1. Viral tropism by geno2pheno as a tool for predicting CD4 decrease in HIV-1 infected naïve patients with high CD4 counts Viral tropism by geno2pheno as a tool for predicting CD4 decrease in HIV-1 infected naïve patients with high CD4 counts Nozza S 1, Canducci F 2, Galli L 1, Cozzi-Lepri A 3, Capobianchi MR 4, Ceresola E 2, Antinori A 3,4, Di Giambenedetto S 3,5, D’Arminio Monforte A 3,6, Castagna A 1,3 and ICONA Foundation 1 Department of Infectious Diseases - IRCCS San Raffaele, Milan, Italy 2 Laboraf, San Raffaele Scientific Institute, Milan, Italy 3 ICONA Foundation, Italy 4 IRCCS Spallanzani, Rome, Italy 5 Catholic University, Rome, Italy 6 Azienda Ospedaliera San Paolo, Milan, Italy TUPDB0103

2. AIM OF THE STUDY To investigate the value of a geno2pheno estimate of viral tropism in predicting CD4+ depletion in HIV-infected naive subjects with high CD4+. Multicenter, cohort study with retrospective assessment of viral tropism on stored plasma samples METHODS  Included HIV-1 naive infected patients with:  CD4+>350 cells/mm 3 at time of first sample  HIV-RNA>500 copies/mL  Follow-up time ranged from the date of first available plasma sample (baseline) to the date of the last visit or the date of cART initiation.  HIV-1 coreceptor usage was determined by algorithm geno2pheno, available at http://coreceptor.bioinf.mpi- inf.mpg.de/, with a cut-off of false-positive rate (FPR) of 10%.

3. Baseline characteristics Median values (IQR) or n (%) Characteristics OVERALL (N=223) R5 (FPR>10%) (N=192) Non-R5 (FPR≤10%) (N=31) P value ( R5 vs non-R5) Age at sample collection (years) 35 (31-40)35 (31-41)33 (30-37)0.183 Nationality Italian Other 211 (95%) 12 (5%) 181 (94%) 11 (6%) 30 (97%) 1 (3%) 0.998 Gender Female Male 86 (39%) 137 (61%) 75 (39%) 117 (61%) 11 (35%) 20 (65%) 0.843 Risk factor for HIV IVDU Heterosex 99 (44%) 124 (56%) 81 (82%) 111 (90%) 18 (18%) 13 (11%) 0.120 Calendar year of HIV infection1997 (1992-2002)1997 (1993-2002)1996 (1989-1999)0.139 Nadir CD4+ (cells/µL) 567 (453-739)575 (453-739)544 (461-730)0.893 Months since HIV infection to sample collection22.0 (3.5-72.7)20.2 (3.0-66.2)36.9 (6.5-107.1)0.178 Months since sample collection to the start of cART 16.4 (3.2-37.2)13.9 (3.2-38.0)18.4 (4.6-34.5)0.777 HCVab Negative Positive Unknown 52 (23%) 51 (23%) 120 (54%) 48 (92%) 43 (84%) 101 (84%) 4 (8%) 8 (16%) 19 (16%) 0.335 CD4+ at sample collection (cells/µL) 571 (458-729)581 (453-731)540 (468-646)0.584 HIV-RNA at sample collection (log10 copies/mL) 4.1 (3.6-4.6) 4.0 (3.5-4.3)0.343

4. Median (IQR) CD4+ change: -218 (-281/-143) cells/µL Median (IQR) CD4+ change: -150(-276/0) cells/µL P=0.038 Fig 1 CD4 Decrease according to viral tropism Fig 2 CD4 Decrease according to gender P=0.255 Median (IQR) CD4+ change: -133 (-272/+0.5) cells/µL Median (IQR) CD4+ change: -166(-284/-60) cells/µL

5. Acknowledgments