Excess inflammation linked to AIDS and other serious complications in adults on treatment for HIV

07 Mar 2024

Prolonged inflammation may increase the risk of serious medical complications in people living with HIV after they start treatment, according to new results from the global START clinical trial.

Higher average inflammation levels over several years were associated with a higher risk of developing opportunistic diseases associated with immunosuppression (known as AIDS), other serious non-AIDS complications or death while taking antiretroviral therapy (ART) for HIV. Delaying the start of treatment led to increased inflammation, which may contribute to higher rates of serious illness or death in people who start ART later. These findings were presented today at the 2024 Conference on Retroviruses and Opportunistic Infections.

Inflammation is part of the body’s immune defence mechanism to fight infections or heal injuries. However, prolonged inflammation which lasts for months or years can damage healthy cells, tissues and organs. HIV is a chronic infection which can lead to higher levels of inflammation over a long period of time. AIDS (acquired immune deficiency syndrome) can occur when the immune system is severely damaged by HIV.

The START trial began in 2009 and ran until 2021, involving 4,685 adults living with HIV from 35 countries. All START participants had relatively healthy immune systems when they entered the trial. Researchers randomly assigned half the participants to begin taking ART immediately, meanwhile the other half did not start treatment until their immune cell count dropped below a threshold or their HIV disease progressed.

In 2015, START revealed that starting ART immediately more than halved the rate of serious illness and death. Therefore, researchers advised all participants across both groups to begin treatment straight away. The trial also found that starting ART immediately lowered inflammation levels and the risk of serious complications. However, it was unclear if the extra risks associated with delaying treatment disappeared once participants began taking ART, or if the risk of complications remained higher after starting treatment because of prolonged inflammation.

In a sub-study of 2,114 START participants, researchers collected blood samples when participants first joined the trial, after 8 months and then annually. This allowed them to measure levels of two biomarker proteins which indicate high levels of inflammation. The team compared average biomarker levels over time in the immediate and delayed treatment groups. This timeframe included 2015, when patients in the delayed treatment group were starting ART. They also recorded all instances of AIDS, serious non-AIDS complications and death among START participants between 2016 and 2021, after the vast majority had started treatment.

They found that the delayed treatment group had higher average biomarker levels over several years, indicating prolonged inflammation. This was associated with higher rates of AIDS, other serious non-AIDS complications or death during six years of continuously taking ART.

The START team say the results should be interpreted with caution but emphasise the need to diagnose HIV and begin treatment early.

START was sponsored by the University of Minnesota. The MRC Clinical Trials Unit at UCL coordinated the work of the 215 START sites, along with the Copenhagen HIV Program at the Rigshospitalet, University of Copenhagen in Denmark; the Kirby Institute at the University of New South Wales in Sydney, Australia; and the Veterans Affairs Medical Center affiliated with George Washington University.

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