The Role of Killer T Cells in an HIV Cure Strategy

Key points

• HIV treatment works—but isn’t a cure. Modern medications can control HIV and keep people healthy for life. But if someone stops taking the medicine, the virus almost always comes back.
• Hidden HIV in the body makes curing the virus difficult. Even when treatment is working, small amounts of HIV stay hidden inside certain cells. Some of this hidden virus can restart infection, and some may still cause inflammation in the body.
• Starting treatment very early makes a big difference. People who begin HIV treatment soon after infection have much smaller amounts of hidden virus, which may improve their chances of controlling HIV long-term without daily medication.
• Certain immune cells help fight hidden HIV. A type of immune cell called CD8+ “killer” T cells can find and destroy HIV-infected cells. Strong early activity from these cells was linked to bigger reductions in hidden HIV over time.
• Future cure efforts may focus on boosting the immune system early. The study suggests that strengthening these immune cells as soon as possible after infection could be an important part of developing an HIV cure strategy.

A new amfAR-funded study provides more insights about what an HIV cure strategy might need to be effective.

People living with HIV can expect to live long, healthy lives thanks to effective antiretroviral therapy (ART). ART suppresses the virus and halts disease progression, but the treatment must be taken for life.

If ART is stopped, the virus almost always rebounds.

Rebound is possible because of the presence in the reservoir of intact proviruses, which can form infectious viruses when activated. But the reservoir is also made up of “defective” proviruses—fragments of HIV DNA which do not produce infectious viruses but play a role in potentially harmful immune activation.

With the virus always ready to rebound, the HIV reservoir remains the main barrier to curing HIV, either by eliminating HIV from the body or controlling the virus long-term.

In order to remove this barrier, scientists need to know more about the HIV reservoir, which is established very early in HIV infection. One focus of investigation is the size of the reservoir.

Reducing the size of the reservoir

Multiple studies have shown that starting ART early—during what’s called the “acute HIV infection”—significantly reduces the size of the reservoir. A smaller reservoir not only decreases chronic inflammation caused by HIV-infected cells but will also make long-term remission without treatment more likely.

In this study, researchers sought to fill in a knowledge gap about early immune responses—in particular, HIV-specific CD8+ “killer” T cells—during early treatment during acute HIV infection. HIV-specific CD8+ “killer” T cells, as their name suggests, identify, attack, and kill HIV-infected cells.

The study aims to understand the role of these T cells in how the reservoir develops and persists.

Why HIV-specific CD8+ “killer” T cells?

Researchers are interested in HIV-specific CD8+ “killer” T cells because studies have shown their responses are strongly associated with controlling the virus’s presence in the blood. The authors of the study point out that strong HIV-specific CD8+ T-cell responses have been shown to control HIV replication without ART in people who have been found to control HIV naturally.

In the study, the size of the HIV reservoir, in terms of intact proviruses and “defective” proviruses, was assessed in 22 men, mean age 38 years.

Twenty of the 22 men started ART within two days of symptoms of an acute HIV infection. HIV-specific CD8+ T cell responses at start of therapy and 6 months and 3 years later were also assessed.

A significant reduction in total and defective HIV DNA, and a trend towards a decrease in intact HIV DNA, were observed at 6 months and 3 years. The response of those T cells to HIV proteins in the test tube, assessed at 6 months, was predictive of the degree in reduction in total and defective HIV DNA at 6 months and 3 years.

This indicates that HIV-specific CD8+ T cells have a role in controlling and reducing the HIV reservoir.

Next steps

The authors conclude that their data suggest that “enforcing HIV-specific immune responses as early as possible after diagnosis of AHI [acute HIV infection] should be a central focus of HIV cure strategies.“

Dr. Laurence is amfAR’s senior scientific consultant.

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