A GLYCOMIMETIC COMPOUND INHIBITS DC-SIGN MEDIATED HIV INFECTION IN CELLULAR AND CERVICAL EXPLANT

Background: CXCR4 phenotype has been associated with increased severity of HIV disease, higher viral load, and decreased CD4 T-cell counts. We thus evaluated whether a genotypic analysis of coreceptor tropism impacts on HIV-related markers such as CD4-cell counts. Methods: 960 HIV-1 B subtype infected patients (all maravirocnaive) with an available V3 sequence were analyzed. Tropism determination was performed by using Geno2Pheno algorithm. All V3 mutations, including the mutations used for tropism prediction (Sing T et al., Antiviral Therapy 2007), with prevalence [1% were considered. The associations of CD4 cell counts with false positive rate (FPR) ranges and V3 mutations were evaluated by Mann– Whitney test, Chi-squared test for trend and Fisher exact test, as appropriate. The Benjamini–Hochberg method was used to identify results that were statistically significant in the presence of multiplehypothesis testing. A false discovery rate of 0.05 was used to determine statistical significance. Results: Overall, 26% of patients (either drug-naive or drug-experienced) were infected by X4 tropic viruses (using the classical 10% FPR cutoff). Among patients with available CD4 cell-counts at V3 genotypic test, 321 were drug-naive and 490 drug-experienced (median [IQR] CD4-cell counts: 331 [201–448] vs. 282 [138–422] cells/mm, p = 0.004). CD4 cell-count \200 cells/mm was observed in 80 drug-naive patients and in 169 drug-experienced patients. For different CD4 cell count ranges, FPR\2% was mostly associated, in experienced patients, with CD4 cell-counts \200 cells/mm (\200 vs. 200–350 vs. 350–500 vs. [500 cells/ mm: 21.3 vs. 7.6 vs. 9.0 vs. 8.0%, respectively, p = 0.0005). This finding was also observed in drug-naive patients, even if with less significance (11.3 vs. 6 vs. 2.6 vs. 1.5%, respectively, p = 0.040). A deeper analysis showed that patients with FPR \2% (both naive and drug-experienced) carried a significantly greater risk of having CD4 counts \200 cells/mm (see figure). Among all V3 mutations analyzed (87 in naive patients and 88 in experienced patients), in drug-experienced patients the X4-related S11R was the only mutation found associated with CD4 cell count \200 cells/mm (17.8 vs. 5.6% in \200 vs. [200 CD4, respectively, p \ 0.001). This significance was confirmed after correction for multiple comparisons. Conclusions: Within the context of genotypically-defined CXCR4 tropism, FPR \2% and the X4-related mutation S11R are associated with low CD4 rank, and thus may be related with a greater risk of disease progression. These findings suggest that FPR, beyond tropism prediction, can be used also as a marker to evaluate the immunological status of HIV-1 infected patients. CO 02 A GLYCOMIMETIC COMPOUND INHIBITS DC-SIGN MEDIATED HIV INFECTION IN CELLULAR AND CERVICAL EXPLANT MODELS A. Berzi*, S. Sattin, J. Reina, M. Sanchez-Navarro, J. Rojo, D. Trabattoni, P. Antonazzo, I. Cetin, A. Bernardi, M. Clerici Department of Clinical Science L. Sacco, University of Milan, Milan, Italy; Department of Organic and Industrial Chemistry, University of Milan, Milan, Italy; Instituto de Investigazione Quı́micas, University of Sevilla, Sevilla, Spain; Unit of Obstetrics and Gynecology, Hospital L. Sacco, Milan, Italy; Air of Immunology, University of Milan, Milan, Italy