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.
Reviewing Editor
- Joshua T Schiffer, Fred Hutchinson Cancer Research Center, United States
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.
Version history
- Received: May 1, 2020
- Accepted: August 21, 2020
- Accepted Manuscript published: August 24, 2020 (version 1)
- Version of Record published: October 1, 2020 (version 2)
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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- Epidemiology and Global Health
- Microbiology and Infectious Disease
Background: Few national-level studies have evaluated the impact of 'hybrid' immunity (vaccination coupled with recovery from infection) from the Omicron variants of SARS-CoV-2.
Methods: From May 2020 to December 2022, we conducted serial assessments (each of ~4000-9000 adults) examining SARS-CoV-2 antibodies within a mostly representative Canadian cohort drawn from a national online polling platform. Adults, most of whom were vaccinated, reported viral test-confirmed infections and mailed self-collected dried blood spots to a central lab. Samples underwent highly sensitive and specific antibody assays to spike and nucleocapsid protein antigens, the latter triggered only by infection. We estimated cumulative SARS-CoV-2 incidence prior to the Omicron period and during the BA.1/1.1 and BA.2/5 waves. We assessed changes in antibody levels and in age-specific active immunity levels.
Results: Spike levels were higher in infected than in uninfected adults, regardless of vaccination doses. Among adults vaccinated at least thrice and infected more than six months earlier, spike levels fell notably and continuously for the nine months post-vaccination. By contrast, among adults infected within six months, spike levels declined gradually. Declines were similar by sex, age group, and ethnicity. Recent vaccination attenuated declines in spike levels from older infections. In a convenience sample, spike antibody and cellular responses were correlated. Near the end of 2022, about 35% of adults above age 60 had their last vaccine dose more than six months ago, and about 25% remained uninfected. The cumulative incidence of SARS-CoV-2 infection rose from 13% (95% CI 11-14%) before omicron to 78% (76-80%) by December 2022, equating to 25 million infected adults cumulatively. However, the COVID-19 weekly death rate during the BA.2/5 waves was less than half of that during the BA.1/1.1 wave, implying a protective role for hybrid immunity.
Conclusions: Strategies to maintain population-level hybrid immunity require up-to-date vaccination coverage, including among those recovering from infection. Population-based, self-collected dried blood spots are a practicable biological surveillance platform.
Funding: Funding was provided by the COVID-19 Immunity Task Force, Canadian Institutes of Health Research, Pfizer Global Medical Grants, and St. Michael's Hospital Foundation. PJ and ACG are funded by the Canada Research Chairs Program.
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- Computational and Systems Biology
- Epidemiology and Global Health
The chemical composition of foods is complex, variable, and dependent on many factors. This has a major impact on nutrition research as it foundationally affects our ability to adequately assess the actual intake of nutrients and other compounds. In spite of this, accurate data on nutrient intake are key for investigating the associations and causal relationships between intake, health, and disease risk at the service of developing evidence-based dietary guidance that enables improvements in population health. Here, we exemplify the importance of this challenge by investigating the impact of food content variability on nutrition research using three bioactives as model: flavan-3-ols, (–)-epicatechin, and nitrate. Our results show that common approaches aimed at addressing the high compositional variability of even the same foods impede the accurate assessment of nutrient intake generally. This suggests that the results of many nutrition studies using food composition data are potentially unreliable and carry greater limitations than commonly appreciated, consequently resulting in dietary recommendations with significant limitations and unreliable impact on public health. Thus, current challenges related to nutrient intake assessments need to be addressed and mitigated by the development of improved dietary assessment methods involving the use of nutritional biomarkers.
