"Validation of the D:A:D Chronic Kidney Disease Risk Score Incorporating Proteinuria in People Living with HIV in Harare, Zimbabwe"​​.

OBJECTIVE We sought to validate the D:A:D risk score for chronic kidney disease (CKD) in people living with HIV (PLWH) in a cohort from Harare, Zimbabwe. Additionally, we aimed to evaluate proteinuria as a predictive variable in the risk score model, being the first study to do so. DESIGN Data from PLWH attending a clinic in Harare was evaluated. Those with a baseline estimated glomerular filtration rate >60ml/min/1.73m2 and at least two subsequent eGFR measurements were included. A modified version of the D:A:D risk score model was applied to categorise participants as 'low', 'medium' and 'high-risk' of progression to CKD. Potential predictors of renal impairment were assessed by logistic regression in univariate and multivariate models. Proteinuria was evaluated in a nested model using D:A:D risk categories. RESULTS 2793 participants were included. 40 participants (1.4% of the cohort) progressed to CKD during the median follow-up time of 4.2 years. Progression rates were 1%, 3% and 12% in the low, medium, and high-risk groups respectively. Proteinuria data was available for 2251 participants. Presence of proteinuria was strongly associated with progression to CKD [OR 7.8, 95% CI 3.9-15.7], and its inclusion in the risk score improved the discrimination of the model with the c-statistic increasing from 0.658 to 0.853). CONCLUSION A modified version of the D:A:D CKD risk score performed well in predicting CKD events among this Sub-Saharan African cohort of people living with HIV. Inclusion of proteinuria into the risk score model significantly improved predictability

Comparison of predictors for early and late mortality in adults commencing HIV antiretroviral therapy in Zimbabwe: a retrospective cohort study.

BACKGROUND People living with HIV (PLWHIV) commencing antiretroviral therapy (ART) in sub-Saharan Africa experience significant mortality within the first year. Previously, identified risk factors for mortality may be biased towards these patients, as compared to those who experience late mortality. AIM To compare risk factors for early and late mortality in PLWHIV commencing ART. METHODS A retrospective cohort study of ART-naïve patients aged ≥ 18 years from an outpatient HIV clinic in Zimbabwe. Data were collected between January 2010 and January 2019. Predictors for early (≤ 1 year) and late mortality (> 1 year) were determined by multivariable cox proportional hazards analyses, with patients censored at 1 year and landmark analysis after 1 year, respectively. RESULTS Three thousand and thirty-nine PLWHIV were included in the analysis. Over a median follow-up of 4.6 years (IQR 2.5-6.9), there was a mortality rate of 8.8%, with 50.4% of deaths occurring within 1 year. Predictors of early mortality included CD4 count < 50 cells/µL (HR 1.84, 95% CI 1.24-2.72, p < 0.01), WHO Stage III (HR 2.05, 95% CI 1.28-3.27, p < 0.01) or IV (HR 2.83, 95% CI 1.67-4.81, p < 0.01), and eGFR < 90 mL/min/1.73 m2 (HR 2.48, 95% CI 1.56-3.96, p < 0.01). Other than age (p < 0.01), only proteinuria (HR 2.12, 95% CI 1.12-4.01, p = 0.02) and diabetes mellitus (HR 3.51, 95% CI 1.32-9.32, p = 0.01) were associated with increased risk of late mortality. CONCLUSIONS Traditional markers of mortality risk in patients commencing ART appear to be limited to early mortality. Proteinuria and diabetes are some of the few predictors of late mortality, and should be incorporated into routine screening of patients commencing ART

Renal function and associated mortality risk in adults commencing HIV antiretroviral therapy in Zimbabwe.

