Association of Residual Plasma Viremia and Intima-Media Thickness in Antiretroviral-Treated Patients with Controlled Human Immunodeficiency Virus Infection

Abstract

BackgroundWhile residual plasma viremia is commonly observed in HIV-infected patients undergoing antiretroviral treatment (ART), little is known about its subclinical consequences.MethodsThis cross-sectional study included 47 male, never-smoking, non-diabetic patients with ≥4 years of ART and controlled HIV-replication (HIV-viral load, VL <20 copies/mL for ≥1 year). Residual HIV-VL was measured using an ultrasensitive assay (quantification limit: 1 copy/ml). Patients were categorized as having detectable (D; 1-20 copies/mL, n = 14) or undetectable (UD; <1 copies/mL, n = 33) HIV-VL. Linear regression was used to model the difference in total carotid intima-media thickness [c-IMT, measures averaged across common carotid artery (cca), bifurcation, and internal carotid artery] and cca-IMT alone across detection groups. Multivariable models were constructed for each endpoint in a forward-stepwise approach.ResultsNo significant differences were observed between viremia groups with respect to median ART-duration (9.6 years, IQR = 6.8–10.9), nadir CD4+T-cell (208/mm3, IQR = 143–378), and CD4+T-cell count (555/mm3, IQR = 458–707). Median adjusted inflammatory markers tended to be higher in patients with D- than UD-viremia, with differences in IL-10 being significant (p = 0.03). After adjustment on age, systolic blood pressure, and insulin resistance, mean cca-IMT was significantly lower in patients with undetectable (0.668 mm±0.010) versus detectable viremia (0.727 mm±0.015, p = 0.002). Cca-IMT was also independently associated with age and insulin resistance. Mean adjusted total c-IMT was no different between viremia groups (p = 0.2), however there was large variability in bifurcation c-IMT measurements.ConclusionsHigher cca-IMT was observed in patients with detectable, compared to undetectable, HIV-VL in never-smoking ART-controlled patients, suggesting that residual HIV viremia may be linked to atherosclerosis.

Association of Incomplete Adherence to Antiretroviral Therapy With Cardiovascular Events and Mortality in Virologically Suppressed Persons With HIV: The Swiss HIV Cohort Study

“…While a recent AIDS Clinical Trials Group study (A5321) did not find a correlation between residual viral replication (using single-copy assays) and residual inflammation, this analysis focused on a highly selected cohort of participants who had long-standing viral suppression (median, 7 years) and were originally enrolled in clinical trials [ 49 ]. In comparison, other studies in different cohorts have identified associations of residual viremia and HIV-DNA with inflammation [ 14 , 50 , 51 ] and with increased cardiovascular morbidity [ 26 , 27 ]. Given the well-established association between residual inflammation and morbidity/mortality in HIV [ 24 , 25 ], it remains plausible that suboptimal ART adherence could trigger episodes of residual HIV replication and heightened inflammation that result in adverse non-AIDS clinical outcomes despite virologic suppression in plasma.…”

INSTI-Based Triple Regimens in Treatment-Naïve HIV-Infected Patients Are Associated With HIV-RNA Viral Load Suppression at Ultralow Levels

“…As persistent residual viremia appears to impact immune activation, inflammation, and microbial translocation [24, 25], VLs at ultralow levels could bear some clinical importance. The ongoing presence of virus despite low viral concentrations could prevent some systemic inflammatory markers from returning to normal levels; however, the association between residual inflammation and residual HIV-1 replication is probably bi-directional and complex [26].…”

Cardiovascular Profile of South African Adults with Low-Level Viremia during Antiretroviral Therapy

“…Higher progression in carotid intima-media thickness was present in individuals with persistent non-suppressed viremia (>400 copies/mL) in a United States study [ 30 ]. Furthermore, persons with residual viremia (detectable VL < 20 copies/mL) had higher carotid intima-media thickness than those with undetectable VL in a French cross-sectional study [ 31 ]. However, in Brazilian PWH, higher cumulative exposure to viremia, measured as viremia-copy-years, was not associated with carotid intima-media thickness after adjustment for traditional risk factors such as smoking, body mass index, family history of CVD, and hypertension [ 32 ].…”