CROI 2015 Program and Abstracts

Abstract Listing

Poster Abstracts

were elevated blood pressure (17.7%), anemia (13.1%) and IFG (11.4%). 48% had at least one comorbidity and 14% had ≥ 2. 12% had ≥ 1 ICO and 41% had ≥ 1 NICO. Those with ≥ 2 comorbidities had significantly higher age (p<0.0001), lower CD4 count (p=0.004) and higher body mass index (BMI) (p=0.01) than those without comorbidity. Multivariate regression revealed independent association of age (p<0.0001), BMI (p=0.02), CD4 count (p=0.03) and female gender (p=0.02) with total NICOs. Conclusions: The cohort demonstrates considerable HIV associated multimorbidity in a largely rural African context. Body mass and CD4 count are potentially modifiable predictors of NICOs. Future analyses will prospectively assess the impact of expanded ART eligibility on these outcomes.

TUESDAY, FEBRUARY 24, 2015 Session P-Q2 Poster Session

Poster Hall

2:30 pm– 4:00 pm Bone Metabolism and ART: Mechanisms and Outcomes 765 Bone Metabolism and Tenofovir: Evidence of Direct Effect on Calcium-Sensing Receptor Paolo Bonfanti 2 ; Caterina Brasacchio 3 ; Chiara Molteni 2 ; Barbara Menzaghi 1 ; Laura Soldati 3 ;Tiziana Quirino 1 ; Stefano Mora 4

1 Busto Arsizio Hospital, Busto Arsizio, Italy; 2 A. Manzoni Lecco Hospital, Lecco, Italy; 3 Department of Health Sciences, University of Milan, Milan, Italy; 4 San Raffaele Scientific Institute, Milan, Italy Background: Bone health impairment is a common finding in HIV-infected patients on antiretroviral treatment. Bone mineral derangement is the result of bone metabolism alterations, associated to some antiretroviral agents. We previously reported high serum parathyroid hormone (PTH) concentration in patients on HAART containing tenofovir disoproxil fumarate (TDF). Hyperparathyroidism in these patients was not always sustained by a reduction in vitamin D concentration. We thus hypothesized a direct inhibitory effect of TDF on the calcium sensing receptor (CaR), leading to hyperparathyroidism, responsible for the bone complication. Methods: Human embryonic kidney cells transfected with CaR wild-type gene (HEK-293-CaR WT) were used. Cells were grown in standard conditions (37°C, 5%CO2) and the activity of CaR was assessed after stimulation with different concentrations of CaCl2 (0.5mM-1mM-3mM-5mM) and TDF (100nM-1 μ M) (kindly provided by Gilead Sciences, Inc). We evaluated by western blot and Image J software phospho-p44/42 ERK expression levels as a marker of CaR activity. Results: Calcium alone lead to the activation of CaR with all concentrations of CaCl2 tested. However, the highest CaR activity was detected at 3mM CaCl2 and this concentration was used for the subsequent stimulation analyses. We observed a marked reduction of CaR activity by adding TDF to cell cultures (Figure). The stimulation by CaCl2 3mM and TDF 100nM lead to decrease of 52% CaR activity, whereas the stimulation by CaCl2 3mM and TDF 1 μ M reduced the activity by 67%. Both reductions were statistically significant (P=0.03, and P=0.009, respectively).

Poster Abstracts

Conclusions: The stimulation of CaR by its natural ligand, calcium, leads to the suppression of PTH secretion by the parathyroid glands. Our experiments demonstrated that TDF is able to inhibit the stimulation of CaR in a dose-dependent manner. Hyperparathyroidism observed in TDF-treated patients may be therefore promoted by the direct effect of the drug on CaR. 766 Bone Turnover on DRV/r + Either RAL or TDF/FTC as First-Line ART: NEAT 001 / ANRS 143 Jose I Bernardino 1 ; Amanda Mocroft 2 ; Laura Richert 3 ; Abdel Babiker 4 ; Antonio Buño 1 ; Antonella Castagna 5 ; Pierre-Marie Girard 6 ; Genevieve Chene 3 ; Jose R Arribas 1 ; François Raffi 7 1 Hospital Universitario La Paz. IdiPAZ, Madrid, Spain; 2 University College London, London, United Kingdom; 3 University of Bordeaux, Bordeaux, France; 4 MRC Clinical Trials Unit at University College London, London, United Kingdom; 5 San Raffaele Scientific Institute, Milan, Italy; 6 Hospital St Antoine and Inserm, Paris, France; 7 Université Nantes, Nantes, France Background: Darunavir/ritonavir (DRV/r) + raltegravir (RAL) was associated with significantly less bone mineral density (BMD) loss over 96 weeks than DRV/r + tenofovir/ emtricitabine (TDF/FTC) in first-line treatment of HIV-infected patients. Changes in bone and inflammatory biomarkers could partially explain differences in BMD loss. Methods: NEAT001/ANRS143 is a randomised 1:1, open-label trial comparing DRV/r + RAL or TDF/FTC in 805 ART naive HIV-infected adults. 146 patients were included in the bone substudy (70 and 76) prior to randomised treatment allocation. We measured 25-OH vit D and a variety of bone and inflammatory biomarkers at baseline and 48 weeks. BMD was measured by DXA at baseline, 48 and 96 weeks. Changes in bone and inflammatory markers were evaluated by parametric comparisons. Associations between baseline values and changes in BMD at both 48 and 96 weeks were explored by linear and logistic regression. Results: 133 patients had at least one biomarker measured at randomisation; 91.7%male, 12.0% black, median age 39 yrs, median BMI 23.1 Kg/m 2 , 41.4%were current smokers. Osteopenia/osteoporosis was evidenced at baseline in 24/5 patients in lumbar spine and in 19/1 patients in total hip. 21 patients had a previous history of fracture. There were no significant differences between treatment arms in biomarkers at baseline. Significantly greater changes in bone biomarkers were seen at 48 week in the DRV/r + TDF/FTC arm but there were no differences in changes in inflammatory markers (Table). In multivariate analysis, baseline level of P1NP ≤ 44.7 ng/mL was associated with a total hip BMD loss ^ 5% at 48 weeks (OR 10.76; 95% CI 1.29, 90.2) and femoral neck BMD loss ^ 5% at 96 weeks (OR 4.63; 95% CI 1.29, 46.6). Baseline osteopontin level ≤ 5423 pg/mL was associated with a lumbar spine BMD loss ≥ 5% at 96 weeks (OR 0.17; 95% CI 0.09, 0.68).

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CROI 2015