Reduced Immune Activation During Tenofovir–Emtricitabine Therapy in HIV-Negative Individuals

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Abstract

Background:

Elevated immune activation is associated with an increased risk of HIV acquisition. Tenofovir (TFV) has immunomodulatory properties in vitro, but how this extends in vivo remains unknown.

Methods:

HIV-negative adults received daily coformulated TFV disoproxil fumarate 300 mg/emtricitabine (FTC) 200 mg for 30 days followed by a 30-day washout. Markers of T-cell activation, inflammation, and cytokines were measured before drug and on days 30 (on drug) and 60 (30-day washout). Data were analyzed using one-way analysis of variance/pairwise comparisons. Intracellular disposition of TFV-diphosphate and FTC-triphosphate in CD4+ and CD8+ T-cells and monocytes was characterized, and the relationship with immune activation was evaluated using Pearson's correlation coefficient.

Results:

T-cell activation was available in 19 participants. CD38/HLA-DR coexpression on CD8+ T-cells decreased from baseline to day 30 (3.97% vs. 2.71%; P = 0.03) and day 60 (3.97% vs. 2.41%; P = 0.008). Soluble CD27 decreased from baseline to day 60 (184.1 vs. 168.4 pg/mL; P = 0.001). Cytokines and inflammation markers were not significantly different. TFV-diphosphate and FTC-triphosphate were approximately 4-fold higher in monocytes vs. CD4+ and CD8+ T-cells but neither correlated with activation markers.

Conclusions:

TFV disoproxil fumarate/FTC therapy was associated with decreased T-cell activation in HIV-negative adults, which could contribute to the antiviral effect of pre-exposure prophylaxis (NCT01040091; www.clinicaltrials.gov).

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