Association of Endothelial Dysfunction and Antiretroviral Therapy in Early HIV Infection
Authors: Kelvin N. V. Bush, Julie L. Teel, James A. Watts, Rosco S. Gore, Gadiel Alvarado, Nathan L. Harper, Jason F. Okulicz
Journal: JAMA Network Open (2019)

<h3>Importance</h3> Human immunodeficiency virus (HIV) infection is associated with increased cardiovascular disease (CVD) events. Endothelial dysfunction (EDF) is involved in CVD pathogenesis; however, EDF onset after HIV acquisition and the potential for reversibility with antiretroviral therapy (ART) have not been evaluated to date. <h3>Objective</h3> To evaluate endothelial function with noninvasive reactive hyperemia index (RHI) in patients with early HIV infection at baseline and after ART initiation. <h3>Design, Setting, and Participants</h3> Cohort study in which 61 members of the United States Air Force diagnosed with HIV infection from September 1, 2015, through September 30, 2017, were evaluated for baseline EDF. Natural log–transformed RHI values (lnRHI) of less than 0.51 and at least 0.51 were defined as abnormal and normal, respectively. The RHI interval changes were evaluated in a subgroup of 40 patients. Data were analyzed from September 30, 2017, through January 30, 2018. <h3>Exposure</h3> Early HIV infection. <h3>Main Outcomes and Measures</h3> Baseline EDF at HIV diagnosis and interval changes associated with ART initiation. <h3>Results</h3> The 61 patients included in the analysis were predominantly male (58 [95%]) and mostly African American (35 [57%]), with a mean (SD) age of 28.1 (6.7) years at HIV diagnosis. Median time from estimated date of HIV seroconversion to RHI assessment was 10.6 months (interquartile range [IQR], 5.1-13.2 months), and the median CD4 lymphocyte count was 552/μL (IQR, 449/μL-674/μL). Patients had a mean (SD) body mass index of 26.2 (4.0), median (IQR) low-density lipoprotein cholesterol level of 97 (80-126) mg/dL, median (IQR) total cholesterol level of 163 (146-195) mg/dL, and no diabetes diagnoses. Overall mean (SD) lnRHI was 0.70 (0.29) at HIV diagnosis. Baseline RHI was normal in 47 patients (77%; mean [SD] lnRHI, 0.82 [0.20]) and was abnormal in 14 patients (23%; mean [SD] lnRHI, 0.30 [0.18]). Age (per 10-year increase) was not associated with an abnormal lnRHI (odds ratio, 2.15; 95% CI, 0.89-5.19;<i>P</i> = .09). Of the 41 patients with follow-up RHI assessments, 40 started ART immediately and repeated the RHI assessments at a median (IQR) of 6.4 (6.0-7.8) months. Use of ART was associated with an overall significan increase in mean (SD) lnRHI (0.13 [0.33];<i>P</i> = .02). A greater increase in mean (SD) lnRHI was associated with abnormal (n = 11) compared with normal (n = 29) lnRHI at HIV diagnosis (0.33 [0.34];<i>P</i> = .01 vs 0.04 [0.30];<i>P</i> = .38). Among those with abnormal baseline lnRHI, 8 (73%) showed improved endothelial function after ART. The patient who declined ART converted from having a normal lnRHI (0.60) to an abnormal lnRHI (0.11) lnRHI after 8.3 months. <h3>Conclusions and Relevance</h3> In this study, EDF was common in early HIV infection, with associated reversal in most patients taking ART. Results suggest that persistent EDF and CVD complications may be associated with delayed ART. Further studies are necessary to define the role of noninvasive endothelial function testing in patients with HIV infection.