Ethical and practical considerations for mitigating risks to sexual partners during analytical treatment interruptions in HIV cure-related research

Abstract Background Analytical treatment interruptions (ATI) are commonly used clinical endpoints to assess interventions aimed at curing HIV or achieving antiretroviral therapy (ART)-free HIV remission. Understanding the acceptability of ATI amongst people living with HIV (PLHIV) and their HIV healthcare providers (HHP) is limited. Methods Two online surveys for PLHIV and HHP assessed awareness and acceptability of ATI, and understanding of the prospect for HIV cure in the future. Responses were collected from July 2017–January 2018. A descriptive analysis was performed and similar questions across the two surveys were compared using χ squared test. Results 442 PLHIV and 144 HHP completed the survey. 105/400 (26%) PLHIV had ever interrupted ART, 8% of which were in a clinical trial. Altruistic motivations were drivers of participation of PLHIV in cure related research. 81/135 (60%) HHP would support their patients wishing to enrol in an HIV cure-focused trial, but fewer would promote and allow such participation (25% and 31% respectively). Compared to HHP, PLHIV were more likely to believe that an HIV cure would be achievable within 10 years (55% vs. 19%, p < 0.001), had less awareness of ATI (46% vs. 62%, p < 0.001) and were less likely to have had experience of either participation or enrolment in an ATI study (5% vs. 18%, p < 0.001) Conclusion PLHIV were more optimistic about the potential for HIV cure. HHP had more direct experience with HIV cure-focused studies. Educational strategies are required for both groups to increase understanding around ATIs in HIV cure research but should be tailored specifically to each group.

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“We Need to Deploy Them Very Thoughtfully and Carefully”: Perceptions of Analytical Treatment Interruptions in HIV Cure Research in the United States—A Qualitative Inquiry

AIDS Research and Human Retroviruses ◽

10.1089/aid.2017.0067 ◽

2018 ◽

Vol 34 (1) ◽

pp. 67-79 ◽

Cited By ~ 23

Author(s):

Karine Dubé ◽

David Evans ◽

Lynda Dee ◽

Laurie Sylla ◽

Jeff Taylor ◽

...

Keyword(s):

United States ◽

The United States ◽

Qualitative Inquiry ◽

Hiv Cure ◽

Analytical Treatment ◽

Treatment Interruptions ◽

Hiv Cure Research

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How Unavoidable Are Analytical Treatment Interruptions in HIV Cure–Related Studies?

The Journal of Infectious Diseases ◽

10.1093/infdis/jiz222 ◽

2019 ◽

Vol 220 (Supplement_1) ◽

pp. S24-S26 ◽

Cited By ~ 4

Author(s):

David M Margolis ◽

Steven G Deeks

Keyword(s):

Clinical Trial ◽

Human Immunodeficiency Virus ◽

Antiretroviral Therapy ◽

Virus Infection ◽

Human Immunodeficiency Virus Infection ◽

Outcome Measure ◽

Hiv Cure ◽

Analytical Treatment ◽

Treatment Interruptions ◽

Immunodeficiency Virus

Abstract In this discussion, 2 established researchers and clinical trialists debate their opposing views on the utility, benefits, and risks of the use of analytical interruption of antiretroviral therapy as a clinical trial end point and outcome measure in human studies seeking to induce remission of or eradicate human immunodeficiency virus infection.

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Virological outcome measures during analytical treatment interruptions in chronic HIV-1 infected patients

Open Forum Infectious Diseases ◽

10.1093/ofid/ofz485 ◽

2019 ◽

Cited By ~ 1

Author(s):

Csaba Fehér ◽

Lorna Leal ◽

Montserrat Plana ◽

Nuria Climent ◽

Alberto Crespo Guardo ◽

...

