A5345: HIV Rebound & Control Biomarkers

Identification of Biomarkers to Predict Time to Plasma HIV RNA Rebound and Post-Treatment Viral Control during an Intensively Monitored Antiretroviral Pause (IMAP)

Treatment Category: 

Treatment Experienced

Study Description

This study uses an intensively monitored antiretroviral pause (known as an IMAP) in which participants stop taking anti-HIV medications until they meet criteria for restarting them. Blood will be collected at various time points and then tested for the presence of biomarkers that can predict certain events, including when HIV will be “seen” again in blood after stopping anti-HIV medications (this is known as “rebounding”) and when HIV will be controlled again after re-starting anti-HIV medications.    

Why is this study being done?

  • To collect blood samples that can help to find and develop tests that can predict when HIV will rebound after people interrupt their anti-HIV medications and when HIV will be controlled again after anti-HIV medications are re-started. 
  • To study changes in HIV reservoirs (places where HIV “hides”) after anti-HIV medications are stopped.

Who can join?

  • HIV infected men and women, 18 to 70 years old
  • On anti-HIV medications with undetectable HIV viral load for at least 2 years
  • CD4 at least 500 now, and never had a CD4 less than 200
  • Must be willing to stop and restart anti-HIV medications

What do I need to do in the study?

During the IMAP, participants will have frequent visits (beginning at twice per week and possibly decreasing to once every two weeks) and frequent checks for HIV in their blood. Participants will be closely monitored so that anti-HIV medications can be restarted as soon as they need to be. The study will involve the collection of large amounts of blood and at least one leukapheresis procedure.   

The length of time on study will depend on if and when HIV rebounds during IMAP, and how long it takes for the HIV to be controlled again after anti-HIV medications are restarted. Most participants will likely be on study for 1 year or less. 

What treatments or drugs are involved with this study?

Participants must be taking anti-HIV medications, except during the IMAP. The anti-HIV medications will not be supplied through this study. Some people may have to switch their anti-HIV medications at the beginning of the study.

Is there anything else I need to know about this study?

Separate but related fluid and tissue samples will be collected in a substudy of A5345 known as A5347s (Reservoir Sampling Substudy of A5345). Participants will undergo different types of procedures to help understand how and where HIV might remain even though the level of HIV in their blood has been very low. See below.


A5347s: Anatomic Reservoir Substudy of A5345

Why is this substudy, A5347s, being done?

The main goal of this substudy is to collect samples from multiple anatomic compartments at as many of the following A5345 time points as possible:

  • before the antiretroviral pause (in A5345 Step 1)
  • very close to the time of virologic rebound (in A5345 Step 2)
  • shortly after completion of 24 weeks off antiretroviral treatment (ART) for any participants who reach this time point (in A5345 Step 2) without meeting any ART re-initiation criteria

This substudy will compare samples from different reservoirs to learn more about the following:

  • Where HIV can be found.
  • Whether the amount of HIV is different in different reservoirs.
  • What the best way is to measure the amount of HIV in different reservoirs.
  • Whether the amount of HIV found in any one reservoir can tell us anything about the amount of HIV in any of the other reservoirs.
  • Whether it could become possible to predict what will happen when a person stops taking ART.

Study Status

The substudy is open to accrual

Who can join the substudy, A5347s?

A5345 participants are eligible to enroll in the A5347s substudy if they:

  • Agree to undergo at least one rectal biopsy (tissue collection from the rectum)

There will be two groups of participants in the substudy. Category 1 is for A5345 participants with a Step 1 week 4 plasma HIV-1 RNA level of <20 copies/mL. Category 2 is for A5345 participants who complete 24 weeks on Step 2 of A5345 without meeting ART re-initiation criteria.

What do I need to do in the substudy, A5347s?

Participants will undergo one or more of the following procedures: 

  • RB Sampling Group – rectosigmoidal biopsies by flexible sigmoidoscopy (all participants must be in this group)
  • LN Sampling Group – lymph node biopsies
  • CSF Sampling Group – collection of cerebrospinal fluids by lumbar puncture
  • GTS Sampling Group – collection of genital tract secretions

How long will I be in A5347s?

The duration of the substudy will depend on events in A5345 and on which group (or category) you are in. Category 1 participants could be in the substudy for 2 to 3 months or could remain in substudy for more than 2 years if they agree to CSF collections. Participants who enter A5347s as Category 2 participants could be in the substudy for as little as 4 weeks or, if they agree to CSF collections, for more than 2 years.


Study Status: