Improving healthspan in HIV

Advances in HIV treatment over recent years have greatly improved the longevity of people living with HIV (PLHIV) – highly potent antiretroviral therapies (ART) have enabled PLHIV to have lifespans comparable to HIV-negative people. However, their “healthspans” paint a different picture – PLHIV begin experiencing chronic health issues, like liver and heart disease, an average of 16 years earlier than HIV-negative people.

This disparity in the healthspans of HIV-positive and -negative individuals has been linked to ongoing inflammation, which persists despite an undetectable viral load achieved by ART. Recent research from the University of Montréal Hospital Research Centre has identified the gp120 protein as a driver of this inflammation.

Gp120 is present on the outer surface of HIV and aids the virus in infecting immune cells. Findings now suggest it may also contribute to chronic inflammation, heart disease and immune dysfunction. An analysis of gp120 levels in the plasma of 347 male and 39 female PLHIV, all with undetectable viral loads, revealed elevated levels in a third of them. These people were also more likely to present higher levels of inflammatory cytokines and low-grade coronary artery disease.

Further investigation using fostemsavir, a gp120 inhibitor marketed as RUKOBIA by ViiV for multi-drug resistant HIV, evidenced gp120 inhibition indeed reduces chronic inflammation biomarkers in PLHIV. This has incited funding of a two-year clinical trial to further asses if addition of fostemsavir to ART regimens can alleviate inflammation-linked comorbidities in PLHIV.

The trial is expected to commence in 2024 and if conclusive, it can lead to a paradigm shift in the current treatment landscape, paving way for personalized ART regimens for PLHIV with elevated gp120 levels and improving their quality of life.

Written by Zaraa Malvat