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.

Disparities in the Prevalence of Osteoporosis and Osteopenia in Men and Women Living in Sub-Saharan Africa, the UK, and the USA.

PURPOSE: To review the rising prevalence of osteopenia and osteoporosis in sub-Saharan Africa and the challenges this poses to governments and healthcare services. Using existing studies, we compare the prevalence of osteopenia and osteoporosis in men and women from sub-Saharan Africa to US and UK cohorts. Context-specific disparities in healthcare are discussed particularly the challenges in diagnosis and treatment of osteoporosis. RECENT FINDINGS: There are few epidemiological data describing the burden of osteoporosis in sub-Saharan Africa. In the studies and cohorts presented here, osteoporosis prevalence varies by sex, country and area of residence, but is generally higher in African populations, than has previously been appreciated. Risk factors contributing to poorer bone health include HIV, malnutrition and "inflammaging." Reprioritization towards care of ageing populations is urgently required. Equitable access to implementable preventative strategies, diagnostic services, treatments and pathways of care for bone health (for example embedded within HIV services) need now to be recognized and addressed by policy makers.

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.

Validation of the global lung initiative 2012 multi-ethnic spirometric reference equations in healthy urban Zimbabwean 7-13 year-old school children: a cross-sectional observational study.

BACKGROUND: The 2012 Global Lung Function Initiative (GLI2012) provide multi-ethnic spirometric reference equations (SRE) for the 3-95 year-old age range, but Sub-Saharan African populations are not represented. This study aimed to evaluate the fit of the African-American GLI2012 SRE to a population of healthy urban and peri-urban Zimbabwean school-going children (7-13 years). METHODS: Spirometry and anthropometry were performed on black-Zimbabwean children recruited from three primary schools in urban and peri-urban Harare, with informed consent and assent. Individuals with a history or current symptoms of respiratory disease or with a body mass index-z score (BMI) < - 2 were excluded. Spirometry z-scores were generated from African-American GLI2012 SRE, which adjust for age, sex, ethnicity and height, after considering all GLI2012 modules. Anthropometry z-scores were generated using the British (1990) reference equations which adjust for age and sex. The African-American GLI2012 z-score distribution for the four spirometry measurements (FVC, FEV1, FEV1/FVC and MMEF) were evaluated across age, height, BMI and school (as a proxy for socioeconomic status) to assess for bias. Comparisons between the African-American GLI2012 SRE and Polgar equations (currently adopted in Zimbabwe) on the percent-predicted derived values were also performed. RESULTS: The validation dataset contained acceptable spirometry data from 712 children (344 girls, mean age: 10.5 years (SD 1.81)). The spirometry z-scores were reasonably normally distributed, with all means lower than zero but within the range of ±0.5, indicating a good fit to the African-American GLI2012 SRE. The African-American GLI2012 SRE produced z-scores closest to a normal distribution. Z-scores of girls deviated more than boys. Weak correlations (Pearson's correlation coefficient < 0.2) were observed between spirometry and anthropometry z-scores, and scatterplots demonstrated no systematic bias associated with age, height, BMI or socioeconomic status. The African-American GLI2012 SRE provided a better fit for Zimbabwean paediatric spirometry data than Polgar equations. CONCLUSION: The use of African-American GLI2012 SRE in this population could help in the interpretation of pulmonary function tests.

Prevalence of HIV-associated osteoporosis and fracture risk in midlife 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 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.

Improved access to treatment for HIV now means women 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 underrecognized and undertreated in Zimbabwe, where clinical fracture risk prediction tools need to be modified for the specific context.

Perinatal HIV infection is associated with deficits in muscle function in children and adolescents in Zimbabwe.

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.

Changes in peripheral quantitative computed tomography measured bone density, size and strength in Zimbabwean children with and without HIV over one year: a cohort study.

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.

We measured bone density, bone size and bone strength at 0 and 12 months in 609, 8-16 year old children living with (CWH) and children living without HIV (CWOH). CWH were more likely to be orphans, to be of a lower socio-economic status, to be shorter and to have lower bone density, size and strength than CWOH who are of the same age. After 12 months, there were persistent bone deficits in CWH, despite that CWH who were in their mid/late puberty (especially males) showed greater increases in bone size than CWOH. Investigations of bone accrual in early life and beyond puberty are necessary.

