Dataset Information

The effect of community-based support for caregivers on the risk of virological failure in children and adolescents with HIV in Harare, Zimbabwe (ZENITH): an open-label, randomised controlled trial.

ABSTRACT:

Background

Children and adolescents have poorer HIV treatment outcomes than adults. We aimed to assess the effect of community-based support for caregivers of HIV-infected children and adolescents, who are key mediators to children engaging with care, on treatment outcomes.

Methods

In this open-label, randomised contolled trial, we recruited children aged 6-15 years with newly-diagnosed HIV attending primary health-care clinics in Harare, Zimbabwe. Children were randomly assigned to receive decentralised primary health-care clinic-based HIV care (control group), according to national guidelines for 18 months, or decentralised care plus structured support visits by trained community health workers (intervention group) according to national guidelines for 18 months. Primary outcomes were the proportion of participants who died or had an HIV viral load of 400 copies per mL or higher at 12 months after antiretroviral therapy (ART) initiation (among those who started ART within 6 months of enrolment); and the proportion who missed two or more scheduled clinic visits by 18 months post-enrolment (among all participants). Analyses were complete-case, modified-intention-to-treat. This trial is registered with the Pan African Clinical Trials Registry, number PACTR201212000442288.

Findings

Between January, 2013, and January, 2015, 470 participants tested HIV-positive at seven study primary health-care clinics and were screened for eligibility. Of the 334 eligible children and adolescents, 166 were randomly assigned to the intervention group and 168 to the control group. The median age of participants was 11 years (IQR 8-13) and 178 (53%) were girls. Among the 238 participants who started ART within 6 months of enrolment, the proportion who died or had a viral load of 400 copies/mL or higher at 12 months post-ART initiation was significantly lower in the intervention group than in the control group (31 [33%] of 94 participants vs 42 [49%] of 86 participants, respectively, adjusted odds ratio [aOR] 0·46, 95% CI 0·23-0·89; p=0·02). The proportion of children missing two or more scheduled visits was similar in the intervention group and control group (27 [17%] of 155 vs 30 [18%] of 165, aOR 0·92, 95% CI 0·49-1·74; p=0·79). One participant withdrew from the trial 240 days after enrolment and 12 died during follow-up (five in the intervention group; seven in the control group).

Interpretation

Community-based support for caregivers has high potential for scalability and could have a substantial effect on HIV virological suppression in children and adolescents, a group with disproportionately poor treatment outcomes.

Funding

Wellcome Trust.

SUBMITTER: Ferrand RA

PROVIDER: S-EPMC5656092 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Similar Datasets

Project description:BackgroundCommunity 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.MethodsField 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.ResultsThe 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.ConclusionsThe 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 registrationThe 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 .

Project description:INTRODUCTION:Key to pharmacovigilance is spontaneously reporting all Adverse Drug Reactions (ADR) during post-market surveillance. This facilitates the identification and evaluation of previously unreported ADR's, acknowledging the trade-off between benefits and potential harm of medications. Only 41% Antiretroviral (ARV) ADR's documented in Harare city clinical records for January to December 2016 were reported to Medicines Control Authority of Zimbabwe (MCAZ). We investigated reasons contributing to underreporting of ARV ADR's in Harare city. METHODS:A descriptive cross-sectional study and the Centers for Disease Control (CDC) guided surveillance evaluation was conducted. Two hospitals were purposively included. Seventeen health facilities and 52 health workers were randomly selected. Interviewer-administered questionnaires, key informant interviews and WHO pharmacovigilance checklists were used to collect data. Likert scales were applied to draw inferences and Epi info 7 used to generate frequencies and proportions. RESULTS:Of the 52 participants, 32 (61.5%) distinguished the ARV ADR defining criteria. Twenty-nine (55.8%) knew system's purpose whilst 28 (53.8%) knew the reporting process. Knowledge scored average on the 5-point-Likert scale. Thirty-eight (73.1%) participants identified ARV ADR's following client complaints and nine (1.3%) enquired clients' medication response. Forty-six (88.5%) cited non-feedback from MCAZ for underreporting. Inadequate ARV ADR identification skills were cited by 21 (40.4%) participants. Reporting forms were available in five (26.3%) facilities and reports were generated from hospitals only. Forty-two (90.6%) clinicians made therapeutic decisions from ARV ADR's. Averaged usefulness score was 4, on the 5-point-Likert scale. All 642 generated signals were committed to Vigiflow by MCAZ, reflecting a case detection rate of 4/ 100 000. Data quality was 0.75-1.0 (WHO) and all reports were causally assessed. CONCLUSION:The pharmacovigilance system was useful, simple, and acceptable despite being unstable, not representative and not sensitive. It was threatened by suboptimal health worker knowledge, weak detection strategies and referral policy preventing ARV ADR identification by person place and time. Revisiting local policy, advocacy, communication and health worker orientation might improve pharmacovigilance performance in Harare city.

