2019 Ryan White HIV/AIDS Program CLINICAL CONFERENCE

0.6

None

0.5

0.4

ATG

0.3

Anti-IL2

0.2

0.1

0.0

• Infection common > 50% first year (AIDS-defining ~10%) • Neither ATG or IL2 associated with higher infection risk • ATG associated with lower risk of CMV, CDI, pneumonia

Kucirka L,Locke JE, etal. Induction immunosuppressionand clinicaloutcomes inkidney transplantrecipients infectedwith HIV,2016;16(8):2368-76

Slide46of63FromJELocke,MD,MPHatNewOrleans,LA,December4-7,2019,RyanWhiteHIV/AIDSProgramCLINICAL CONFERENCE, IAS  USA.

Potential Etiologies for High Rates of Acute Rejection

2. Drug interactions resulting in altered exposure to IS

Stock PG, et al.NEJM 2010

 Pharmacokinetic curve of tacrolimus inHIV patients receiving protease inhibitors does not show the normal peak-and-trough pattern  Resembles a flat line with half-life ofup to20 days secondary to strong inhibition of CYP3A  Trough levels of tacrolimus in patients receiving protease inhibitors should be higher to achieve AUCs equal topatients not on protease inhibitors  17.5 ng/mL at1-month  10 ng/mL at1-year

VanMaarseveenEM,van ZuilenAD,MudrikovaT. CorrespondenceNEJM2010.

Slide47of63FromJELocke,MD,MPHatNewOrleans,LA,December4-7,2019,RyanWhiteHIV/AIDSProgramCLINICAL CONFERENCE, IAS  USA.

Antiretroviral Therapy & Risk for Graft Loss

HazardRatio (95%CI)

P-value

PatientCharacteristics Protease inhibitors

1.84 (1.22-2.77) 1.79 (1.06-3.04) 1.86 (1.11-3.11) 0.95 (0.52-1.73) 2.46 (1.51-3.99) 1.24 (0.68-2.26)

0.003

Male

0.03 0.02 0.86

African American

EPTS> 20%

Hazard Ratio (95% CI)

P-value

HCVantibody+

<0.001

PRA ≥30%

0.48

DonorCharacteristics KDPI 0-20%

Protease inhibitors

Ref

0-365 days post-

4.48 (1.75- 11.48)

0.002

21-85%

1.97 (1.29-3.00) 1.93 (0.95-3.89)

0.002

transplant

>85%

0.07

Immunosuppression CNImaintenance Lymphodepleting induction

>365 days post-

1.40 (0.84-2.32) 0.20

0.64 (0.46-0.88) 1.45 (0.96-2.17)

0.01 0.08

transplant

TransplantEra 2000-2004

2.07 (1.34-3.20) 1.34 (0.78-2.33)

0.001

2004-2008 2008-2012

0.29

SheltonBand Locke JEet. al. Impactofprotease inhibitor-basedanti-retroviral therapy on outcomes forHIV+kidney transplantrecipients. Am JTransplantation 2017, [Epubaheadof print].

Ref

Slide48of63FromJELocke,MD,MPHatNewOrleans,LA,December4-7,2019,RyanWhiteHIV/AIDSProgramCLINICAL CONFERENCE, IAS  USA.