The Impact of Human Immunodeficiency Virus and Menopause on Bone Mineral Density: A Longitudinal Study of Urban-Dwelling South African Women.

An estimated 25% of South African women live with human immunodeficiency virus (HIV). Antiretroviral therapy roll-out has improved life expectancy, so many more women now reach menopause. We aimed to quantify changes in bone mineral density (BMD) during the menopausal transition in urban-dwelling South African women with and without HIV and determine whether HIV infection modified the effect of menopause on BMD changes. A 5-year population-based longitudinal study recruited women aged 40-60 years residing in Soweto and collected demographic and clinical data, including HIV status, anthropometry, and BMD, at baseline and at 5-year follow-up. All women were staged as pre-, peri-, or postmenopausal at both time points. Multivariable linear regression assessed relationships and interactions between HIV infection, menopause, and change in BMD. At baseline, 450 women had mean age 49.5 (SD 5.7) years, 65 (14.4%) had HIV, and 140 (31.1%), 119 (26.4%), and 191 (42.4%) were pre-, peri-, and postmenopausal, respectively; 34/205 (13.6%) women ≥50 years had a total hip (TH) or lumbar spine (LS) T-score ≤ -2.5. At follow-up 38 (8.4%), 84 (18.7%), and 328 (72.9%) were pre-, peri-, and postmenopausal. Those with HIV at baseline lost more total body (TB) BMD (mean difference -0.013 [95% confidence interval -0.026, -0.001] g/cm2 , p = 0.040) and gained more weight 1.96 [0.32, 3.60] kg; p = 0.019 than HIV-uninfected women. After adjusting for age, baseline weight, weight change, and follow-up time, the transition from pre- to postmenopause was associated with greater TB BMD losses in women with HIV (-0.092 [-0.042, -0.142] g/cm2 ; p = 0.001) than without HIV (-0.038 [-0.016, -0.060] g/cm2 , p = 0.001; interaction p = 0.034). Similarly, in women who were postmenopausal at both time points, those with HIV lost more TB BMD (-0.070 [-0.031, -0.108], p = 0.001) than women without HIV (-0.036 [-0.015, -0.057], p = 0.001, interaction p = 0.049). Findings were consistent but weaker at the LS and TH. Menopause-related bone loss is greater in women with HIV, suggesting women with HIV may be at greater risk of osteoporotic fractures. HIV services should consider routine bone health assessment in midlife women as part of long-term HIV care delivery. © 2023 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).

Impaired Bone Architecture in Peripubertal Children With HIV, Despite Treatment With Antiretroviral Therapy: A Cross-Sectional Study From Zimbabwe.

HIV infection has multi-system adverse effects in children, including on the growing skeleton. We aimed to determine the association between chronic HIV infection and bone architecture (density, size, strength) in peripubertal children. We conducted a cross-sectional study of children aged 8 to 16 years with HIV (CWH) on antiretroviral therapy (ART) and children without HIV (CWOH) recruited from schools and frequency-matched for age strata and sex. Outcomes, measured by tibial peripheral quantitative computed tomography (pQCT), included 4% trabecular and 38% cortical volumetric bone mineral density (vBMD), 4% and 38% cross-sectional area (CSA), and 38% stress-strain index (SSI). Multivariable linear regression tested associations between HIV status and outcomes, stratified by sex and puberty (Tanner 1-2 versus 3-5), adjusting for age, height, fat mass, physical activity, and socioeconomic and orphanhood statuses. We recruited 303 CWH and 306 CWOH; 50% were female. Although CWH were similar in age to CWOH (overall mean ± SD 12.4 ± 2.5 years), more were prepubertal (ie, Tanner 1; 41% versus 23%). Median age at ART initiation was 4 (IQR 2-7) years, whereas median ART duration was 8 (IQR 6-10) years. CWH were more often stunted (height-for-age Z-score <-2) than those without HIV (33% versus 7%). Both male and female CWH in later puberty had lower trabecular vBMD, CSA (4% and 38%), and SSI than those without HIV, whereas cortical density was similar. Adjustment explained some of these differences; however, deficits in bone size persisted in CWH in later puberty (HIV*puberty interaction p = 0.035 [males; 4% CSA] and p = 0.029 [females; 38% CSA]). Similarly, puberty further worsened the inverse association between HIV and bone strength (SSI) in both males (interaction p = 0.008) and females (interaction p = 0.004). Despite long-term ART, we identified deficits in predicted bone strength in those living with HIV, which were more overt in the later stages of puberty. This is concerning, as this may translate to higher fracture risk later in life. © 2022 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).

