XVIII International AIDS Conference

Abstract

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

K. Crawford1,2, X. Niu3, F. Farhat4, S. Nekhai3, C. Maxwell4, J. Kwagyan5

1Howard 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.


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