Pentoxifylline, inflammation, and endothelial function in HIV-infected persons: a randomized, placebo-controlled trial

Abstract

Background: Untreated HIV may increase the risk of cardiovascular events. Our preliminary in vitro and in vivo research suggests that pentoxifylline (PTX) reduces vascular inflammation and improves endothelial function in HIV-infected persons not requiring antiretroviral therapy.

Methods: We performed a randomized, placebo-controlled trial of PTX 400 mg orally thrice daily for 8 weeks in 26 participants. The primary endpoint was change in flow-mediated dilation (FMD) of the brachial artery after 8 weeks. Nitroglycerin-mediated dilation (NTGMD) and circulating markers of inflammation, cellular immune activation, coagulation, and metabolism were also assessed.

Results: The difference in mean absolute change (SD) in FMD after 8 weeks between the placebo [-1.06 (1.45)%] and PTX [-1.93 (3.03)%] groups was not significant (P = 0.44). No differences in NTGMD were observed. The only significant between-group difference in the changes in biomarkers from baseline to week 8 was in soluble tumor necrosis factor receptor-1 (sTNFRI) [-83.2 pg/mL in the placebo group vs. +65.9 pg/mL in the PTX group; P = 0.03]. PTX was generally well-tolerated.

Conclusions: PTX did not improve endothelial function and unexpectedly increased the inflammatory biomarker sTNFRI in HIV-infected participants not requiring antiretroviral therapy. Additional interventional research is needed to reduce inflammation and cardiovascular risk in this population.

Trial registration: ClinicalTrials.gov NCT00796822.

Conflict of interest statement

Competing Interests: SKG reports having received unrestricted research grant support from Gilead Sciences, Inc., Merck & Co., and Janssen (Tibotec) Therapeutics and receives consultant fees from Bristol-Myers Squibb. MPD reports having received research grant support from ViiV Healthcare/GlaxoSmithKline and grant support from Serono. CKS reports having received statistical consulting fees from Merck & Co. and serves on a Data and Safety Monitoring Committee for Merck & Co. JHS serves on the Data and Safety Monitoring Committees for Abbott, Lilly, and Takeda. KJM reports having received research support for unrelated projects from Merck & Co. All other authors have declared that no competing interests exist. This does not alter the authors’ adherence to all the PLOS ONE policies on sharing data and materials.

Figures

Figure 1. Flow of participants through the trial.

Figure 2. Changes in flow-mediated dilation (FMD) of the brachial artery and soluble tumor necrosis factor receptor-1 (sTNFRi) from baseline to week 8.

Panel A shows the changes in FMD; Panel B shows the changes in sTNFRI. Circles indicate actual values. Top and bottom of boxes indicate 75th and 25th percentiles, respectively. Internal horizontal lines indicate median values and plus-signs indicate mean values. External horizontal lines/whiskers indicate 25th or 75th percentiles ± (1.5 times interquartile range).

Figure 3. Individual changes in FMD by treatment group (pentoxifylline vs. placebo) and by sex (female vs. male).