scholarly journals Risk to Nonparticipants in HIV Remission Studies With Treatment Interruption: A Symposium

2019 ◽  
Vol 220 (Supplement_1) ◽  
pp. S1-S4 ◽  
Author(s):  
Nir Eyal ◽  
Steven G Deeks
Keyword(s):  
Human Subjects ◽  
Treatment Interruption ◽  
Sex Partners ◽  
Hiv Cure ◽  
Ethical Guidelines ◽  
Treatment Interruptions ◽  
Immunodeficiency Virus ◽  
Practical Challenge ◽  
Guidelines And Recommendations ◽  
Study Participants

AbstractEthical guidelines and recommendations for human subjects research typically focus on protecting the individuals who directly participate in that research. However, additional people, including sex partners of research participants, can also face harms and burdens from medical studies. In human immunodeficiency virus (HIV) cure–related research, a persistent ethical and practical challenge surrounds the use of analytical antiretroviral treatment interruptions. The challenge is usually discussed in relation to risks to study participants, but serious dangers accrue to nonparticipants, including sex partners of study participants. This multidisciplinary supplement relays the risks for nonparticipating sex partners in HIV cure–related studies and addresses the ethical dilemmas raised by these studies, with recommendations for researchers, advocates, sponsors, and oversight bodies.

scholarly journals Preexposure Prophylaxis for Mitigating Risk of HIV Transmission During HIV Cure–Related Clinical Trials With a Treatment Interruption

2019 ◽  
Vol 220 (Supplement_1) ◽  
pp. S16-S18 ◽  
Author(s):  
Jean-Daniel Lelièvre
Keyword(s):  
Human Immunodeficiency Virus ◽  
Clinical Trials ◽  
Hiv Transmission ◽  
Treatment Interruption ◽  
Sex Partners ◽  
Hiv Cure ◽  
Analytical Treatment ◽  
Secondary Transmission ◽  
Preexposure Prophylaxis ◽  
Immunodeficiency Virus

AbstractAnalytical treatment interruption performed during human immunodeficiency virus (HIV) cure–related clinical trials exposes sex partners of participants in these trials to a risk of HIV transmission. Preexposure prophylaxis (PrEP), which emerged in recent years as a key strategy for preventing HIV transmission, is often considered a useful tool to prevent this risk. This article supports offering PrEP to the stable sex partners of participants in these trials but also notes limitations that must be addressed. It concludes that PrEP cannot on its own eliminate the risk of secondary transmission in this context.

scholarly journals Operationalizing Human Immunodeficiency Virus Cure-related Trials with Analytic Treatment Interruptions During the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Pandemic: A Collaborative Approach

2020 ◽  
Author(s):  
Michael J Peluso ◽  
Lynda Dee ◽  
Shirley Shao ◽  
Jeff Taylor ◽  
Danielle Campbell ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Severe Acute Respiratory Syndrome ◽  
Treatment Interruption ◽  
Experimental Therapy ◽  
Hiv Cure ◽  
Analytic Treatment ◽  
Treatment Interruptions ◽  
Immunodeficiency Virus ◽  
Study Implementation ◽  
Hiv Cure Research

Abstract Efforts to recognize and minimize the risk to study participants will be necessary to safely and ethically resume scientific research in the context of the ongoing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic. These efforts are uniquely challenging in the context of human immunodeficiency virus (HIV) cure clinical trials, which often involve complex experimental therapy regimens and perhaps analytic treatment interruption, in which participants pause antiretroviral therapy. In this viewpoint, we discuss our approach to reopening an HIV cure trial in this context, with a focus on key considerations regarding study design, informed consent and participant education, and study implementation. These recommendations might be informative to other groups seeking to resume HIV cure research in settings similar to ours.

scholarly journals Is it ethical to isolate study participants to prevent HIV transmission during trials with an analytical treatment interruption?