Evaluation of two methods of bone age assessment in peripubertal children in Zimbabwe.

OBJECTIVES: Bone age (BA) measurement in children is used to evaluate skeletal maturity and helps in the diagnosis of growth disorders in children. The two most used methods are Greulich and Pyle (GP), and Tanner and Whitehouse 3 (TW3), both based upon assessment of a hand-wrist radiograph. To our knowledge no study has compared and validated the two methods in sub-Saharan Africa (SSA), and only a few have determined BA despite it being a region where skeletal maturity is often impaired for example by HIV and malnutrition. This study aimed to compare BA as measured by two methods (GP and TW3) against chronological age (CA) and determine which method is most applicable in peripubertal children in Zimbabwe. METHODS: We conducted a cross-sectional study of boys and girls who tested negative for HIV. Children and adolescents were recruited by stratified random sampling from six schools in Harare, Zimbabwe. Non-dominant hand-wrist radiographs were taken, and BA assessed manually using both GP and TW3. Paired sample Student t-tests were used to calculate the mean differences between BA and chronological age (CA) in boys and girls. Bland-Altman plots compared CA to BA as determined by both methods, and agreement between GP and TW3 BA. All radiographs were graded by a second radiographer and 20 % of participants of each sex were randomly selected and re-graded by the first observer. Intraclass correlation coefficient assessed intra- and inter-rater reliability and coefficient of variation assessed precision. RESULTS: We recruited 252 children (111 [44 %] girls) aged 8.0-16.5 years. The boys and girls were of similar mean ± SD CA (12.2 ± 2.4 and 11.7 ± 1.9 years) and BA whether assessed by GP (11.5 ± 2.8 and 11.5 ± 2.1 years) or TW3 (11.8 ± 2.5 and 11.8 ± 2.1 years). In boys BA was lower than CA by 0.76 years (95 % CI: -0.95, -0.57) when using GP, and by 0.43 years (95 % CI: -0.61, -0.24) when using TW3. Among the girls there was no difference between BA and CA by either GP [-0.19 years (95 % CI: -0.40, 0.03)] or TW3 [0.07 years (95 % CI: -0.16, 0.29)]. In both boys and girls, there were no systematic differences between CA and TW3 BA across age groups whereas agreement improved between CA and GP BA as children got older. Inter-operator precision was 1.5 % for TW3 and 3.7 % for GP (n = 252) and intra-operator precision was 1.5 % for TW3 and 2.4 % for GP (n = 52). CONCLUSION: The TW3 BA method had better precision than GP and did not systematically differ from CA, meaning that TW3 is the preferred method of assessment of skeletal maturity in Zimbabwean children and adolescents. TW3 and GP methods do not agree for estimates of BA and therefore cannot be used interchangeably. The systematic differences in GP BA assessments over age means it is not appropriate for use in all age groups or stages of maturity in this population.

Menopause is associated with bone loss, particularly at the distal radius, in black South African women: Findings from the Study of Women Entering and in Endocrine Transition (SWEET).

