2019 Ryan White HIV/AIDS Program CLINICAL CONFERENCE

Why are Integrase Inhibitors preferred?

DrugClass

Effect onCNI/mTOR levels

Metabolism

NRTIs

none

NonCYP3A4

NNRTIs

Decrease*

CYP3A4 variable

PI

Increase

CYP3A4 inhibitor

Fusion Inhibitors

none

CYP3A4 substrate

CCR5RAntagonist

none

NonCYP3A4

Integrase Inhibitors

none

NonCYP3A4

*exceptions:delavirdineand rilpvirine(incr/noeffect) Ritonavirhas thegreatesteffectofPIs

VanMaarseveenetalAIDSPatient careandSTDs2012

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TDF use posttransplant

• 104 HIV+ KTx 2001-2014

• 3yr graft loss: 26% TDF vs 28% non-TDF

• TDF associated with AKI and CKD • Fanconi’s syndrome – mitochondrial toxicity • TAF – prodrug, intracellular conversion to TDF in lymphocytes, lower plasma exposure

Boyle etal Transplant Infect Dis 2017

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HIV control does not prevent renal infection

• 68% of HIV+ recipients with undetectable VL had HIV detectable in their kidneys • Infection had 2 forms: podocyte and tubular • Podocyte infection was associated with more rapid decline in renal function and graft loss • Urine HIV RNA and DNA screening test developed – correlates with biopsy • Rationale for protocol biopsies?

Canaud et al JASN 2014

Slide51of63FromJELocke,MD,MPHatNewOrleans,LA,December4-7,2019,RyanWhiteHIV/AIDSProgramCLINICAL CONFERENCE, IAS  USA.