CROI 2016 Abstract eBook

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Oral Abstracts

Results: There were 243 incident MIs among 11,338 PLWH during a mean follow-up of 4.3 years. ASCVD had a significantly better AUC than other scores for all MI and for T2MI (Table) including the DAD AUC (p<0.001), and was not inferior to the other AUCs for T1MI. Our results were similar in the subset of PLWH with time-updated smoking status. Conclusions: The large size, comprehensive clinical data and central adjudication of MI by type in CNICS allows for direct comparison of clinical risk scores in PLWH. Some variations across risk scores are to be expected given differences in the outcome (i.e. predicting CVD vs. MI). The addition of HIV-specific variables as in the DAD score did not improve discrimination compared with ASCVD, however inclusion of different HIV-specific measures may lead to improved discrimination and is planned in future analyses. ASCVD performed as well or better than other risk scores across all MI events and the superior performance in detecting T2MI is worthy of additional investigation.

43 Stroke Incidence Highest inWomen and Black HIV-Infected Participants in ALLRT Cohort Felicia Chow 1 ; Michael R.Wilson 1 ; KunlingWu 2 ; Ron Ellis 3 ; Ronald Bosch 2 ; Benjamin P. Linas 4

1 Univ of California San Francisco, San Francisco, CA, USA; 2 Harvard Sch of PH, Boston, MA, USA; 3 Univ of California San Diego, San Diego, CA, USA; 4 Boston Univ Sch of Med, Boston, MA, USA Background: While rates of stroke are higher in HIV-infected compared with age-matched HIV-uninfected individuals, many questions persist regarding the nature of cerebrovascular disease in HIV. We leveraged the large ACTG Longitudinal Linked Randomized Trials (ALLRT) cohort and its parent studies to investigate stroke incidence and associated risk factors in HIV-infected individuals. Methods: We conducted a prospective observational cohort study of ART-naïve participants without a history of stroke who initiated ART from June 1998 to June 2011. The primary outcome was first-ever stroke or transient ischemic attack (TIA) documented at study follow up visits through centralized reporting. Age-adjusted Poisson regression models with time-updated covariates were used to identify traditional and HIV-specific risk factors for incident stroke/TIA. Results: Of 6,933 participants included in the analysis, 20%were women, 37%were non-Hispanic Blacks and 21%were Hispanic. Median pre-ART age was 37 years, pre-ART CD4 count was 243 cells/uL and pre-ART HIV RNA was 57,624 copies/mL. Fifty-four stroke/TIAs occurred over 32,023 person-years (PY). The incidence rate of stroke/TIA in women was 0.29 per 100 PY versus 0.14 per 100 PY in men [age-adjusted relative risk (RR) for female sex 1.72, 95% CI 0.96-3.08]. Incidence of stroke/TIA in non-Hispanic Blacks was 0.25 per 100 PY compared with 0.08 per 100 PY in Hispanics/Other (age-adjusted RR 2.94, 95% CI 1.22-7.14) and 0.16 per 100 PY in Whites (RR 1.67, 95% CI 0.95-2.94). In a multivariable model (Table), traditional risk factors that conferred greater risk of stroke/TIA were older age, LDL ≥ 160 mg/dL and hypertension. Of HIV-related factors, time-updated CD4 count ≤ 200 cells/uL and HIV RNA > 200 copies/mL were associated with increased risk of stroke/TIA. We found no statistically significant association of injection drug use, hepatitis C infection or recent use of any class of ART with stroke/TIA. Conclusions: Age-adjusted incidence of stroke/TIA was highest in women and non-Hispanic Blacks in this cohort of HIV-infected participants. Investigation into the association between female sex and non-Hispanic Black race with stroke/TIA in HIV is merited. In addition to an association with several modifiable traditional risk factors, stroke/TIA was also associated with immunodeficiency and poor virologic control. This raises the possibility that immunologic sequelae of uncontrolled viremia may also contribute to stroke risk in HIV infection.

Oral Abstracts

44LB Aspirin Fails to Impact Immune Activation or Endothelial Function in Treated HIV Meagan K. O’Brien 1 ; Douglas Kitch 2 ; PeterW. Hunt 3 ; Karin Klingman 4 ; James H. Stein 5 ; NicholasT. Funderburg 6 ; Jeffrey S. Berger 7 ; PabloTebas 8 ; Judith Aberg 1 ; for the ACTG A5331 StudyTeam 1 Icahn Sch of Med at Mount Sinai, New York, NY, USA; 2 Harvard Sch of PH, Boston, MA, USA; 3 Univ of California San Francisco, San Francisco, CA, USA; 4 NIAID, NIH, Bethesda, MD, USA; 5 Univ of Wisconsin-Madison, Madison, WI, USA; 6 Ohio State Univ, Columbus, OH, USA; 7 New York Univ School of Med, New York, NY, USA; 8 Univ of Pennsylvania, Philadelphia, PA, USA Background: Immune activation persists despite optimally treated HIV infection and predicts non-AIDS co-morbidities including cardiovascular disease and certain cancers. Activated platelets play a key role in thrombosis and inflammation, and HIV induces platelet activation by direct and indirect mechanisms. Aspirin is a potent inhibitor of platelet activation. We hypothesized that aspirin would reduce immune activation and improve endothelial function in antiretroviral therapy (ART)-suppressed HIV-infected individuals. Methods: ACTG A5331 was a prospective, double-blind, randomized, placebo-controlled 3-arm trial of HIV-infected participants on suppressive ART for >48 weeks randomized to daily aspirin 100mg, aspirin 300mg or placebo for 12 weeks followed by a 4 week washout. The primary outcome was sCD14 and secondary outcomes included FMD, D-dimer, other soluble and cellular immune activation markers, and thromboxane (a direct readout of cyclooxygenase inhibition). Multivariable linear regression was used to assess differences and differential effects between treatment arms at a 5% α level.

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CROI 2016