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.

Exhaled nitric oxide is associated with inflammatory biomarkers and risk of acute respiratory exacerbations in children with HIV-associated chronic lung disease.

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.

Prevalence, factors and quality of life associated with frailty and pre-frailty in middle-aged and older adults living with HIV in Zimbabwe: A cross-sectional study.

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.

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.

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).

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.

The impact of HIV infection on skeletal maturity in peripubertal children in Zimbabwe: a cross-sectional study.

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.

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.

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.

Use of a Sustainable Livelihood Framework-Based Measure to Estimate Socioeconomic Impact of Tuberculosis on Households.

Tuberculosis (TB) disproportionally affects impoverished members of society. The adverse socioeconomic impact of TB on households is mostly measured using money-centric approaches, which have been criticized as one-dimensional and risk either overestimating or underestimating the true socioeconomic impacts of TB. We propose the use of the sustainable livelihood framework, which includes 5 household capital assets (human, financial, physical, natural, and social) and conceptualizes that households employ accumulative strategies in times of plenty and coping (survival) strategies in response to shocks such as TB. The proposed measure ascertains to what extent the 5 capital assets are available to households affected by TB as well as the coping costs (reversible and nonreversible) that are incurred by households at different time points (intensive, continuation, and post-TB treatment phase). We assert that our approach is holistic and multidimensional and draws attention to multisectoral responses to mitigate the socioeconomic impact of TB on households.

Delivery of index-linked HIV testing for children: learnings from a qualitative process evaluation of the B-GAP study in Zimbabwe.

BACKGROUND: Index-linked HIV testing for children, whereby HIV testing is offered to children of individuals living with HIV, has the potential to identify children living with undiagnosed HIV. The "Bridging the Gap in HIV Testing and Care for Children in Zimbabwe" (B-GAP) study implemented and evaluated the provision of index-linked HIV testing for children aged 2-18 years in Zimbabwe. We conducted a process evaluation to understand the considerations for programmatic delivery and scale-up of this strategy. METHODS: We used implementation documentation to explore experiences of the field teams and project manager who delivered the index-linked testing program, and to describe barriers and facilitators to index-linked testing from their perspectives. Qualitative data were drawn from weekly logs maintained by the field teams, monthly project meeting minutes, the project coordinator's incident reports and WhatsApp group chats between the study team and the coordinator. Data from each of the sources was analysed thematically and synthesised to inform the scale-up of this intervention. RESULTS: Five main themes were identified related to the implementation of the intervention: (1) there was reduced clinic attendance of potentially eligible indexes due to community-based differentiated HIV care delivery and collection of HIV treatment by proxy individuals; (2) some indexes reported that they did not live in the same household as their children, reflecting the high levels of community mobility; (3) there were also thought to be some instances of 'soft refusal'; (4) further, delivery of HIV testing was limited by difficulties faced by indexes in attending health facilities with their children for clinic-based testing, stigma around community-based testing, and the lack of familiarity of indexes with caregiver provided oral HIV testing; (5) and finally, test kit stockouts and inadequate staffing also constrained delivery of index-linked HIV testing. CONCLUSIONS: There was attrition along the index-linked HIV testing cascade of children. While challenges remain at all levels of implementation, programmatic adaptations of index-linked HIV testing approaches to suit patterns of clinic attendance and household structures may strengthen implementation of this strategy. Our findings highlight the need to tailor index-linked HIV testing to subpopulations and contexts to maximise its effectiveness.

Menopausal symptoms by HIV status and association with health-related quality of life among women in Zimbabwe: a cross-sectional study.

