Hide and seek: new trial to help find hidden HIV

HIV plays a game of hide and seek during treatment. Australian researchers have launched a new study to find a better way to see hidden HIV. They hope to develop a non-invasive way of measuring the HIV that remains in the tissues of people on antiretroviral treatment.

Why do we need a better way to find HIV?

Once a person with HIV starts treatment, the amount of virus in the blood quickly drops. For most people on treatment, regular viral load tests can’t detect any HIV in the blood. HIV becomes ‘undetectable’. Routine monitoring for people with HIV on treatment involves regular blood tests. This checks that the virus stays undetectable and that immune function is maintained.

Undetectable does not, however, mean that HIV is eliminated from the body. When treatment starts, HIV does not disappear. The virus merely retreats to hiding places, mostly in the tissues, where it lurks and waits. This is HIV latency. Latent HIV is the major barrier to an HIV cure.

Latent HIV hides in places like lymph nodes and the lining of the gastrointestinal tract (or gut). Sometimes antiretroviral drugs don’t easily infiltrate these tissues. At the moment, the HIV remaining in these places can only be detected through invasive procedures such as biopsies. Biopsies can be risky. They only allow a small part of tissue to be studied and may not sample the exact spot where the greatest amount of HIV is hiding. There’s also a limit to how many and how often biopsies can be done.

Lead researcher on the new study, Dr James McMahon from Alfred Health and Monash University, says

we need better ways to determine the amount of residual or latent HIV in people on treatment and where this virus is hiding if we are to develop ways to tackle this remaining virus

What is the aim of the study?

The study aims to develop a non-invasive way to see HIV in the body. It would enable researchers to see where and how much HIV remains in people with HIV infection who are on treatment.

What are the researchers going to do?

The researchers will combine an anti-HIV antibody (called 3BNC117) with a radioisotope or label (called copper-64). Researchers will then inject a small dose of this labelled antibody into study participants. The drug will bind to HIV and cells infected with HIV and give out a signal that can be detected on a scanner.

The scanner combines Magnetic Resonance Imaging (MRI) and Positron Emission Tomography (PET). The MRI part of the scanner enables researchers to see all the internal organs and tissue sites in the body and the PET part detects the signal from the copper isotope linked to the antibody. The antibody and copper isotope have both been safely used in other clinical trials. A similar strategy has been used to detect simian immunodeficiency virus (SIV) infected cells in monkey model of HIV infection.

The researchers will first test the strategy in two people without HIV infection. People with no HIV infection will not have HIV infected cells. Anything detected by the MRI/PET in these people will be due to background, non-specific, binding.

If the first tests are successful, study staff will recruit four people with untreated HIV infection. This will show whether the technique is able to find HIV when it is known to be present at detectable levels.

Staff will recruit a final four people if the MRI/PET method can find HIV in people with detectable levels of HIV in the blood. These final four participants will be people with HIV who are on treatment, with undetectable levels of HIV in the blood and see if the scan can detect the otherwise hidden HIV that remains in tissues.

Dr McMahon explains

this technique could mean we could assess the amount of remaining HIV in the organs or tissues of someone with HIV without needing to do invasive biopsies

What will the study involve for participants?

Eligible participants will have a total of six study visits.

A screening check will ensure eligibility and that the 3BNC117 antibody reacts with their virus. The screening visit can take place up to six weeks before the study begins.

The remaining five visits will take place over a two week period. These visits include three separate imaging visits (at the Monash Biomedical Imaging facility) and two follow-ups (at Alfred or Monash Health sites). Participants will get a single injection of the radiolabelled antibody and the first MRI/PET scan at the first of these visits. Participants will have a second scan 24 hours after the injection, and a third at 48 hours. Each MRI/PET scan takes 60 – 90 minutes. Study staff will collect blood samples at each of the study visits. These will enable tests to check that the antibody doesn’t interfere with normal functions.

How do I find out more?

Find study details at clinicaltrials.gov.

If you are interested in the study, please contact the Alfred Clinical Research Unit at gaclinresearch@alfred.org.au or 03 9076 6908