2019 ◽  
Vol 220 (Supplement_1) ◽  
pp. S19-S21
Author(s):  
Nir Eyal ◽  
Monica Magalhaes
Keyword(s):  
Human Immunodeficiency Virus ◽  
Hiv Transmission ◽  
Treatment Interruption ◽  
Sex Partners ◽  
Analytical Treatment ◽  
Immunodeficiency Virus ◽  
Study Participants

Abstract This commentary considers an extreme idea for protecting against human immunodeficiency virus (HIV) transmission to sex partners of individuals participating in HIV remission studies with an analytical treatment interruption (ATI). Other human challenge studies, such as studies of influenza, commonly isolate participants during the trial, to protect their contacts and the community against infection. Why should HIV studies with a treatment interruption be any different, one might wonder? This article concludes that isolation should not be used in HIV remission studies with an ATI but also shows that the matter is complex.

scholarly journals Infectious Virus Persists in CD4+T Cells and Macrophages in Antiretroviral Therapy-Suppressed Simian Immunodeficiency Virus-Infected Macaques

2019 ◽  
Vol 93 (15) ◽  
Author(s):  
Celina M. Abreu ◽  
Rebecca T. Veenhuis ◽  
Claudia R. Avalos ◽  
Shelby Graham ◽  
Suzanne E. Queen ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Antiretroviral Therapy ◽  
Infectious Virus ◽  
Treatment Interruption ◽  
Viral Rebound ◽  
Hiv Cure ◽  
Macaque Model ◽  
Immunodeficiency Virus ◽  
Latently Infected

ABSTRACTUnderstanding the cellular and anatomical sites of latent virus that contribute to human immunodeficiency virus (HIV) rebound is essential for eradication. In HIV-positive patients, CD4+T lymphocytes comprise a well-defined functional latent reservoir, defined as cells containing transcriptionally silent genomes able to produce infectious virus once reactivated. However, the persistence of infectious latent virus in CD4+T cells in compartments other than blood and lymph nodes is unclear. Macrophages (Mϕ) are infected by HIV/simian immunodeficiency virus (SIV) and are likely to carry latent viral genomes during antiretroviral therapy (ART), contributing to the reservoir. Currently, the gold standard assay used to measure reservoirs containing replication-competent virus is the quantitative viral outgrowth assay (QVOA). Using an SIV-macaque model, the CD4+T cell and Mϕ functional latent reservoirs were measured in various tissues using cell-specific QVOAs. Our results showed that blood, spleen, and lung in the majority of suppressed animals contain latently infected Mϕs. Surprisingly, the numbers of CD4+T cells, monocytes, and Mϕs carrying infectious genomes in blood and spleen were at comparable frequencies (∼1 infected cell per million). We also demonstrate thatex vivoviruses produced in the Mϕ QVOA are capable of infecting activated CD4+T cells. These results strongly suggest that latently infected tissue Mϕs can reestablish productive infection upon treatment interruption. This study provides the first comparison of CD4+T cell and Mϕ functional reservoirs in a macaque model. It is the first confirmation of the persistence of latent genomes in monocytes in blood and Mϕs in the spleen and lung of SIV-infected ART-suppressed macaques. Our results demonstrate that transcriptionally silent genomes in Mϕs can contribute to viral rebound after ART interruption and should be considered in future HIV cure strategies.IMPORTANCEThis study suggests that CD4+T cells found throughout tissues in the body can contain replication-competent SIV and contribute to rebound of the virus after treatment interruption. In addition, this study demonstrates that macrophages in tissues are another cellular reservoir for SIV and may contribute to viral rebound after treatment interruption. This new insight into the size and location of the SIV reservoir could have great implications for HIV-infected individuals and should be taken into consideration for the development of future HIV cure strategies.

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

2020 ◽  
Vol 17 (1) ◽  
Author(s):  
Jillian S. Y. 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.

scholarly journals Viral Dynamics during Structured Treatment Interruptions of Chronic Human Immunodeficiency Virus Type 1 Infection

2002 ◽  
Vol 76 (3) ◽  
pp. 968-979 ◽  
Author(s):  
Simon D. W. Frost ◽  
Javier Martinez-Picado ◽  
Lidia Ruiz ◽  
Bonaventura Clotet ◽  
Andrew J. Leigh Brown
Keyword(s):  
Human Immunodeficiency Virus ◽  
Viral Load ◽  
Immune Responses ◽  
Treatment Interruption ◽  
Viral Rebound ◽  
Viral Dynamics ◽  
Viral Loads ◽  
Treatment Interruptions ◽  
Immunodeficiency Virus

