People who have a higher proportion of CD4 immune cells that have gut-homing proteins on their surface are at higher risk of contracting HIV and, if infected, of disease progression. Researchers hope this finding may help them develop an antibody treatment that can induce a state of viral remission.
Called alpha-4 beta-7, the protein causes the CD4 cells onto which it is attached to migrate toward the gut, an area of the body rich in immune cells that is a major target of HIV.
Publishing their findings in Science Translational Medicine, researchers compared the percentage of alpha-4 beta-7–displaying CD4 cells in blood samples taken from South African women participating in the CAPRISA 004 study. This study tested the safety and efficacy of a tenofovir-based gel for preventing HIV between 2007 and 2010.
The researchers analyzed blood samples taken from 59 women shortly before they contracted HIV and compared them with samples taken from women who did not contract the virus. The women ranged in age from 18 to 40 years old. The investigators also analyzed samples from a cohort of 41 female sex workers in Kenya.
For each 1 percent increase in the proportion of cells with alpha-4 beta-7, the women’s risk of HIV rose by 18 percent. Such an association was similar in experiments with primates exposed vaginally to a simian version of HIV.
After infection with the virus, the women who had higher preinfection levels of alpha-4 beta-7 saw their CD4 levels decline twice as fast as the women who had lower preinfection levels of the protein. Higher preinfection levels of the protein were also associated with a higher viral load a few months into infection. These differences were probably driven by the alpha-4 beta-7 protein guiding HIV-infected cells to the gut, where the ever-replicating virus caused greater damage.
Previous research conducted in Thailand has found that starting antiretrovirals (ARVs) very soon after an HIV diagnosis does not prevent a major drop in CD4 cells in the gut, nor does such prompt treatment ultimately cause a complete reversal of the loss of such cells.
Scientists recently began an early human trial of the alpha-4 beta-7–targeting antibody vedolizumab. In a primate study, a version of the antibody modified for monkeys led the near-complete restoration of CD4 cells in monkeys who had seen their immune cells destroyed by a simian form of HIV. The human trial will determine whether short-term treatment with vedolizumab combined with ARVs may lead to an extended period of a controlled viral load without the need for daily ARVs.
To read a press release about the study, click here.