HIV Co-receptor usage in HIV-related non-hodgkin's lymphoma

Highly active antiretroviral treatment (HAART) has prolonged survival in HIV infected individuals [1], however, HIV associated malignancies remain relatively common [2]. Lymphoma is a frequent HIV-related malignancy [3], that generally presents in late HIV disease, possibly related to worsening immune function that allows latent Epstein Barr Virus (EBV) in memory B cells to generate a proliferative condition [4,5]. We considered what HIV factors may also play a role in lymphoma and noted that with later HIV disease stages the virus acquires CXCR4 co-receptor usage [6]. In early stage HIV infection, at most, only about 15% are dual/mixed (DM) tropic for CCR5 and CXCR4 [7,8], then in late disease stages, DM tropism or pure CXCR4 tropism reaches up to 60% when measured by the enhanced tropism assay [9], and is the highest with CD4 ≤ 200 cells/ml [10,11]. The chemokine receptor CXCR4 is also highly expressed in hematological malignancies [12,13]. The chemokine for CXCR4, stromal cell derived factor 1 (SDF1), has also been associated with HIV associated Non-Hodgkin's lymphoma (NHL) when individuals have a polymorphism in the SDF1 gene from G to A transition at position 801 (SDF1-3'A) that increased with homozygosity [14]. In North America, SDF1-3'A is expected in 21% of Caucasians [15]. Although there was some suggestion that SDF1-3'A is associated with HIV disease progression [16], and CXCR4 tropic virus [17]. Based on these observations, we examined whether HIV co-receptor usage and the SDF1 polymorphisms were associated with HIV-related NHL.A study protocol was submitted and approved to the AIDS and Cancer Specimen Resource (ACSR) to supply 16 samples of NHL from HIV-infected individuals that had plasma and PBMC samples at a time of viral load greater than 1000, the threshold required for the Trofile assay (Monogram Biosciences Inc.). An IRB approval was obtained to collect and test these samples with diagnosis, demographics, HIV viral load, CD4 count for each subject