Scientists have shown an association between the proportion of key immune cells and health outcomes. These cells display high levels of a gut-homing protein called alpha-4 beta-7 at the time of HIV infection.
Previous research illustrated this relationship in monkeys having a simian form of HIV. The new study found that women who had more CD4+ T cells were at risk of getting HIV. These cells had high levels of alpha-4 beta-7 on their surface. The virus damaged their immune systems more rapidly than women with fewer such cells.
Centre for the AIDS Programme of Research in South Africa (CAPRISA) conducted this study. South African Medical Research Council collaborated in this study. It is a part of the U.S.–South Africa Program for Collaborative Biomedical Research. National Institute of Allergy and Infectious Diseases (NIAID) also collaborated. It is a part of NIH. The report appears online in the journal Science Translational Medicine.
Having a high frequency of alpha-4 beta-7-expressing CD4+ T cells leads to more HIV-infected CD4+ T cells moving to the gut. Consequently, it leads to extensive damage to gut-based immune cells.
What did the researchers do?
The research team evaluated the percentage of CD4+ T cells in blood samples from 59 women shortly before they acquired HIV. These cells displayed high levels of alpha-4 beta-7. They compared the percentage to the percentage of such cells in 106 women who remained HIV negative. Aged 18 to 40 years, scientists selected the women from participants in the CAPRISA 004 study. It evaluated the safety and efficacy of tenofovir gel for HIV prevention in South Africa, from 2007 to 2010.
The proportion of CD4+ T cells with high levels of alpha-4 beta-7 had an effect on the risk of acquiring HIV among the participants. These participants included women in CAPRISA study and a separate cohort of 41 female sex workers in Kenya. The risk of HIV acquisition rose by 18 percent for each one percent increase in alpha-4 beta-7 protein. There was a similar association in vaginally exposed monkeys to a simian form of HIV.
What did the researchers find?
The proportion of CD4+ T cells with high levels of alpha-4 beta-7 affected how quickly HIV damaged the immune system. The cell levels declined among women with higher pre-infection levels of alpha-4 beta-7. It was a double decline among women with lower pre-infection levels. HIV was greater in women with higher levels of alpha-4 beta-7 than in women with lower pre-infection levels. The mechanism for the immune system damage likely was HIV-related damage to the gut. It was because higher pre-infection levels of alpha-4 beta-7 reflected higher levels of a biological marker of gut damage.
What does the study suggest?
HIV targets CD4+ T cells displaying alpha-4 beta-7 very early in infection. These findings suggest that interventions are necessary for restoring CD4+ T cells in the GI tracts of people living with HIV. One such intervention could be an anti-alpha-4 beta-7 antibody called vedolizumab.