CROI 2016 Abstract eBook

Abstract Listing

Poster Abstracts

700 Racial Differences in Bioavailable Vitamin DWith Supplementation: ACTG A5280 Michael T. Yin 1 ; Ellen S. Chan 2 ;ToddT. Brown 3 ; PabloTebas 4 ; Grace A. McComsey 5 ; Kathy Melbourne 6 ; Royce Hardin 7 ; Heather J. Ribaudo 8 ; EdgarT. Overton 9 ; for the ACTG 5280 Study Team 1 Columbia Univ Med Cntr, New York, NY, USA; 2 Harvard Univ, Boston, MA, USA; 3 Johns Hopkins Univ, Baltimore, MD, USA; 4 Univ of Pennsylvania, Philadelphia, PA, USA; 5 Case Western Reserve Univ, Cleveland, OH, USA; 6 Gilead Scis, Inc, Foster City, CA, USA; 7 Univ of North Carolina at Chapel Hill, Chapel Hill, NC, USA; 8 Harvard Sch of PH, Boston, MA, USA; 9 Univ of Alabama at Birmingham, Birmingham, AL, USA Background: Vitamin D and calcium (VitD/Ca) supplementation prevents bone loss after ART initiation for both blacks and non-black HIV-infected individuals despite racial differences in vitamin D levels. Low levels of total 25-hydroxyvitamin D (25OHD) are common among black, but bioavailable 25OHD may be preserved since vitamin D binding protein (VDBP) levels are also lower in blacks. Methods: ACTG A5280 is a 48-week, randomized, double-blind, placebo-controlled study evaluating the effect of vitamin D3 (4000 IU/day) and calcium carbonate (1000 mg/ day) supplementation in HIV-infected participants initiating ART with efavirenz/emtricitabine/tenofovir DF. In this secondary analysis, total 25OHD (D2 and D3), VDBP, estimated bioavailable 25OHD, and parathyroid hormone (PTH) levels were assessed at baseline and 48 weeks. Wilcoxon signed-rank tests and Wilcoxon rank sum tests were used to test change within and differences between race groups (black vs non-black), respectively. Results: Of 165 eligible participants enrolled, 129 participants (40 blacks and 89 non-blacks) had calciotropic hormone data at baseline and 48 weeks. At baseline, blacks had lower total 25OHD [median (Q1,Q3) 22.6 (15.8, 26.9) vs. 31.1 (23.1, 38.8) ng/ml, p<0.001] and VDBP [125.6 (79.0, 264.0) vs. 289.6 (207.7, 393.2) ug/ml, p<0.001] but higher bioavailable 25OHD [2.9 (1.5, 5.2) vs. 2.0 (1.5, 3.0) ng/ml, p=0.022], and similar PTH levels than non-blacks. In the placebo arm, VDBP and PTH levels increased similarly over 48 weeks in blacks and non-blacks, but total and bioavailable 25OHD levels remained unchanged (Table). In the VitD/Ca arm, bioavailable 25OHD increased more in blacks than non- blacks (median 3.9 vs. 1.1ng/mL, p<0.001), but change in VDBP did not differ between race groups . VitD/Ca prevented the expected PTH increase after ART; the effect appeared to be greater in blacks than non-blacks but did not reach statistical significance (p=0.11). Conclusions: Despite a total 25OHD in the insufficient range (median <30ng/ml), black HIV-infected individuals had higher bioavailable 25OHD at baseline, and greater increases in bioavailable 25OHD with VitD/Ca supplementation than non-blacks. In addition, VitD/Ca may prevent rise in PTH more in blacks than non-blacks. Measurement of bioavailable 25OHD may help to elucidate racial differences in calciotropic hormone physiology.

701 Blood Microbiome in Treatment-Naive HIV-1-Infected Persons Developing Hyperglycemia Under ART

Jacques Amar 1 ; Mathilde Ghislain 2 ; CorinneVigouroux 3 ; Jacqueline Capeau 4 ; Cecile Goujard 5 ; Beverley Balkau 2 ; Jean Philippe Bastard 3 ; Laurence Meyer 6 ; Pierre Delobel 7 1 INSERM 1048, Toulouse, France; 2 INSERM, UMR-S 1018, Paris, France; 3 Sorbonne Univs, Paris, France; 4 INSERM UMR-S 938, CDR Saint-Antoine, Paris, France; 5 INSERM, UMR-S 1018, CESP, Paris, France; 6 INSERM, CESP U1018, Le Kremlin-Bicêtre, France; 7 CHU Toulouse, Toulouse, France Background: Increased bacterial translocation from the gut lumen into the bloodstream has been reported in HIV-1-infected persons. To investigate the role of bacterial translocation on the onset of metabolic diseases, we studied the relationship between the blood microbiome and the occurrence of hyperglycemia in HIV-1-infected persons before antiretroviral (ART) initiation and after 2 years on ART. Methods: We carried out a nested case control study in naive HIV-1-infected persons with normal glucose levels at initiation of ART in the ANRS COPANA cohort. We compared 37 patients (43 years; range 38-51) who developed type 2 diabetes or impaired fasting plasma glucose (>5.6mmol/L) and 102 controls (35 years; range 29-44) with normal glucose values during the follow-up. Patients and controls were matched according to age, sex, type of ART and duration of follow-up. The median duration of follow-up was 24 months (range 13-35). At baseline, the blood microbiome was assessed using 16S targeted metagenomics sequencing (VAIOMER SA, Labège). Plasma adipokines (adiponectin, leptin) and inflammatory markers (C-reactive protein, I-FABP, lipoprotein binding protein, sCD163, sCD14, IL-1RA) concentrations were assessed. Results: We observed a higher proportion of taxa belonging to the class Clostridia, the order Clostridiales the family Clostridiadaceae and the genus Clostridium sensu stricto in cases as compared with controls (table). However no significant differences were observed in inflammatory markers and adipokines between the two groups. p-value are from rank sumWilcoxon test or Mc Nemar test Conclusions: Interestingly, it has been shown (PMID:23023125/Nature 2012) that the proportion of the class Clostridia in the gut is associated with type 2 diabetes. We propose that bacterial translocation of the class Clostridia may play a role in the onset of hyperglycemia in HIV-1-infected patients.

Poster Abstracts

cases

control

P-value

relative abundance % class/clostridia order/clostridiales family/clostridiadaceae

Median Mean Q1

Q3 Median Mean Q1

Q3

3.512 5.587 1.452 6.498 0.029 1.897 0.015 2.2606 3.512 5.587 1.452 6.498 0.029 1.896 0.015 2.2605 10.782 10.782 6.490 15.075 0.020 0.501 0.0126 1.1555

0.001 0.001 0.030 0.030

genus/clostridium sensu stricto 10.601 10.601 6.375 14.827 0.02 0.499 0.0126 1.1555

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CROI 2016