About The Study

This pilot study explored how small bits of HIV, known as glycoprotein 120 or gp120, can remain present in the blood of people living with HIV on antiretroviral therapy, and whether they are associated with age-related conditions like cardiovascular disease. Researchers aimed to understand the effect of gp120 on the immune system and whether a treatment to limit gp120 could be appropriate in some people.

Background

People living with HIV taking antiretroviral therapy (ART) now have a life expectancy very close to that of their HIV-negative peers. However, people living with HIV develop age-related diseases, like cancer, heart disease, and diabetes, on average about 15 years earlier than people not living with HIV. One of the theories for this gap is the chronic inflammation caused by viral particles that continuously stimulate the immune system, despite consistent ART and viral suppression. Glycoprotein 120 is part of the HIV machinery that is needed for the virus to enter our cells. Previous research showed that gp120 can be shed from the viral membrane and accumulate in the blood of people living with HIV, causing immune dysfunction and negatively affecting CD4 cells. Scientists theorize that targeting gp120 could help reduce immune dysfunction and age-related diseases.

Fostemsavir, a type of ART reserved for people with highly resistant HIV, has been shown in the lab to prevent gp120 from negatively affecting the immune system. This means that it may be a potential treatment to help reduce harmful immune activation. However, this drug is very expensive so we need to identify who could benefit most from receiving it. Furthermore, aging with HIV is different in each person and we know very little about gp120 levels, how they vary with age and sex, how they change over time, and their exact effect on inflammatory diseases.

Study Approach

This study assessed gp120 levels and immune markers in biobanked samples of 386 people enrolled in the Canadian HIV and Aging Cohort Study (CTN 272). Previously collected cardiovascular imaging was also used from 145 people to assess the presence and extent of cardiovascular disease by measuring arterial plaque. All participants consented to the secondary use of this information. Researchers explored statistical associations between gp120 levels, immune dysfunction, and heart disease.

Results

Nearly 30 per cent of participants had detectable levels of gp120 and about 10 per cent of participants had noticeably high levels. People with high levels of gp120 had lower CD4 counts and CD4:CD8 ratios, and higher levels of inflammatory markers. In people with detectable levels of plaque in the arteries (a risk factor for heart disease), the total size of the plaques was correlated with gp120 levels.

Conclusion

Evidence from this study suggests that soluble gp120 may act as a ‘pan toxin,’ causing immune dysfunction and persistent inflammation in a portion of people living with HIV, contributing to the early development of age-related diseases. This means that, in some people, gp120 may be a good target for treatment using drugs like fostemsavir, but this needs to be tested in a large clinical trial before definitive conclusions can be made.