Advertisement

 

 

Analysis of the Endogenous Deoxynucleoside Triphosphate Pool in HIV-Positive and -Negative Individuals Receiving Tenofovir-Emtricitabine.

Analysis of the Endogenous Deoxynucleoside Triphosphate Pool in HIV-Positive and -Negative Individuals Receiving Tenofovir-Emtricitabine.
Author Information (click to view)

Chen X, Castillo-Mancilla JR, Seifert SM, McAllister KB, Zheng JH, Bushman LR, MaWhinney S, Anderson PL,


Chen X, Castillo-Mancilla JR, Seifert SM, McAllister KB, Zheng JH, Bushman LR, MaWhinney S, Anderson PL, (click to view)

Chen X, Castillo-Mancilla JR, Seifert SM, McAllister KB, Zheng JH, Bushman LR, MaWhinney S, Anderson PL,

Advertisement
Share on FacebookTweet about this on TwitterShare on LinkedIn

Antimicrobial agents and chemotherapy 2016 08 2260(9) 5387-92 doi 10.1128/AAC.01019-16

Abstract

Tenofovir (TFV) disoproxil fumarate (TDF) and emtricitabine (FTC), two nucleos(t)ide analogs (NA), are coformulated as an anti-HIV combination tablet for treatment and preexposure prophylaxis (PrEP). TDF/FTC may have effects on the deoxynucleoside triphosphate (dNTP) pool due to their similar structures and similar metabolic pathways. We carried out a comprehensive clinical study to characterize the effects of TDF/FTC on the endogenous dNTP pool, from baseline to 30 days of TDF/FTC therapy, in both treatment-naive HIV-positive and HIV-negative individuals. dATP, dCTP, dGTP, and TTP were quantified in peripheral blood mononuclear cells (PBMC) with a validated liquid chromatography-tandem mass spectrometry (LC-MS/MS) methodology. Forty individuals (19 HIV-positive) were enrolled and underwent a baseline visit and then received TDF/FTC for at least 30 days. Longitudinal measurements were analyzed using mixed-model segmented linear regression analysis. The dNTPs were reduced by 14% to 37% relative to the baseline level within 3 days in both HIV-negative and HIV-positive individuals (P ≤ 0.003). These reductions persisted to various degrees at day 30. These findings indicate that dNTP pools are influenced by TDF/FTC therapy. This may alter cellular homeostasis and could increase the antiviral effect through a more favorable analog/dNTP ratio. Further work is needed to elucidate mechanisms, to evaluate the clinical significance of these findings, and to further probe differences between HIV-negative and HIV-positive individuals. (This study has been registered at ClinicalTrials.gov under identifier NCT01040091.).

Submit a Comment

Your email address will not be published. Required fields are marked *

three × 1 =

[ HIDE/SHOW ]