A Partner Protection Package for HIV Cure-related Trials Involving Analytical Treatment Interruptions

Overview

Journal Lancet Infect Dis

Specialty Infectious Diseases

Date 2023 Jun 9

PMID 37295453

Authors

Karine Dube

Tia Morton

Lawrence Fox

Lynda Dee

David Palm

Thomas J Villa

William Freshwater

Jeff Taylor

Gail Graham

William B Carter

John A Sauceda

Michael J Peluso

Annette Rid

Affiliations

Soon will be listed here.

Abstract

Analytical treatment interruptions (ATIs) have become a key methodological approach to evaluate the effects of experimental HIV cure-related research interventions. During ATIs, sex partners of trial participants might be at risk of acquiring HIV. This risk raises both ethical and feasibility concerns about ATI trials. We propose a partner protection package (P3) approach to address these concerns. A P3 approach would provide guidance to investigators, sponsors, and those who are designing and implementing context-specific partner protections in HIV cure-related trials involving ATIs. The approach would also help assure institutional review boards, trial participants, and communities that ATI trials with a P3 would provide appropriate partner protections. We offer a prototype P3 framework that delineates three basic considerations for protecting participants' sex partners during ATI trials: (1) ensuring the scientific and social value of the ATI and the trial, (2) reducing the likelihood of unintended HIV transmission, and (3) ensuring prompt management of any acquired HIV infection. We outline possible ways of implementing these basic considerations.

Citing Articles

'It is scary to pause treatment': perspectives on HIV cure-related research and analytical treatment interruptions from women diagnosed during acute HIV in Durban, South Africa.

Mthimkhulu D, Dong K, Ngcobo M, Mindry D, Zulu A, Langa N HIV Res Clin Pract. 2025; 26(1):2455917.

PMID: 39862155 PMC: 11829625. DOI: 10.1080/25787489.2025.2455917.

HIV Clinical Providers' Awareness, Attitudes, and Willingness to Support Patient Outreach Efforts for HIV Cure-Directed Research in Philadelphia, United States.

Meanley S, Carter W, Short W, Metzger D, Onorato A, Montaner L Open Forum Infect Dis. 2024; 11(12):ofae687.

PMID: 39660018 PMC: 11631357. DOI: 10.1093/ofid/ofae687.

Partner protections in HIV cure-related trials involving analytical treatment interruption: Updated toolkit to mitigate HIV transmission risk.

Dube K, Villa T, Freshwater W, Mauk B, Rid A, Peluso M J Virus Erad. 2024; 10(3):100386.

PMID: 39364082 PMC: 11447310. DOI: 10.1016/j.jve.2024.100386.

"This Is Actually a Really Unique Moment in Time": Navigating Long-Acting HIV Treatment and HIV Cure Research with Analytical Treatment Interruptions-A Qualitative Interview Study in the United States.

Dube K, Perez-Brumer A, Patel H, Zhou C, Dee L, Graham G AIDS Res Hum Retroviruses. 2024; 40(8):455-463.

PMID: 38386494 PMC: 11386995. DOI: 10.1089/AID.2023.0105.

Participant experiences in a combination HIV cure-related trial with extended analytical treatment interruption in San Francisco, United States.

Dube K, Ndukwe S, Korolkova A, Dee L, Sugarman J, Sauceda J HIV Res Clin Pract. 2024; 25(1):2312318.

PMID: 38348830 PMC: 10951555.

References

Wikler D . Bystanders and ethical review of research: Proceed with caution. Bioethics. 2020; 34(9):937-940. DOI: 10.1111/bioe.12823. View

Zheng L, Tierney C, Bosch R . Analytical Treatment Interruption in HIV Trials: Statistical and Study Design Considerations. Curr HIV/AIDS Rep. 2021; 18(5):475-482. PMC: 8251690. DOI: 10.1007/s11904-021-00569-8. View

Sugarman J, Celum C, Donnell D, Mayer K . Ethical considerations for new HIV prevention trials. Lancet HIV. 2019; 6(8):e489-e491. DOI: 10.1016/S2352-3018(19)30184-5. View

Power J, Dowsett G, Westle A, Tucker J, Hill S, Sugarman J . The significance and expectations of HIV cure research among people living with HIV in Australia. PLoS One. 2020; 15(3):e0229733. PMC: 7055878. DOI: 10.1371/journal.pone.0229733. View

Lewin S, Attoye T, Bansbach C, Doehle B, Dube K, Dybul M . Multi-stakeholder consensus on a target product profile for an HIV cure. Lancet HIV. 2020; 8(1):e42-e50. PMC: 7773628. DOI: 10.1016/S2352-3018(20)30234-4. View

