Association Between Vitamin D Insufficiency and Impaired Bone Density Among Adolescents With Perinatally Acquired HIV Infection.

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 D3 (25[OH]D3) was measured. Dual-energy X-ray absorptiometry measured total-body-less-head bone mineral density adjusted for height (TBLH-BMDHT), 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-BMDHT  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-BMDHT  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-BMDHT and LS-BMAD z scores. Low dietary vitamin D and calcium were associated with lower adjusted TBLH-BMDHT  z scores. Lower 25(OH)D3 was associated with lower adjusted TBLH-BMDHT 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.

Systematic scoping review of cluster randomised trials conducted exclusively in low-income and middle-income countries between 2017 and 2022.

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.

Electronic monitoring device informed interventions for treatment adherence and clinical outcomes in children and adolescents: A systematic review.

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_dzavakwa @KatharinaKranz4 @dopapus @hilda_mujuru @rashida_abbferr @vickysimms_epi.

Factors Associated With the Use of Digital Technology Among Youth in Zimbabwe: Findings From a Cross-Sectional Population-Based Survey.

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.

Prevalence of HIV-associated osteoporosis and fracture risk in mid-life women: a cross-sectional study in Zimbabwe.

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 living with HIV (WLH)) was conducted in Harare, Zimbabwe. Menopause, fracture and HIV history were collected, and anthropometry and bone mineral density (BMD, by dual-energy x-ray absorptiometry (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 mean(SD) age of 49.6(SD = 5.8) years and mean(SD) BMI 29.1(6) kg/m2. 95% of WLH were ART established (85% TDF) 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, though 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.

Improved access to treatment for HIV now means women living with HIV are able to live well into older adulthood; however, this puts them at risk of age-related diseases such as osteoporosis. HIV and some of its treatments are known to cause bone loss, as does menopause, but studies on osteoporosis and fracture risk are scarce in southern Africa, where most people with HIV live. In this study in Zimbabwe, we found women with HIV were more likely to have osteoporosis and to have had a fracture, and a higher risk of having a major osteoporotic fracture over the next 10 years, compared with women without HIV (calculated using FRAX®: a fracture risk prediction tool), although the risk was surprisingly low. Older age, being underweight, and having HIV were strongly related to lower bone density at hip (an important site for fractures). Higher risk of future fracture was associated with older age, previous fracture, having HIV, and having a parent who had a hip fracture. Despite these findings, no woman had ever been offered any anti-osteoporosis medication. Our findings suggest that osteoporosis is under-recognized and undertreated in Zimbabwe, where clinical fracture risk prediction tools need to be modified for the specific context.

Insights into tuberculosis burden in Karachi, Pakistan: A concurrent adult tuberculosis prevalence and child Mycobacterium tuberculosis infection survey.

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.

Longitudinal lung function trajectories in response to azithromycin therapy for chronic lung disease in children with HIV infection: a secondary analysis of the BREATHE trial.

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 (FEV1) z-score <-1.0. Participants had a further follow-up period of 24 weeks after intervention cessation. FEV1, forced vital capacity (FVC) and FEV1/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 FEV1 z-score was - 2.0 (0.7) with 44.7% (n = 155) having an FEV1 z-score <-2, and 10.1% had microbiological evidence of azithromycin resistance. In both trial arms, FEV1 and FVC z-scores improved by 24 weeks but appeared to decline thereafter. The adjusted overall mean difference in FEV1 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.

Interdisciplinary perspectives on multimorbidity in Africa: Developing an expanded conceptual model.

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.

Characterization of bacterial and viral pathogens in the respiratory tract of children with HIV-associated chronic lung disease: a case-control study.

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 × 104 genomic equivalents [GE/ml] vs. 3 × 102 GE/ml, p = 0.006) and MC (1 × 104 GE/ml vs. 1 × 103 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).

Cardiovascular health in people with perinatally acquired HIV - where do we stand?

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.

Understanding the impact of the COVID-19 pandemic and its control measures on women and children: A Zimbabwe case study.

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.

Higher loss of livelihood and impoverishment in households affected by tuberculosis compared to non-tuberculosis affected households in Zimbabwe: A cross-sectional study.

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.

Risk factors for curable sexually transmitted infections among youth: findings from the STICH population survey in Zimbabwe.

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.

HIV-Associated Cardiovascular Disease Pathogenesis: An Emerging Understanding Through Imaging and Immunology.

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.

D3/Penta 21 clinical trial design: A randomised non-inferiority trial with nested drug licensing substudy to assess dolutegravir and lamivudine fixed dose formulations for the maintenance of virological suppression in children with HIV-1 infection, aged 2 to 15 years.

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.

High uptake of menstrual health information, products and analgesics within an integrated sexual reproductive health service for young people in Zimbabwe.

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.

Beyond tuberculosis: a person-centred and rights-based approach to screening for household contacts.

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.

Clinical characteristics and outcomes of patients admitted with COVID-19 at a public-sector hospital over the first two waves of SARS-CoV-2 infection in Harare, Zimbabwe: A prospective cohort study.

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.

Evaluation of a comprehensive health check offered to frontline health workers in Zimbabwe.

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.