Current Efavirenz (EFV) or Ritonavir-Boosted Lopinavir (LPV/r) Use Correlates with Elevate Markers of Atherosclerosis in HIV-Infected Subjects in Addis Ababa, Ethiopia

<div><p>Background</p><p>HIV patients on antiretroviral therapy have shown elevated incidence of dyslipidemia, lipodystrophy, and cardiovascular disease (CVD). Most studies, however, focus on cohorts from developed countries, with less data available for these co-morbidities in Ethiopia and sub-Saharan Africa.</p><p>Methods</p><p>Adult HIV-negative (<i>n</i> = 36), treatment naïve (<i>n</i> = 51), efavirenz (EFV)-treated (<i>n</i> = 91), nevirapine (NVP)-treated (<i>n</i> = 95), or ritonavir-boosted lopinavir (LPV/r)-treated (<i>n</i>=44) subjects were recruited from Black Lion Hospital in Addis Ababa, Ethiopia. Aortic pressure, augmentation pressure, and pulse wave velocity (PWV) were measured via applanation tonometry and carotid intima-media thickness (cIMT) and carotid arterial stiffness, and brachial artery flow-mediated dilation (FMD) were measured via non-invasive ultrasound. Body mass index, waist-to-hip circumference ratio (WHR), skinfold thickness, and self-reported fat redistribution were used to quantify lipodystrophy. CD4+ cell count, plasma HIV RNA levels, fasting glucose, total-, HDL-, and LDL-cholesterol, triglycerides, hsCRP, sVCAM-1, sICAM-1, leptin and complete blood count were measured.</p><p>Results</p><p>PWV and normalized cIMT were elevate and FMD impaired in EFV- and LPV/r-treated subjects compared to NVP-treated subjects; normalized cIMT was also elevated and FMD impaired in the EFV- and LPV/r-treated subjects compared to treatment-naïve subjects. cIMT was not statistically different across groups. Treated subjects exhibited elevated markers of dyslipidemia, inflammation, and lipodystrophy. PWV was associated with age, current EFV and LPV/r used, heart rate, blood pressure, triglycerides, LDL, and hsCRP, FMD with age, HIV duration, WHR, and glucose, and cIMT with age, current EFV use, skinfold thickness, and blood pressure.</p><p>Conclusions</p><p>Current EFV- or LPV/r-treatment, but not NVP-treatment, correlated with elevated markers of atherosclerosis, which may involve mechanisms distinct from traditional risk factors.</p></div

Baseline characteristics, body composition.

<p>Continuous variables are reported as median (interquartile range). BMI = body mass index, and WHR = waist-to-hip ratio, mm = millimeters.</p><p>A, a = p<0.005 or p<0.05 versus HIV-negative controls, respectively;</p><p>B, b = p<0.005 or p<0.05 versus HAART-naive, respectively;</p><p>D, d = p<0.005 or p<0.05 versus EFV, respectively;</p><p>E, e = p<0.005 or p<0.05 versus NVP, respectively.</p><p>Baseline characteristics, body composition.</p

Preclinical markers of atherosclerosis are elevated in EFV-treated and LPV/r-treated subjects compared to HAART-naïve and NVP-treated.

<p>Wilcoxon rank sum test <i>p</i>-values are shown. *Note: Although the pairwise Wilcoxon rank sum test showed differences in cIMT between EFV- and LPV/r-treated and NVP-treated subject, ANOVA yielded a <i>p</i> = 0.12, which is above the defined criteria of <i>p</i><0.05 for statistical significance. When normalized to carotid artery diameter (cIMT-norm = cIMT/(<i>D</i>/2), where <i>D</i> = carotid diameter), EFV- and LPV/r-treated subjects exhibited significantly increased values compared to NVP-treated and HAART-naïve subject.</p

Cardiovascular metrics.

<p>Continuous variables are reported as median (interquartile range). bpm = beats per minute, mmHg = millimeters of mergury, SBP = systolic blood pressure, DBP = diastolic blood pressure, MP = mean preasure, PP = pulse pressure, AP = augmentation pressure, AIx = augmentation index, AIx = 75 = augmentation index, normalize to a heart rate of 75 bpm, mm = millimeters, kPa = kiloPascals, TC = total cholesterol, TG = triglycerides, HDL = high density lipoprotein cholesterol, LDL = low density lipoprotein cholesterol, hs-CRP = high sensitivity C-reactive protein, sICAM = soluble intercellular adhesion molecule-1, sVCAM = soluble vascular cell adhesion molecule-1, mg = milligrams, ug = micrograms, ng = nanograms, dL = deciliter, mL = milliliters.</p><p>A, a = p<0.005 or p<0.05 versus HIV-negative controls, respectively;</p><p>B, b = p<0.005 or p<0.05 versus HAART-naive, respectively;</p><p>D, d = p<0.005 or p<0.05 versus EFV, respectively;</p><p>E, e = p<0.005 or p<0.05 versus NVP, respectively.</p><p>Cardiovascular metrics.</p