Keyword(s):

Outcome Measures ◽

Surrogate Marker ◽

Confounding Factors ◽

Hiv Cure ◽

Analytical Treatment ◽

Set Point ◽

Delta Set ◽

Treatment Interruptions ◽

Virological Outcome ◽

Hiv 1

Abstract Background Analytical treatment interruptions (ATI) are essential in research on HIV cure. However, the heterogeneity of virological outcome measures used in different trials hinders the interpretation of the efficacy of different strategies. Methods A retrospective analysis of viral load (VL) evolution in 334 ATI episodes in chronic HIV-1 infected patients collected from 11 prospective studies. Quantitative [baseline VL, set point, delta set point, VL and delta VL at given weeks after ATI, peak VL, delta peak VL, and area under the rebound curve], and temporal parameters [time to rebound (TtR), set point, peak, and certain absolute and relative VL thresholds] were described. Pairwise correlations between parameters were analyzed, and potential confounding factors (sex, age, time of known HIV infection, time on ART, and immunological interventions) were evaluated. Results Set point was lower than baseline VL (median delta set point -0.26. p< 0.001). This difference was >1 log10 copies/mL in 13.9% of the cases. Median TtR was 2 weeks; no patients had undetectable VL at week 12. Median time to set point was 8 weeks: by week 12, 97.4% of the patients had reached the set point. TtR and baseline VL were correlated with most temporal and quantitative parameters. The variables independently associated with TtR were baseline VL and the use of immunological interventions. Conclusions TtR could be an optimal surrogate marker of response in HIV cure strategies. Our results underline the importance of taking into account baseline VL and other confounding factors in the design and interpretation of these studies.

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“I would really want to know that they had my back”: Transgender women’s perceptions of HIV cure-related research in the United States

PLoS ONE ◽

10.1371/journal.pone.0244490 ◽

2020 ◽

Vol 15 (12) ◽

pp. e0244490

Author(s):

Tonia Poteat ◽

Anushka Aqil ◽

Dana Corbett ◽

David Evans ◽

Karine Dubé

Keyword(s):

Undetectable Viral Load ◽

The United States ◽

Transgender Women ◽

Test Subject ◽

Hiv Treatment ◽

Hiv Care ◽

Hiv Cure ◽

Related Research ◽

Treatment Interruptions ◽

Living With Hiv

Forty-four percent of Black transgender women are living with HIV, and many face challenges with HIV care engagement. An HIV cure has much to offer this population, however little HIV cure-related research has included them. We conducted 19 face-to-face in-depth interviews with 10 Black transgender women living with HIV. Interviews were audio recorded, transcribed verbatim, coded, and analyzed using content analysis. Our interview guide contained three categories: 1) perceptions of HIV cure-related research and participation, 2) perceptions of HIV treatment and treatment interruptions, and 3) considerations for transgender women and HIV cure-related research. Salient themes included skepticism about HIV cure strategies and limited benefits compared with an undetectable viral load. Willingness to interrupt HIV treatment for research was low and linked to being able to go back on the same HIV treatment without consequence when the study ended. Concerns about being a test subject and perceptions of risks versus benefits of various strategies also affected willingness to take part in HIV cure-related research. Centering the dignity and autonomy of research participants as well as building upon and supporting existing social networks were identified as important facilitators for engaging Black transgender women in HIV cure-related research. Specific to Black transgender women, other concerns included the desire for gender-affirming research staff, community-building among transgender women, and safety issues associated with risk of transphobic violence when traveling to study visits. Participants stressed the importance of HIV cure-related researchers providing accessible and complete information and expressing genuine care and concern for transgender communities.

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Acceptability, motivation and the prospect of cure for people living with HIV and their healthcare providers in HIV cure-focused treatment interruption studies

10.21203/rs.2.22755/v1 ◽

2020 ◽

Author(s):

Jillian SY Lau ◽

Miranda Z Smith ◽

Brent Allan ◽

Cipriano Martinez ◽

Jennifer Power ◽

...

