Reduced immune activation during tenofovir-emtricitabine therapy in HIV-negative individuals.

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).