Kenyon C, Wouters K, Platteau T, Buyze J, Florence E . Increases in condomless chemsex associated with HIV acquisition in MSM but not heterosexuals attending a HIV testing center in Antwerp, Belgium. AIDS Res Ther. 2018; 15(1):14. PMC: 6195714. DOI: 10.1186/s12981-018-0201-3. View

Eyal N . Removing One Barrier to Protecting Sex Partners in HIV Remission Studies With a Treatment Interruption. J Infect Dis. 2019; 220(220 Suppl 1):S22-S23. PMC: 6603972. DOI: 10.1093/infdis/jiz162. View

Barr L, Jefferys R . A landscape analysis of HIV cure-related clinical research in 2019. J Virus Erad. 2020; 6(4):100010. PMC: 7695817. DOI: 10.1016/j.jve.2020.100010. View

Dube K, Eskaf S, Hastie E, Agarwal H, Henley L, Roebuck C . Preliminary Acceptability of a Home-Based Peripheral Blood Collection Device for Viral Load Testing in the Context of Analytical Treatment Interruptions in HIV Cure Trials: Results from a Nationwide Survey in the United States. J Pers Med. 2022; 12(2). PMC: 8879991. DOI: 10.3390/jpm12020231. View

10.

Lau J, Smith M, Allan B, Martinez C, Power J, Lewin S . Perspectives on Analytical Treatment Interruptions in People Living with HIV and Their Health Care Providers in the Landscape of HIV Cure-Focused Studies. AIDS Res Hum Retroviruses. 2019; 36(4):260-267. PMC: 7185349. DOI: 10.1089/AID.2019.0118. View

11.

Dube K, Agarwal H, Stockman J, Auerbach J, Sauceda J, Conroy A . "I Would Absolutely Need to Know That My Partner Is Still Going to be Protected": Perceptions of HIV Cure-Related Research Among Diverse HIV Serodifferent Couples in the United States. AIDS Res Hum Retroviruses. 2022; 39(8):400-413. PMC: 10387158. DOI: 10.1089/AID.2022.0036. View

12.

Allers K, Hutter G, Hofmann J, Loddenkemper C, Rieger K, Thiel E . Evidence for the cure of HIV infection by CCR5Δ32/Δ32 stem cell transplantation. Blood. 2010; 117(10):2791-9. DOI: 10.1182/blood-2010-09-309591. View

13.

Lelievre J, Hocqueloux L . Unintended HIV-1 Transmission to a Sex Partner in a Study of a Therapeutic Vaccine Candidate. J Infect Dis. 2019; 220(220 Suppl 1):S5-S6. PMC: 6603976. DOI: 10.1093/infdis/jiz012. View

14.

Gaebler C, Nogueira L, Stoffel E, Oliveira T, Breton G, Millard K . Prolonged viral suppression with anti-HIV-1 antibody therapy. Nature. 2022; 606(7913):368-374. PMC: 9177424. DOI: 10.1038/s41586-022-04597-1. View

15.

Margolis D, Deeks S . How Unavoidable Are Analytical Treatment Interruptions in HIV Cure-Related Studies?. J Infect Dis. 2019; 220(220 Suppl 1):S24-S26. PMC: 6636248. DOI: 10.1093/infdis/jiz222. View

16.

Reverby S . Compensation and reparations for victims and bystanders of the U.S. Public Health Service research studies in Tuskegee and Guatemala: Who do we owe what?. Bioethics. 2020; 34(9):893-898. DOI: 10.1111/bioe.12784. View

17.

Resnik D, Sharp R . Protecting third parties in human subjects research. IRB. 2006; 28(4):1-7. PMC: 3951397. View

18.

Eyal N . How to Address the Risk of HIV Transmission in Remission Studies With Treatment Interruption: The Low-Hanging Fruit Approach. J Infect Dis. 2019; 220(220 Suppl 1):S7-S11. PMC: 6603962. DOI: 10.1093/infdis/jiz163. View

19.

Lounsbury D, Reynolds T, Rapkin B, Robson M, Ostroff J . Protecting the privacy of third-party information: recommendations for social and behavioral health researchers. Soc Sci Med. 2006; 64(1):213-22. DOI: 10.1016/j.socscimed.2006.08.035. View

20.

Haire B, Folayan M, Hankins C, Sugarman J, McCormack S, Ramjee G . Ethical considerations in determining standard of prevention packages for HIV prevention trials: examining PrEP. Dev World Bioeth. 2013; 13(2):87-94. PMC: 3716830. DOI: 10.1111/dewb.12032. View