CROI 2015 Program and Abstracts

Abstract Listing

Poster Abstracts

Conclusions: In this healthy HIV adult cohort with predominantly controlled viremia, total hip BMD decline was associated with IL-6, replicative senescent T-cells, CCR5+ and tissue factor expressing monocytes. Memory CD4+ and CD8+ CD28+ T cells were associated with increases in BMD. Immunologic alterations that persist after virologic suppression may contribute to ongoing loss of BMD. 773 RANKL Predicts 96-Week BMD Changes in ATV/r Monotherapy: A MODAt Trial Sub-Study Vincenzo Spagnuolo 1 ; Marco Borderi 2 ; Giuseppina Musumeci 2 ; Laura Galli 1 ; CamillaTincati 3 ; Stefano Rusconi 3 ; Giovanni Guaraldi 4 ; Alba Bigoloni 1 ; Adriano Lazzarin 1 ; Antonella Castagna 1 1 San Raffaele Scientific Institute, Milan, Italy; 2 Alma Mater Studiorum University of Bologna, Bologna, Italy; 3 University of Milan, Milan, Italy; 4 University of Modena and Reggio Emilia, Modena, Italy Background: To evaluate the association between bone biomarkers and changes in bone mineral density (BMD) over 96 weeks in patients treated with atazanavir/ritonavir (ATV/r) monotherapy vs ATV/r+2 N(t)RTIs. Methods: MODAt (NCT01511809) is a multicentric, randomized, open-label, non-inferiority trial. Patients on ATV/r 300/100mg+2 N(t)RTIs since ≥ 48 weeks, virologically suppressed since ≥ 24 weeks, randomized to ATV/r monotherapy (arm A) or to maintain ATV/r+2N(t)RTIs (Arm B). This sub-study included patients who maintained for 96 weeks the antiretroviral treatment assigned at randomization. Participants underwent DXA scan and tested bone biomarkers at baseline (BL), week 48, week 96/discontinuation. Results as median (IQR). Linear regression to evaluate the predictors of 96-week percent changes in vertebral and femoral (total proximal) BMD. Results: 69 patients [29 patients on ATV/r monotherapy, 40 patients on ATV/r+2N(t)RTIs], age 42 (35-46) years, 84%males, 58% smokers, 17% HCV co-infected, BMI 23.6 (21.6- 25.6) kg/m 2 , BL CD4+ 599 (432-744) cells/ μ L, 87% on TDF at randomization. At lumbar spine, BL BMD was 0.975 (0.920 ; 1.047) g/cm 2 and 1.016 (0.933; 1.103) g/cm 2 in arm A and B, respectively (p=0.359); %change from BL to week 48 were 1.772 (-0.010; 3.998) and -0.988 (-2.270; 1.143) in arm A and B, respectively (p=0.002) while %change from BL to week 96 were 0.830 (-0.299; 2.388) and -0.811 (-3.207; 1.833) in arm A and B, respectively (p=0.075). At total proximal femur, BL BMD was 0.929 (0.874; 0.973) g/cm 2 and 0.959 (0.871; 1.024) g/cm 2 in arm A and B, respectively (p=0.458); %change from BL to week 48 were 1.301 (0.020; 3.912) and -0.199 (-1.835; 1.738) in arm A and B, respectively (p=0.069) while %change from BL to week 96 were 1.321 (-0.649; 2.671) and -0.471 (-2.440; 1.209) in arm A and B, respectively (p=0.071). BL values of bone biomarkers were similar in the two arms [Arm A: osteocalcin, 20.4 (14.2; 29.5) ng/ml; CTX-I, 0.63 (0.44; 0.82) ng/ml; vitamin D, 62 (52; 113) nmol/L; OPG, 988 (707; 1395) pg/ml; RANKL, 31 (31; 61) pg/ml; Arm B: osteocalcin, 25.2 (15.9; 33.3) ng/ml (p=0.342); CTX-I, 0.48 (0.35; 0.69) ng/ml (p=0.095); vitamin D, 99 (59; 142) nmol/L (p=0.167); OPG, 1046 (726; 1418) pg/ml (p=0.985); RANKL, 31 (31; 42)pg/ml (p=0.685)]. Results frommultivariate analysis in Table 1.

Poster Abstracts

Conclusions: At 96-week of ATV/r monotherapy, this strategy was associated with an increase in BMD; the benefit of ATV/r monotherapy was more evident in patients with low baseline values of RANKL. 774 Predictors of Longitudinal Change in Bone Mineral Density in a Cohort of HIV Positive and Negative Subjects Willard Tinago 1 ; Aoife Cotter 1 ; Caroline Sabin 2 ; Alan Macken 1 ; Eoin Kavanagh 3 ; Jennifer Brady 4 ; Geraldine McCarthy 5 ; Juliet Compston 6 ; PatrickW. Mallon 1 HIV UPBEAT Study Group 1 University College Dublin, Dublin, Ireland; 2 Research Department of Infection and Poulation Health, London, United Kingdom; 3 Mater Misericordiae University Hospital, Dublin, Ireland; 4 Mater Misericordiae University Hospital, Dublin, Ireland; 5 Mater Misericordiae University Hospital, Dublin, Ireland; 6 University of Cambridge, London, United Kingdom Background: Although HIV infection is associated with low bone mineral density (BMD) in cross-sectional studies, whether it is associated with greater declines in BMD over time remains unclear. We aimed to compare rates of, and factors associated with, change in BMD over time between HIV-positive and -negative subjects, and to determine HIV-related predictors of change in BMD. Methods: A prospective, 3-year, cohort enrolled HIV positive and negative subjects; demographic, clinical, and medication data were collected, with annual dual xray absorptiometry (DXA) at femoral neck (FN), total hip (TH) and lumbar spine (LS) and fasting bloods, including alkaline phosphatase (ALP) and bone biomarkers (C-terminal cross- linking telopeptide of type-1 collagen (CTX-1), procollagen type-1 amino-terminal propeptide (P1NP), osteocalcin (OC). Of the 384 subjects (176 (45.8%) HIV positive),120 subjects contributed two and 264 contributed 3 BDM annual measurements. Longitudinal mixed models were used to compare and determine predictors of rate of absolute change in BMD in the whole cohort and within the HIV sub-group.

473

CROI 2015