Reports of HIV 'breakthrough' and 'cure' are premature

“HIV breakthrough could lead to a cure,” the Mail Online says, reporting on a study which looked at the phenomenon known as post-treatment control – where people with HIV remain in remission, even after treatment with antiretroviral (ARV) drugs is withdrawn.

In most people, once ARV is stopped HIV virus levels begin to increase. This process is referred to as “viral rebound”. But in a minority of people the levels of HIV remain at low, undetectable levels.

This study aimed to find cellular markers that would indicate the likely length of time to an HIV viral rebound after stopping ARV treatment. The research used data from 154 participants taken from previous research.

Researchers found people who had three specific types of biomarker associated with the destruction of immune cells called T cells (PD-1, Tim-3 and Lag-3) were significantly more likely to experience a rapid viral rebound.

Talks of a cure are far too premature, but finding out about what does and doesn’t help lead to post-treatment control, and so prevent viral rebound, is always going to be useful. 

Where did the story come from?

The study was carried out by researchers from a number of institutions, including John Radcliffe Hospital in the UK and the University of New South Wales, Australia. Funding was provided by the Wellcome Trust.

It was published in the peer-reviewed medical journal Nature Communications on an open-access basis, so it is free to read online.

The Mail Online article gives reliable coverage, with a number of useful quotes from the researchers. However, the word “cure” in the headline could give false hope – it is too early to call this a “breakthrough” or a “possible cure”, as these preliminary findings need further analysis in a larger trial.  

What kind of research was this?

This laboratory research used data from a subgroup of people in the SPARTAC trial to assess whether it was possible to identify biomarkers that could predict how long the HIV virus remains undetectable after antiretroviral treatment is stopped.

These drugs are usually given to try to control the virus and reduce it to undetectable levels. In some people virus levels remain at low, undetectable levels after they stop treatment, while they start to increase again in others.

This research aimed to try to find cellular markers that indicate the length of time viral levels would be controlled.

The SPARTAC trial was a randomised control trial that ran from 2003-11. It compared antiretroviral therapy for either 12 or 48 weeks in adults who had a newly acquired HIV infection.  

What did the research involve?

This study included 154 participants from the SPARTAC trial who had recently been infected with one of the more common strains of HIV (subtype B HIV-1) and had adequate blood samples available.

T cells are the particular immune cells that are attacked by the HIV virus. The researchers therefore selected 18 T cell biomarkers to assess as indicators of remaining HIV infection hidden in these cells (HIV reservoir).

The aim was to determine whether these biomarkers can be used to predict how long it would take for the virus to return to detectable levels when antiretroviral treatment was stopped.

As part of the main trial, participants’ blood samples were tested for the specified biomarkers before and after the treatment period. The findings were analysed in this study.  

What were the basic results?

The researchers carried out final analyses in 47 participants with available samples.

They identified three biomarkers (PD-1, Tim-3 and Lag-3) that were statistically significant predictors of viral rebound, both before and after adjustment for HIV virus levels at baseline and after treatment ended.

People with high levels of these three biomarkers were more likely to experience an earlier rebound after treatment had been stopped.

How did the researchers interpret the results?

The researchers concluded that, “We show that immunological biomarkers can predict time to viral rebound after stopping [antiretroviral therapy].”

They go on to say their results “may open new avenues for understanding the mechanisms underlying [post-treatment control], and eventually HIV-1 eradication”. 

Conclusion

This study aimed to identify cellular markers that could indicate the likelihood of rebound HIV infection in the weeks after stopping antiretroviral treatment.

It found three indicators of T cell exhaustion (PD-1, Tim-3 and Lag-3) taken from the participants’ blood samples before treatment could be strongly linked to how long it took for detectable HIV virus levels to return.

Antiretroviral therapy works by stopping the virus replicating in the body, allowing the immune system to repair itself and preventing further damage. However, it is not a cure – HIV remains “hidden” within the immune cells, even at low, undetectable levels.

For some people antiretroviral treatment allows extended periods where the virus remains undetectable after treatment has stopped (remission), but in others the infection rebounds quite quickly.

Identifying markers that predict the time to the viral rebound may increase our understanding of how the viral load increases and why this differs between people.

This study found levels of the PD-1, Tim-3 and Lag-3 markers measured before antiretroviral treatment strongly predicted how long it took for the virus to return.

But this study does have limitations. These include the small sample size, especially the number of participants available for final analysis: just 47. We do not know the reasons for the loss of participant data, but this may have altered the findings.

Despite the media mention of a “cure”, at this early stage it is too soon to know whether these findings could one day lead to the development of different treatments or treatment protocols targeted at people with different cellular profiles.  

The results could have an important practical implication for identifying people who can safely stop taking ARV drugs, at least short term. While these drugs are usually safe, they can cause side effects such as nausea and diarrhoea. They can also be expensive, especially for people in the developing world, where the burden of HIV is heaviest.

Using data from the SPARTAC trial provides preliminary data that can be used to design larger trials to explore these questions further.  

Links To The Headlines

HIV breakthrough could lead to a CURE: Scientists identify markers on immune cells that ‘predict who can stop drug therapy and stay well’. Mail Online, October 9 2015

Links To Science

Hurst J, Hoffmann M, Pace M, et al. Immunological biomarkers predict HIV-1 viral rebound after treatment interruption. Nature Communications. Published online October 9 2015