Keyword(s):

Descriptive Analysis ◽

Healthcare Providers ◽

Treatment Interruption ◽

People Living With Hiv ◽

Hiv Cure ◽

Educational Strategies ◽

Analytical Treatment ◽

Clinical Endpoints ◽

Treatment Interruptions ◽

Living With Hiv

Abstract Background Analytical treatment interruptions (ATI) are commonly used clinical endpoints to assess interventions aimed at curing HIV or achieving antiretroviral therapy (ART)-free HIV remission. Understanding the acceptability of ATI amongst people living with HIV (PLHIV) and their HIV healthcare providers (HHP) is limited. Methods Two online surveys for PLHIV and HHP assessed awareness and acceptability of ATI, and understanding of the prospect for HIV cure in the future. Responses were collected from July 2017-January 2018. A descriptive analysis was performed and similar questions across the two surveys were compared using χ squared test. Results 442 PLHIV and 144 HHP completed the survey. 105/400 (26%) PLHIV had ever interrupted ART, 8% of which were in a clinical trial. Altruistic motivations were drivers of participation of PLHIV in cure related research. 81/135 (60%) HHP would support their patients wishing to enrol in an HIV cure-focused trial, but fewer would promote and allow such participation (25% and 31% respectively). Compared to HHP, PLHIV were more likely to believe that an HIV cure would be achievable within 10 years (55% vs 19%, p<0.001), had less awareness of ATI (46% vs 62%,p<0.001) and were less likely to have had experience of either participation or enrolment in an ATI study (5% vs 18%,p<0.001) Conclusion PLHIV were more optimistic about the potential for HIV cure. HHP had more direct experience with HIV cure-focused studies. Educational strategies are required for both groups to increase understanding around ATIs in HIV cure research but should be tailored specifically to each group.

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Perspectives on Analytical Treatment Interruptions in People Living with HIV and Their Health Care Providers in the Landscape of HIV Cure-Focused Studies

AIDS Research and Human Retroviruses ◽

10.1089/aid.2019.0118 ◽

2020 ◽

Vol 36 (4) ◽

pp. 260-267 ◽

Cited By ~ 7

Author(s):

Jillian S.Y. Lau ◽

Miranda Z. Smith ◽

Brent Allan ◽

Cipriano Martinez ◽

Jennifer Power ◽

...

Keyword(s):

Health Care ◽

Health Care Providers ◽

People Living With Hiv ◽

Care Providers ◽

Hiv Cure ◽

Analytical Treatment ◽

Treatment Interruptions ◽

Living With Hiv

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Systematic Review of the Current Literature on Structured Treatment Interruptions in HIV-infected Patients Receiving Antiretroviral Therapy – Implications for Future HIV Cure Trials

10.26226/morressier.572768e4d462b8029237f3ac ◽

2016 ◽

Author(s):

Melanie Stecher

Keyword(s):

Systematic Review ◽

Antiretroviral Therapy ◽

Current Literature ◽

Hiv Cure ◽

Treatment Interruptions

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Transient viral replication during analytical treatment interruptions in SIV infected macaques can alter the rebound-competent viral reservoir

PLoS Pathogens ◽

10.1371/journal.ppat.1009686 ◽

2021 ◽

Vol 17 (6) ◽

pp. e1009686

Author(s):

Taina T. Immonen ◽

Christine M. Fennessey ◽

Leslie Lipkey ◽

Abigail Thorpe ◽

Gregory Q. Del Prete ◽

...

Keyword(s):

Antiretroviral Therapy ◽

Viral Replication ◽

Rhesus Macaques ◽

Treatment Strategies ◽

Viral Reservoir ◽

Virus Population ◽

Analytical Treatment ◽

Treatment Interruptions ◽

The Impact ◽

Hiv 1

Analytical treatment interruptions (ATIs) of antiretroviral therapy (ART) play a central role in evaluating the efficacy of HIV-1 treatment strategies targeting virus that persists despite ART. However, it remains unclear if ATIs alter the rebound-competent viral reservoir (RCVR), the virus population that persists during ART and from which viral recrudescence originates after ART discontinuation. To assess the impact of ATIs on the RCVR, we used a barcode sequence tagged SIV to track individual viral lineages through a series of ATIs in Rhesus macaques. We demonstrate that transient replication of individual rebounding lineages during an ATI can lead to their enrichment in the RCVR, increasing their probability of reactivating again after treatment discontinuation. These data establish that the RCVR can be altered by uncontrolled replication during ATI.

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