Early treatment may hold key to HIV 'functional cure'

BBC News reports that one in 10 people diagnosed with HIV who receive early treatment could be 'functionally cured'. The news is based on a French study that found 14 people achieved a functional cure three months after they started treatment for HIV. Once treatment stopped, the researchers found that the patients' viral levels were controlled and their immune systems remained stable for just over seven years.

The researchers compared the 14 patients with other people infected with HIV, including patients who also started early treatment but did not respond as positively. They identified various differences among the patients, including important differences in their immune systems.

The news follows a recent story about a baby born with HIV who achieved a functional cure following aggressive early treatment. 

A functional cure means that the HIV virus is still present in the body but at such low levels that it can no longer be detected by standard blood tests. HIV treatment aims to achieve this, as the disease is less likely to progress and the long-term outlook for patients is improved. 

More research is needed to understand how and why a functional cure can be achieved in some people, and whether it can be extended to more people with the disease.

Where did the story come from?

The study was carried out by researchers from Unité de Régulation des Infections Rétrovirales, Paris, and other institutions in France, and was funded by the ANRS and the French National Agency for Research on AIDS and Viral Hepatitis.

It was published in the peer-reviewed scientific journal PLOS Pathogens, which is published on an open access basis (freely available for download).

The media coverage of the study must be read in the correct context: the researchers have reported the experiences of a select sample of 14 people who managed to achieve a functional cure with early treatment.

This does not represent a new treatment or cure for HIV. Rather, it is an examination of the characteristics of a select sample of people who achieved the optimal response to existing HIV treatment.

Reports that "one in 10 people could be functionally cured" are slightly misleading. It comes from the researchers' estimate that between 5 and 15% of people who successfully respond to antiretroviral therapy and come off treatment would be able to maintain control of their viral levels (a functional cure) for about two years, like the people in this study. It does not mean that one in 10 people with HIV can be functionally cured.

What kind of research was this?

This was a case series reporting on 14 individuals infected with HIV whose virus levels remained controlled at low levels for several years, even after stopping their long-term antiretroviral treatment.

HIV is treated with a combination of antiretroviral drugs. Antiretroviral therapy (ART) is not considered to be a cure for HIV, but aims to stop the virus replicating and reduce its levels so that they cause less harm to the body's immune system.

The overall aim of ART is to reduce the viral load (the number of particles of HIV present in each millilitre of blood) to levels that can no longer be detected by standard blood tests (undetectable levels). If this is achieved and the virus can no longer be detected on standard tests, this is known as a functional cure.

It is called a functional cure because the virus has not completely gone from the body and can still be detected at very low levels on extremely sensitive tests. However, a person with a functional cure should have a good life expectancy and a reduced risk of the disease progressing or developing associated complications. A person with HIV normally has to continue on ART long-term to prevent viral levels from increasing again (viral rebound).

One of the factors that researchers say can have an influence on the success of treatment is how soon people start treatment after they acquire the infection.

This study reports on a small number of people with HIV who started ART very early and were later able to come off it, with the virus continuing to be controlled at undetectable levels for several years, even without treatment. The researchers say that these people may "hold important clues in the search for a functional HIV cure".

What did the research involve?

The researchers identified 14 people who started ART early. These people were able to come off treatment as they had achieved a functional cure. The people were all diagnosed in the late 1990s or early 2000s.

The researchers looked at the characteristics of these 14 'responders', including when their levels became undetectable, how long they were treated for, and how long their levels remained undetectable off treatment.

They compared them with three other groups:

• people who also received early treatment but did not respond
• people who started treatment later, which is representative of many people affected by HIV
• eight people whose bodies naturally spontaneously controlled their HIV levels (likely due to some factor in their own biology rather than due to early treatment – these people are thought to be rare)

What were the basic results?

In the first two months after being infected with HIV, the 14 responders had similar amounts of the HIV virus in their blood (viral load) compared with those who did not respond to early treatment. However, they had higher viral levels than those whose bodies managed to spontaneously control their HIV levels.

The 14 people received the standard combination ART that was available at the time, and their viral levels became undetectable an average of three months after treatment began. The average duration of ART was 36.5 months, and during this time almost all but two of these people demonstrated an increase in the levels of a particular immune cell HIV normally targets (CD4 cells).

After stopping treatment, their viral levels remained controlled and CD4 levels remained stable for around 89 months. During this time, eight of the people had levels that remained undetectable on all tested blood samples, while for six people there were occasional increases.

They found several other differences between the 14 responders, the spontaneous controllers, and people who did not respond to early treatment or who started treatment late. For example, the functioning of certain immune cells in the responders differed from that of the spontaneous controllers.

They also found that, like spontaneous controllers, the responders had lower levels of HIV genetic material in their blood during treatment compared with those who did not respond to early treatment or who were late starting treatment.

The differences observed between the 14 responders and the spontaneous controllers suggested that the way these two groups achieve HIV control is through at least partly different ways.

The researchers estimated that about 15% of people who achieve undetectable HIV levels with ART and come off treatment would be able to maintain control of their viral levels (a functional cure) for about two years. 

How did the researchers interpret the results?

The researchers say that their results show that early and prolonged combined ART may allow some individuals to achieve undetectable HIV levels that can be controlled for several years without treatment. They say that these people "may hold important clues about a functional cure for HIV".

Conclusion

While such a case series suggests that it is possible that some people can have a functional cure from early HIV treatment, only a very small sample of people with HIV experienced this. Although maintaining HIV at undetectable levels in the body even without treatment is the ultimate goal for all people with HIV, it may not be possible in all people.

Whether an individual is able to achieve a functional cure from HIV may be influenced by various things, such as:

• how soon after infection they started treatment
• which drug regimen they received (in the developing world obtaining access to the most effective combinations may be more difficult)
• compliance with drug regimens
• the person's individual biology and how they respond to treatment 

A small number of people infected with HIV (less than 1%) are somehow able to spontaneously control their HIV levels at undetectable levels. This is likely to be due to some factor in their biological make-up. As the researchers say, this makes it difficult to translate their mechanisms of control to other people.

The group of 14 individuals who are the focus of the current study achieved long-term viral control, which appears to at least partly be a result of early ART treatment. This may offer useful information that could help researchers translate their success to other people. For example, if achieving a functional cure depends on how soon people start treatment after becoming infected, it could be a finding that could have a huge impact on HIV treatment.

However, even though starting treatment early seems achievable, this may not always be possible as it relies upon knowing that infection has occurred. This is likely to rely on factors such as the person developing symptoms when they first contract the infection (this can often be a mild flu-like illness), or the person being aware that they could have been exposed to the virus.

For many people with HIV, early treatment is not possible, as they only find out they have the condition when HIV has already damaged their immune system to the point where they start becoming ill. This may be many years, and even up to a decade, after they first contracted HIV.

This is why it is important to get regular HIV tests if you are in a high-risk group for HIV. Read more about HIV testing.

This study unfortunately does not present a complete cure for HIV, but a functional cure where early antiretroviral treatment was able to reduce the viral load of HIV to undetectable levels. This is the ultimate aim of all antiretroviral treatment: preventing the disease from progressing and giving people a positive outlook and a good life expectancy.