Antiretroviral Guidelines

US DHHS Guidelines with Australian commentary

Antiretroviral Dosing Recommendations in Patients with Renal or Hepatic Insufficiency

Last Updated: April 8, 2015; Last Reviewed: April 8, 2015

Panel's Recommendations Regarding Poor CD4 Cell Recovery and Persistent Inflammation Despite Viral Suppression

See the reference section at the end of this table for CrCl calculation formulas and criteria for Child-Pugh classification.

ARVs
Generic Name
(Abbreviation)
Trade Name

Usual Daily Dose^a

Dosing in Patients with Renal Insufficiency^b

Dosing in Patients with Hepatic Impairment

NRTIs
Stribild should not be initiated in patients with CrCl <70 mL/min. The following FDCs are not recommended in patients with CrCl <50 mL/min: Atripla, Combivir, Complera, Delstrigo, Epzicom, Triumeq, or Trizivir. Biktarvy, Descovy, Genvoya, Odefsey, Symtuza, and Truvada are not recommended in patients with CrCl <30 mL/min.

Abacavir
(ABC)
Ziagen

300 mg PO BID, or
600 mg PO once daily

No dose adjustment necessary.

Child-Pugh Class A:

200 mg PO BID (use oral solution)

Child-Pugh Class B or C:

Contraindicated

Didanosine EC
(ddI)
Videx EC

Body Weight ≥60 kg:

400 mg PO once daily

Body Weight <60 kg:

250 mg PO once daily

Once-Daily Dose by Body Weight
CrCl (mL/min)	≥60 kg	<60 kg
30–59	200 mg	125 mg
10–29	125 mg	125 mg
<10, HD,^c or CAPD	125 mg	75 mg oral solution

No dose adjustment necessary.

Didanosine Oral Solution
(ddI)
Videx

Body Weight ≥60 kg:

200 mg PO BID, or
400 mg PO once daily

Body Weight <60 kg:

250 mg PO once daily, or
125 mg PO BID

Once-Daily Dose by Body Weight
CrCl (mL/min)	≥60 kg	<60 kg
30–59	200 mg	150 mg
10–29	150 mg	100 mg
<10, HD,^c or CAPD	100 mg	75 mg

No dose adjustment necessary.

Emtricitabine
(FTC)
Emtriva

200 mg oral capsule once daily, or
240 mg (24 mL) oral solution once daily

Dose
CrCL (mL/min)	Capsule	Solution
30–49	200 mg q48h	120 mg q24h
15–29	200 mg q72h	80 mg q24h
<15 or on HD^c	200 mg q96h	60 mg q24h

No dose recommendation.

Lamivudine
(3TC)
Epivir

300 mg PO once daily, or
150 mg PO BID

CrCl (mL/min)	Dose
30–49	150 mg q24h
15–29	1 x 150 mg, then 100 mg q24h
5–14	1 x 150 mg, then 50 mg q24h
<5 or on HD^c	1 x 50 mg, then 25 mg q24h

No dose adjustment necessary.

Stavudine
(d4T)
Zerit

Body Weight ≥60 kg:

40 mg PO BID

Body Weight <60 kg:

30 mg PO BID

Dose
CrCl (mL/min)	≥60 kg	<60 kg
26–50	20 mg q12h	15 mg q12h
10–25 or on HD^c	20 mg q24h	15 mg q24h

No dose recommendation.

Tenofovir Alafenamide/ Emtricitabine
(TAF/FTC)
Descovy

TAF for HIV treatment is only available as a component of FDCs (i.e., Descovy, Genvoya, Odefsey, Biktarvy, and Symtuza).
TAF 10 mg PO daily with EVG/c (Genvoya) or DRV/c (Symtuza)
TAF 25 mg PO daily in other FDCs

CrCl (mL/min)	Dose
<30 or on HD^c	Not recommended

Child-Pugh Class A or B:

No dose adjustment

Child-Pugh Class C:

No dose recommendation

Tenofovir Disoproxil Fumarate
(TDF)
Viread

300 mg PO once daily

CrCl (mL/min)	Dose
30–49	300 mg q48h
10–29	300 mg twice weekly (every 72–96 hours)
<10 and not on HD	No recommendation
On HD^c	300 mg q7d

No dose adjustment necessary.