BACKGROUND: The scale-up of antiretroviral therapy programmes has resulted in increased life expectancy of people with HIV in Africa. Little is known of the menopausal experiences of African women, including those living with HIV. We aimed to determine the prevalence and severity of self-reported menopause symptoms in women at different stages of menopause transition, by HIV status, and evaluate how symptoms are related to health-related quality of life (HRQoL). We further sought to understand factors associated with menopause symptoms. METHODS: A cross-sectional study recruited women resident in Harare, Zimbabwe, sampled by age group (40-44/45-49/50-54/55-60 years) and HIV status. Women recruited from public-sector HIV clinics identified two similarly aged female friends (irrespective of HIV status) with phone access. Socio-demographic and medical details were recorded and women staged as pre-, peri- or post-menopause. The Menopausal Rating Scale II (MRS), which classified symptom severity, was compared between those with and without HIV. Linear and logistic regression determined factors associated with menopause symptoms, and associations between symptoms and HRQoL. RESULTS: The 378 women recruited (193[51.1%] with HIV), had a mean (SD) age of 49.3 (5.7) years; 173 (45.8%), 51 (13.5%) and 154 (40.7%) were pre-, peri and post-menopausal respectively. Women with HIV reported more moderate (24.9% vs. 18.1%) and severe (9.7% vs. 2.6%) menopause symptoms than women without HIV. Peri-menopausal women with HIV reported higher MRS scores than those pre- and post-menopausal, whereas in HIV negative women menopausal stage was not associated with MRS score (interaction p-value = 0.014). With increasing severity of menopause symptoms, lower mean HRQoL scores were observed. HIV (OR 2.02[95% CI 1.28, 3.21]), mood disorders (8.80[2.77, 28.0]), ≥ 2 falls/year (4.29[1.18, 15.6]), early menarche (2.33[1.22, 4.48]), alcohol consumption (2.16[1.01, 4.62]), food insecurity (1.93[1.14, 3.26]) and unemployment (1.56[0.99, 2.46]), were all associated with moderate/severe menopause symptoms. No woman reported use of menopausal hormone therapy. CONCLUSIONS: Menopausal symptoms are common and negatively impact HRQoL. HIV infection is associated with more severe menopause symptoms, as are several modifiable factors, including unemployment, alcohol consumption, and food insecurity. Findings highlight an unmet health need in ageing women in Zimbabwean, especially among those living with HIV.

Fertility preservation and protection: young women's decision-making about contraceptive use in Zimbabwe.

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.

Feasibility and economic costs of syphilis self-testing to expand test uptake among gay, bisexual and transgender men: results from a randomised controlled trial in Zimbabwe.

BACKGROUND: Access to syphilis testing and treatment is frequently limited for men who have sex with men (MSM). A two-armed randomised controlled trial compared feasibility and costs of facility-based syphilis testing with self-testing among MSM in Zimbabwe. METHODS: This randomised controlled trial was conducted in Harare, with participants randomised 1:1. Syphilis self-testing was offered in community-based settings. The primary outcome was the relative proportion of individuals taking up testing. Total incremental economic provider and user costs, and cost per client tested, diagnosed and treated were assessed using ingredients-based costing in 2020US$. RESULTS: A total of 100 men were enrolled. The two groups were similar in demographics. The mean age was 26years. Overall, 58% (29/50) and 74% (37/50) of facility- and self-testing arm participants, respectively, completed syphilis testing. A total of 28% of facility arm participants had a reactive test, with 50% of them returning for confirmatory testing yielding 28% reactivity. In the self-testing arm, 67% returned for confirmatory testing, with a reactivity of 16%. Total provider costs were US$859 and US$736, and cost per test US$30 and US$15 for respective arms. Cost per reactive test was US$107 and US$123, and per client treated US$215 and US$184, respectively. The syphilis test kit was the largest cost component. Total user cost per client per visit was US$9. CONCLUSION: Syphilis self-testing may increase test uptake among MSM in Zimbabwe. However, some barriers limit uptake including lack of self-testing and poor service access. Bringing syphilis testing services to communities, simplifying service delivery and increasing self-testing access through community-based organisations are useful strategies to promote health-seeking behaviours among MSM.

Interrupted Access to and Use of Family Planning Among Youth in a Community-Based Service in Zimbabwe During the First Year of the COVID-19 Pandemic.

The COVID-19 pandemic has had serious impacts on economic, social, and health systems, and fragile public health systems have become overburdened in many countries, exacerbating existing service delivery challenges. This study describes the impact of the COVID-19 pandemic on family planning services within a community-based integrated HIV and sexual and reproductive health intervention for youth aged 16-24 years being trialled in Zimbabwe (CHIEDZA). It examines the experiences of health providers and clients in relation to how the first year of the pandemic affected access to and use of contraceptives.

Psychological distress among healthcare workers accessing occupational health services during the COVID-19 pandemic in Zimbabwe.