Menopause transition is associated with accelerated bone loss, though data are limited from sub-Saharan African (SSA). Our objective was to describe bone density, geometry and estimated strength in women by menopause status and to explore whether patterns differed within those living with HIV. METHODS: Radius and tibia peripheral QCT data were collected for Black South African women (n = 430) aged 40-61 years with verified menopause and HIV status. pQCT outcomes were distal 4 % radius and tibia total cross-sectional area (CSA), total volumetric bone mineral density (vBMD), and compressive bone strength (BSIc); proximal 66 % radius and 38 % tibia cortical vBMD, total CSA, cortical thickness, and Stress-strain Index (SSI). Linear regression assessed associations between pre, peri-, and postmenopausal groups and pQCT outcomes adjusting for age, height, and weight, and then stratified by HIV status. Mean [95%CI] and tests for trend (p-trend) across menopausal groups are presented. RESULTS: Women were mean (SD) age 49.2 (5.3) years, with a body mass index (BMI) of 32.4 (6.3) m/kg2, and 18 % were living with HIV. After adjustment, later menopause stage was associated with lower 4 % radius total mean [95%CIs] vBMD (premenopause: 345.7 [335.8,355.5] vs. postmenopause: 330.1 [322.7,337.6] mg/cm3, p-trend = 0.017) and BSIc (premenopause: 0.39 [0.37,0.41] vs. postmenopause: 0.36 [0.35,0.37] g2/cm4; p-trend = 0.012). Similar trends were observed at the 66 % radius for cortical vBMD (premenopause: 1146.8 [1138.9,1154.6] vs. postmenopause: 1136.1 [1130.1,1142.0] mg/cm3; p-trend = 0.028) and cortical thickness (premenopause: 2.01 [1.95,2.06] vs. postmenopause: 1.93 [1.89,1.98] mm; p-trend = 0.036). After stratification by HIV status a similar patten was observed in women with HIV (cortical vBMD premenopause: 1152.9 [1128.5,1177.2] mg/cm3 vs. postmenopause: 1123.6 [1106.0,1141.2] mg/cm3, p-trend = 0.048). Total CSA varied little by menopause or HIV status at either radius sites; few differences were found at the tibia. CONCLUSION: In black South African women, menopause is associated with lower bone density and strength at the distal radius, a common site of osteoporotic fracture, in addition to lower cortical density and thickness at the proximal radius. Although the sample size was small, following stratification by HIV, women living with HIV had evidence of lower cortical density across menopause stages, unlike those without HIV. These findings raise concern for the incidence of Colles' fractures in postmenopausal women in South Africa; longitudinal studies of fracture incidence and implications of living with HIV are required.

Osteoporosis, Rather Than Sarcopenia, Is the Predominant Musculoskeletal Disease in a Rural South African Community Where Human Immunodeficiency Virus Prevalence Is High: A Cross-Sectional Study.

The rollout of antiretroviral therapy globally has increased life expectancy across Southern Africa, where 20.6 million people now live with human immunodeficiency virus (HIV). We aimed to determine the prevalence of age-related osteoporosis and sarcopenia, and investigate the association between HIV, bone mineral density (BMD), muscle strength and lean mass, and gait speed. A cross-sectional community-based study of individuals aged 20-80 years in rural South Africa collected demographic and clinical data, including HIV status, grip strength, gait speed, body composition, and BMD. Sarcopenia was defined by the European Working Group on Sarcopenia in Older People 2 (EWGSOP2) guidelines, and osteoporosis as BMD T-score ≤ -2.5 (if age ≥50 years). The mean ± standard deviation (SD) age of 805 black South African participants was 44.6 ± 14.8 years, 547 (68.2%) were female; 34 (13.2%) were men, and 129 (23.6%) women had HIV, with 88% overall taking anti-retroviral therapy. A femoral neck T-score ≤ -2.5, seen in four of 95 (4.2%) men and 39 of 201 (19.4%) women age ≥50 years, was more common in women with than without HIV (13/35 [37.1%] versus 26/166 [15.7%]; p = 0.003). Although no participant had confirmed sarcopenia, probable sarcopenia affected more men than women (30/258 [11.6%] versus 24/547 [4.4%]; p = .001]. Although appendicular lean mass (ALM)/height2 index was lower in both men and women with HIV, there were no differences in grip strength, gait speed, or probable sarcopenia by HIV status. Older age, female sex, lower ALM/height2 index, slower gait speed, and HIV infection were all independently associated with lower femoral neck BMD. In conclusion, osteoporosis rather than sarcopenia is the common musculoskeletal disease of aging in rural South Africa; older women with HIV may experience greater bone losses than women without HIV. Findings raise concerns over future fracture risk in Southern Africa, where HIV clinics should consider routine bone health assessment, particularly in aging women. © 2021 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).

Effect of HIV infection on growth and bone density in peripubertal children in the era of antiretroviral therapy: a cross-sectional study in Zimbabwe.

