Progression of carotid intima-media thickness in a contemporary human immunodeficiency virus cohort

Abstract

Background: Persons with human immunodeficiency virus (HIV) infection are at risk for premature cardiovascular disease (CVD). Predictors of atherosclerotic disease progression in contemporary patients have not been well described.

Methods: Using data from a prospective observational cohort of adults infected with HIV (Study to Understand the Natural History of HIV/AIDS in the Era of Effective Therapy), we assessed common carotid artery intima-media thickness (CIMT) at baseline and year 2 by ultrasound. We examined HIV-associated predictors of CIMT progression after adjusting for age, sex, race/ethnicity, body mass index, smoking, hypertension, diabetes, low-density lipoprotein cholesterol level, and baseline CIMT using linear regression.

Results: Among 389 participants (median age at baseline, 42 years; male sex, 77%; median CD4+ cell count at baseline, 485 cells/mm³; 78% receiving antiretroviral therapy), the median 2-year CIMT change was 0.016 mm (interquartile range, -0.003 to 0.033 mm; P < .001). Lesser CIMT progression was associated with a suppressed viral load at baseline (-0.009 mm change; P = .015) and remaining virologically suppressed throughout follow-up (-0.011 mm change; P < .001). After adjusting for additional risk factors and a suppressed viral load during follow-up, nonnucleoside reverse transcriptase inhibitor versus protease inhibitor exposure was associated with lesser CIMT progression (-0.011 mm change; P = .02).

Conclusions: Suppressing HIV replication below clinical thresholds was associated with less progression of atherosclerosis. The proatherogenic mechanisms of HIV replication and the net CVD benefit of different antiretroviral drugs should be a focus of future research.

Figure 1.

Distribution of 2-year carotid artery intima-media thickness (CIMT) change among Study to Understand the Natural History of HIV/AIDS in the Era of Effective Therapy participants (n = 389). Histogram includes distribution of the 2-year change in CIMT.

Figure 2.

Two-year carotid artery intima-media thickness (CIMT) progression, human immunodeficiency virus (HIV) RNA viral load and baseline combined antiretroviral therapy (cART) use among Study to Understand the Natural History of HIV/AIDS in the Era of Effective Therapy (SUN Study) participants (n = 389). Median 2-year change in CIMT is plotted in mm for the following subgroups: SUN cohort overall (A, black square); participants stratified by suppressed viral load at all follow-up visits versus detectable viral load at ≥1 visit (A, dark gray diamonds); participants with a detectable viral load during follow-up stratified by cART use at baseline (A, dark gray triangles); participants receiving cART at baseline (B, white square); participants receiving cART stratified by exclusively nonnucleoside reverse-transcriptase inhibitor (NNRTI)–based versus protease inhibitor (PI)–based cART use at baseline (B, light gray diamond); participants receiving cART stratified by exclusively tenofovir versus abacavir use at baseline (B, light gray triangle). Error bars represent interquartile range for change. 1. Adjusted for age, sex, race/ethnicity, body mass index (defined as weight in kilograms divided by the square of height in meters), smoking status, hypertension, diabetes, low-density lipoprotein cholesterol (LDL-C), and baseline CIMT. 2. Adjusted for same covariates above and a suppressed viral load (<400 copies/mL) throughout follow-up. 3. Comparison excludes participants receiving both an NNRTI and a PI (n = 5) or those receiving neither (n = 105). 4. Comparison excludes participants taking both tenofovir and abacavir (n = 24) or neither (n = 182)

Figure 3.

Median carotid artery intima-media thickness (CIMT) progression among Study to Understand the Natural History of HIV/AIDS in the Era of Effective Therapy (SUN Study) participants (n = 274) stratified by viral suppression and combined antiretroviral therapy (cART). Median 2-year CIMT change is reported for the following subgroups of SUN participants: (a) nonnucleoside reverse-transcriptase inhibitor (NNRTI)–based cART use at baseline with a suppressed human immunodeficiency virus (HIV) RNA viral load throughout follow-up (white), (b) protease inhibitor (PI)–based cART use at baseline with a suppressed HIV viral load throughout follow-up (dark gray), (c) NNRTI-based cART use at baseline with ≥1 detectable HIV viral load during follow-up (light gray), and (d) PI-based cART use at baseline with ≥1 detectable HIV viral load during follow-up (black). In a multivariate model adjusting for traditional risk factors (see Table 3 for covariates), regression coefficients (95% confidence intervals) were: 0.009 mm (−.0003 to .018 mm; P = .059) for b versus a; 0.008 mm (−.004 to .022 mm; P = .174) for c versus a; 0.014 mm (−.0000 to .027 mm; P = .05) for d versus b; and 0.013 mm (−.003 to .030 mm; P = .112) for d versus c.