A stepped-wedge randomized trial on the impact of early ART initiation on HIV patients' economic welfare in Eswatini
- Technical University of Munich, Germany
- Clinton Health Acccess Initiative, United States
- Duke University, United States
- University of Göttingen, Germany
- Heidelberg Institute of Global Health, Germany
- Ministry of Health of the Kingdom of Eswatini, Eswatini
- University of Heidelberg, Germany
- Stanford University, United States
Abstract
Background: Since 2015, the World Health Organisation (WHO) recommends immediate initiation of antiretroviral therapy (ART) for all HIV-positive patients. Epidemiological evidence points to important health benefits of immediate ART initiation; however, the policy's economic impact remains unknown. Methods: We conducted a stepped-wedge cluster-randomised controlled trial in Eswatini to determine the causal impact of immediate ART initiation on patients' economic welfare. Fourteen healthcare facilities were non-randomly matched in pairs and then randomly allocated to transition from the standard of care (ART eligibility at CD4 counts of < 350 cells/mm3 until September 2016 and <500 cells/mm3 thereafter) to the 'Early Initiation of ART for All' (EAAA) intervention at one of seven timepoints. Patients, healthcare personnel, and outcome assessors remained unblinded. Data was collected via standardised paper-based surveys with HIV-positive, ART-naïve adults who were neither pregnant nor breastfeeding. Outcomes were patients' time use, employment status, household expenditures and household wealth. Results: A total sample of 3,019 participants were interviewed over the duration of the study. The mean number of participants approached at each facility and time step varied from 4 to 112 participants. Using mixed-effects negative binomial regressions accounting for time trends and clustering, we found no significant difference between study arms for any economic outcome. Specifically, the EAAA intervention had no significant effect on non-resting time use (RR= 1.00, [CI: 0.96, 1.05, p=0.93]) or income-generating time use (RR= 0.94, [CI: 0.73,1.20, p=0.61]). Employment and household expenditures decreased slightly but not significantly in the EAAA group, with risk ratios of 0.93 [CI: 0.82, 1.04, p=0.21] and 0.92 [CI: 0.79, 1.06, p=0.26], respectively. We also found no significant treatment effect on households' asset ownership and living standards (RR=0.96, [CI 0.92, 1.00, p=0.253]). Lastly, there was no evidence of heterogeneity in effect estimates by patients' sex, age, education, timing of HIV diagnosis and ART initiation. Conclusions: Given the neutral effect on patients' economic welfare but positive effects on health, our findings support further investments into scaling-up immediate ART for all HIV patients. Trial Registration: ClinicalTrials.gov, NCT02909218 and NCT03789448; ethical approval: Eswatini National Health Service Review Board & Harvard T.H. Chan School of Public Health Review Board.
Data availability
All data generated or analysed during this study are included in the manuscript and supporting files. Source data files have been provided for Figures 2-4 and all supplementary fogures (Figures S1-S9).
Article and author information
Author details
Janina Isabel Steinert
Jan-Walter De Neve
Funding
Dutch Postcode Lottery in the Netherlands (NA)
- Till Bärnighausen
Alexander von Humboldt-Stiftung
- Till Bärnighausen
the Embassy of the Kingdom of the Netherlands in South Africa/Mozambique
- Till Bärnighausen
British Columbia Centre of Excellence in Canada
- Till Bärnighausen
Doctors Without Borders
- Till Bärnighausen
National Center for Advancing Translational Sciences of the National Institutes of Health (Award Number KL2TR003143)
- Pascal Geldsetzer
Joachim Herz Foundation
- Janina Isabel Steinert
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Human subjects: Ethical approval for this study was obtained from the Eswatini National Health Service Review Board in July 2014 (Reference Number: MH/599C/FWA 000 15267). Respondents gave verbal and written consent before completing the interview and were informed about their right to decline or withdraw their participation at any point in time. The study was further granted an exemption for non-human subjects research from the ethics review board of the Harvard T.H. Chan School of Public Health.
