without HIV; differences were consistent but smaller in girls. Mediation analysis suggested the negative effect of HIV on jumping power in boys was partially mediated by muscle density ( P  = 0.032). CWH taking tenofovir disoproxil fumarate (TDF) had lower muscle density [0.56 (0.00-1.13)mg/cm 3 , P  = 0.049] independent of fat mass, than CWH on other ART., Conclusion: Perinatally acquired HIV is associated, particularly in male individuals, with reduced upper and lower limb muscle function, not mass. Intra-muscular fat (poorer muscle quality) partially explained reductions in lower limb function. TDF is a novel risk factor for impaired muscle quality., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Despite being integral to women's well-being, achieving good menstrual health (MH) remains a challenge. This study examined MH services uptake (including information, analgesics, and a choice of MH products - the menstrual cup and reusable pads) and sustained use of MH products within an integrated sexual and reproductive health intervention for young people in Zimbabwe., Methods: This mixed-methods study was nested within a cluster randomised trial of integrated sexual and reproductive health services (CHIEDZA) for youth in three provinces (Harare, Mashonaland East, and Bulawayo). The study collected qualitative and quantitative data from 27,725 female clients aged 16-24 years, who accessed CHIEDZA from April 2019 - March 2022. Using a biometric (fingerprint recognition) identification system, known as SIMPRINTS, uptake of MH information, products, and analgesics and other services was tracked for each client. Descriptive statistics and logistic regression were used to investigate MH service uptake and product choice and use over time, and the factors associated with these outcomes. Thematic analysis of focus group discussions and interviews were used to further explore providers' and participants' experiences of the MH service and CHIEDZA intervention., Results: Overall, 36,991 clients accessed CHIEDZA of whom 27,725 (75%) were female. Almost all (n = 26,448; 95.4%) took up the MH service at least once: 25433 took up an MH product with the majority (23,346; 92.8%) choosing reusable pads. The uptake of cups varied across province with Bulawayo province having the highest uptake (13.4%). Clients aged 20-24 years old were more likely to choose cups than reusable pads compared with those aged 16-19 years (9.4% vs 6.0%; p < 0.001). Over the implementation period, 300/1819 (16.5%) of clients swapped from the menstrual cup to reusable pads and 83/23346 (0.4%) swapped from reusable pads to the menstrual cup. Provision of the MH service encouraged uptake of other important SRH services. Qualitative findings highlighted the provision of free integrated SRH and MH services that included a choice of MH products and analgesics in a youth-friendly environment were key to high uptake and overall female engagement with SRH services., Conclusions: High uptake demonstrates how the MH service provided much needed access to MH products and information. Integration of MH within an SRH intervention proved central to young women accessing other SRH services., (© 2024. The Author(s).)

Households affected by tuberculosis have syndemic vulnerability, reflecting a concentration of and interactions between multiple biomedical, psychosocial, and structural determinants of health. Traditional approaches to tuberculosis screening do not address pre-existing risks, such as undernutrition and other chronic conditions, or the indirect effects of tuberculosis, such as loss of livelihood. These pre-existing risks and consequences not only perpetuate the global tuberculosis epidemic but, for those affected, lead to poor health and deepen poverty. We propose reimagining tuberculosis screening as an opportunity to deliver a contextually relevant package of services that address the needs of households affected by tuberculosis. This approach puts people and their rights at the centre of efforts to end tuberculosis, and has equity at the core. This approach could support progress towards universal health coverage, benefiting communities and health systems. Leadership, flexibility in funding allocation, and