Editor's Note

Several studies have introduced CRISPR-Cas9 as a prominent genome-editing technology. CRISPR was first established as a bacterial immune system and was later founded as a new genome-editing technology by Jennifer Doudna and colleagues around the turn of the decade. CRISPR is preceded by zinc-finger nucleases (ZFN) and transcription activator-like effector nucleases (TALENs); however, it improves upon these previous genome-editing designs by using RNA as its binding domain and by already containing nucleases—reducing the need to intentionally engineer these domains into the technology. Complementarity between the different RNAs (tracrRNA and crRNA) and protein aspects (Cas systems) of CRISPR act in conjunction to both efficiently assemble and confer its intended purpose. After extensive use in mammalian cell cultures and various model organisms, the CRISPR-Cas system has subsequently been used to mediate several genetic diseases such as sickle cell anemia and some cancers in humans. CRISPR-Cas9’s potential to mediate all other genetic mutations induced by sequence polymorphisms remains promising.

Objectives

In the general population, the lower socioeconomic status (SES) associates with greater systemic and arterial inflammation and a greater risk of cardiovascular disease. Because arterial inflammation is heightened in individuals living with HIV, we tested the hypothesis that SES associates with arterial inflammation in this population.

Settings

Prospective cohort study.

Methods

Men living with HIV were recruited. Arterial inflammation and leukopoietic activity (ie, bone marrow activity) were measured using 18F-fluorodeoxyglucose positron emission tomography/computed tomography. Zip code-level SES measures were derived from the US Census Bureau. Linear regression and mediation analyses were used to assess associations between SES, arterial inflammation, leukopoietic activity, C-reactive protein (CRP), and interleukin-6.

Results

Thirty-nine virologically suppressed men living with HIV were studied (mean ± SD age 50.5 ± 11.1 years). The median CD4 count was 663 cells/mm3 (interquartile range: 399-922); 82% were receiving antiretroviral therapies. Local median income inversely associated with arterial inflammation [standardized β (95% confidence interval): -0.42 (-0.76 to -0.08)] after adjusting for age, Framingham risk score, statin use, antiretroviral use, and nadir CD4 count. The high-school graduation rate independently associated with arterial inflammation [-0.45 (-0.78 to -0.12)] and CRP [-0.49 (-0.86 to -0.012)]. Mediation analysis demonstrated the impact of SES on arterial inflammation was partially mediated by heightened circulating inflammatory levels: ↓SES (as high school graduation rate) →↑CRP →↑arterial inflammation accounting for 44% of the total effect (P < 0.05).

Conclusion

In individuals living with HIV, lower SES independently associated with higher leukopoietic activity, circulating markers of inflammation, and arterial inflammation. Furthermore, the link between SES and arterial inflammation was mediated by increased systemic inflammation.