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Early Antiretroviral Therapy Does Not Improve Vascular Function: A START Substudy
Jason V. Baker1; Katherine Huppler Hullsiek2; Nicole Wyman Engen2; Daniel Duprez2; for the INSIGHT START (Strategic Timing of AntiRetroviral Treatment) Arterial Elasticity Substudy Team
1Hennepin County Med Cntr, Univ of Minnesota, Minneapolis, MN, USA;2Univ of Minnesota, Minneapolis, MN, USA
Both HIV infection and antiretroviral therapy (ART) may increase cardiovascular disease (CVD) risk. Assessments of vascular function can be used to study the pathogenesis and progression of CVD. We compared the effect of early ART initiation (CD4 counts >500 cells/mm3) with untreated HIV/deferred ART (until CD4 3) on small and large arterial elasticity (SAE and LAE) among a subset of ART-naïve adults in the START trial.
Radial artery waveforms were recorded non-invasively using a tonometer at baseline, months 4, 8, 12, and then annually. SAE and LAE were derived from analysis of the diastolic pulse waveform (CR2000, HDI). Randomized treatment groups (early vs. deferred ART) were compared with linear models at each visit and longitudinal mixed models overall. Additional analyses included censoring deferred group participants who started ART and for protocol-specified subgroups.
Among 332 participants at 21 sites in 8 countries on 6 continents: mean (SD) age was 35 (10), 70% male, 66% non-white, 30% smokers, 5% taking BP-lowering therapy, 3% taking lipid lowering therapy, and median [IQR] duration of HIV diagnosis 1.3 years [0.4, 3.1], CD4 count 625 cells/mm3 [562, 729], HIV RNA 4.2 log10 copies/mL [3.7, 4.7], and 10-year Framingham risk score for coronary heart disease 1.2% [0.3, 4.2]. Mean (SD) SAE and LAE values at baseline were 7.3 (2.9) mL/mmHg x100 and 16.6 (4.1) mL/mmHg x10, respectively. Median follow-up was 40 months. Median time on ART was 30 and 7 months in the early and deferred ART groups, respectively. Neither treatment group demonstrated significant within-person changes in SAE or LAE over follow-up. Differences in SAE and LAE between early and deferred ART over time are shown in the table. The lack of significant differences persisted in comparisons restricted to ≤1 (or >1) year of follow-up, after censoring participants in deferred group who started ART, and among subgroups defined by CVD and HIV risk factors.
Among a diverse global population of HIV+ persons with high CD4 counts, early ART initiation did not improve arterial elasticity. These randomized data suggest that early ART treatment may not have a substantial influence vascular function among younger HIV+ individuals with preserved immunity.