Study to Explore Natural Daily Variation and Impact of Stress in HIV Levels
Condition: HIV
Study type: Observational

Summary: 
      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.
    

Detailed description: 
      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.
    

Intervention name(s): Diurnal Variation Group; External Stress Group
Intervention type(s): Other; Other
Intervention description(s): 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).; 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.
Observational model: Cohort
Time perspective: Prospective
Sampling method: Non-Probability Sample
Study population: 
        Cohort 1: Open to study participants who meet the inclusion/exclusion criteria and have
        been either referred by their health care provider or self-referred to the study team.

        Cohort 2: Open to study participants who meet the inclusion/exclusion criteria;
        participants will be primarily drawn from the pool of Options and Scope study participants
        who have consented to being contacted for future studies
      
Biospecimen description: 
      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
    
Keywords: diurnal variation; stress