innovative care models will be required to realise this approach at scale., Competing Interests: Declaration of interests CJC and RAF acknowledge funding from the Wellcome Trust. All other authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Youth living with HIV are at higher risk than adults of disengaging from HIV care. Differentiated models of care such as community delivery of antiretroviral therapy (ART) may improve treatment outcomes. We investigated outcomes across the HIV cascade among youth accessing HIV services in a community-based setting. This study was nested in a cluster-randomised controlled trial (CHIEDZA: Clinicaltrials.gov, Registration Number: NCT03719521) conducted in three provinces in Zimbabwe and aimed to investigate the impact of a youth-friendly community-based package of HIV services, integrated with sexual and reproductive health services for youth (16-24 years), on population-level HIV viral load (VL). HIV services included HIV testing, ART initiation and continuous care, VL testing, and adherence support. Overall 377 clients were newly diagnosed with HIV at CHIEDZA, and linkage to HIV care was confirmed for 265 (70.7%, 234 accessed care at CHIEDZA and 31 with other providers); of these 250 (94.3%) started ART. Among those starting ART at CHIEDZA who did not transfer out and had enough follow up time (>6 months), 38% (68/177) were lost-to-follow-up within six months. Viral suppression (HIV Viral Load <1000 copies/ml) among those who had a test at 6 months was 90% (96/107). In addition 1162 clients previously diagnosed with HIV accessed CHIEDZA; 714 (61.4%) had a VL test, of whom 565 (79.1%) were virally suppressed. This study shows that provision of differentiated services for youth in the community is feasible. Linkage to care and retention during the initial months of ART was the main challenge and needs concerted attention to achieve the ambitious 95-95-95 UNAIDS targets., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: Chido Dziva Chikwari has been a guest Editor for Plos Global Public Health. The other authors have declared that no competing interests exist., (Copyright: © 2024 Dziva Chikwari et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Objectives: Chronic lung disease is a recognized complication in children with HIV. Acute respiratory exacerbations (ARE) are common among this group and cause significant morbidity. Exhaled nitric oxide (eNO) is a known marker of local airway inflammation. We investigated the association between eNO and ARE, biomarkers of systemic inflammation, and the effect of azithromycin on eNO levels., Methods: Individuals aged 6-19 years with HIV-associated chronic lung disease in Harare, Zimbabwe, were enrolled in a placebo-controlled randomized trial investigating the effect of 48-week azithromycin treatment on lung function and ARE. eNO levels and biomarkers were measured at inclusion and after treatment in a consecutively enrolled subset of participants. Linear regression and generalized linear models were used to study associations between eNO and ARE, biomarkers, and the effect of azithromycin on eNO levels., Results: In total, 172 participants were included in this sub-study, 86 from the placebo group and 86 from the azithromycin group. Participants experiencing at least one ARE during follow-up had significantly higher eNO levels at baseline than participants who did not (geometric mean ratio 1.13, 95% confidence interval [CI] 1.03-1.24, p = 0.015), adjusted for trial arm, age, sex and history of tuberculosis. Matrix metalloproteinase (MMP)-3, -7, and -10 were significantly associated with higher baseline eNO levels. At 48 weeks, azithromycin treatment did not affect eNO levels (geometric mean ratio 0.86, 95% CI 0.72-1.03, p = 0.103)., Conclusion: Higher baseline eNO levels were a risk factor for ARE. eNO was associated with proinflammatory biomarkers previously found to contribute to the development of chronic lung disease. The potential use of eNO as a marker of inflammation and risk factor for ARE in HIV-associated chronic lung disease needs further investigation., (© 2023 The Authors. HIV Medicine published by John Wiley & Sons Ltd on behalf of British HIV Association.)

