A stepped-wedge randomized trial on the impact of early ART initiation on HIV patients' economic welfare in Eswatini

  1. Janina Isabel Steinert  Is a corresponding author
  2. Shaukat Khan
  3. Khudzie Mlambo
  4. Fiona J Walsh
  5. Emma Mafara
  6. Charlotte Lejeune
  7. Cebele Wong
  8. Anita Hettema
  9. Osondu Ogbouji
  10. Sebastian Vollmer
  11. Jan-Walter De Neve
  12. Sikhathele Mazibuko
  13. Velephi Okello
  14. Till Bärnighausen
  15. Pascal Geldsetzer
  1. Technical University of Munich, Germany
  2. Clinton Health Acccess Initiative, United States
  3. Duke University, United States
  4. University of Göttingen, Germany
  5. Heidelberg Institute of Global Health, Germany
  6. Ministry of Health of the Kingdom of Eswatini, Eswatini
  7. University of Heidelberg, Germany
  8. 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

  1. Janina Isabel Steinert

    TUM School of Governance, Technical University of Munich, Munich, Germany
    For correspondence
    janina.steinert@tum.de
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-7120-0075
  2. Shaukat Khan

    Clinton Health Acccess Initiative, Boston, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Khudzie Mlambo

    Clinton Health Acccess Initiative, Boston, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Fiona J Walsh

    Clinton Health Acccess Initiative, Boston, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Emma Mafara

    Clinton Health Acccess Initiative, Boston, United States
    Competing interests
    The authors declare that no competing interests exist.
  6. Charlotte Lejeune

    Clinton Health Acccess Initiative, Boston, United States
    Competing interests
    The authors declare that no competing interests exist.
  7. Cebele Wong

    Clinton Health Acccess Initiative, Boston, United States
    Competing interests
    The authors declare that no competing interests exist.
  8. Anita Hettema

    Clinton Health Acccess Initiative, Boston, United States
    Competing interests
    The authors declare that no competing interests exist.
  9. Osondu Ogbouji

    Duke Global Health Institute, Duke University, Durham, United States
    Competing interests
    The authors declare that no competing interests exist.
  10. Sebastian Vollmer

    Development Economics, University of Göttingen, Göttingen, Germany
    Competing interests
    The authors declare that no competing interests exist.
  11. Jan-Walter De Neve

    Medical Faculty and University Hospital, Heidelberg University, Heidelberg Institute of Global Health, Heidelberg, Germany
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-0090-8249
  12. Sikhathele Mazibuko

    Ministry of Health of the Kingdom of Eswatini, Mbabane, Eswatini
    Competing interests
    The authors declare that no competing interests exist.
  13. Velephi Okello

    Ministry of Health of the Kingdom of Eswatini, Mbabane, Eswatini
    Competing interests
    The authors declare that no competing interests exist.
  14. Till Bärnighausen

    Institute of Public Health, University of Heidelberg, Heidelberg, Germany
    Competing interests
    The authors declare that no competing interests exist.
  15. Pascal Geldsetzer

    Division of Primary Care and Population Health, Department of Medicine, Stanford University, Stanford, United States
    Competing interests
    The authors declare that no competing interests exist.

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.

Reviewing Editor

  1. Joshua T Schiffer, Fred Hutchinson Cancer Research Center, United States

Publication history

  1. Received: May 1, 2020
  2. Accepted: August 21, 2020
  3. Accepted Manuscript published: August 24, 2020 (version 1)
  4. 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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  1. Janina Isabel Steinert
  2. Shaukat Khan
  3. Khudzie Mlambo
  4. Fiona J Walsh
  5. Emma Mafara
  6. Charlotte Lejeune
  7. Cebele Wong
  8. Anita Hettema
  9. Osondu Ogbouji
  10. Sebastian Vollmer
  11. Jan-Walter De Neve
  12. Sikhathele Mazibuko
  13. Velephi Okello
  14. Till Bärnighausen
  15. Pascal Geldsetzer
(2020)
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

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