Project description:Nearly half of all sub-Saharan African countries lack operational Diabetes Mellitus policies. This represents an opportunity to build reliable evidence to underpin such policies when they are eventually developed. Representing the interests of those with the experience of living with the condition in national diabetes policies is important, particularly the interests regarding medicine access, a key pillar in diabetes management. One way to achieve this representation is to publish patient perceptions. Patient perspectives are especially valuable in the context of diabetes in Sub-Saharan Africa, where much of the empirical work has focused on clinical and epidemiological questions. We therefore captured the challenges and suggestions around medicine access articulated by a population of diabetes patients and their caregivers. This was a qualitative interpretivist study based on data from focus group discussions with adult diabetes patients and their caregivers. Eight FGDs of 4–13 participants each whose duration averaged 13.35 minutes were conducted. Participants were recruited from diabetes outpatient clinics at two health facilities in Harare. One site was Parirenyatwa Hospital, the largest public referral and teaching hospital in Zimbabwe. The other was a private for-profit facility. Ethics approval was granted by the Joint Research Ethics Committee for University of Zimbabwe College of Health Sciences and the Parirenyatwa Group of Hospitals (Ref: JREC 295/18). Diabetes patients and their caregivers are interested in affordable access to medicines of acceptable form and quality with minimum effort. Yet, they often find themselves privileging one dimension of access over another e.g. prioritising affordability over acceptability. Based on participants’ articulations, a sound diabetes policy should: 1. provide for financial and consumer protections, 2. regulate healthcare business practices and medicine prices, 3. provide for a responsive health workforce attentive to patient problems, 4. accord the same importance to diabetes that is accorded to communicable diseases, 5. decentralize diabetes management to lower levels of care, 6. limit wastage, corruption, bad macro-financial governance and a lack of transparency about how funding for health is used, and 7. provide support to strengthen patients’ and caregivers’ psychosocial networks. A diabetes policy acceptable to patients is one infused with principles of good governance, fairness, inclusiveness and humanity; characterised by: financial protection and price regulation, consumer protection, equity in the attention accorded to different diseases, decentralized service delivery, inclusion of patient voice in political decision-making, a responsive compassionate health workforce, psychosocial support for patients and their caregivers and allocative efficiency and transparency in public expenditure.

Project description:BackgroundTyphoid fever remains a significant public health problem in developing countries. In October 2011, a typhoid fever epidemic was declared in Harare, Zimbabwe - the fourth enteric infection epidemic since 2008. To orient control activities, we described the epidemiology and spatiotemporal clustering of the epidemic in Dzivaresekwa and Kuwadzana, the two most affected suburbs of Harare.MethodsA typhoid fever case-patient register was analysed to describe the epidemic. To explore clustering, we constructed a dataset comprising GPS coordinates of case-patient residences and randomly sampled residential locations (spatial controls). The scale and significance of clustering was explored with Ripley K functions. Cluster locations were determined by a random labelling technique and confirmed using Kulldorff's spatial scan statistic.Principal findingsWe analysed data from 2570 confirmed and suspected case-patients, and found significant spatiotemporal clustering of typhoid fever in two non-overlapping areas, which appeared to be linked to environmental sources. Peak relative risk was more than six times greater than in areas lying outside the cluster ranges. Clusters were identified in similar geographical ranges by both random labelling and Kulldorff's spatial scan statistic. The spatial scale at which typhoid fever clustered was highly localised, with significant clustering at distances up to 4.5 km and peak levels at approximately 3.5 km. The epicentre of infection transmission shifted from one cluster to the other during the course of the epidemic.ConclusionsThis study demonstrated highly localised clustering of typhoid fever during an epidemic in an urban African setting, and highlights the importance of spatiotemporal analysis for making timely decisions about targetting prevention and control activities and reinforcing treatment during epidemics. This approach should be integrated into existing surveillance systems to facilitate early detection of epidemics and identify their spatial range.

Project description:BACKGROUND:Glucose management is challenging in patients who require nutritional support in hospital. We aimed to assess whether fully closed-loop insulin delivery would improve glycaemic control compared with conventional subcutaneous insulin therapy in inpatients receiving enteral or parenteral nutrition or both. METHODS:We did a two-centre (UK and Switzerland), open-label, randomised controlled trial in adult inpatients receiving enteral or parenteral nutrition (or both) who required subcutaneous insulin therapy. Patients recruited from non-critical care surgical and medical wards were randomly assigned (1:1) using a computer-generated minimisation schedule (stratified by type of nutritional support [parenteral nutrition on or off] and pre-study total daily insulin dose [<50 or ≥50 units]) to receive fully closed-loop insulin delivery with faster-acting insulin aspart (closed-loop group) or conventional subcutaneous insulin therapy (control group) given in accordance with local clinical practice. Continuous glucose monitoring in the control group was masked to patients, ward staff, and investigators. Patients were followed up for a maximum of 15 days or until hospital discharge. The primary endpoint was the proportion of time that sensor glucose concentration was in target range (5·6-10·0 mmol/L), assessed in the intention-to-treat population. This trial is registered with ClinicalTrials.gov, number NCT01774565. FINDINGS:Between Feb 8, 2018, and Sept 21, 2018, 90 patients were assessed for eligibility, of whom 43 were enrolled and randomly assigned to the closed-loop group (n=21) or the control group (n=22). The proportion of time that sensor glucose was in the target range was 68·4% [SD 15·5] in the closed-loop group and 36·4% [26·6] in the control group (difference 32·0 percentage points [95% CI 18·5-45·5; p<0·0001]). One serious adverse event occurred in each group (one cardiac arrest in the control group and one episode of acute respiratory failure in the closed-loop group), both of which were unrelated to study interventions. There were no adverse events related to study interventions in either group. No episodes of severe hypoglycaemia or hyperglycaemia with ketonaemia occurred in either study group. INTERPRETATION:Closed-loop insulin delivery is an effective treatment option to improve glycaemic control in patients receiving nutritional support in hospital. FUNDING:Diabetes UK, Swiss National Science Foundation, National Institute for Health Research Cambridge Biomedical Research Centre, Wellcome Trust, and European Foundation for the Study of Diabetes.

Project description:BackgroundHIV 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.MethodsThis 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.FindingsBetween Aug 4, and Dec 18, 2015, 2050 eligible households were enrolled in the prevalence survey. 649 (32%) households were assigned no incentive, 740 (34%) households were assigned a $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%) households in the no-incentive group, 654 (39%) households in the $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.InterpretationFixed 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.FundingWellcome Trust.