Background: Hypertension is the greatest driver of cardiovascular mortality and onset might be in youth. We aimed to investigate the prevalence of and risk factors for elevated blood pressure (hypertension ≥140 mm Hg systolic, ≥90 mm Hg diastolic, or both) and high-normal blood pressure (130-139 mm Hg systolic, 85-89 mm Hg diastolic, or both) among youth in Zimbabwe., Methods: A population-based, cross-sectional survey of randomly sampled youth aged 18-24 years from 24 urban and peri-urban communities in three provinces (Harare, Bulawayo, and Mashonaland East) in Zimbabwe was conducted between Oct 4, 2021, and June 2, 2022. Standardised questionnaires were used by research assistants to collect sociodemographic, behavioural, and clinical data. Height, bodyweight, and blood pressure were recorded. Three seated blood pressure measurements were taken at standardised timepoints during participant interview using a digital sphygmomanometer and cuffs sized on mid-upper arm circumference. The association of potential risk factors with elevated blood pressure was examined using multivariable logistic regression., Findings: 17 682 (94·4%) of 18 729 eligible participants were recruited, 17 637 (99·7%) of whom had complete data, and 16 883 (95·7%) of whom were included in the final study sample after excluding 754 (4·3%) pregnant women. The median age was 20 years (IQR 19-22), 9973 (59·1%) participants were female, and 6910 (40·9%) were male. The prevalence of hypertension was 7·4% (95% CI 7·0-7·8) and high-normal blood pressure was 12·2% (11·7-12·7). Overall, prevalence of hypertension was higher in men (8·7% [95% CI 8·2-9·6]) than in women (6·6% [6·0-6·9]), but with age increased to similar levels (at age 18 years 7·3% [6·2-8·6] and 4·3% [3·5-5·2]; at age 23-24 years 10·9% [9·3-12·6] and 9·5% [8·4-10·7] in men and women, respectively). After adjusting for factors associated with hypertension in the crude analysis, hypertension was associated with male sex (adjusted odds ratio 1·53 [95% CI 1·36-1·74]), increasing age (age 19-20 years 1·20 [1·00-1·44]; age 21-22 years 1·45 [1·20-1·75]; age 23-24 years 1·90 [1·57-2·30], vs age 18 years), and BMI of 30·0 kg/m 2 or more (1·94 [1·53-2·47] vs 18·5-24·9 kg/m 2 ). A BMI of 18·5 kg/m 2 or less (0·79 [0·63-0·98] vs 18·5-24·9 kg/m 2 ) and living with HIV (0·71 [0·55-0·92]) were associated with lower odds of hypertension., Interpretation: Prevalence of elevated blood pressure is high among urban and peri-urban youth in Zimbabwe and increases rapidly with age. Further research is needed to understand drivers of blood pressure elevation and the extent of target organ damage in youth in Zimbabwe and similar sub-Saharan African settings, to guide implementation of prevention and management strategies., Funding: Wellcome Trust., Competing Interests: Declaration of interests RAF's institution received a grant from the Wellcome Trust. Salary support for VS and RJH was in part from a grant from the Medical Research Council (MRC) and the UK Department for International Development (DFID) under the MRC/DFID Concordat (MR/K012126/1). All other authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Background: We investigated the clinical profile, complications, and outcomes of inpatients with COVID-19 at Parirenyatwa Hospital, Harare, across the first two waves of SARS-CoV-2 infection, and factors associated with mortality., Methods: We conducted a prospective cohort study on all patients admitted to the COVID-19 unit. Data were extracted from medical records and negative binomial regression with robust standard errors was used to assess the association between sociodemographic and clinical characteristics and mortality. Cox Regression was used for sensitivity analysis., Results: Of 563 people admitted with COVID-19 between 2 July 2020 and 19 March 2021, 214 (38.0%) died, 340 were discharged and 9 transferred. The median age was 56 (IQR 44-68) years and 53.8% were male. Overall, 38.8% experienced a complication, the most common being acute kidney injury (17.9%) and hyperglycaemia (13.1%). The most common comorbidity was hypertension (41.3%) followed by diabetes (28.6%), HIV (12.1%), cardiovascular disease (10.9%) and chronic kidney disease (7.8%). Among participants who stayed in the ward for more than 1 night, mortality was higher in patients with comorbidity compared to those without any comorbidity (38.7% vs 25.5%, risk ratio (RR) = 1.52 (95% CI 1.11, 2.07), p = 0.008). After adjusting for oxygen saturation, comorbidities, sex and pregnancy, mortality was higher in the second wave than in the first (adjusted RR 1.23, 95% CI 1.00-1.51, p = 0.05). In the second wave 57/161 (35.4%) deaths were attributed to lack of resources, mainly human resources., Conclusion: The mortality rate was high and clinical COVID-19 care needs to pay careful attention to patient monitoring for complications and management of comorbidities. This will require addressing the critical health workforce shortage issues. Prevention of COVID-19 including vaccination particularly among individuals with comorbidities remains a high priority., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Fryatt et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