Tenofovir Disoproxil Fumarate/ Emtricitabine
(TDF/FTC)
Truvada

1 tablet PO once daily

CrCl (mL/min)	Dose
30–49	1 tablet q48h
<30 or on HD	Not recommended

No dose recommendation.

Tenofovir Disoproxil Fumarate/ Lamivudine
(TDF/3TC)
Cimduo

1 tablet PO once daily

CrCl (mL/min)	Dose
<50 or on HD	Not recommended

No dose recommendation.

Zidovudine
(ZDV)
Retrovir

300 mg PO BID

CrCL (mL/min)	Dose
<15 or HD^c	100 mg TID or 300 mg once daily

No dose recommendation.

NNRTIs

Doravirine
(DOR)
Pifeltro

1 tablet PO once daily

No dose adjustment required in mild, moderate, or severe renal impairment. Has not been studied in ESRD or HD.

Child-Pugh Class A or B:

No dose adjustment

Child-Pugh Class C:

Not studied

Doravirine/ Tenofovir Disoproxil Fumarate/ Lamivudine
(DOR/TDF/3TC)
Delstrigo

1 tablet PO once daily

Not recommended if CrCl <50 mL/min.

Child-Pugh Class A or B:

No dose adjustment

Child-Pugh Class C:

Not studied

Efavirenz
(EFV)
Sustiva

600 mg PO once daily, on an empty stomach, preferably at bedtime

No dose adjustment necessary.

No dose recommendation; use with caution in patients with hepatic impairment.

Efavirenz/ Tenofovir Disoproxil Fumarate/ Emtricitabine
(EFV/TDF/FTC)
Atripla

1 tablet once daily on an empty stomach, preferably at bedtime

Not recommended if CrCl <50 mL/min. Instead, use the individual drugs and adjust TDF and FTC doses according to CrCl level.

No dose recommendation; use with caution in patients with hepatic impairment.

Efavirenz 600 mg/ Tenofovir Disoproxil Fumarate/ Lamivudine
(EFV/TDF/3TC)
Symfi

1 tablet once daily on an empty stomach, preferably at bedtime

Not recommended if CrCl <50 mL/min or if patient is on HD. Instead, use the individual drugs and adjust TDF and 3TC doses according to CrCl level.

Not recommended for patients with moderate or severe hepatic impairment. Use caution in patients with mild hepatic impairment.

Efavirenz 400 mg/ Tenofovir Disoproxil Fumarate/ Lamivudine
(EFV/TDF/3TC)
Symfi Lo

1 tablet once daily on an empty stomach, preferably at bedtime

Not recommended if CrCl <50 mL/min or if patient is on HD. Instead, use the individual drugs and adjust TDF and 3TC doses according to CrCl level.

Not recommended for patients with moderate or severe hepatic impairment. Use caution in patients with mild hepatic impairment.

Etravirine
(ETR)
Intelence

200 mg PO BID

No dose adjustment necessary.

Child-Pugh Class A or B:

No dose adjustment

Child-Pugh Class C:

No dose recommendation

Nevirapine
(NVP)
Viramune
or
Viramune XR

200 mg PO BID, or
400 mg PO once daily (using Viramune XR formulation)

No dose adjustment for patients with renal impairment.

Patients on HD should receive an additional dose of 200 mg following each dialysis treatment.

Child-Pugh Class A:

No dose adjustment

Child-Pugh Class B or C:

Contraindicated

Rilpivirine
(RPV)
Edurant

25 mg PO once daily

No dose adjustment necessary.

Child-Pugh Class A or B:

No dose adjustment

Child-Pugh Class C:

No dose recommendation

Rilpivirine/ Tenofovir Alafenamide/ Emtricitabine
(RPV/TAF/FTC)
Odefsey

1 tablet PO once daily

Not recommended if CrCl <30 mL/min.

