Menu
Menu
Menu
Menu
Introduction HIV-exposed children show signs of developmental delay. We assessed the impact of a pragmatic multicomponent intervention for caregivers of HIV-exposed children aged 0-2 years in Zimbabwe. Methods We conducted a cluster-randomised trial from 2016 to 2018. Clusters were catchments surrounding clinics, allocated (1:1) to either National HIV guidelines standard of care or standard care plus an 18-session group intervention comprising i) early childhood stimulation (ECS) and parenting training with home visits to reinforce skills and retention in HIV care; ii) economic strengthening. Primary outcomes measured 12 months after baseline (4.5 months postintervention completion) included: i) global child development measured using the Mullen early learning composite score; ii) retention in HIV care. Analysis used mixed effects regression to account for clustering and adjusted minimally for baseline prognostic factors and was by intention to treat. Results Thirty clusters, 15 in each arm, were randomised. 574 dyads were recruited with 89.5% retained at follow-up. Ninety one of 281 (32.4%) were recorded as having received the complete intervention package, with 161/281 (57.3%) attending ≥14 ECS sessions. There was no evidence of an intervention effect on global child development (intervention mean 88.1 vs standard of care mean 87.6; adjusted mean difference=0.06; 95% CI -2.68 to 2.80; p=0.97) or infant retention in care (proportion of children who had missed their most recent HIV test: intervention 21.8% vs standard of care 16.9%, p=0.18). There was weak evidence that the proportion of caregivers with parental stress was reduced in the intervention arm (adjusted OR (aOR)=0.69; 95% CI 0.45 to 1.05; p=0.08) and stronger evidence that parental distress specifically was reduced (intervention arm 17.4% vs standard of care 29.1% scoring above the cut-off; aOR=0.56; 95% CI 0.35 to 0.89; p=0.01). Conclusion This multicomponent intervention had no impact on child development outcomes within 4.5 months of completion, but had an impact on parental distress. Maternal mental health remains a high priority. Trial registration number PACTR201701001387209.
The methods have been previously published.26 A brief overview is provided here. The CHIDO trial is a pragmatic parallel-arm cluster randomised controlled trial conducted in 30 primary care clinic catchment areas in two districts in Zimbabwe (Goromonzi and Mudzi). Detailed mapping of all health facilities and their communities was conducted to select trial sites, which are at least 15 km apart. Community sensitisation was carried out in phases. First, the local leaders (including traditional and political leaders, health and educational professionals) were given information about the study, its objectives, the target population and encouraged to ask questions or raise any concerns. They were then invited to take part in the site randomisation process. The caregivers were identified from the HIV-exposed infant registers kept at trial clinics and were eligible for inclusion if they were the primary caregivers (biological and non-biological), the biological mother had been living with HIV and cared for a child aged 0–24 months. Caregivers who gave written informed consent/assent in English or Shona were enrolled into the trial, completed a baseline assessment and were followed up after 12 months. In intervention communities, caregiver-infant dyads were encouraged to engage in all CHIDO intervention activities. While they attended the clinic specifically for the intervention sessions, they could also attend clinic services if scheduled/required. Extended Consolidated Standards of Reporting Trials guidelines were followed for reporting the results of this trial. Patients and village health workers were involved in formative work undertaken at which the CHIDO intervention was developed. Clinics were randomised in a 1:1 allocation ratio to the CHIDO intervention or Ministry of Health and Child Care (MoHCC) standard of care. Restricted randomisation was used to ensure balance by district (20 in Goromonzi district and 10 in Mudzi district) and on the number of HIV-exposed infants aged between 0 and 24 months per clinic by stratifying the clinics into those able to run one group of 12 dyads (12 clusters) and those of sufficient size to run two groups of 12 dyads (18 clusters). To maximise transparency and buy-in from stakeholders, a public randomisation procedure was undertaken in each district (on 19 January 2016 in Goromonzi and on 31 May 2016 in Mudzi) involving MoHCC, and district-level government and medical representatives. Assessors conducting the endline survey procedures were blind to trial arm. The intervention included three elements: (i) an 18-session health, nutrition and early childhood stimulation (ECS) parenting programme (table 1); (ii) an internal savings and lending scheme (ISALS) with ISALS sessions held immediately after each ECS session and (iii) village health workers who visited participants at home each month (or more frequently in the case of non-attendance at group sessions or other problems). The parenting programme content evolved out of formative work and the number of sessions was set after piloting and feedback from participants about preferred length and frequency of sessions. Parenting programme content CHW, Community Health Worker; PMTCT, Prevention of mother to child transmission. Participant enrolment was conducted in parallel in intervention and standard of care communities between 16 January and 8 September 2016. At enrolment, all participating caregiver-child dyads were allocated a unique identifier. Questionnaire data which included demographic, socioeconomic, maternal mental health and household food security information were collected using an interviewer-administered questionnaire with data entered directly onto tablets preprogrammed using Open Data Kit with