High Levels of Gut-Homing Protein Cause More Severe HIV Impacts

Lyle McKinnon, PhD, University of Manitoba

Lyle McKinnon, PhD

A new study finds that when CD4+ T cells show high levels of a gut-homing protein, the patient faces a higher risk of HIV infection, and is likely to experience more rapid immune system damage.

The study, led by researchers from the National Institutes of Health and the South African Medical Research Council, focuses on the protein alpha-4 beta-7 (a4b7) protein as a culprit in exacerbating negative outcomes from HIV exposure.

“Our findings suggest that having a high frequency of alpha-4 beta-7-expressing CD4+ T cells, which HIV preferentially infects, leads to more HIV-infected CD4+ T cells moving to the gut, which in turn leads to extensive damage to gut-based immune cells,” said Anthony S. Fauci, MD, co-author, director, National Institute of Allergy and Infectious Disease, NIH, in a press release.

The study looked at a4b7 levels in 165 South African women ages 18 to 40. Of those, 59 would become HIV-infected shortly after the samples were taken, while the other 106 women remained HIV-negative. The researchers also looked at a cohort of 41 sex workers in Kenya.

In both the South African and Kenyan cohorts, the risk of HIV infection increased with the level of a4b7 proteins present. Specifically, each 1% increase in a4b7 led to an 18% increase in HIV infection risk.

However, the more striking finding came from tracking disease progression. CD4+ T cell levels declined twice as fast in women with high levels of a4b7 compared to women with low levels of the protein. The researchers also found that the amount of virus present in the blood in the months following infection was higher in the women with the higher a4b7 levels.

According to the research, HIV targets CD4+ T cells with high levels of a4b7, particularly those in the gut, early on in infection. Data from a separate study showed that this depletion of CD4+ T cells occurred even when antiretroviral therapy (ART) was initiated shortly after infection.

Lyle McKinnon, PhD, University of Manitoba, told MD Magazine the findings suggest that these patients might require supplemental treatment in addition to antiretroviral therapy.

“Gut homing tends to be impaired in HIV infection and not corrected by ART — not just for a4b7 but for other gut-homing receptors such as CCR9,” he said. “In our paper we also show that the a4b7+ cells in the gut are not restored, even after 2 years of ART. This is why ART plus a4b7 is being considered — and in non-human primates, this treatment was associated with CD4 restoration.”

McKinnon said it’s not known for sure why some people have higher levels of a4b7 than others, and the study underlying the new data wasn’t designed to find that out. He said there’s some evidence to suggest that African-Americans have higher expression of a4B7, and other research has suggested that Herpes Simplex Virus Type 2 is associated with higher a4B7 levels. More work is needed in the area to better understand why and how these levels differ, said McKinnon.

The study titled, “Integrin a4b7 expression on peripheral blood CD4+ T cells predicts HIV acquisition and disease progression outcomes” was published last month in Science Translational Medicine.

Related Coverage >>>

The Spleen is a "Sanctuary" for HIV Despite Successful Viral Suppression with cART

FDA Approves Bictegravir/FTC/TAF Combination HIV Therapy

Rural Adults with HIV Saw Depression Symptoms Drop with Tele-Counseling