CROI 2015 Program and Abstracts

Abstract Listing

Poster Abstracts

Conclusions: Compared to the nucleos(t)ide sparing regimen of DRV/r + RAL, patients treated with DRV/r + TDF/FTC had significantly greater changes in bone turnover biomarkers. Measuring bone biomarkers before starting ART could help to identify those patients at greater risk of BMD loss ≥ 5% on ART. 767 Tenofovir Replacement in Patients With Osteoporosis Increased Sclerostin Levels Eugenia Negredo 3 ; Adolfo Díez-Pérez 2 ; Pere Domingo 4 ; Nuria Pérez-Álvarez 6 ; Mar Gutierrez 4 ; Gracia Mateo 4 ; Jordi Puig 1 ; Patricia Echeverria 1 ; Anna Bonjoch 1 ; Bonaventura Clotet 5 1 Lluita Contra la Sida Foundation, Germans Trias i Pujol University Hospital, Universitat Autònoma de Barcelona, Barcelona, Spain; 2 Hospital del Mar-IMIM, Universitat Autònoma de Barcelona and RETICEF, Instituto Carlos III Madrid, Barcelona, Spain; 3 Lluita Contra la Sida Foundation, Germans Trias i Pujol University Hospital, Universitat Autònoma de Barcelona, Universitat de Vic–Universitat Central de Catalunya, Barcelona, Spain; 4 Santa Creu i Sant Pau Hospital, Universitat Autònoma de Barcelona, Barcelona, Spain; 5 Lluita Contra la Sida Foundation, Germans Trias i Pujol University Hospital, Universitat Autònoma de Barcelona, Irsicaixa Foundation, Germans Trias i Pujol University Hospital, Barcelona, Spain; 6 Lluita Contra la Sida Foundation, Germans Trias i Pujol University Hospital, Universitat Autònoma de Barcelona, Statistics and Operations Research Department, Universitat Politècnica de Catalunya, Barcelona, Spain Background: Tenofovir is one of the antiretroviral drugs involved in accelerated bone mineral density (BMD) loss. Methods: We recently published changes in 54 virologically suppressed patients during a tenofovir-containing regimen and criteria for osteopenia/osteoporosis who were randomized to switch from tenofovir to abacavir (n=26) or to continue with tenofovir (n=28). Forty-eight weeks after switching to abacavir, hip BMD improved by 2.1% (95% CI, –0.6, 4.7) (p=0.043). Now we present changes from baseline to week 48 in bone markers in 44 of these patients: 1) C-terminal telopeptide of collagen type 1 (CTX) (resorption), and 2) osteocalcin (OCN) and procollagen type 1 N propeptide (P1NP) (bone formation). Additionally, we assessed changes in circulating levels of 3 proteins involved in bone regulation: osteoprotegerin (OPG), receptor activator for nuclear factor K B ligand (RANKL) and sclerostin (SOST), a selective regulator of bone formation through the Wnt pathway, no previously explored in this population. To compare between study groups, chi-Squared or Fisher and Student t tests were performed according to each variable distribution. Results: CTX, OCN and P1NP significantly decreased only in the abacavir group [mean (SD) CTX, from 0.543 (0.495) to 0.301 (0.306) ng/mL (p<0.001); OCN, from 23.72 (22.20) to 13.95 (12.40) ng/mL (p=0.209); P1PN, from 54.68 (54.52) to 28.65 (27.48) ng/mL (p<0.001)], reaching significant differences between groups at week 48. Osteoprotegerin did not vary in any group but SOST significantly increased in the abacavir group (from 29.53 (27.91) to 35.56 (34.59) pmol/L, p=0.002). No significant differences in OPG and SOST were detected between groups at week 48. RANKL values were below the limit of detection in all samples assessed. Conclusions: The switch from tenofovir to abacavir seems to induce a positive effect on bone tissue since bone remodelling decreased and circulating sclerostin levels increased, both associated with better bone properties (density, microarchitecture and strength), and decreased risk of fracture. 768 Relationship Between Phosphate Reabsorption, Age, Tenofovir and Bone Mineral Density Lisa Hamzah 2 ; Amanda Samarawickrama 1 ; KarenWalker-Bone 3 ;Yvonne Gilleece 4 ; Martin Fisher 1 ; Frank A. Post 5 1 Brighton and Sussex Medical School, London, United Kingdom; 2 King’s College London, London, United Kingdom; 3 University of Southampton, Southampton, United Kingdom; 4 Brighton and Sussex Hospitals NHS Trust, Brighton, United Kingdom; 5 King’s College Hospital NHS Foundation Trust, London, United Kingdom Background: The functional capacity of renal tubules to reabsorb phosphate declines with age. The extent to which this is affected by tenofovir (TDF) exposure and its effects on bone are unknown. We investigated the association between phosphate reabsorption, age, TDF exposure and bone mineral density (BMD). Methods: Male HIV-positive patients taking part in a prospective study to evaluate BMD were analysed for phosphate wasting using maximum threshold for phosphate reabsorption (TmPO 4 /GFR), derived by the Kenny and Glen algorithm. Bone resorption was assessed by serum carboxy-terminal collagen crosslinks (CTX), bone formation by type 1 procollagen (P1NP), and BMD by dual-energy x-ray absorptiometry. Correlation coefficients and linear regression were used to evaluate relationships between variables. Results: 411 men (mean age 47.4 [SD 9.8] years, 94.3%white, 92.9%MSM, diagnosed for a median 9.6 [IQR 5.0-15.5] years, 69.4% on TDF) were included. TmPO 4 /GFR correlated with age (r 2 =-0.2, p=0.006), parathyroid hormone (PTH) concentrations (r 2 =0.1, p=0.02) and, in those over 50 years, with lumbar spine BMD (r 2 =-0.2, p=0.02). Among subjects aged 30-70 years on antiretroviral therapy, TmPO 4 /GFR did not differ among those exposed versus those not exposed to TDF (Figure). In multivariable analysis, TmPO 4 / GFR remained associated with older age ( β -0.03 [95% CI -0.05, -0.01] per 10 years, p=0.003) and 25 (OH) vitamin D ( β 0.001 [95% CI 0.0001, 0.002] p=0.03), while univariable associations with nadir CD4 cell count, prior AIDS, HIV viral load, TDF and protease inhibitor exposure, P1NP and PTH were no longer significant after adjustment. TmPO 4 /GFR was not associated with CTX (p=0.9), BMD spine (p=0.1), BMD total hip (p=0.5) or BMD femoral neck (p=0.5).

Poster Abstracts

470

CROI 2015