range and consistency checks incorporated. Maternal mental health was measured using the Edinburgh Postnatal Depression Scale (EPDS),27 28 which is a diagnostic tool that has been locally validated in Zimbabwe,28 plus the 8-item Shona Symptoms Questionnaire (SSQ-8), a locally developed and validated scale which determines risk of common mental disorders (including anxiety and depression).29 Finally, parental stress was measured using the Parental Stress Index Short Form (PSI-SF).30 The more sensitive questions were self-completed using audio computer-assisted survey instrument to maximise validity. This was followed by a developmental assessment of the child conducted by one of two trained research nurses. Developmental assessments were videoed, and a small randomly selected sample was reviewed by a highly experienced assessor. This was done as part of quality control and assurance, and to minimise differences between assessors. Intervention implementation commenced within 3 months of participant enrolment in all communities and ran over 12 months between 7 March 2016 and 7 July 2017. An endline assessment was conducted between 10 April 2017 and 18 January 2018 among enrolled caregiver-child dyads 12 months after the baseline survey and within 0–5 months after completion of intervention delivery. The endline survey was conducted in parallel, with pairs of intervention and control trial sites being assessed at the same survey venue to minimise unblinding of assessors. Survey procedures were as described at baseline. At endline a dried blood spot sample was collected from all biological mothers to determine HIV viral load and infants to test for HIV antibody status and viral load. Programme attendance records and village healthcare worker diaries were reviewed, and data double entered into password protected Access databases. Dried blood spot samples were air dried, stored at room temperature and submitted weekly to the respective laboratories. Infant samples were sent to the National Microbiology Reference Laboratory in Harare for HIV-1 antibody testing using COBAS AmpliPrep/COBAS TaqMan. Samples confirmed HIV positive were sent for viral load testing. Caregiver samples were sent to flow cytometry laboratory for viral load testing using Biomerieux NucliSENS easyMag and EasyQ. There were two primary outcomes for the trial: (i) change in the mean age-standardised Mullen early learning composite (ELC) score31 of children; (ii) the proportion of HIV-exposed or HIV-positive children with full retention in care (>80%) of scheduled HIV treatment and care visits at 12 months. In the absence of locally validated robust child development measures, the Mullen ELC score was chosen as it had been used to determine impact of caregiver interventions over a similar time period in Africa.32 33 We assessed seven prespecified secondary end points as previously reported, reflecting factors intended to be affected by the intervention, which were analysed by the same analytical framework as the primary outcome (table 2). Secondary outcomes of the CHIDO trial BMI, body mass index; CHIDO, Child Health Intervention for Developmental Outcomes; HFIAS, Household Food Insecurity Access Scale. Our sample-size calculations have been described previously.26 We estimated that we would need 15 clusters per arm with a harmonic mean of 16 caregiver-child dyads per cluster at endline, and assuming 20% loss to follow-up over 12 months to have 80% power to detect an effect size (difference in means/SD) of 1.23 for the Mullen ELC score and 82% power to detect a risk difference in retention in care of HIV-exposed children of at least 17% assuming 65% are retained in the control arm. The overall recruitment target was therefore 528 caregiver-child dyads in total from 30 clinics. We recruited 574 dyads to ensure a harmonic mean of 24 dyads was enrolled from the larger seven clinics (to allow two groups to run at these sites) and a harmonic mean of 12 dyads was enrolled from the smaller eight clinics, where just one ECS/ISALS group was run. The statistical analysis followed a prespecified analytical plan differing from the published protocol by using individual-level analysis (see online supplementary materials), which allowed for greater flexibility. Data were analysed in STATA V.15.1 (StataCorp, College Station, Texas, USA) using intention-to-treat principles incorporating random effects for clusters and adjusting minimally for baseline prognostic factors. Mean differences and 95% CIs were used to estimate the effect of the intervention for quantitative outcomes using mixed effects linear regression. ORs and 95% CI were used to estimate the effect of the intervention for binary outcomes using mixed effects logistic regression. Mental health questions were categorised as at risk or not at risk, with cut-points of 12/30 for the EPDS,28 6/8 for the SSQ-829 and at the 90th percentile of the reference range for PSI-SF domain and total scores.30 Baseline factors adjusted for a priori were the baseline measurement, strata in Goromonzi (two groups based on the number of children on the clinic register), district (Goromonzi or Mudzi), infant age (0 to <6 months, 6 to <12 months and 12–24 months) and for quantitative Mullen outcomes, a categorical covariate representing the assessor at baseline. Sensitivity analyses were performed using a cluster-level analysis for the ELC score.34 Evidence for effect modification in the ELC score was assessed by incorporating interaction terms with baseline Mullen ELC score or with baseline caregiver’s mental health as measured by EPDS, SSQ-8 and PSI-SF. The effect of the intervention was also examined in a per-protocol analysis comparing those in the intervention arm who attended most ECS sessions (either at least 14/18 sessions in total, or at least 7/9 sessions addressing child development) with those in the standard of care arm. bmjgh-2019-001651supp002.pdf
N/A
