International AIDS Society

Immune Activation Limits Anti-HIV Effect of Tenofovir Gel in Women

Author: Mark Mascolini

12 September 2012

Activation of soluble and cellular immune mediators among South African women enrolled in the CAPRISA 004 study of vaginal tenofovir raised their risk of HIV acquisition. Analyzing findings from this case-control substudy of the CAPRISA 004 microbicide trial, researchers suggest “an innate immune activation suppressant could be added to tenofovir gel as a potential combination gel strategy in developing the next generation of higher efficacy antiretroviral microbicides.”

CAPRISA 004, a placebo-controlled trial of 1% tenofovir gel to prevent HIV acquisition in South African women, found that using the gel lowered HIV risk 39%. Because the protective effect rose only to 54% in women who used the gel most consistently, and because 1% tenofovir gel did not protect women from HIV in a larger trial, researchers are analyzing the limits of this strategy and seeking to improve it.

The case-control study involved plasma and peripheral blood mononuclear cell (PBMC) samples from 44 women who acquired HIV infection (cases) and from 37 women who did not become infected (controls). Samples from the HIV-infected cases came from the last HIV-negative visit from which samples were available. HIV-negative controls were selected if they reported high sexual exposure during the trial, and their samples came from the visit at which they reported the greatest sexual frequency in the preceding month.

Despite tenofovir use, women who acquired HIV had significantly higher systemic innate immune activation before infection than did women who remained free of HIV. Activation of soluble (cytokine) immune mediators and cellular (natural killer cell) immune mediators was associated with HIV acquisition. Compared with women who remained uninfected, those who acquired HIV also had higher levels of proinflammatory cytokines, platelets, and spontaneous cytotoxic T-cell degranulation in blood.

The authors “infer from these collective data that systemic innate immune activation enhances HIV acquisition, and thus modulating activation may provide a new strategy for improving the efficacy of antiretroviral agents in preventing HIV acquisition.”

Source: Vivek Naranbhai, Salim S. Abdool Karim, Marcus Altfeld, Natasha Samsunder, Raveshni Durgiah, Sengeziwe Sibeko, Quarraisha Abdool Karim, William H. Carr, and the CAPRISA004 TRAPS team. Innate immune activation enhances HIV acquisition in women, diminishing the effectiveness of tenofovir microbicide gel. Journal of Infectious Diseases. 2012; 206:993-1001.

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