1. 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

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

3. 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 Follow-up 6 months.
Mimicking RCT comparing
Regime A: start ART within 14 days of CM diagnosis
Regime B : defer ART until 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.

4. 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 ( )
Adjusted 1.30 ( )
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.

5. 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

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

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

8. 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 (vs. 50–59) years
Age ≥60 (vs. 50–59) years
Hypertension
Diabetes
eGFR (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

9. 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