Community health worker support to improve HIV treatment outcomes for older children and adolescents in Zimbabwe: a process evaluation of the ZENITH trial.

BACKGROUND: Community health worker (CHW)-delivered support visits to children living with HIV and their caregivers significantly reduced odds of virological failure among the children in the ZENITH trial conducted in Zimbabwe. We conducted a process evaluation to assess fidelity, acceptability, and feasibility of this intervention to identify lessons that could inform replication and scale-up of this approach. METHODS: Field manuals kept by each CHW, records from monthly supervisory meetings, and participant data collected throughout the trial were used to assess the intervention's implementation. Data extracted from field manuals included visit type, content, and duration. Minutes from monthly supervisory meetings were used to capture CHW attendance. RESULTS: The trial enrolled 172 participants in the intervention arm of whom 5 subsequently refused all visits, 1 died before the intervention could be delivered, and 1 could not be located. Manuals for 8 participants were not returned, 3 were incorrectly entered, and 1 manual was lost. We had 154 manuals available for analysis. A total of 1553 visits were successfully conducted (median 11 per participant, range 1-20). Additionally, CHWs made 85 visits where they were unable to make contact with the family. Thirteen (8.4%) participants received 5 or fewer visits, 10 moved out of the study area, and 3 died. CHWs discussed disclosure with the child/family for over 89% of participants and assisted clients with developing and reviewing their personal treatment plan with over 85% of participants. Of the 20 CHWs (3 male, 17 female) selected to implement the intervention, 19 were retained at the end of the trial. CONCLUSIONS: The intervention was acceptable to participants with most receiving and accepting the required number of visits. Key strenghts were high staff retention and fidelity to the intervention. This community-based intervention was an acceptable and feasible approach to reduce virological failure among children living with HIV. TRIAL REGISTRATION: The ZENITH trial was registered on 25 October 2012 in the Pan African Clinical Trials Registry under the trial registration number PACTR201212000442288 . It can be found at http://www.pactr.org/ATMWeb/appmanager/atm/atmregistry?dar=true&tNo=PACTR201212000442288

Implementation and Operational Research: The Effectiveness of Routine Opt-Out HIV Testing for Children in Harare, Zimbabwe.

OBJECTIVE: HIV testing is the entry point to access HIV care. For HIV-infected children who survive infancy undiagnosed, diagnosis usually occurs on presentation to health care services. We investigated the effectiveness of routine opt-out HIV testing (ROOT) compared with conventional opt-in provider-initiated testing and counseling (PITC) for children attending primary care clinics. METHODS: After an evaluation of PITC services for children aged 6-15 years in 6 primary health care facilities in Harare, Zimbabwe, ROOT was introduced through a combination of interventions. The change in the proportion of eligible children offered and receiving HIV tests, reasons for not testing, and yield of HIV-positive diagnoses were compared between the 2 HIV testing strategies. Adjusted risk ratios for having an HIV test in the ROOT compared with the PITC period were calculated. RESULTS: There were 2831 and 7842 children eligible for HIV testing before and after the introduction of ROOT. The proportion of eligible children offered testing increased from 76% to 93% and test uptake improved from 71% to 95% in the ROOT compared with the PITC period. The yield of HIV diagnoses increased from 2.9% to 4.5%, and a child attending the clinics post intervention had a 1.99 increased adjusted risk (95% CI: 1.85 to 2.14) of receiving an HIV test in the ROOT period compared with the preintervention period. CONCLUSION: ROOT increased the proportion of children undergoing HIV testing, resulting in an overall increased yield of positive diagnoses, compared with PITC. ROOT provides an effective approach to reduce missed HIV diagnosis in this age group

Adolescents' and caregivers' perceptions of caregiver-provided testing and HIV self-testing using oral mucosal transudate tests in Zimbabwe: a short report.