BACKGROUND People living with HIV (PLWHIV) in sub-Saharan Africa appear to have a higher incidence of renal disease than other global regions, but data are limited. This renal impairment may be associated with an increased mortality risk. AIMS To define the prevalence of renal disease and explore its association with mortality risk in a cohort from Zimbabwe commencing antiretroviral therapy (ART) for HIV-infection. METHODS A retrospective study of all patients aged ≥18 years, commenced on ART for HIV-infection at the Newlands Clinic in Harare, Zimbabwe between January 2007 and September 2019 was conducted. Data were extracted from electronic medical records. Patients with no baseline creatinine measurement were excluded. Baseline characteristics were assessed as potential predictors for mortality by Cox proportional hazard regression. RESULTS 3039 patients were eligible for inclusion. Most were female (62.1%), with a median age of 36 years (IQR 30 to 43). At baseline, 7.3% had an eGFR ≤90 mL/min/1.73m2 and 11.4% had proteinuria. Over a median follow-up period of 4.6 years (IQR 2.5 to 6.9), the mortality rate was 8.7%. One half of deaths (49.2%) occurred within the first year. In multivariable analysis, a baseline eGFR between 60 and 90 mL/min/1.73m2 (HR 2.22, 95%CI 1.46 to 3.33, p < 0.001) and proteinuria (HR 2.10, 95%CI 1.35 to 3.27, p < 0.001) were associated with increased mortality risk. CONCLUSION Baseline renal impairment was common. Both a reduced eGFR or proteinuria were independently associated with a doubling of mortality risk. These should serve as markers in the clinical setting of at-risk patients

Cervical cancer screening cascade for women living with HIV: a cohort study from Zimbabwe

Countries with high HIV prevalence, predominantly in sub-Sahahran Africa, have the highest cervical cancer rates globally. HIV care cascades successfully facilitated the scale-up of antiretroviral therapy. A cascade approach could similarly succeed to scale-up cervical cancer screening, supporting WHO's goal to eliminate cervical cancer. We defined a Cervical Cancer Screening Cascade for women living with HIV (WLHIV), evaluating the continuum of cervical cancer screening integrated into an HIV clinic in Zimbabwe. We included WLHIV aged ≥18 years enrolled at Newlands Clinic in Harare from June 2012-2017 and followed them until June 2018. We used a cascade approach to evaluate the full continuum of secondary prevention from screening to treatment of pre-cancer and follow-up. We report percentages, median time to reach cascade stages, and cumulative incidence at two years with 95% confidence intervals (CI). We used univariable Cox proportional hazard regressions to calculate cause-specific hazard ratios with 95% CIs for factors associated with completing the cascade stages. We included 1624 WLHIV in the study. The cumulative incidence of cervical screening was 85.4% (95% CI 83.5-87.1) at two years. Among the 396 WLHIV who received screen-positive tests in the study, the cumulative incidence of treatment after a positive screening test was 79.5% (95% CI 75.1-83.2) at two years. The cumulative incidence of testing negative at re-screening after treatment was 36.1% (95% CI 31.2-40.7) at two years. Using a cascade approach to evaluate the full continuum of cervical cancer screening, we found less-than 80% of WLHIV received treatment after screen-positive tests and less-than 40% were screen-negative at follow-up. Interventions to improve linkage to treatment for screen-positive WLHIV and studies to understand the clinical significance of screen-positive tests at follow-up among WLHIV are needed. These gaps in the continuum of care must be addressed in order to prevent cervical cancer

Characterizing the double-sided cascade of care for adolescents living with HIV transitioning to adulthood across Southern Africa

