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The DIANA Study: Continued Access to Darunavir/Ritonavir (DRV/r) and Long-Term Safety Follow-Up in HIV-1-Infected Pediatric Patients Aged 3 to < 18 Years

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Abstract

Introduction

Darunavir is a human immunodeficiency virus type 1 (HIV-1) protease inhibitor boosted with ritonavir (DRV/r) or cobicistat.

Objective

This study provided continued access to DRV/r and assessed long-term safety in patients aged 3 to < 18 years.

Methods

Patients who had completed treatment in the DELPHI (TMC114-C212), DIONE (TMC114-TiDP29-C230), or ARIEL (TMC114-TiDP29-C228) studies were eligible to participate if they derived benefit from using DRV/r in countries where it was not available to them. DRV/r dosing was continued based on original study protocols. Only safety data were collected. Reportable adverse events (AEs) included AEs considered at least possibly related to treatment with DRV/r, AEs leading to discontinuation or treatment interruption, and serious AEs (SAEs).

Results

Forty-six patients rolled over to this study and received at least one dose of DRV/r. Median duration of DRV/r intake was 4.2 years. Overall, 15/46 patients experienced one or more reportable AEs, 10/46 patients experienced one or more grade 3 or 4 AEs, and 12/46 patients experienced one or more SAEs. The most common grade 3 or 4 and SAEs were pneumonia (3/46) and asthma (2/46). Only one AE (grade 1 lipoatrophy) was considered probably related to DRV/r (DIONE, n = 1). Overall, 3/46 patients experienced an HIV-related AE (grade 3 pneumonia SAE; grade 2 tuberculosis SAE, and grade 2 lipoatrophy AE), none of which were considered related to DRV/r or led to study discontinuation. Two AEs leading to discontinuation were pregnancies.

Conclusion

These long-term safety results continue to support DRV/r as a valuable therapeutic option for the treatment of HIV-1 infection in pediatric patients aged ≥ 3 years.

Trial Registration

ClinicalTrials.gov: NCT01138605/EudraCT number: 2009-017013-29; first submitted 8 April 2010.

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Acknowledgements

The authors thank the patients and their families for their participation and support during the study, the central and local Janssen study teams, study center staff, and the principal investigators, in particular Patricia Flynn for her review of this manuscript. The authors also thank other Janssen staff members for their input into this manuscript, and acknowledge Ian Woolveridge (Zoetic Science, an Ashfield company, Macclesfield, UK) for assistance in drafting the manuscript and coordinating and collating author contributions, which was funded by Janssen.

Author information

Authors and Affiliations

  1. Perinatal HIV Research Unit, Chris Hani Baragwanath Hospital, University of the Witwatersrand, Johannesburg, South Africa

    Avy Violari

  2. Shandukani Research Centre, Wits RHI, Johannesburg, South Africa

    Maysseb Masenya

  3. Pediatric Immunology-Hematology Unit, Hôpital Necker–Enfants Malades, Assistance Publique-Hôpitaux de Paris (AP-HP) and Faculté de Médecine Paris Descartes, Paris, France

    Stephane Blanche

  4. Janssen Pharmaceutica NV, Beerse, Belgium

    Simon Vanveggel, Veerle Hufkens & Magda Opsomer

  5. Janssen Research and Development, High Wycombe, UK

    Polan Chetty

Authors
  1. Avy Violari
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  2. Maysseb Masenya
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  3. Stephane Blanche
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  4. Simon Vanveggel
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  7. Magda Opsomer
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Corresponding author

Correspondence to Avy Violari.

Ethics declarations

Funding

This study was sponsored by Janssen.

Conflict of interest

Avy Violari is a Data and Safety Monitoring Board member for study TMC114IFD3001, but has no commercial interests with Janssen. Maysseb Masenya and Stephane Blanche have no conflicts of interest to declare in relation to the DIANA study. Simon Vanveggel, Veerle Hufkens, Polan Chetty and Magda Opsomer are all full-time employees of Janssen and potential stockholders of Johnson and Johnson.

Ethics approval

The study protocol and amendments were reviewed by an Independent Ethics Committee/Institutional Review Board (IEC/IRB). This study was conducted in accordance with the ethical principles that have their origin in the Declaration of Helsinki and that are consistent with Good Clinical Practices and applicable regulatory requirements.

Consent to participate

Patients (where appropriate, depending on age) and their parent(s) or legal representative(s) had to sign the informed consent form voluntarily.

Consent for publication

All authors made the decision to submit the manuscript for publication.

Availability of data and material

The data sharing policy of Janssen Pharmaceutical Companies of Johnson & Johnson is available at https://www.janssen.com/clinical-trials/transparency. As noted on this site, requests for access to the study data can be submitted through the Yale Open Data Access (YODA) Project site at http://yoda.yale.edu.

Code availability

Not applicable.

Author contributions

Avy Violari was an investigator in the trial and reported data for those patients. Simon Vanveggel, Veerle Hufkens, Polan Chetty, and Magda Opsomer were involved in the data analyses. All authors were involved in the development of the primary manuscript and interpretation of data, have read and approved the final version, and have met the criteria for authorship as established by the International Committee of Medical Journal Editors (ICMJE).

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Violari, A., Masenya, M., Blanche, S. et al. The DIANA Study: Continued Access to Darunavir/Ritonavir (DRV/r) and Long-Term Safety Follow-Up in HIV-1-Infected Pediatric Patients Aged 3 to < 18 Years. Drug Saf 44, 439–446 (2021). https://doi.org/10.1007/s40264-020-01032-0

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  • DOI: https://doi.org/10.1007/s40264-020-01032-0

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