Copyright
© 2020, Steinert et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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A stepped-wedge randomized trial on the impact of early ART initiation on HIV patients' economic welfare in Eswatini
eLife 9:e58487.
https://doi.org/10.7554/eLife.58487
Further reading
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In many settings, a large fraction of the population has both been vaccinated against and infected by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Hence, quantifying the protection provided by post-infection vaccination has become critical for policy. We aimed to estimate the protective effect against SARS-CoV-2 reinfection of an additional vaccine dose after an initial Omicron variant infection.
Methods:
We report a retrospective, population-based cohort study performed in Shanghai, China, using electronic databases with information on SARS-CoV-2 infections and vaccination history. We compared reinfection incidence by post-infection vaccination status in individuals initially infected during the April–May 2022 Omicron variant surge in Shanghai and who had been vaccinated before that period. Cox models were fit to estimate adjusted hazard ratios (aHRs).
Results:
275,896 individuals were diagnosed with real-time polymerase chain reaction-confirmed SARS-CoV-2 infection in April–May 2022; 199,312/275,896 were included in analyses on the effect of a post-infection vaccine dose. Post-infection vaccination provided protection against reinfection (aHR 0.82; 95% confidence interval 0.79–0.85). For patients who had received one, two, or three vaccine doses before their first infection, hazard ratios for the post-infection vaccination effect were 0.84 (0.76–0.93), 0.87 (0.83–0.90), and 0.96 (0.74–1.23), respectively. Post-infection vaccination within 30 and 90 days before the second Omicron wave provided different degrees of protection (in aHR): 0.51 (0.44–0.58) and 0.67 (0.61–0.74), respectively. Moreover, for all vaccine types, but to different extents, a post-infection dose given to individuals who were fully vaccinated before first infection was protective.
Conclusions:
In previously vaccinated and infected individuals, an additional vaccine dose provided protection against Omicron variant reinfection. These observations will inform future policy decisions on COVID-19 vaccination in China and other countries.
Funding:
This study was funded the Key Discipline Program of Pudong New Area Health System (PWZxk2022-25), the Development and Application of Intelligent Epidemic Surveillance and AI Analysis System (21002411400), the Shanghai Public Health System Construction (GWVI-11.2-XD08), the Shanghai Health Commission Key Disciplines (GWVI-11.1-02), the Shanghai Health Commission Clinical Research Program (20214Y0020), the Shanghai Natural Science Foundation (22ZR1414600), and the Shanghai Young Health Talents Program (2022YQ076).
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Background:
The role of circulating metabolites on child development is understudied. We investigated associations between children’s serum metabolome and early childhood development (ECD).
Methods:
Untargeted metabolomics was performed on serum samples of 5004 children aged 6–59 months, a subset of participants from the Brazilian National Survey on Child Nutrition (ENANI-2019). ECD was assessed using the Survey of Well-being of Young Children’s milestones questionnaire. The graded response model was used to estimate developmental age. Developmental quotient (DQ) was calculated as the developmental age divided by chronological age. Partial least square regression selected metabolites with a variable importance projection ≥1. The interaction between significant metabolites and the child’s age was tested.
Results:
Twenty-eight top-ranked metabolites were included in linear regression models adjusted for the child’s nutritional status, diet quality, and infant age. Cresol sulfate (β=–0.07; adjusted-p <0.001), hippuric acid (β=–0.06; adjusted-p <0.001), phenylacetylglutamine (β=–0.06; adjusted-p <0.001), and trimethylamine-N-oxide (β=–0.05; adjusted-p=0.002) showed inverse associations with DQ. We observed opposite directions in the association of DQ for creatinine (for children aged –1 SD: β=–0.05; pP=0.01;+1 SD: β=0.05; p=0.02) and methylhistidine (–1 SD: β = - 0.04; p=0.04;+1 SD: β=0.04; p=0.03).
Conclusions:
Serum biomarkers, including dietary and microbial-derived metabolites involved in the gut-brain axis, may potentially be used to track children at risk for developmental delays.
Funding:
Supported by the Brazilian Ministry of Health and the Brazilian National Research Council.