Child-Pugh Class A or B:

No dose adjustment

Child-Pugh Class C:

No dose recommendation

Rilpivirine/ Tenofovir Disoproxil Fumarate/ Emtricitabine
(RPV/TDF/FTC)
Complera

1 tablet PO once daily

Not recommended if CrCl <50 mL/min. Instead, use the individual drugs and adjust TDF and FTC doses according to CrCl level.

Child-Pugh Class A or B:

No dose adjustment

Child-Pugh Class C:

No dose recommendation

Rilpivirine/Dolutegravir
(RPV/DTG)
Juluca

1 tablet PO once daily with food

No dose adjustment necessary.

In patients with CrCl <30 mL/min, monitor closely for adverse effects.

Child-Pugh Class A or B:

No dose adjustment

Child-Pugh Class C:

No dose recommendation

PIs

Atazanavir
(ATV)
Reyataz

400 mg PO once daily, or
(ATV 300 mg plus RTV 100 mg) PO once daily

No dose adjustment for patients with renal dysfunction who do not require HD.

In ARV-Naive Patients on HD:

(ATV 300 mg plus RTV 100 mg) once daily

In ARV-Experienced Patients on HD:

ATV or ATV/r not recommended

Child-Pugh Class B:

300 mg once daily (unboosted) for ARV-naive patients only

Child-Pugh Class C:

Not recommended

RTV boosting is not recommended in patients with hepatic impairment.

Atazanavir/ Cobicistat
(ATV/c)
Evotaz

1 tablet PO once daily

If Used with TDF:

Not recommended for use in patients with CrCl <70 mL/min

Not recommended in patients with hepatic impairment.

Darunavir
(DRV)
Prezista

In ARV-Naive Patients and ARV-Experienced Patients with No DRV Resistance Mutations:

(DRV 800 mg plus RTV 100 mg) PO once daily with food

In ARV-Experienced Patients with at Least 1 DRV Resistance Mutation:

(DRV 600 mg plus RTV 100 mg) PO BID

No dose adjustment necessary.

In Patients with Mild-to-Moderate Hepatic Impairment:

No dose adjustment

In Patients with Severe Hepatic Impairment:

Not recommended

Darunavir/ Cobicistat
(DRV/c)
Prezcobix

1 tablet PO once daily

If Used with TDF:

Not recommended for use in patients with CrCl <70 mL/min

Child-Pugh Class A or B:

No dose adjustment

Child-Pugh Class C:

Not recommended

Darunavir/ Cobicistat/ Tenofovir Alafenamide/ Emtricitabine
(DRV/c/TAF/FTC)
Symtuza

1 tablet PO once daily

Not recommended if CrCl <30 mL/min.

Not recommended for patients with severe hepatic impairment.

Fosamprenavir
(FPV)
Lexiva

1400 mg PO BID, or
(FPV 1400 mg plus RTV 100–200 mg) PO once daily, or
(FPV 700 mg plus RTV 100 mg) PO BID

No dose adjustment necessary.

In PI-Naive Patients Only
Child-Pugh Score 5–9:

700 mg BID

Child-Pugh Score 10–15:

350 mg BID

In PI-Naive or PI-Experienced Patients
Child-Pugh Score 5–6:

(FPV 700 mg BID plus RTV 100 mg) once daily

Child-Pugh Score 7–9:

(FPV 450 mg BID plus RTV 100 mg) once daily

Child-Pugh Score 10–15:

(FPV 300 mg BID plus RTV 100 mg) once daily

Indinavir
(IDV)
Crixivan

800 mg PO q8h

No dose adjustment necessary.

In Patients with Mild-to-Moderate Hepatic Insufficiency Due to Cirrhosis:

600 mg q8h

Lopinavir/ Ritonavir
(LPV/r)
Kaletra

(LPV 400 mg plus RTV 100 mg) PO BID, or
(LPV 800 mg plus RTV 200 mg) PO once daily

Avoid once-daily dosing in patients on HD.

