CROI 2015 Program and Abstracts

Abstract Listing

Oral Abstracts

change between groups was 0.014 mm/yr. Among those without carotid plaque at baseline, there was no difference in development of new plaque by week 96 (4.9% vs. 6.5%, statin vs. placebo, p=0.82). Among those without CAC at baseline, there was a trend towards more detectable CAC after 96 weeks of statin (15% vs. 6%, statin vs. placebo, p=0.19).

Change in mean-mean common carotid artery intima-media thickness (CCA-IMT) over 96 weeks according to study group assignment. Conclusions: Rosuvastatin 10 mg daily appears to halt progression of carotid IMT in HIV-infected patients on ART with low LDL-cholesterol and high levels of immune activation. The effect on IMT progression is similar in magnitude to studies of HIV-uninfected populations and provides further justification for clinical outcomes trials in this population. 138 Calcified Plaque Burden Is AssociatedWith Serum Gut Microbiota-Generated TMA in HIV Suman Srinivasa 1 ; KathleenV. Fitch 1 ; Janet Lo 1 ; Hanane Kadar 2 ; KimberlyWong 1 ; Suhny Abbara 3 ; Dominique Gauguier 2 ; Jacqueline Capeau 2 ; Franck Boccara 2 ; Steven K. Grinspoon 1 1 Massachusetts General Hospital, Harvard Medical School, Boston, MA, US; 2 University Pierre & Marie Curie, Paris, France; 3 University of Texas Southwestern Medical Center, Dallas, TX, US Background: Some gut microbiota-generated metabolites of phosphatidylcholine are recognized to be pro-atherogenic. The HIV population is more vulnerable to cardiovascular disease (CVD) than the general population and can develop impaired intestinal wall integrity and dysbiosis associated with inflammation. We investigated the novel relationship between microbiota-derived choline-related metabolites and coronary atherosclerosis in HIV. Methods: 155 HIV-infected and 67 non-HIV-infected subjects without known CVD were previously recruited in a prospective study to assess coronary plaque by cardiac CT angiography. In the current study, we evaluated serum choline, trimethylamine (TMA) and trimethylamine N-oxide (TMAO) in association with plaque features and systemic inflammatory markers. A mass spectrometry-based method was designed to assay choline-related metabolites from serum. Linear regression was performed by Pearson’s correlation after non-normally distributed variables were log transformed. Results: Young, asymptomatic HIV-infected subjects(mean age 47 ± 7 yrs, duration HIV 14 ± 6 yrs, duration ART 8 ± 5 yrs, CD4 + count 552 ± 290 cells/ μ l, undetectable VL 86%) demonstrated significantly higher prevalence of plaque(53 vs. 35%, P=0.01) and total plaque segments(1.8 ± 2.5 vs. 1.2 ± 2.2, P=0.03) when compared to well-matched non-infected subjects with similar co-morbidities. TMA was significantly associated with number of total(r=0.20, P=0.02) and calcified(r=0.18, P=0.03) plaque segments; calcium score(r=0.22, P=0.006); calcium plaque volume (r=0.19, P=0.02) and mass(r=0.22, P=0.009); and lipopolysaccharides (LPS) (r=0.19, P=0.03) in the HIV cohort only. In multivariate modeling among HIV-infected subjects, TMA remained significantly associated with number of total(P=0.005) and calcified(P=0.02) plaque segments; calcium score(P=0.008); and calcium plaque volume(P=0.01) and mass(P=0.007), independent of Framingham Risk Score (FRS). Furthermore, TMA was still an independent predictor of total plaque segments(P=0.03), calcium score(P=0.04), and calcium plaque mass(P=0.03), after controlling for FRS and LPS. In contrast, there was no association of TMAO to plaque features in either cohort. Conclusions: TMA, a microbiota-derived precursor of TMAO, may be a non-traditional cardiovascular risk factor which has independent effects on the number of coronary plaque segments and severity of calcified plaque burden in HIV. This relationship may derive from altered gut flora or microbial translocation unique to HIV. 139 Varenicline vs Placebo for Smoking Cessation: ANRS 144 Inter-ACTIV Randomized Trial Patrick Mercie 3 ; Caroline Roussillon 1 ; Christine Katlama 4 ; Aurélie Beuscart 1 ; Samuel Ferret 2 ; NathalieWirth 5 ; David Zucman 6 ; Xavier Duval 7 ; Genevieve Chene 1 ANRS 144 inter-ACTIV study group 1 Inserm U897, Bordeaux, France; 2 Hosp. Saint-Louis, Paris, France; 3 Hosp. Saint-André, Bordeaux, France; 4 Hosp. La Pitié-Salpêtrière, Paris, France; 5 Hosp. De Brabois, Vandoeuvre les Nancy, France; 6 Hosp. Foch, Suresnes, France; 7 CIC 1425, Paris, France Background: About half of HIV-infected patients are regular tobacco smokers in Europe, a higher prevalence than the general population. Tobacco is an important determinant of non AIDS morbidity and mortality (including vascular diseases and malignancies), a major reason to promote tobacco cessation. It is unclear whether varenicline is safe and efficacious for smoking cessation in HIV-infected patients. We evaluated varenicline at 48 weeks in regular smokers motivated to quit smoking. Methods: Randomized (1:1), placebo-controlled clinical trial with a 12-week treatment period (from 0.5 mg once daily to 1 mg twice daily at the end of the first week) and a further 36-week follow-up, including smoking cessation counseling in both arms, conducted in 30 ANRS centers from Oct. 2009 to Jan. 2014. Self-reported tobacco abstinence was confirmed by exhaled carbon monoxide measurements at 9 weeks and at intervals up to 48 weeks. The primary endpoint was continuous abstinence rate fromweek 9 to 48. Secondary endpoints included continuous abstinence rate fromweek 9 to 12 and adverse events. Results: 248 smokers were randomized; 213 included in the modified intention-to-treat analysis (102 varenicline, 111 placebo), others did not start trial treatment. Median age was 45 years, 83%male, median nadir CD4+ 213/mm 3 , baseline CD4+ 617/mm 3 and undetectable HIV RNA 73%. Varenicline was associated with a higher continuous abstinence rate at 48 weeks than placebo: 17.6% vs 7.2% ( p=0.02) and 34.3% vs 12.6% at 12 weeks ( p=0.0002) . At 48 weeks, median CD4+ was 615/mm 3 and 80% had undetectable HIV RNA, without difference between arms. Grade 3/4 drug-related effects were reported in 7 patients in each arm, including 9 psychiatric side effects (5 in the varenicline arm vs 4 in

Oral Abstracts

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CROI 2015