The burden of non-communicable diseases (NCDs) in southern Africa is expanding and is superimposed on high HIV prevalence. Healthcare workers are a scarce resource; yet are vital to health systems. There are very limited studies on the burden of chronic conditions among healthcare workers in Africa, and none exploring multimorbidity (≥2 chronic conditions). We describe the epidemiology of infectious (HIV) and non-communicable chronic conditions, and multimorbidity, among Zimbabwean healthcare workers. Healthcare workers (≥18 years) in eight Zimbabwean provinces were invited to a voluntary, cross-sectional health-check, including HIV, diabetes, hypertension and mental health screening. Statistical analyses described the prevalence and risk factors for multimorbidity (two or more of HIV, diabetes, hypertension or common mental disorder) and each condition. Missing data were handled using multiple imputation. Among 6598 healthcare workers (July 2020-July 2022) participating in the health-check, median age was 37 years (interquartile range 29-44), 79% were women and 10% knew they were living with HIV. Half had at least one chronic condition: 11% were living with HIV, 36% had elevated blood pressure, 12% had elevated HbA1c and 11% had symptoms of common mental disorder. The overall prevalence of multimorbidity was 15% (95% CI: 13-17%); 39% (95% CI: 36-43%) among people aged 50 and older. Whilst most HIV was diagnosed and treated, other chronic conditions were usually undiagnosed or uncontrolled. Limiting our definition of multimorbidity to two or more screened conditions sought to reduce bias due to access to diagnosis, however, may have led to a lower reported prevalence than that found using a wider definition. Half of healthcare workers screened were living with a chronic condition; one in seven had multimorbidity. Other than HIV, most conditions were undiagnosed or untreated. Multisectoral action to implement contextually relevant, chronic disease services in Africa is urgently needed. Specific attention on health workers is required to protect and retain this critical workforce., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Calderwood et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Health workers are essential for a functioning healthcare system, and their own health is often not addressed. During the COVID-19 pandemic health workers were at high risk of SARS-CoV-2 infection whilst coping with increased healthcare demand. Here we report the development, implementation, and uptake of an integrated health check combining SARS-CoV-2 testing with screening for other communicable and non-communicable diseases for health workers in Zimbabwe during the COVID-19 pandemic. Health checks were offered to health workers in public and private health facilities from July 2020 to June 2022. Data on the number of health workers accessing the service and yield of screening was collected. Workshops and in-depth interviews were conducted to explore the perceptions and experiences of clients and service providers. 6598 health workers across 48 health facilities accessed the service. Among those reached, 5215 (79%) were women, the median age was 37 (IQR: 29-44) years and the largest proportion were nurses (n = 2092, 32%). 149 (2.3%) healthcare workers tested positive for SARS-CoV-2. Uptake of screening services was almost 100% for all screened conditions except HIV. The most common conditions detected through screening were elevated blood pressure (n = 1249; 19%), elevated HbA1c (n = 428; 7.7%) and common mental disorder (n = 645; 9.8%). Process evaluation showed high acceptability of the service. Key enablers for health workers accessing the service included free and comprehensive service provision, and availability of reliable point-of-care screening methods. Implementation of a comprehensive health check for health workers was feasible, acceptable, and effective, even during a pandemic. Conventional occupational health programmes focus on infectious diseases. In a society where even health workers cannot afford health care, free comprehensive occupational health services may address unmet needs in prevention, diagnosis, and treatment for chronic non-communicable conditions., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Marambire et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)