No dose recommendation; use with caution in patients with hepatic impairment.

Nelfinavir
(NFV)
Viracept

1250 mg PO BID

No dose adjustment necessary.

In Patients with Mild Hepatic Impairment:

No dose adjustment

In Patients with Moderate-to-Severe Hepatic Impairment:

Not recommended

Ritonavir
(RTV)
Norvir

As a PI-Boosting Agent:

100–400 mg per day

No dose adjustment necessary.

Refer to recommendations for the primary PI.

Saquinavir
(SQV)
Invirase

(SQV 1000 mg plus RTV 100 mg) PO BID

No dose adjustment necessary.

In Patients with Mild-to-Moderate Hepatic Impairment:

Use with caution

In Patients with Severe Hepatic Impairment::

Contraindicated

Tipranavir
(TPV)
Aptivus

(TPV 500 mg plus RTV 200 mg) PO BID

No dose adjustment necessary.

Child-Pugh Class A:

Use with caution

Child-Pugh Class B or C:

Contraindicated

INSTIs

Bictegravir/ Tenofovir Alafenamide/ Emtricitabine
(BIC/TAF/FTC)
Biktarvy

1 tablet once daily

Not recommended for use in patients with CrCl <30 mL/min.

Child-Pugh Class C:

Not recommended

Dolutegravir
(DTG)
Tivicay

50 mg once daily, or
50 mg BID

No dose adjustment necessary.

Child-Pugh Class A or B:

No dose adjustment

Child-Pugh Class C:

Not recommended

Dolutegravir/ Abacavir/ Lamivudine
(DTG/ABC/3TC)
Triumeq

1 tablet once daily

Not recommended if CrCl <50 mL/min. Instead, use the individual drugs and adjust 3TC dose according to CrCl.

Child-Pugh Class A:

Patients with mild hepatic impairment require a dose reduction of ABC. Use the individual drugs instead of the fixed-dose combination in these patients.

Child-Pugh Class B or C:

Contraindicated, due to the ABC component

Dolutegravir/ Rilpivirine
(DTG/RPV)
Juluca

1 tablet PO once daily with food

No dose adjustment necessary.

In patients with CrCl <30 mL/min, monitor closely for adverse effects.

Child-Pugh Class A or B:

No dose adjustment

Child-Pugh Class C:

No dose recommendation

Elvitegravir/ Cobicistat/ Tenofovir Alafenamide/ Emtricitabine
(EVG/c/TAF/FTC)
Genvoya

1 tablet once daily

Not recommended for use in patients with CrCl <30 mL/min.

In Patients with Mild-to-Moderate Hepatic Insufficiency:

No dose adjustment necessary

In Patients with Severe Hepatic Insufficiency:

Not recommended

Elvitegravir/ Cobicistat/Tenofovir Disoproxil Fumarate/ Emtricitabine
(EVG/c/TDF/FTC)
Stribild

1 tablet once daily

EVG/c/TDF/FTC should not be initiated in patients with CrCl <70 mL/min.

Discontinue EVG/c/TDF/FTC if CrCl declines to <50 mL/min while patient is on therapy.

In Patients with Mild-to-Moderate Hepatic Insufficiency:

No dose adjustment necessary

In Patients with Severe Hepatic Insufficiency:

Not recommended

Raltegravir
(RAL)
Isentress
Isentress HD

400 mg BID (using Isentress formulation), or
1200 mg once daily (use Isentress HD formulation only)

No dose adjustment necessary.

In Patients with Mild-to-Moderate Hepatic Insufficiency:

No dose adjustment necessary

In Patients with Severe Hepatic Insufficiency:

No recommendation

Fusion Inhibitor

Enfuvirtide
(T-20)
Fuzeon

90 mg subcutaneous BID

No dose adjustment necessary.