Uptake of HIV testing remains lower among children and adolescents compared to adults. This study explored adolescents' perceptions of HIV self-testing (HIVST) and caregivers' perceptions of testing their children using an oral mucosal transudate (OMT) rapid HIV test (caregiver-provided testing). We conducted 31 interviews with adolescents aged 16-18 years and caregivers of children aged 2-15 years who received an OMT test. Participants described barriers to HIV testing including lack of privacy and the potential for discrimination by community members towards children and adolescents who received an HIV test. Most participants felt caregiver-provided testing and HIVST could address these barriers through increased privacy. Some participants expressed worry about their ability to correctly perform the OMT and their anxious reactions to a positive result. Counseling and assistance from health care workers were viewed as ways to alleviate concerns. Concerns shaped participants' preferences for facility-based HIVST and caregiver-provided testing. Findings demonstrate HIVST performed by adolescents and caregiver-provided testing could increase the uptake of HIV testing. Concerns related to being able to test correctly and the availability of post-test counseling must be addressed in any future delivery mechanisms

Validation of a screening tool to identify older children living with HIV in primary care facilities in high HIV prevalence settings.

OBJECTIVE: We previously proposed a simple tool consisting of five items to screen for risk of HIV infection in adolescents (10-19 years) in Zimbabwe. The objective of this study is to validate the performance of this screening tool in children aged 6-15 years attending primary healthcare facilities in Zimbabwe. METHODS: Children who had not been previously tested for HIV underwent testing with caregiver consent. The screening tool was modified to include four of the original five items to be appropriate for the younger age range, and was administered. A receiver operator characteristic analysis was conducted to determine a suitable cut-off score. The sensitivity, specificity and predictive value of the modified tool were assessed against the HIV test result. RESULTS: A total of 9568 children, median age 9 (interquartile, IQR: 7-11) years and 4971 (52%) men, underwent HIV testing. HIV prevalence was 4.7% (95% confidence interval, CI:4.2-5.1%) and increased from 1.4% among those scoring zero on the tool to 63.6% among those scoring four (P < 0.001). Using a score of not less than one as the cut-off for HIV testing, the tool had a sensitivity of 80.4% (95% CI:76.5-84.0%), specificity of 66.3% (95% CI:65.3-67.2%), positive predictive value of 10.4% and a negative predictive value of 98.6%. The number needed to screen to identify one child living with HIV would drop from 22 to 10 if this screening tool was used. CONCLUSION: The screening tool is a simple and sensitive method to identify children living with HIV in this setting. It can be used by lay healthcare workers and help prioritize limited resources

Chronic Morbidity Among Older Children and Adolescents at Diagnosis of HIV Infection.

BACKGROUND: Substantial numbers of children with HIV present to health care services in older childhood and adolescence, previously undiagnosed. These "slow-progressors" may experience considerable chronic ill health, which is not well characterized. We investigated the prevalence of chronic morbidity among children aged 6-15 years at diagnosis of HIV infection. METHODS: A cross-sectional study was performed at 7 primary care clinics in Harare, Zimbabwe. Children aged 6-15 years who tested HIV positive following provider-initiated HIV testing and counseling were recruited. A detailed clinical history and standardized clinical examination was undertaken. The association between chronic disease and CD4 count was investigated using multivariate logistic regression. RESULTS: Of the 385 participants recruited [52% female, median age 11 years (interquartile range 8-13)], 95% were perinatally HIV infected. The median CD4 count was 375 (interquartile range 215-599) cells per cubic millimeter. Although 78% had previous contact with health care services, HIV testing had not been performed. There was a high burden of chronic morbidity: 23% were stunted, 21% had pubertal delay, 25% had chronic skin disease, 54% had a chronic cough of more than 1 month-duration, 28% had abnormal lung function, and 12% reported hearing impairment. There was no association between CD4 count of <500 cells per cubic millimeter or <350 cells per cubic millimeter with WHO stage or these chronic conditions. CONCLUSIONS: In children with slow-progressing HIV, there is a substantial burden of chronic morbidity even when CD4 count is relatively preserved. Timely HIV testing and prompt antiretroviral therapy initiation are urgently needed to prevent development of chronic complications

Human Immunodeficiency Virus-Associated Chronic Lung Disease in Children and Adolescents in Zimbabwe: Chest Radiographic and High-Resolution Computed Tomographic Findings.

