Background:  There is continued interest about the level of risk for coronary artery disease in the setting of treated HIV infection. High sensitivity CRP (hs-CRP) levels have been shown to predict risk for coronary artery disease independent of other risk factors. There is little information on the impact of treatment of HIV infection on hs-CRP levels over time. Our objective was to measure baseline CRP levels prior to starting potent indinavir-based highly active antiretroviral therapy (HAART) and at subsequent time points in a cohort of study subjects with durable HIV suppression.

Methods:  A random sample of 99 durably suppressed indinavir treated subjects enrolled in ACTG 372A study subjects had CRP levels measured after an average of 42 months of HAART. Pre-HAART CRP levels were determined for 79 of the 99 during participation in an earlier study (ACTG 320) and an additional CRP value obtained after an average of 31 additional months of HAART was available for 56 of the subjects. The CRP values were assigned to coronary artery disease risk categories and evaluated for trends over time and association with demographic, surrogate marker, or metabolic parameters.

Results:  Pre-HAART (ACTG 320), mean/median CRP levels were 3.83/2.39 and the distribution of coronary artery disease risk was:  average = 19%, slightly increased = 14%, moderately increased = 19%, and high risk = 48%. At an average of 42 months of HAART, mean/ median levels were 4.08/2.29; coronary artery disease risk distribution: average = 22%, slightly increased = 15%, moderately increased = 13%, and high risk = 49%. At an average of 73 months of HAART, mean/median levels were 3.11/1.72; coronary artery disease risk distribution: average = 20%, slightly increased = 20%, moderately increased = 21%, high risk = 39%. For the subset of 50 subjects with CRP levels at all 3 points, the mean and median values were:  4.55/2.75, 4.83/2.19, and 3.32/2.03 (p = 0.02 by Friedman’s Multi-sample test for trend). For all subjects (n = 99), CRP levels at the second time point were correlated with higher fibrinogen levels, lower HDL levels, lower percentage of lymphocytes, higher white blood cell levels and fewer months on indinavir (all p <0.05).

Conclusions:  Indinavir-based HAART is associated with stable or decreasing hs-CRP levels over extended periods of exposure. In addition, CRP levels were correlated with some standard coronary artery disease or inflammatory risk factors. A high proportion of virologically suppressed HAART treated patients maintain their risk values of CRP despite successful treatment of HIV infection and ongoing medical care.

Keywords: C-reactive protein; coronary heart disease; indinavir