INTRODUCTION: As adolescents and young people living with HIV (AYLH) age, they face a "transition cascade," a series of steps associated with transitions in their care as they become responsible for their own healthcare. In high-income countries, this usually includes transfer from predominantly paediatric/adolescent to adult clinics. In sub-Saharan Africa, paediatric HIV care is mostly provided in decentralized, non-specialist primary care clinics, where "transition" may not necessarily include transfer of care but entails becoming more autonomous for one's HIV care. Using different age thresholds as proxies for when "transition" to autonomy might occur, we evaluated pre- and post-transition outcomes among AYLH. METHODS: We included AYLH aged <16 years at enrolment, receiving antiretroviral therapy (ART) within International epidemiology Databases to Evaluate AIDS Southern Africa (IeDEA-SA) sites (2004 to 2017) with no history of transferring care. Using the ages of 16, 18, 20 and 22 years as proxies for "transition to autonomy," we compared the outcomes: no gap in care (≥2 clinic visits) and viral suppression (HIV-RNA <400 copies/mL) in the 12 months before and after each age threshold. Using log-binomial regression, we examined factors associated with no gap in care (retention) in the 12 months post-transition. RESULTS: A total of 5516 AYLH from 16 sites were included at "transition" age 16 (transition-16y), 3864 at 18 (transition-18y), 1463 at 20 (transition-20y) and 440 at 22 years (transition-22y). At transition-18y, in the 12 months pre- and post-transition, 83% versus 74% of AYLH had no gap in care (difference 9.3 (95% confidence interval (CI) 7.8 to 10.9)); while 65% versus 62% were virally suppressed (difference 2.7 (-1.0 to 6.5%)). The strongest predictor of being retained post-transition was having no gap in the preceding year, across all transition age thresholds (transition-16y: adjusted risk ratio (aRR) 1.72; 95% CI (1.60 to 1.86); transition-18y: aRR 1.76 (1.61 to 1.92); transition-20y: aRR 1.75 (1.53 to 2.01); transition-22y: aRR 1.47; (1.21 to 1.78)). CONCLUSIONS: AYLH with gaps in care need targeted support to prevent non-retention as they take on greater responsibility for their healthcare. Interventions to increase virologic suppression rates are necessary for all AYLH ageing to adulthood

Models of support for disclosure of HIV status to HIV-infected children and adolescents in resource-limited settings

Introduction: Disclosure of HIV status to HIV-infected children and adolescents is a major care challenge. We describe current site characteristics related to disclosure of HIV status in resource-limited paediatric HIV care settings within the International Epidemiology Databases to Evaluate AIDS (IeDEA) consortium. Methods: An online site assessment survey was conducted across the paediatric HIV care sites within six global regions of IeDEA. A standardized questionnaire was administered to the sites through the REDCap platform. Results: From June 2014 to March 2015, all 180 sites of the IeDEA consortium in 31 countries completed the online survey: 57% were urban, 43% were health centres and 86% were integrated clinics (serving both adults and children). Almost all the sites (98%) reported offering disclosure counselling services. Disclosure counselling was most often provided by counsellors (87% of sites), but also by nurses (77%), physicians (74%), social workers (68%), or other clinicians (65%). It was offered to both caregivers and children in 92% of 177 sites with disclosure counselling. Disclosure resources and procedures varied across geographical regions. Most sites in each region reported performing staff members' training on disclosure (72% to 96% of sites per region), routinely collecting HIV disclosure status (50% to 91%) and involving caregivers in the disclosure process (71% to 100%). A disclosure protocol was available in 14% to 71% of sites. Among the 143 sites (79%) routinely collecting disclosure status process, the main collection method was by asking the caregiver or child (85%) about the child's knowledge of his/her HIV status. Frequency of disclosure status assessment was every three months in 63% of the sites, and 71% stored disclosure status data electronically. Conclusion: The majority of the sites reported offering disclosure counselling services, but educational and social support resources and capacities for data collection varied across regions. Paediatric HIV care sites worldwide still need specific staff members' training on disclosure, development and implementation of guidelines for HIV disclosure, and standardized data collection on this key issue to ensure the long-term health and wellbeing of HIV-infected youth

Optimal timing of antiretroviral treatment initiation in HIV-positive children and adolescents: a multiregional analysis from Southern Africa, West Africa and Europe