Background: Chronic respiratory symptoms are common among children living with human immunodeficiency virus (HIV). We investigated the radiological features of chronic lung disease in children aged 6-16 years receiving antiretroviral therapy for ≥6 months in Harare, Zimbabwe. Methods: Consecutive participants from a HIV clinic underwent clinical assessment and chest radiography. Participants with an abnormal chest radiograph (assessed by a clinician) and/or those meeting a clinical case definition for chronic lung disease underwent high-resolution computed tomography (HRCT). Radiological studies were scored independently and blindly by 2 thoracic radiologists. Relationships between radiological abnormalities and lung function were examined. Results: Among 193 participants (46% female; median age, 11.2 years; interquartile range, 9.0-12.8 years), the median CD4 cell count was 720/µL (473-947/µL), and 79% had a human immunodeficiency virus (HIV) load of <400 copies/mL. The most common chest radiographic finding was ring/tramline opacities (55 of 193 participants; 29%). HRCT scans were evaluated in 84 participants (69%); decreased attenuation (present in 43%) was the dominant abnormality seen. The extent of decreased attenuation was strongly correlated with both the severity and extent of bronchiectasis (rs = 0.68 and P < .001 for both). The extent of decreased attenuation was also negatively correlated with forced expiratory volume in first second of expiration (rs = -0.52), forced vital capacity (rs = -0.42), and forced expiratory flow, midexpiratory phase (rs = -0.42) (P < .001 for all). Conclusions: The HRCT findings strongly suggest that obliterative bronchiolitis may be the major cause of chronic lung disease in our cohort. Further studies to understand the pathogenesis and natural history are urgently needed

Clinical outcomes in children and adolescents initiating antiretroviral therapy in decentralized healthcare settings in Zimbabwe.

INTRODUCTION: Decentralized HIV care for adults does not appear to compromise clinical outcomes. HIV care for children poses additional clinical and social complexities. We conducted a prospective cohort study to investigate clinical outcomes in children aged 6-15 years who registered for HIV care at seven primary healthcare clinics (PHCs) in Harare, Zimbabwe. METHODS: Participants were recruited between January 2013 and December 2014 and followed for 18 months. Rates of and reasons for mortality, hospitalization and unscheduled PHC attendances were ascertained. Cox proportional modelling was used to determine the hazard of death, unscheduled attendances and hospitalization. RESULTS: We recruited 385 participants, median age 11 years (IQR: 9-13) and 52% were female. The median CD4 count was 375 cells/mm3 (IQR: 215-599) and 77% commenced ART over the study period, with 64% of those who had viral load measured achieving an HIV viral load <400 copies/ml. At 18 months, 4% of those who started ART vs. 24% of those who remained ART-naïve were lost-to-follow-up (p < 0.001). Hospitalization and mortality rates were low (8.14/100 person-years (pyrs) and 2.86/100 pyrs, respectively). There was a high rate of unscheduled PHC attendances (34.94/100 pyrs), but only 7% resulted in hospitalization. Respiratory disease was the major cause of hospitalization, unscheduled attendances and death. CD4 count <350cells/mm3 was a risk factor for hospitalization (aHR 3.6 (95%CI 1.6-8.2)). CONCLUSIONS: Despite only 64% of participants achieving virological suppression, clinical outcomes were good and high rates of retention in care were observed. This demonstrates that in an era moving towards differentiated care in addition to implementation of universal treatment, decentralized HIV care for children is achievable. Interventions to improve adherence in this age-group are urgently needed

Racial Variation in Echocardiographic Reference Ranges for Left Chamber Dimensions in Children and Adolescents: A Systematic Review.