CCR5 Antagonist

Maraviroc
(MVC)
Selzentry

The recommended dose differs based on concomitant medications and potential for drug-drug interactions. See Appendix B, Table 6 for detailed dosing information.

In Patients with CrCl <30 mL/min or Patients Who Are on HD
Without Potent CYP3A Inhibitors or Inducers:

300 mg BID; reduce to 150 mg BID if postural hypotension occurs

With Potent CYP3A Inducers or Inhibitors:

Not recommended

No dose recommendations. MVC concentrations will likely be increased in patients with hepatic impairment.

CD4 Post-Attachment Inhibitor

Ibalizumab
(IBA)
Trogarzo

Loading dose of 2000 mg IV, followed by a maintenance dose of 800 mg IV every 2 weeks

No dose adjustment recommended.

No recommendation.

^a Refer to Appendix B, Tables 1–7 for additional dosing information.
^b Including patients who are on CAPD and HD.
^c On dialysis days, take dose after HD session.

Key to Acronyms: 3TC = lamivudine; ABC = abacavir; ARV = antiretroviral; ATV = atazanavir; ATV/c = atazanavir/cobicistat; ATV/r = atazanavir/ritonavir; AZT = zidovudine; BIC = bictegravir; BID = twice daily; CAPD = chronic ambulatory peritoneal dialysis; COBI = cobicistat; CrCl = creatinine clearance; CYP = cytochrome P; d4T = stavudine; ddI = didanosine; DLV = delavirdine; DRV = darunavir; DRV/c = darunavir/cobicistat; DTG = dolutegravir; DOR = doravirine; EC = enteric coated; EFV = efavirenz; ESRD = end stage renal disease; ETR = etravirine; EVG = elvitegravir; EVG/c = elvitegravir/cobicistat; FDC = fixed-dose combination; FPV = fosamprenavir; FTC = emtricitabine; HD = hemodialysis; IBA = ibalizumab; IDV = indinavir; INSTI = integrase strand transfer inhibitor; IV = intravenous; LPV = lopinavir; LPV/r = lopinavir/ritonavir; MVC = maraviroc; NFV = nelfinavir; NNRTI = non-nucleoside reverse transcriptase inhibitor; NRTI = nucleoside reverse transcriptase inhibitor; NVP = nevirapine; PI = protease inhibitor; PO = orally; q(n)d = every (n) days; q(n)h = every (n) hours; RAL = raltegravir; RPV = rilpivirine; RTV = ritonavir; SQV = saquinavir; T-20 = enfuvirtide; TAF = tenofovir alafenamide; TDF = tenofovir disoproxil fumarate; TID = three times daily; TPV = tipranavir; XR = extended release; ZDV = zidovudine

Component	Points Scored
Component	1	2	3
Encephalopathy^a	None	Grade 1–2	Grade 3–4
Ascites	None	Mild or controlled by diuretics	Moderate or refractory despite diuretics
Albumin	>3.5 g/dL	2.8–3.5 g/dL	<2.8 g/dL
Total bilirubin or	<2 mg/dL (<34 µmol/L)	2–3 mg/dL (34–50 µmol/L)	>3 mg/dL (>50 µmol/L)
Modified total bilirubin^b	<4 mg/dL	4–7 mg/dL	>7 mg/dL
Prothrombin time (seconds prolonged) or	<4	4–6	>6
International normalized ratio (INR)	<1.7	1.7–2.3	>2.3
^a Encephalopathy Grades Grade 1: Mild confusion, anxiety, restlessness, fine tremor, slowed coordination Grade 2: Drowsiness, disorientation, asterixis Grade 3: Somnolent but rousable, marked confusion, incomprehensible speech, incontinence, hyperventilation Grade 4: Coma, decerebrate posturing, flaccidity ^b Modified total bilirubin is used for patients who have Gilbert’s syndrome or who are taking indinavir or atazanavir.

Child-Pugh Classification	Total Child-Pugh Score^a
Class A	5–6 points
Class B	7– points
Class C	>9 points
^a Sum of points for each component of the Child-Pugh Score