BACKGROUND: Faltered linear growth and pubertal delay, which are both common in children with HIV in sub-Saharan Africa, might affect adolescent bone accrual and future fragility fracture risk. We investigated the association of HIV with bone density adjusted for skeletal size in peripubertal children in Zimbabwe. METHODS: We did a cross-sectional study of baseline data from the IMVASK cohort, which enrolled children aged 8-16 years with HIV who had been taking antiretroviral therapy (ART) for at least 2 years, and children of the same age without HIV. Children with HIV were recruited from public sector HIV clinics at Parirenyatwa General Hospital and Harare Central Hospital (Harare, Zimbabwe), and children without HIV were recruited from six schools in the same suburbs that the hospitals serve. Sociodemographic, clinical, and anthropometric data were collected. Dual-energy X-ray absorptiometry (DXA) was used to measure the bone outcomes of total-body less-head bone mineral content for lean mass adjusted for height (TBLH-BMCLBM), and lumbar spine bone mineral apparent density (LS-BMAD), and we assessed the prevalence of low TBLH-BMCLBM and low LS-BMAD (defined by Z-scores of less than -2·0). Size adjustment techniques were used to overcome the size dependence of DXA measurement. We used linear regression models, with multiple imputation for missing data, to assess relationships between risk factors and TBLH-BMCLBM and LS-BMAD Z-scores in children with and without HIV. FINDINGS: We recruited 303 children with HIV (mean age 12·4 years [SD 2·5]; 151 [50%] girls) and 306 children without HIV (mean age 12·5 years [SD 2·5]; 155 [51%] girls). In children with HIV, median age of HIV diagnosis was 3·0 years (IQR 1·2-5·8), and median ART duration was 8·1 years (6·2-9·5); for 102 (34%) children, ART included tenofovir disoproxil fumarate (TDF). Children with HIV had a higher prevalence of low TBLH-BMCLBM Z-score than children without HIV (29 [10%] of 279 children with available data vs 18 [6%] of 292 with available data; p=0·066) and a higher prevalence of low LS-BMAD Z-score (40 [14%] of 279 vs 17 [6%] of 293 with available data; p=0·0007). HIV and male sex were associated with earlier pubertal (Tanner) stage. The negative associations between HIV and Z-scores for TBLH-BMCLBM and LS-BMAD were more pronounced with pubertal maturation, particularly in girls. Among children with HIV, TDF exposure and orphanhood were associated with lower TBLH-BMCLBM Z-score in confounder-adjusted analysis. Current TDF use (vs non-TDF-based ART) was associated with a reduction in TBLH-BMCLBM Z-score of 0·41 (95% CI 0·08-0·74; p=0·015) and in LS-BMAD Z-score of 0·31 (0·08-0·69; p=0·12). INTERPRETATION: Despite ART, HIV is associated with substantial skeletal deficits towards the end of puberty. The extent of bone deficits associated with TDF and its widespread use in children in sub-Saharan Africa are a concern for future adult fracture risk. FUNDING: Wellcome Trust.

The healthcare seeking behaviour of adult patients with asthma at Chitungwiza Central Hospital, Zimbabwe.

BACKGROUND: Although asthma is a serious public health concern in Zimbabwe, there is lack of information regarding the decision to seek for healthcare services among patients. This study aimed to determine the health care seeking behaviour of adult patients with asthma attending Chitungwiza Central Hospital in Zimbabwe. METHODS: A cross-sectional study was conducted among 400 patients with asthma. A questionnaire with four thematic areas (i) patients' demographic characteristics, (ii) types of health seeking behaviours (iii) knowledge of asthma treatment and (iv) attitudes on asthma treatment was used. RESULTS: We determined the sequence of remedial action that people undertake to rectify perceived ill health commonly referred to as health care seeking behaviours in 400 adult patients with asthma. This behaviour was considered good if the patient sought care at the hospital/clinic and or private practitioners. Poor health seeking behaviour was adjudged if patients sought no treatment, self-treated or resorted to traditional or faith healers for care.The majority 261(65.3%) of the study participants were females mainly between ages 29-39 years who lived in the urban setting. Distance to health facility, perception of supportive roles of healthcare providers, perceived good quality of service and knowledge of asthma complications were key determinants for health seeking behaviour. The results showed that majority 290 (72.5%) reported good health seeking behaviour. The correlates of good health seeking behaviour included financial capacity to pay for medical care [OR: 0.50 (CI: 0.31-0.83); p = 0.008)] and receiving good quality of asthma treatment [OR: 0.59 (CI: 0.37-0.93); p = 0.03)]. The inability to voluntarily seek own asthma treatment [OR: 1.68 (CI: 1.05-2.70); p = 0.03) was a significant risk factor (68% more likely) for poor health seeking behaviour. CONCLUSIONS: We concluded that prior to scaling up asthma treatment programmes in Zimbabwe, there is need to address, individual-level, community-level and health service level barriers to health seeking among asthma patients.