Study to Explore Natural Daily Variation and Impact of Stress in HIV Levels (CHRONOS)
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|ClinicalTrials.gov Identifier: NCT02895087|
Recruitment Status : Active, not recruiting
First Posted : September 9, 2016
Last Update Posted : March 5, 2020
Despite advances in AntiRetroviral Therapy (ART) leading to a rapid control of the HIV virus in individuals affected, HIV can persist indefinitely and there is no cure. The HIV virus has been shown to have a unique ability to hide within the human gene inside human cells and in tissues, remaining 'silent' and rapidly reactivate 'waking up" if ART is stopped.
There are a number of ways to measure the silent HIV reservoir, including a common research-based laboratory test called Cell-Associated UnSpliced (CA-US) HIV RNA. This is an early marker of the HIV virus waking up. It is often used to test how well new drugs developed to eliminate the silent virus might work.
This study is examining whether the diurnal variation (daily rhythm) and/or stress can affect CA-US HIV RNA levels in individuals diagnosed with HIV and receiving ART.
|Condition or disease||Intervention/treatment|
|HIV||Other: Diurnal Variation Group Other: External Stress Group|
Undetectable or low circulating levels of HIV virus in blood are the result of people who have been diagnosed with a HIV-infection and who have adhered to a HIV AntiRetroviral Therapy (ART) regimen. However, the ART has not eradicated the virus from the body and individuals who cease ART can rapidly revert from a well-controlled state to showing high levels of HIV virus in the blood. The HIV virus has been shown to have a unique ability to hide within the human gene inside human cells and in tissues, remaining 'silent' and rapidly reactivate [or wake up] if ART is stopped. Efforts are underway to explore novel ways to entirely eradicate HIV from individuals, so that people who are HIV-infected can stop treatment and still have undetectable HIV viral load and remain well despite not being on HIV treatment.
There are a number of ways to measure the silent HIV reservoir, including a common research-based laboratory test called Cell-Associated UnSpliced (CA-US) HIV RNA. This is an early marker of the HIV virus reactivating. It is often used to test how well new drugs developed to eliminate the silent virus might work.
Recently as investigators involved in another clinical study, an unexpected observation was noted in a group of HIV study participants on ART between the CA-US HIV RNA levels and time of blood collection. Levels of CA-US HIV RNA appeared to be lower when blood samples were collected earlier in the morning. However, at the time of this observation, as investigators were unable to establish whether this discrepancy could be due to (i) the diurnal variation or (ii) unknown stress factors that may have been experienced by the study participants. It has previously been demonstrated that individuals with untreated HIV infection there is a variation in HIV RNA levels and the time of day. However, the effects of external factors such as time of day or stresses on CA-US HIV RNA levels in individuals while on ART have not been previously examined.
This study hopes to explore and answer the questions (i) Does the diurnal variation play a role in regulating the levels of CA-US HIV RNA in blood of individuals diagnosed with HIV and receiving ART and (ii) Does stress affect the levels of CA-US HIV RNA.
Understanding some factors that affect levels of CA-US HIV RNA may provide a new perspective on ways to eliminate the silent virus.
|Study Type :||Observational|
|Actual Enrollment :||40 participants|
|Official Title:||Circadian HIV RNA Oscillations and Outcomes of Stress|
|Actual Study Start Date :||March 2015|
|Actual Primary Completion Date :||January 2017|
|Estimated Study Completion Date :||December 2020|
Cohort 1: Diurnal Variation Group
Cohort recruitment - open to recruitment
Other: Diurnal Variation Group
This intervention occurs over one 24-hour period. Eligible participants will be required to be admitted into a supervised environment for 24-hours arriving no later than 0730. Blood draws will then be taken every 4 hours (0800, 1200, 1600, 2000, 2400 and 0400). Care will be taken to ensure the total blood draws (including the screening visit) stay within Red Cross Guidelines (less than 500 ml every 8 weeks).
Cohort 2: External Stress Group
Cohort recruitment - closed to recruitment
Other: External Stress Group
2 visits will be required, each lasting approximately 2.5 hours in the afternoon.
At both visits participants will rest quietly for 15 minutes, then have 3 blood draws and 4 saliva samples over approximately one hour. Participants will also be required to complete short questionnaires about their mood and experience.
At the second visit, participants will also complete some thinking and talking tasks. In addition the autonomic nervous system of the participant's will be monitored throughout the visit.
- Diurnal variation effects on HIV transcription [ Time Frame: 24 hours ]To determine if there are diurnal variations in cortisol and catecholamine in HIV transcription in latently-infected cells in HIV-infected participants on ART.
- Stress Factor effects on HIV transcription [ Time Frame: Baseline (visit 1) and visit 2 (approximately 1 - 7 days later) ]To determine the effects of stress-induced changes in cortisol and catecholamine on HIV transcription, in latently infected cells in HIV-infected participants on ART.
Biospecimen Retention: Samples With DNA
Part 1: Diurnal Variation cohort (total 15 participants) - no longer recruiting Blood samples
Part 2: Stress cohort (total 20 participants) - no longer recruiting Blood samples Saliva Samples
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02895087
|United States, California|
|Osher Center, University of California San Francisco|
|San Francisco, California, United States, 94115|
|United States, Wisconsin|
|Division of Infectious Diseases|
|Milwaukee, Wisconsin, United States, 53226|
|Principal Investigator:||Sharon R Lewin, FRACP, PhD||The Doherty Institute for Infection and Immunity, Melbourne University|
|Principal Investigator:||Frederick M Hecht, MD||University of California, San Francisco|