Immune activation fostered HIV acquisition in women using tenofovir gel
New data from the CAPRISA trial indicate that suppressing innate immune activation could potentially be used as a combination strategy with tenofovir gel for the prevention of HIV transmission to women.
Previous study results are conflicted as to the role of immune activation in HIV acquisition, with some showing that it increases the risk and some showing it is protective.
“Our study showed that amongst women who acquired HIV in the CAPRISA004 tenofovir gel trial, systemic innate immune activation preceded acquisition, even after accounting for other factors linked to HIV acquisition,” Salim Abdool Karim, MD, PhD, director of CAPRISA and professor of clinical epidemiology, Mailman School of Public Health, Columbia University, told Infectious Disease News. “Since we know that non-specific immune activation makes target cells more infectable by HIV and may handicap specific immune responses, it seems plausible that systemic innate immune activation is in the causal pathway of HIV acquisition.”
Salim Abdool Karim
The researchers studied plasma and peripheral blood mononuclear cells (PBMCs) from 44 women who acquired HIV during the study and from 37 women who reported the highest sexual exposure but did not acquire HIV. Plasma samples were analyzed for 13 cytokines and PBMCs were analyzed for natural killer cell and T-cell activation.
Among those who acquired HIV, there were higher concentrations of the proinflammatory and T-cell homeostatic cytokines tumor necrosis factor alpha, interleukin-2, interleukin-7 and interleukin-12p70 compared with those who did not acquire HIV. In addition, these women had significantly higher platelet counts and higher proportions of activated natural killer cells.
“The imperative now is to elucidate this potential causal pathway and identify nodes where we may intervene,” Karim said. “We and others are now working to define what drives innate immune activation in women at risk for HIV. If we can identify these switches of activation, we could potentially try to turn them off.”
Disclosure: The researchers report no relevant financial disclosures.