ABSTRACT Although antiviral agents which block human immunodeficiency virus (HIV) replication can result in long-term suppression of viral loads to undetectable levels in plasma, long-term therapy fails to eradicate virus, which generally rebounds after a single treatment interruption. Multiple structured treatment interruptions (STIs) have been suggested as a possible strategy that may boost HIV-specific immune responses and control viral replication. We analyze viral dynamics during four consecutive STI cycles in 12 chronically infected patients with a history (>2 years) of viral suppression under highly active antiretroviral therapy. We fitted a simple model of viral rebound to the viral load data from each patient by using a novel statistical approach that allows us to overcome problems of estimating viral dynamics parameters when there are many viral load measurements below the limit of detection. There is an approximate halving of the average viral growth rate between the first and fourth STI cycles, yet the average time between treatment interruption and detection of viral loads in the plasma is approximately the same in the first and fourth interruptions. We hypothesize that reseeding of viral reservoirs during treatment interruptions can account for this discrepancy, although factors such as stochastic effects and the strength of HIV-specific immune responses may also affect the time to viral rebound. We also demonstrate spontaneous drops in viral load in later STIs, which reflect fluctuations in the rates of viral production and/or clearance that may be caused by a complex interaction between virus and target cells and/or immune responses.

scholarly journals Characterization of Physicians That Might Be Reluctant to Propose HIV Cure-Related Clinical Trials with Treatment Interruption to Their Patients? The ANRS-APSEC Study

Vaccines ◽  
2020 ◽  
Vol 8 (2) ◽  
pp. 334
Author(s):  
Christel Protiere ◽  
Lisa Fressard ◽  
Marion Mora ◽  
Laurence Meyer ◽  
Marie Préau ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Hiv Transmission ◽  
Negative Impact ◽  
Treatment Interruption ◽  
Department Head ◽  
Professional Activity ◽  
Hiv Cure ◽  
Continuous Training ◽  
Treatment Interruptions ◽  
The Impact

HIV cure-related clinical trials (HCRCT) with analytical antiretroviral treatment interruptions (ATIs) have become unavoidable. However, the limited benefits for participants and the risk of HIV transmission during ATI might negatively impact physicians’ motivations to propose HCRCT to patients. Between October 2016 and March 2017, 164 French HIV physicians were asked about their level of agreement with four viewpoints regarding HCRCT. A reluctance score was derived from their answers and factors associated with reluctance identified. Results showed the highest reluctance to propose HCRCT was among physicians with a less research-orientated professional activity, those not informing themselves about cure trials through scientific literature, and those who participated in trials because their department head asked them. Physicians’ perceptions of the impact of HIV on their patients’ lives were also associated with their motivation to propose HCRCT: those who considered that living with HIV means living with a secret were more motivated, while those worrying about the negative impact on person living with HIV’s professional lives were more reluctant. Our study highlighted the need to design a HCRCT that minimizes constraints for participants and for continuous training programs to help physicians keep up-to-date with recent advances in HIV cure research.

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

2019 ◽  
Vol 220 (Supplement_1) ◽  
pp. S24-S26 ◽  
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.

scholarly journals Human Immunodeficiency Virus Transmission Risk in Analytical Treatment Interruption Studies: Relational Factors and Moral Responsibility

2019 ◽  
Vol 220 (Supplement_1) ◽  
pp. S12-S15 ◽  
Author(s):  
Liza Dawson
Keyword(s):  
Human Immunodeficiency Virus ◽  
Risk Mitigation ◽  
Healthcare Providers ◽  
Virus Transmission ◽  
Treatment Interruption ◽  
Mitigation Strategies ◽  
Transmission Risk ◽  
Analytical Treatment ◽  
Immunodeficiency Virus ◽  
Study Participants

Abstract Analytical treatment interruption (ATI) is becoming common in human immunodeficiency virus (HIV) cure-related research, but its use is controversial. ATI raises concerns about risks of HIV transmission to sexual partners of study participants. Researchers may have difficulty addressing these risks, given that study participants’ private behavior is implicated, the partners are not enrolled in the research, and behavioral HIV risk mitigation strategies usually fall outside the study objectives. This analysis argues that researchers should assume some responsibility for partners’ risks, based on the importance of partner relationships for the study participants themselves, and out of concern for the partners’ welfare. Adding this responsibility is reasonable since the risk is created in part by research procedures, and since concern for third parties is often part of professional standards for healthcare providers. Study participants and their partners also bear some responsibility. Specific recommendations for measures to address risk are discussed.

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

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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