Antiretroviral Guidelines

US DHHS Guidelines with Australian commentary


Characteristics of Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTIs)


Last Updated: October 25, 2018;

Last Reviewed: October 25, 2018

Note: DLV is not included in this table. Please refer to the DLV Food and Drug Administration package insert for related infor


Generic Name
(Abbreviation)
Trade Name
Formulations Dosing Recommendationsa Elimination/ Metabolic Pathway Serum 
Half-Life
Adverse Eventsb
Doravirine 
(DOR) 
Pifeltro
Pifeltro:
  • 100 mg tablet
Pifeltro:
  • 1 tablet once daily
CYP3A4/5 substrate 15 hours
  • Nausea
  • Dizziness
  • Abnormal dreams
(DOR/TDF/3TC) 
Delstrigo
Delstrigo:
  • (DOR 100 mg plus TDF 300 mg plus 3TC 300 mg) tablet
Delstrigo:
  • 1 tablet once daily
Efavirenz 
(EFV) 
Sustiva 

Note: Generic product is available.
Sustiva:
  • 50 and 200 mg capsules
  • 600 mg tablet
Generic:
  • 600 mg tablet
Sustiva:
  • 600 mg once daily, at or before bedtime
  • Take on an empty stomach to reduce side effects.
Metabolized by CYPs 2B6 (primary), 3A4, and 2A6 

CYP3A4 mixed inducer/inhibitor (more an inducer than an inhibitor) CYP2C9 and 2C19 inhibitor; 2B6 inducer
40–55 hours
  • Rashc
  •  Neuropsychiatric symptomsd
  • Increased transaminase levels
  • Hyperlipidemia
  • False-positive results with some cannabinoid and benzodiazepine screening assays reported
  • QT interval prolongation
(EFV/TDF/FTC) 
Atripla
Atripla:
  • (EFV 600 mg plus TDF 300 mg plus FTC 200 mg) tablet
Atripla:
  • 1 tablet once daily on an empty stomach, preferably at bedtime
(EFV/TDF/3TC) 
Symfi
Symfi:
  • (EFV 600 mg plus TDF 300 mg plus 3TC 300 mg) tablet
Symfi:
  • 1 tablet once daily on an empty stomach, preferably at bedtime
(EFV/TDF/3TC) 
Symfi Lo
Symfi Lo:
  • (EFV 400 mg plus TDF 300 mg plus 3TC 300 mg) tablet
Symfi Lo:
  • 1 tablet once daily on an empty stomach, preferably at bedtime
Etravirine 
(ETR) 
Intelence
Intelence:
  • 25, 100, and 200 mg tablets
Intelence:
  • 200 mg BID
  • Take following a meal.
CYP3A4, 2C9, and 2C19 substrate 

3A4 inducer; 2C9 and 2C19 inhibitor
41 hours
  • Rash, including Stevens-Johnson syndromec
  • HSRs, characterized by rash, constitutional findings, and sometimes organ dysfunction (including hepatic failure) have been reported.
  • Nausea
Nevirapine 
(NVP) 
Viramune or Viramune XR 

Note: Generic is available for 200 mg tablets and oral suspension.
  • 200 mg tablet
  • 400 mg XR tablet
  • 50 mg/5 mL oral suspension
  • 200 mg once daily for 14 days (lead-in period); thereafter, 200 mg BID, or 400 mg (Viramune XR tablet) once daily
  • Take without regard to meals.
  • Repeat lead-in period if therapy is discontinued for >7 days.
  • In patients who develop mild-to-moderate rash without constitutional symptoms, continue lead-in period until rash resolves, but do not administer for longer than 28 days total.
CYP450 substrate, inducer of 3A4 and 2B6; 80% excreted in urine (glucuronidated metabolites, <5% unchanged); 10% in feces 

Contraindicated in patients with moderate to severe hepatic impairment. 

Dose adjustment is recommended in patients on hemodialysis (see Appendix B, Table 8).
25–30 hours
  • Rash, including Stevens-Johnson syndromec
  • Symptomatic hepatitis, including fatal hepatic necrosis, has been reported:
    • Rash reported in approximately 50% of cases.
    • Occurs at significantly higher frequency in ARV-naive female patients with pre-NVP CD4 counts >250 cells/mm3 and in ARV-naive male patients with pre-NVP CD4 counts >400 cells/mm3. NVP should not be initiated in these patients unless the benefit clearly outweighs the risk.
Rilpivirine 
(RPV) 
Edurant
Edurant:
  • 25 mg tablet
Edurant:
  • 25 mg once daily
  • Take with a meal.
CYP3A4 substrate 50 hours
  • Rashc
  • Depression, insomnia, headache
  • Hepatotoxicity
  • QT interval prolongation
(RPV/DTG) 
Juluca
Juluca:
  • (RPV 25 mg plus DTG 50 mg) tablet
Juluca:
  • 1 tablet once daily
  • Take with a meal.
(RPV/TAF/FTC) 
Odefsey
Odefsey:
  • (RPV 25 mg plus TAF 25 mg plus FTC 200 mg) tablet
Odefsey:
  • 1 tablet once daily
  • Take with a meal.
(RPV/TDF/FTC)Complera Complera:
  • (RPV 25 mg plus TDF 300 mg plus FTC 200 mg) tablet
Complera:
  • 1 tablet once daily
  • Take with a meal.
a For dose adjustments in patients with renal or hepatic insufficiency, see Appendix B, Table 8. 
b Also see Table 15. 
c Rare cases of Stevens-Johnson syndrome have been reported with most NNRTIs; the highest incidence of rash was seen with NVP. 
d Adverse events can include dizziness, somnolence, insomnia, abnormal dreams, depression, suicidality (suicide, suicide attempt or ideation), confusion, abnormal thinking, impaired concentration, amnesia, agitation, depersonalization, hallucinations, and euphoria. Approximately 50% of patients receiving EFV may experience any of these symptoms. Symptoms usually subside spontaneously after 2 to 4 weeks but may necessitate discontinuation of EFV in a small percentage of patients. 

Key to Acronyms: 3TC = lamivudine; ARV = antiretroviral; BID = twice daily; CD4 = CD4 T lymphocyte; CYP = cytochrome P; DLV = delavirdine; DOR = doravirine; DTG = dolutegravir; EFV = efavirenz; ETR = etravirine; FTC = emtricitabine; HSR = hypersensitivity reaction; NNRTI = non-nucleoside reverse transcriptase inhibitor; NVP = nevirapine; RPV = rilpivirine; TAF = tenofovir alafenamide; TDF = tenofovir disoproxil fumarate; XR = extended release