BACKGROUND: Healthcare workers (HCWs) have experienced anxiety and psychological distress during the COVID-19 pandemic. We established and report findings from an occupational health programme for HCWs in Zimbabwe that offered screening for SARS-CoV-2 with integrated screening for comorbidities including common mental disorder (CMD) and referral for counselling. METHODS: Quantitative outcomes were fearfulness about COVID-19, the Shona Symptom Questionnaire (SSQ-14) score (cutpoint 8/14) and the number and proportion of HCWs offered referral for counselling, accepting referral and counselled. We used chi square tests to identify factors associated with fearfulness, and logistic regression was used to model the association of fearfulness with wave, adjusting for variables identified using a DAG. Qualitative data included 18 in-depth interviews, two workshops conducted with HCWs and written feedback from counsellors, analysed concurrently with data collection using thematic analysis. RESULTS: Between 27 July 2020-31 July 2021, spanning three SARS-CoV-2 waves, the occupational health programme was accessed by 3577 HCWs from 22 facilities. The median age was 37 (IQR 30-43) years, 81.9% were women, 41.7% said they felt fearful about COVID-19 and 12.1% had an SSQ-14 score ≥ 8. A total of 501 HCWs were offered referral for counselling, 78.4% accepted and 68.9% had ≥1 counselling session. Adjusting for setting and role, wave 2 was associated with increased fearfulness over wave 1 (OR = 1.26, 95% CI 1.00-1.60). Qualitative data showed high levels of anxiety, psychosomatic symptoms and burnout related to the pandemic. Mental wellbeing was affected by financial insecurity, unmet physical health needs and inability to provide quality care within a fragile health system. CONCLUSIONS: HCWs in Zimbabwe experience a high burden of mental health symptoms, intensified by the COVID-19 pandemic. Sustainable mental health interventions must be multisectoral addressing mental, physical and financial wellbeing.

Growth improvement following antiretroviral therapy initiation in children with perinatally-acquired HIV diagnosed in older childhood in Zimbabwe: a prospective cohort study.

BACKGROUND: Children who initiate antiretroviral therapy (ART) before age 5 years can recover height and weight compared to uninfected peers, but growth outcomes are unknown for children initiating ART at older ages. We investigated factors associated with growth failure at ART initiation and modelled growth by age on ART. METHODS: We conducted secondary analysis of cohort of children aged 6-15 years late-diagnosed with HIV in Harare, Zimbabwe, with entry at ART initiation in 2013-2015. Factors associated with height-for-age (HAZ), weight-for-age (WAZ) and BMI-for-age (BAZ) z-scores <- 2 (stunting, underweight and wasting respectively) at ART initiation were assessed using multivariable logistic regression. These outcomes were compared at ART initiation and 12 month follow-up using paired t-tests. HAZ and BAZ were modelled using restricted cubic splines. RESULTS: Participants (N = 302; 51.6% female; median age 11 years) were followed for a median of 16.6 months (IQR 11.0-19.8). At ART initiation 34.8% were stunted, 34.5% underweight and 15.1% wasted. Stunting was associated with age ≥ 12 years, CD4 count < 200 cells/µl, tuberculosis (TB) history and history of hospitalisation. Underweight was associated with older age, male sex and TB history, and wasting was associated with older age, TB history and hospitalisation. One year post-initiation, t-tests showed increased WAZ (p = 0.007) and BAZ (p = 0.004), but no evidence of changed HAZ (p = 0.85). Modelling showed that HAZ and BAZ decreased in early adolescence for boys on ART, but not girls. CONCLUSION: Stunting and underweight were prevalent at ART initiation among late-diagnosed children, and HAZ did not improve after 1 year. Adolescent boys with perinatally acquired HIV and late diagnosis are particularly at risk of growth failure in puberty.

Risk factors for sustained virological non-suppression among children and adolescents living with HIV in Zimbabwe and Malawi: a secondary data analysis.

BACKGROUND: We investigated risk factors for sustained virological non-suppression (viral load ≥ 1000 copies/ml on two tests 48 weeks apart) among children and adolescents accessing HIV care in public sector clinics in Harare, Zimbabwe and Blantyre, Malawi. METHODS: Participants were enrolled between 2016 and 2019, were aged 6-19 years, living with HIV, had chronic lung disease (FEV z-score < -1) and had taken antiretroviral therapy (ART) for at least six months. We used multivariate logistic regression to identify risk factors for virological non-suppression after 48 weeks, among participants who were non-suppressed at enrolment. RESULTS: At enrolment 258 participants (64.6%) were on first-line ART and 152/347 (43.8%) had virological non-suppression. After 48 weeks 114/313 (36.4%) were non-suppressed. Participants non-suppressed at baseline had almost ten times higher odds of non-suppression at follow-up (OR = 9.9, 95%CI 5.3-18.4, p < 0.001). Of those who were non-suppressed at enrolment, 87/136 (64.0%) were still non-suppressed at 48 weeks. Among this group non-suppression at 48 weeks was associated with not switching ART regimen (adjusted OR = 5.55; 95%CI 1.41-21.83); p = 0.014) and with older age. Twelve participants switched regimen in Zimbabwe and none in Malawi. CONCLUSIONS: Viral non-suppression was high among this group and many with high viral load were not switched to a new regimen, resulting in continued non-suppression after 48 weeks. Further research could determine whether improved adherence counselling and training clinicians on regimen switches can improve viral suppression rates in this population. TRIAL REGISTRATION: Secondary cohort analysis of data from BREATHE trial (Clinicaltrials.gov NCT02426112 ).

