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Attitudes About Analytic Treatment Interruption (ATI) in HIV Remission Trials with Different Antiretroviral Therapy (ART) Resumption Criteria

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Abstract

HIV remission trials often require temporary stopping of antiretroviral therapy (ART)—an approach called analytic treatment interruption (ATI). Trial designs resulting in viremia raise risks for participants and sexual partners. We conducted a survey on attitudes about remission trials, comparing ART resumption criteria (lower-risk “time to rebound” and higher-risk “sustained viremia”) among participants from an acute HIV cohort in Thailand. Analyses included Wilcoxon-Ranks and multivariate logistic analysis. Most of 408 respondents supported ATI trials, with slightly higher approval of, and willingness to participate in, trials using time to rebound versus sustained viremia criteria. Less than half of respondents anticipated disclosing trial participation to partners and over half indicated uncertainty or unwillingness about whether partners would be willing to use PrEP. Willingness to participate was higher among those who rated higher trial approval, lower anticipated burden, and those expecting to make the decision independently. Our findings support acceptability of ATI trials among most respondents. Participant attitudes and anticipated behaviors, especially related to transmission risk, have implications for future trial design and informed consent.

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Acknowledgements

We would like to thank our study participants.

Funding

The study was funded in entirety by the National Institutes of Health, National Institute of Allergy and Infectious Diseases (1R01AI127024). The investigators acknowledge expert input supported by the University of North Carolina at Chapel Hill Center for AIDS Research (P30 AI50410). The participants were from the RV254/SEARCH 010, which is supported by cooperative agreements (WW81XWH-18-2-0040) between the Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc., the U.S. Department of Defense (DOD), an intramural grant from the Thai Red Cross AIDS Research Centre, and by the U.S. National Institute of Allergy and Infectious Diseases. Antiretroviral therapy for RV254/SEARCH 010 participants was supported by the Thai Government Pharmaceutical Organization, Gilead, Merck and ViiV Healthcare. The funding sources have no involvement in study design, data collection and analysis, or writing the report.

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Authors and Affiliations

  1. RTI International, 3040 E Cornwallis Rd., Research Triangle Park, Durham, NC, 27709, USA

    Holly L. Peay & Angela Gwaltney

  2. Social Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA

    Stuart Rennie, R. Jean Cadigan, Nuchanart Ormsby, Sinéad C. Isaacson & Gail E. Henderson

  3. Center of Excellence in Pediatric Infectious Diseases and Vaccines Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand

    Thidarat Jupimai

  4. SEARCH, Thai Red Cross AIDS Research Centre, Bangkok, Thailand

    Nittaya Phanuphak, Eugène Kroon, Carlo Sacdalan, Peeriya Prueksakaew & Khunthalee Benjapornpong

  5. Institute of HIV Research and Innovation, Bangkok, Thailand

    Nittaya Phanuphak, Eugène Kroon, Donn J. Colby, Carlo Sacdalan, Peeriya Prueksakaew & Khunthalee Benjapornpong

  6. US Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD, USA

    Donn J. Colby & Sandhya Vasan

  7. The Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD, USA

    Donn J. Colby & Sandhya Vasan

  8. Department of Global Health, Amsterdam University Medical Centers, University of Amsterdam, and Amsterdam Institute for Global Health and Development, Amsterdam, The Netherlands

    Jintanat Ananworanich

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  1. Holly L. Peay
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  2. Stuart Rennie
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  3. R. Jean Cadigan
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  16. Gail E. Henderson
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Contributions

All authors contributed to the study conception and design or the acquisition, analysis or interpretation of the data. Conceptualization and methodology were led by HP and GH. Data collection was led by TJ with support by PP and KB, with supervision by EK and DC. Analysis were performed by AG and HP. The first draft of the manuscript was written by HP, TJ, NO and GH, and all authors reviewed and revised previous versions of the manuscript. All authors read and approved the manuscript version to be published. All authors agree to be accountable for the work and ensure any questions about the accuracy or integrity are investigated and resolved.

Corresponding author

Correspondence to Holly L. Peay.

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Conflict of interest

DC has received research grant support from Gilead Sciences. All other authors report no conflicts of interest or competing interests.

Ethical Approval

This study was approved by the IRB of the Faculty of Medicine, Chulalongkorn University.

Consent to Participate

All participants provided informed consent to participate in the study.

Consent for Publication

The study informed consent included a section indicating that de-identified study data would be reported.

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Disclaimer The views expressed are those of the authors and should not be construed to represent the positions of the U.S. Army or the Department of Defense. The investigators have adhered to the policies for protection of human subjects as prescribed in AR 70–25.

Appendix 1 Remission trial vignettes utilized in RV254 (SEARCH010) survey to assess trial attitudes and willingness to participate

Appendix 1 Remission trial vignettes utilized in RV254 (SEARCH010) survey to assess trial attitudes and willingness to participate

ATI vignette 1

Now, imagine you are invited to a new SEARCH 010 remission trial. It would test whether a new kind of experimental drug boosts the immune system, and if it is safe. You would get the experimental drug and then stop taking ART. You would come to SEARCH weekly for monitoring. The first time your viral load increases above 1000 copies/mL, you would restart ART

About the experimental drug:

 Safety: The experimental drug would probably be safe, but researchers wouldn’t know for sure

 Side effects: You may have mild side effects

While off ART:

 Monitoring at SEARCH: You would visit SEARCH once a week for health exams and blood draws to monitor your health, viral load, and CD4 count

 Side effects: You would probably not develop HIV symptoms or drug resistance. Longer term side effects are unknown

 Transmission risk: Your risk of transmitting HIV to partners might increase

Re-starting ART:

 Viral load: People restart ART when their viral load increases above the trial’s limit (1000 copies/mL). For most people, this would be about 2 months after stopping ART, although a few people may stay off ART longer

 Researchers expect that once people restart ART, their viral load should decrease and become undetectable

 Long term monitoring: The SEARCH team would continue to monitor your health once a month for a year

ATI vignette 2

Now imagine there is a different type of SEARCH remission trial. This one keeps you off ART longer, which is riskier. This extra time off ART would test whether your immune system can recognize and kill the virus. The SEARCH team would check how your viral load goes up and down over time

Like the first trial,

 You would get the same new experimental drug and then stop ART

 You would come in for a weekly health exam and blood draw

 If you have serious side effects from stopping ART at any time, you would immediately restart ART

 Once you restart ART, your viral load should decrease, and you should become undetectable again

 Once you restart ART, the SEARCH team would continue to monitor your health once a month for 1 year

Different from the first trial

 Your viral load would be allowed to go over 1000 copies/mL to see if your own immune system would start to fight the HIV virus on its own

 If your viral load stays above 1000 copies/mL for 4 weeks in a row, you would restart ART

 As long as your viral load does NOT go over 1000 copies/mL for 4 weeks in a row, you would continue to stay off ART and be monitored weekly

 You would be at much higher risk of transmitting HIV to your partner(s), so you would need to use condoms or abstain from sex

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Peay, H.L., Rennie, S., Cadigan, R.J. et al. Attitudes About Analytic Treatment Interruption (ATI) in HIV Remission Trials with Different Antiretroviral Therapy (ART) Resumption Criteria. AIDS Behav 26, 1504–1516 (2022). https://doi.org/10.1007/s10461-021-03504-5

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