Echocardiography plays a critical role in the assessment of cardiac disease. Important differences in echocardiographically derived cardiac chamber dimensions have been previously highlighted in different population groups in adult studies, but this has not been systematically studied in children, whose body size changes throughout childhood. The aim of this study was to review the distribution of available reference ranges for the left cardiac chamber dimensions in older children and adolescents. The following electronic data bases were searched: Medline, Embase and Web of Science were searched to identify studies which have established echocardiographic reference ranges of left heart parameters in children and adolescents from 1975 to December 2017. There was no geographical limitation. All results were imported into Endnote. Retrieved articles were screened and data extracted by two independent reviewers. A total of 4398 studies were retrieved, with 36 studies finally included in this review. 29 (81%) references were from North America and European (Caucasians) populations, with only one study each from Africa and South America. Two-dimensional and M-mode techniques were the most commonly used echocardiography techniques. There were methodological variations in techniques and normalisation of references. Comparison of selected cardiac measures showed significant differences for interventricular septal thickness among Black African, Indian, German and US American children. Available echocardiographic references cannot be generalised to all settings and therefore, there is need for locally relevant reference ranges. Africa and South America are particularly under-represented. Future studies should focus on developing comprehensive echocardiographic reference ranges for children from different racial backgrounds and should use standardised techniques

Economic incentives for HIV testing by adolescents in Zimbabwe: a randomised controlled trial.

BACKGROUND: HIV testing is the important entry point for HIV care and prevention service, but uptake of HIV testing and thus coverage of antiretroviral therapy are much lower in older children and adolescents than in adults. We investigated the effect of economic incentives provided to caregivers of children aged 8-17 years on uptake of HIV testing and counselling in Harare, Zimbabwe. METHODS: This randomised controlled trial was nested within a household HIV prevalence survey of children aged 8-17 years in Harare. Households with one or more survey participants whose HIV status was unknown were eligible to participate in the trial. Eligible households were randomly assigned (1:1:1) to either receive no incentive, receive a fixed US$2 incentive, or participate in a lottery for$5 or $10 if the participant presented for HIV testing and counselling at a local primary health-care centre. The survey fieldworkers who enrolled participants were not blinded to trial arm allocation, but the statistician was blinded for analysis of outcome. The primary outcome was the proportion of households in which at least one child had an HIV test within 4 weeks of enrolment. HIV test uptake in the incentivised groups was compared with uptake in the non-incentivised group using logistic regression, adjusting for community and number of children as fixed effects and research assistant as a random effect. All analyses were by intention to treat. The trial is registered with the Pan African Clinical Trials Registry, number PACTR201605001615280. FINDINGS: Between Aug 4, and Dec 18, 2015, 2050 eligible households were enrolled in the prevalence survey. 649 (32$2 incentive, and 661 (32%) households were assigned to lottery participation. Children were unavailable in 148 households in the no-incentive group, 63 households in the $2 incentive group, and 81 households in the lottery group. 1688 households had at least one child with unknown HIV status and were enrolled into the trial. 22 households had no undiagnosed child, and one household refused consent. The primary outcome of HIV testing was assessed in 472 (28$2 incentive group, and 562 (33%) households in the lottery group. At least one child was HIV tested in 93 (20%) households in the no-incentive group, in 316 (48%) households in the $2 incentive group (adjusted odds ratio 3·67, 95% CI 2·77-4·85; p<0·0001), and in 223 (40%) of 562 households in the lottery group (2·66, 2·00-3·55; p<0·0001). No adverse events were reported. INTERPRETATION: Fixed incentives and lottery-based incentives increased the uptake of HIV testing by older children and adolescents, a key hard-to-reach population. This strategy would be sustainable in the context of vertical HIV infection as repeated testing would not be necessary until sexual debut. FUNDING: Wellcome Trust