BACKGROUND: There is limited knowledge about the optimal timing of antiretroviral treatment initiation in older children and adolescents. METHODS: A total of 20 576 antiretroviral treatment (ART)-naïve patients, aged 1-16 years at enrolment, from 19 cohorts in Europe, Southern Africa and West Africa, were included. We compared mortality and growth outcomes for different ART initiation criteria, aligned with previous and recent World Health Organization criteria, for 5 years of follow-up, adjusting for all measured baseline and time-dependent confounders using the g-formula. RESULTS: Median (1st;3rd percentile) CD4 count at baseline was 676 cells/mm(3) (394; 1037) (children aged ≥ 1 and 10 years at enrolment we did not find any difference in mortality or growth with immediate ART initiation, with estimated differences of -0.1% (-0.2%; 0.6%) and -0.03 (-0.05; 0.00), respectively. Growth differences in children aged < 10 years persisted for treatment thresholds using higher CD4 values. Regular follow-up led to better height and mortality outcomes. CONCLUSIONS: Immediate ART is associated with lower mortality and better growth for up to 5 years in children < 10 years old. Our results on adolescents were inconclusive

Tuberculosis in Pediatric Antiretroviral Therapy Programs in Low- and Middle-Income Countries: Diagnosis and Screening Practices

Background The global burden of childhood tuberculosis (TB) is estimated to be 0.5 million new cases per year. Human immunodeficiency virus (HIV)-infected children are at high risk for TB. Diagnosis of TB in HIV-infected children remains a major challenge. Methods We describe TB diagnosis and screening practices of pediatric antiretroviral treatment (ART) programs in Africa, Asia, the Caribbean, and Central and South America. We used web-based questionnaires to collect data on ART programs and patients seen from March to July 2012. Forty-three ART programs treating children in 23 countries participated in the study. Results Sputum microscopy and chest Radiograph were available at all programs, mycobacterial culture in 40 (93%) sites, gastric aspiration in 27 (63%), induced sputum in 23 (54%), and Xpert MTB/RIF in 16 (37%) sites. Screening practices to exclude active TB before starting ART included contact history in 41 sites (84%), symptom screening in 38 (88%), and chest Radiograph in 34 sites (79%). The use of diagnostic tools was examined among 146 children diagnosed with TB during the study period. Chest Radiograph was used in 125 (86%) children, sputum microscopy in 76 (52%), induced sputum microscopy in 38 (26%), gastric aspirate microscopy in 35 (24%), culture in 25 (17%), and Xpert MTB/RIF in 11 (8%) children. Conclusions Induced sputum and Xpert MTB/RIF were infrequently available to diagnose childhood TB, and screening was largely based on symptom identification. There is an urgent need to improve the capacity of ART programs in low- and middle-income countries to exclude and diagnose TB in HIV-infected childre

Body mass index and noninfectious comorbidity in HIV-positive patients commencing antiretroviral therapy in Zimbabwe.

OBJECTIVES The aim of the study was to describe the prevalence of elevated body mass index (BMI) in a cohort of treatment-naïve people living with HIV (PLWH) and to investigate the association of BMI with CD4 count and noninfectious comorbidities including hypertension and renal impairment. METHODS A retrospective cohort study of 1598 PLWH at the Newlands Clinic in Harare, Zimbabwe was carried out. Data were extracted from the medical records at baseline and 6 months after initiation of treatment. The univariate association between BMI and CD4 count was assessed and multiple regression models were used to predict factors associated with loss of renal function and change in CD4 count at 6 months. RESULTS Overweight and obesity (BMI ≥ 25 kg/m2 ) were prevalent in this cohort (34%), as was the presence of hypertension (18%). Higher BMI was associated with a higher CD4 count at baseline and 6 months (B = 0.28 and 0.24, respectively; P < 0.001 for both), adjusted for age and sex. The presence of hypertension independently predicted loss of renal function at 6 months (B = -15.31; P < 0.001), adjusted for BMI, CD4 count and sex. High BMI itself was also independently associated with a decline in renal function (B = -0.41; P = 0.003), adjusted for other significant variables. CONCLUSIONS We demonstrate a high prevalence of overweight/obesity and hypertension in an urban cohort of PLWH in Zimbabwe. Higher BMI was associated with a higher CD4 count, both before and 6 months after commencing antiretroviral therapy; it was also associated with loss of renal function in this cohort