clinical case discussion: switching hiv...

Clinical Case Discussion: Switching HIV Therapy

Pavel Khaykin, Frankfurt am Main

The Why and How of Switching in Virologic Suppression

Why

Simplify regimen

(pill number and frequency)

Tolerability

Comorbidity

Drug–drug and drug–food interactions

Pregnancy

Cost

How

Maintain viral suppression to avoid resistance

Need to consider

▪ Previous ART

▪ Previous resistance

▪ Likelihood of adherence

▪ Drug–drug or drug–food interactions

▪ Comorbid conditions

DHHS guidelines. March 2018.

Case 1: HIV and HCV infection

A 53-year-old man with HIV and HCV

▪ Origin: Portugal

▪ Injection heroin use (past); currently in OST

▪ eGFR: <10, End stage kidney disease, Hemodialysis

▪ HIV

‒ ED 2002

‒ CD4+ nadir 83 cells/mm3 and HIV RNA 11.580 copies/mL

‒ HLA-B*5701 negative

▪ HCV

‒ HCV genotype 3a infection with HCV RNA = 1.5 million IU/mL

‒ Liver elastography consistent with stage 3 fibrosis

Dialiysis

2002ABC DDI NFV

2002 2004 2006 2007

CD4-Cells /µl HIV-1-RNA

2002 11.5000

2007 <50 IU/ml

1.000 Zellen/µl

800 Zellen/µl

600 Zellen/µl

400 Zellen/µl

200 Zellen/µl

0 Zellen/µl

2007 ABC 3TC FPV/r


Case 1 HIV and HCV Infection

Dose Adjustment of ARVs for Impaired Renal Function

NRTI/NtRTI: Dose Adjustment or not recommended

NNRTI: No dose adjustment required

PI: No dose adjustment required

Dialysis

2002ABC DDI NFV

2002 2007 2010 2018

CD4-Cells /µl HIV-1-RNA

2002 11.5000

2018 <20 IU/ml

2007 <50 IU/ml

2010 <20 IU/ml

1.000 Zellen/µl

800 Zellen/µl

600 Zellen/µl

400 Zellen/µl

200 Zellen/µl

0 Zellen/µl

2007 ABC 3TC FPV/r

2010LPV/r SQV


HCV Tx

20818 ARV?

Recommendations for First-line HCV Treatment in HCV/HIV Coinfection

Regimen by HCV GT

Duration, Wks

No CirrhosisCompensated

Cirrhosis‡eGFR < 30 mL/min

1, 4

8 GLE/PIB – GLE/PIB‖‖

12GZR/EBR,*

SOF/LDV,† SOF/VELGLE/PIB, GZR/EBR,*SOF/LDV, SOF/VEL

GZR/EBR

2, 38 GLE/PIB – GLE/PIB‖‖

12 SOF/VEL GLE/PIB, SOF/VEL§ –

5, 6

8 GLE/PIB – GLE/PIB‖‖

12 SOF/LDV, SOF/VELGLE/PIB, SOF/LDV,

SOF/VEL–

AASLD/IDSA HCV Guidelines. 2017.

*If GT1a with BL NS5A RASs for EBR, 12 wks not recommended; can increase duration to 16 wks with RBV (alternative). †Some data to support 8 wks in GT1, but 8 wks not recommended in HIV/HCV coinfection. ‡If decompensated cirrhosis, do not use HCV protease inhibitors. §If BL Y93H RAS present in GT3, add RBV or consider SOF/VEL/VOX. ‖If also cirrhotic, increase duration to 12 wks.

