CROI 2015 Program and Abstracts

Abstract Listing

Oral Abstracts

303 sCD163 Increase in HIV/CMV-Coinfected Subjects Included in ICONA Cohort Serena Vita 3 ; Miriam Lichtner 1 ; Giulia Marchetti 2 ; Claudia Mascia 3 ; Esther Merlini 2 ; Paola Cicconi 2 ;VincenzoVullo 3 ; Pier LuigiViale 5 ; Alberto Costantini 4 ; Antonella d’Arminio Monforte 2 For the Icona Foundation Study 1 University of Rome La Sapienza, Polo Pontino, Latina, Italy; 2 San Paolo Hospital, Milano, Italy; 3 University of Rome La Sapienza, Rome, Italy; 4 University of Ancona, Ancona, Italy; 5 University of Bologna, Bologna, Italy Background: Accumulating evidence suggest that inflammatory cytokines produced by monocytes/macrophages play a role in the vascular disease and cognitive decline . In HIV patients, herpes virus coinfection has been proposed as a key factor in sustaining immune activation, even in presence of HIV plasma viral control. In our previous study on the ICONA cohort we showed that in HIV patients (pts), CMV infection is an independent risk factor for non AIDS events/deaths. Methods: We screened all the ICONA pts with an available CMV serology at enrolment (<= 6 months) and a plasma sample after >1 year of successful ART (defined as an undetectable HIV viral load and CD4+ count >200/mc). Pts were grouped according to CMV serostatus in CMV-infected (CMV+) (defined as CMV IgG positive) and CMV-uninfected (CMV-). Pts were also matched 2:1 for the following parameters: age, CD4 nadir, duration of HIV infection, HBV and HCV. We excluded pts with previous or current CMV organ diseases and other active organ disease in the previous 5 years. We detected sCD163, TNF α , sCD14, IL-6 using ELISA tests (R&D Systems) on plasma samples. All sample were retested for anti-CMV IgG (GenWay Biotech). Statistical analysis was performed using Mann-Withney Test and Spearman correlation analysis. Results: A total of 69 subjects were recruited, 46 HIV monoinfected (CMV-) and 23 HIV/CMV (CMV+) coinfected. A higher median of sCD163 level (927.7 vs. 497.8 ng/ml, p=0.018) was found in CMV+ compared to CMV- group. TNF α , sCD14 were also elevated but didn’t reach a significant difference in comparison to HIV/CMV- subjects. In HIV/CMV+ subjects a significant correlation was shown between anti-CMV IgG levels and sCD163 (r=0.49, p=0.006) (Fig.1). Moreover only in CMV+ subjects sCD163 levels were related to the duration of HIV infection (r=0.29, p=0.04). In the CMV positive group comparing CMV IgG levels with CD4 count, at the time of sampling, we found a significant negative correlation (r=0.39, p=0.0006).

Conclusions: CMV chronic infection appears to be linked to an increase in sCD163, a markers of myeloid activation, in HIV infected subjects under successful ART with controlled biological (age and sex) and HIV related (HIV suppression, CD4 nadir and CD4 recovery) factors. The persistent activation of monocytes and macrophages that has been implicated in the accelerated development of vascular and neurological disease in general population, may explain the increased risk of non AIDS events found in CMV/HIV coinfected subjects. 304 Genital CMV Shedding Predicts Syphilis Acquisition in HIV-Infected MSM on ART Sara GianellaWeibel 1 ; David M. Smith 1 ; Eric Daar 2 ; Michael Dube 3 ; Andrea Lisco 4 ; ChristopheVanpouille 5 ; Richard Haubrich 1 ; Sheldon Morris 1 1 University of California San Diego, La Jolla, CA, US; 2 Los Angeles Biomedical Research Institute at Harbor–UCLA Medical Center, Torrance, CA, US; 3 University of Southern California Keck School of Medicine, Los Angeles, CA, US; 4 National Institute of Allergy and Infectious Diseases, Bethesda, MD, US; 5 National Institute of Child Health and Human Development, Bethesda, MD, US Background: Bacterial sexually transmitted infections (STI) are highly prevalent among HIV-infected men who have sex with men (MSM) and are co-factors in HIV transmission. While sexual behavior and networks are important in STI acquisition, other biological factors have not been emphasized as targets for intervention. Methods: As part of a behavioral intervention, 136 HIV-infected MSM on suppressive (<500 copies/ml) ART were followed for 12 months and screened for incident bacterial STI ( Neisseria gonorrhoeae , Chlamydia trachomatis , and syphilis ) every three months. Baseline predictors of bacterial STI were determined using survival analysis of time to incident STI. Tested variables at baseline included: behavioral factors (number of sex partners, number of anal sex acts, use of methamphetamine and other drugs), plasma HIV RNA levels, current and nadir CD4 T and CD8 T cell count, genital shedding of herpes viruses (CMV, EBV, HSV, HHV-6, -7, and -8), serum CMV IgG levels, and soluble markers of genital inflammation (MCP-1, IL-6, TNF-alfa, Interferon-gamma, RANTES and IP-10 in baseline seminal plasma). Results: Thirty-four subjects (26.2%) acquired bacterial STIs during follow-up, sometimes with more than one pathogen (16 syphilis, 20 gonorrhea, 14 chlamydia). Acquisition of syphilis during follow-up was associated with genital CMV shedding at baseline (21% in CMV shedders versus 3% in non-shedders, P=0.003, see figure attached), younger age (P=0.005) and more sex partners (P=0.047). None of the tested variables except partner number was associated with acquisition of other STIs (chlamydia and gonorrhea at any site). For the acquisition of syphilis, in multivariable Cox-proportional hazard model adjusted hazard rates were as follows: baseline CMV shedding 4.87 (95% CI 1.06-22.47), age 0.96 (per year younger [95% 0.91-1.01]) and number of partners past month 1.06 (per partner per month [0.99-1.13]). Also, syphilis cases compared to non-cases had lower baseline levels of seminal MCP-1 (P=0.01), and lower seminal MCP-1 levels were associated with higher levels of seminal CMV DNA (P=0.005).

Oral Abstracts

Kaplan-Meier Plot showing incidence of Syphilis acquisition in participant with (1) and without (0) CMV seminal shedding at baseline.

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CROI 2015