Intriguing Monkey Study Suggests New Approach to HIV Cure

Most CD4 cells in the body reside in gastrointestinal tissues. A cell surface integrin called α4β7 helps guide CD4⁺ cells to the gut mucosa, where they are susceptible to infection and depletion by HIV or simian immunodeficiency virus (SIV). Now, in a study of monkeys infected with SIV, investigators have assessed whether an antibody against α4β7 can tip the balance toward immune control of the virus.

The researchers infected 18 rhesus macaques with SIV and, 5 weeks later, started the monkeys on antiretroviral therapy (ART). After the animals achieved an undetectable viral load, they received either an α4β7 antibody or a nonspecific, placebo antibody every 3 weeks, for eight infusions total. All treatment was then stopped.

As expected, the animals that received the placebo antibody had rapid viral rebound when ART was stopped. By contrast, eight animals that received the anti-integrin antibody maintained low-to-undetectable viral loads for more than 9 months after ART withdrawal. The animals that received the active antibody had restoration of CD4⁺ cells in the circulation and gastrointestinal tissues, perhaps because the virus was not depleting these cells. These animals also had an increase in the proportion of cytokine-synthesizing natural killer cells, indicating innate immune responses were being bolstered by the treatment.