Recommendation for End-Stage Renal Disease

7

HIV/HCV Drug–Drug Interactions

8

ARV(s) GLE/PIB GZR/EBR SOF/LDV SOF/VEL SOF/VEL/VOX

ATV + (RTV or COBI) X X ✓* ✓* X

DRV + (RTV or COBI) X X ✓* ✓* ✓*†‡

LPV + RTV X X ✓* ✓* X

EFV X X ✓* X X

RPV ✓ ✓ ✓* ✓ ✓

BIC ‒§ ‒§✓

† ✓†

✓†

DTG ✓ ✓ ✓* ✓ ✓

RAL ✓ ✓ ✓ ✓ ✓

EVG/COBI/FTC/TDF ✓*† X X ✓* ✓*†

EVG/COBI/FTC/TAF ✓† X ✓ ✓ ✓

†

3TC/ABC ✓ ✓ ✓ ✓ ✓

TAF or TDF ✓ ✓ ✓* ✓* ✓*

Coadministration of HCV and HIV PIs not currently recommended

Case 1 HIV and HCV Coinfection

Dose Adjustment of ARVs for Impaired Renal Function

NRTI/NtRTI: Dose Adjustment or not recommended

NNRTI: No dose adjustment required

PI: No dose adjustment required but not with HCV PI

INSTI: No dose adjustment required

DTG RPV

Principles of ART Regimen Switching in Virologically Suppressed Patients

• Review ART history for previous intolerance or HIV virologic failure

• Review HIV resistance test results

• If previous HIV resistance uncertain, consider a switch only if new regimen likely to maintain suppression of resistant virus

• In patients with HBV/HIV coinfection, continue ARVs active against HBV (even if not needed for HIV suppression)

• Check HIV-1 RNA during first 3 mos after switch to ensure suppression

• Monotherapy with boosted PI or INSTI not recommended

11

Switching After Virologic Failure


First-line regimen failure

Boosted PI + NRTIsBoosted PI + active

INSTI

Yes

2 (preferably 3)fully active drugs

(or partially active drug if no other options)

No‡

Second-line regimen failureand beyond

PI susceptible

Failing regimen (+ NRTI)

▪Boosted PI

▪NNRTI

▪INSTI

Reinforce adherenceModify convenience or toxicity

Boosted PI + NRTIsBoosted PI + INSTIDTG + NRTIs (if 1 fully active)

Boosted PI + NRTIsBoosted PI + active INSTI*DTG + NRTIs (≥ 1 fully active)†


Slide credit: clinicaloptions.com

http://www.clinicaloptions.com/

Case 2 Virologic Failure

A 40-year-old man with HIV

▪ Origin: Germany

▪ MSM

▪ No comorbidity

▪ HIV

‒ ED 2003

‒ First ART 2010

‒ CD4+ nadir 43 cells/mm3 and HIV RNA 9.950.000 copies/mL

‒ HLA-B*5701 negative


Non compliance

2010TDF FTC EFV

2010 2011 2016 2018

CD4-Cells /µl

HIV-1-RNA2010 9.950.000

2018 450 Cop/ml

2011 5600 Cop/ml2016 <20 Cop/ml

1.000 Zellen/µl

800 Zellen/µl

600 Zellen/µl

400 Zellen/µl

200 Zellen/µl

0 Zellen/µl

2011FTC TDF ATV/r

2016TDF FTC EVG/c

Simplification

2018?

virologicalFailure

Case 2. HIV Drug Resistance Test 2018

15


First-line regimen failure

Boosted PI + NRTIsBoosted PI + active

INSTI

Yes

2 (preferably 3)fully active drugs

(or partially active drug if no other options)

No‡

Second-line regimen failureand beyond

PI susceptible

Failing regimen (+ NRTI)

▪Boosted PI

▪NNRTI

▪INSTI

Reinforce adherenceModify for convenience or toxicity

Boosted PI + NRTIsBoosted PI + INSTIDTG + NRTIs (if 1 fully active)

Boosted PI + NRTIsBoosted PI + active INSTI*DTG + NRTIs (≥ 1 fully active)†


TAF FTC DRC/c


Non compliance

2010TDF FTC EFV

2010 2011 2016 2018

CD4-Cells /µl

HIV-1-RNA2010 9.950.000

2018 450 Cop/ml2018 <20 Cop/ml

2011 5600 Cop/ml2016 <20 Cop/ml

1.000 Zellen/µl

800 Zellen/µl

600 Zellen/µl

400 Zellen/µl

200 Zellen/µl

0 Zellen/µl

2011FTC TDF ATV/r

2016TDF FTC EVG/c

Simplification

TAF FTC DRV/c

virologicalFailure

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