Integration of a menstrual health intervention in a community-based sexual and reproductive health service for young people in Zimbabwe: a qualitative acceptability study.

BACKGROUND: Despite being fundamental to the health and well-being of women, menstrual health is often overlooked as a health priority and access to menstrual health education, products, and support is limited. Consequently, many young women are unprepared for menarche and face challenges in accessing menstrual health products and support and in managing menstruation in a healthy and dignified way. In this paper, we examine the acceptability of a comprehensive menstrual health and hygiene (MHH) intervention integrated within a community-based sexual and reproductive health (SRH) service for young people aged 16-24 years in Zimbabwe called CHIEDZA. METHODS: We conducted focus group discussions, that included participatory drawings, with CHIEDZA healthcare service providers (N = 3) and with young women who had attended CHIEDZA (N = 6) between June to August 2020. Translated transcripts were read for familiarisation and thematic analysis was used to explore acceptability. We applied Sekhon's thematic framework of acceptability that looks at seven key constructs (affective attitudes, burden, ethicality, intervention coherence, opportunity costs, perceived effectiveness, and self-efficacy). Data from FGDs and meeting minutes taken during the study time period were used to triangulate a comprehensive understanding of MHH intervention acceptability. RESULTS: The MHH intervention was acceptable to participants as it addressed the severe prevailing lack of access to menstrual health education, products, and support in the communities, and facilitated access to other SRH services on site. In addition to the constructs defined by Sekhon's thematic framework, acceptability was also informed by external contextual factors such as sociocultural norms and the economic environment. Providers highlighted the increased burden in their workload due to demand for MHH products, and how sociocultural beliefs around insertable menstrual products compromising virginity can negatively affect acceptability among young people and community members. CONCLUSIONS: MHH interventions are acceptable to young women in community-based settings in Zimbabwe as there is great unmet need for comprehensive MHH support. The integration of MHH in SRH services can serve as a facilitator to female engagement with SRH services. However, it is important to note that contextual external factors can affect the implementation and acceptability of integrated SRH and MHH services within communities. TRIAL REGISTRATION: Registry: Clinicaltrials.gov, Registration Number: NCT03719521 , Registration Date: October 25, 2018.

Adapting an evidence-based contraceptive behavioural intervention delivered by mobile phone for young people in Zimbabwe.

BACKGROUND: Despite the availability of a range of contraceptive methods, young people around the world still face barriers in accessing and using them. The use of digital technology for the delivery of health interventions has expanded rapidly. Intervention delivery by mobile phone can be a useful way to address young people's needs with regard to sexual and reproductive health, because the information can be digested at a time of the recipients' choosing. This study reports the adaptation of an evidence-based contraceptive behavioural intervention for young people in Zimbabwe. METHODS: Focus group discussions and in depth interviews were used to evaluate the 'fit' of the existing intervention among young people in Harare, Zimbabwe. This involved determining how aligned the content of the existing intervention was to the knowledge and beliefs of young Zimbabweans plus identifying the most appropriate intervention deliver mode. The verbatim transcripts were analysed using a thematic analysis. The existing intervention was then adapted, tested and refined in subsequent focus group discussions and interviews with young people in Harare and Bulawayo. RESULTS: Eleven key themes resulted from the discussions evaluating the fit of the intervention. While there were many similarities to the original study population, key differences were that young people in Zimbabwe had lower levels of personal and smart mobile phone ownership and lower literacy levels. Young people were enthusiastic about receiving information about side effects/side benefits of the methods. The iterative testing and refinement resulted in adapted intervention consisting of 97 messages for female recipients (94 for male), delivered over three months and offered in English, Shona and Ndebele. CONCLUSIONS: Young people in Zimbabwe provided essential information for adapting the existing intervention. There was great support for the adapted intervention among the young people who took part in this study. The adapted intervention is now being implemented within an integrated community-based sexual and reproductive health service in Zimbabwe.