Abstract

Plasma cytokine concentrations are associated with HIV-1 viral tropism in treatment-naive black patients

K. Crawford^1,2, X. Niu³, F. Farhat⁴, S. Nekhai³, C. Maxwell⁴, J. Kwagyan<sup>5

1</sup>Howard University College of Medicine, Pharmacology, Washington DC, United States, ²Johns Hopkins School of Medicine, Clinical Pharmacology, Baltimore, United States, ³Howard University College of Medicine, Biochemistry, Washington DC, United States, ⁴Howard University College of Medicine, Infectious Diseases, Washington DC, United States, ⁵Howard University College of Medicine, General Clinical Research Center, Washington DC, United States

Background: HIV-1 utilizes either chemokine receptor CCR5 (R5-tropic) or CXCR4 (X4-tropic) to infect cells. The emergence of dual/mixed/X4-tropic virus is associated with accelerated immunologic decline and generally occurs in advanced disease. The factors that lead to the emergence of X4-tropic viruses are not well understood. We examined the relationship between cytokine concentration and tropism in a treatment-naïve cohort.
Methods: We studied 40 black patients from the Howard University Naïve Cohort (HUNC) entering care between 5/2007 and 7/2008. Plasma samples were collected prior to initiating HAART (when indicated). Plasma concentrations of cytokines/chemokines were determined by a multiplex cytokine kit using the Bio-Plex suspension array system (Bio-Rad, Hercules,CA). Median cytokine concentrations were compared using the Wilcoxon rank sum test between patients with R5 and dual/mixed/X4 virus. Logistic regression modeling was performed to examine the association of plasma cytokines and other covariates with tropism.
Results: Of 40 subjects enrolled, 36 were African-American (all clade B) and 4 were African (3 clade C, 1 clade F2), 57.5% were male, and 10 HIV-controls. 42% of subjects (all clade B) had dual/mixed virus by enhanced Trophile (Monogram Biosciences, CA). Differences in median cytokine concentrations for R5-tropism vs. dual/mixed-tropism were observed for IL-4 (1.73 vs. 1.28 pg/ml, p=0.036), IL-5 (2. 5 vs. 1.7pg/ml , p=0.078), IL-7 ( 4.84 vs. 2.69 pg/ml , p=0.01) , IL-8 (8.24 vs. 3.26 pg/ml , p=0.01) and γ-interferon (87.9 vs. 41.31, p=0.006, ). The selected multivariate model showed that the odds of having dual/mixed tropism were associated with decreased IL-7(OR=0.51, CI=0.28-0.9,p=0.028) an increase in age (1.19,1.0-1.43, p=0.05) and an increase in HIV RNA (1.00, 0.99-1.00, p=0.23); pseudoR²=0.62.
Conclusions: Plasma cytokine concentration and age may influence the evolution of viral tropism in naive patients. These findings should be confirmed in larger sample sets . Cytokine dyrsegulation may result from immune activation, medical co-morbidities or genetic polymorphisms.