Cases from the Clinic(ians): Case-based Panel Discussion Michael S. Saag, MD Professor of Medicine Associate Dean for Global Health University of Alabama at Birmingham Birmingham, Alabama FORMATTED: 11/17/2015 New Orleans, Louisiana: December 15-17, 2015

European AIDS Society Continues to Recommend ATP Initial Regimen for ART-Naïve Adult HIV-positive persons (11/14)

Research Question: Methods: Effect of delaying ART in naïve patients presenting with CM in high-income settings Methods: Observational cohorts contributing to COHERE, NA-ACCORD and CNICS Diagnosis of CM between 1998 and 2009. Follow-up 6 months. Mimicking RCT comparing Regime A: start ART within 14 days of CM diagnosis Regime B : defer ART until 14 -56 days after CM diagnosis. Marginal structural modelling to adjust for selection bias Pooled logistic regression model, adjusted for clustering on patient IDs to estimate the association of regime with mortality. adjusted for: age, gender, transmission risk group, year, country, AIDS (other than CM), CD4 and HIV viral load.

Results: Conclusions: 235 patients from 28 cohorts 84% male, median age at CM 38 years. Death rate at 6 months: 42/235 (18%) Hazard Ratios (95% CI) for deferred vs early ART Crude 1.29 (0.68-2.43) Adjusted 1.30 (0.66-2.55) Conclusions: Early ART does not seem to be associated with higher mortality in resource rich settings, in contrast to data from resource limited settings Underpowered to provide robust evidence Limitation: lack of data on CM treatment and disease management. We aim to obtain this in the future.

ARV Interaction Score Card Simeprevir Sofosbuvir Ledipasvir Daclatasvir PrOD DDI Substrate of CYP3A4, OATP1B1/3 Substrate of P-gp and BCRP Inhibitor/Substrate of P-gp and BCRP Inhibitor of OATP1B1/3, BCRP, Substrate of P-gp and CYP3A4 Inhibit/Sub of UGT1A1,OATP1B1/3, BCRP, CYP3A4, CYP2C8, P-gp ATV/r No data LDV ↑; ATV ↑ DCV ↑* ATV ↔; ABT450 ↑ DRV/r SIM ↑; DRV ↔ SOF ↑; DRV ↔ LDV ↑; DRV ↔ DRV ↓; PrOD ↓ LPV/r LPV ↔; ABT450 ↑ TPV/r EFV SIM ↓; EFV ↔ SOF ↔; EFV ↔ LDV ↓; EFV ↓ DCV ↓* No PK data** RPV SIM ↔; RPV ↔ SOF ↔; RPV ↔ LDV ↔; RPV ↔ ABT450 ↑; RPV ↑ ETV RAL SIM ↔; RAL ↔ SOF ↔; RAL ↔ LDV ↔; RAL ↔ PrOD ↔; ↑ RAL ELV/cobi DLG MVC TDF SIM ↔; TFV ↔ SOF ↔; TFV ↔ LDV ↔; ↑TFV DCV ↔; TFV ↔ PrOD ↔; TFV ↔ Slide courtesy of Jennifer Kiser SOF RAL decreased 27% and with LDV RAL decreased 15% * Decrease DCV dose to 30mg QD, Increase DCV dose to 90mg QD, ** PrOD + EFV led to premature study discontinuation due to toxicities

Switch from TDF to E/C/F/TAF Pts CrCl 69-30 cc/ml CROI 2015: Pozniak, et al. Abst 795

Switch from TDF to E/C/F/TAF Pts CrCl 69-30 cc/ml CROI 2015: Pozniak, et al. Abst 795

Abacavir and Risk for Myocardial Infarction- NA-ACCORD Adjusted hazard ratios of select established CVD risk factors that remained significantly associated with MI ● Restricted study population ● Full study population Recent ABC use Age <40 (vs. 50–59) years Age 40-49 (vs. 50–59) years Age ≥60 (vs. 50–59) years Hypertension Diabetes eGFR 30-59 (vs. ≥60) ml/min/1.73m2 eGFR <30 (vs. ≥60) ml/min/1.73m2 High (≥240 vs. <240 mg/dL) total cholesterol High (≥300 vs. <300 mg/dL) triglycerides Statin use Palella FJ et al, Abstract 749 CROI Seattle 2015

Risk Factors for Non-AIDS Defining Cancers in NA-ACCORD Smoking is a much higher risk for HIV-infected persons than other HIV-associated factors like low CD4 counts, detectable HIV RNA or clinical AIDS dx Treating HIV should also help NADCs Limitations: no BMI or alcohol use data Althoff K et al. CROI 2015 #726