ART in Adults & Adolescents

This resource summarizes critical information regarding antiretroviral (ARV) therapy (ART) most commonly used in adults and adolescents with HIV such as dosing (including renal dosing recommendations), available dosage forms used in the treatment of adolescents and adults, side effects, and important patient (pt) counseling points. Unless otherwise noted, information is adapted from the Panel on Antiretroviral Guidelines for Adults and Adolescents. Guidelines for the Use of Antiretroviral Agents in Adults and Adolescents Living with HIV. Department of Health and Human Services (hereafter referred to as the Guidelines). Last updated June 3, 2021. Available at: https://clinicalinfo.hiv.gov/en/guidelines/adult-and-adolescent-arv. Accessed June 4, 2021.

Information on crushing and liquid ART formulations available at:
https://www.hivclinic.ca/main/drugs_extra_files/Crushing%20and%20Liquid%20ARV%20Formulations.pdf

The information contained in this publication is intended for medical professionals, as a quick reference to the national guidelines. This resource does not replace nor represent the comprehensive nature of the published guidelines. Recognizing the rapid changes that occur in this field, clinicians are encouraged to consult with their local experts or research the literature for the most up-to-date information to assist with individual treatment decisions for their patient. If your patient should experience a serious adverse event, please report the event to the FDA (www.fda.gov/Safety/MedWatch/HowToReport/default.htm) to help increase patient safety.

Special Thanks to Colorado AIDS Education and Training Center for medication images (images are not actual size and colors may vary) and www.poz.com for phonetic pronounciations.

Table 1. Regimens for Treatment of HIV-1 in Non-Pregnant Antiretroviral-Naïve Adults/Adolescents
- Pregnancy & Perinatal Guidelines
- Recommended Initial Regimens for Most People with HIV
- Recommended Initial Regimens in Certain Clinical Situations
Table 2. Initiation of ART While Awaiting Results of Resistance Testing and Other Labs
Table 3. Antiretroviral Drugs, Regimens, or Components Not Recommended at Any Time
- Antiretroviral Drugs Not Recommended
- Antiretroviral Regimens Not Recommended
- Antiretroviral Components Not Recommended
Table 4. Renal Dose Adjustments
- NRTIs
- NNRTIs
- PIs
- INSTI
- Pharmacokinetic Enhancers
Table 5. Renal Dosing for Combo Products
Table 6. Statin Interactions with ART
- Protease Inhibitor (PI) Interactions
- Stribild® (EVG/c/TDF/FTC) & Genvoya® (EVG/c/TAF/FTC) Interactions
Table 7. Oral Rilpivirine Interactions with Acid-reducing Agents (ARAs)
Table 8. Atazanavir Dosing with Acid-reducing Agents
Table 9. INSTI Interactions with Acid-reducing Agents and Polyvalent Cations
Table 10. Cabenuva Adult dose: Oral Lead-In and Ventrogluteal Intramuscular (IM) Injection Schedule
Table 11. Antiretrovirals Not Included in This Resource
Nucleoside/Nucleoside Reverse Transcriptase Inhibitors (NRTIs)
Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTIs)
Pharmacokinetic (PK) Enhancers
Protease Inhibitors (PIs)
Protease Inhibitors (PIs)
Combination Products
- Full Regimen Combinations
- NRTI Combinations
- PI Combinations

Editors:

Jennifer Janelle, MD
Elizabeth Sherman, PharmD, AAHIVP
Joanne Urban, PharmD, AAHIVP

Defintion of Symbols
= Generic Available
= Take with Food = Take without food = Take with or without food
= Interaction with Oral Contraceptives. See Table 3 in Recommendations for the Use of Antiretroviral Drugs in Pregnant Women with HIV Infection and Interventions to Reduce Perinatal HIV Transmission in the United States	= Hepatic Adjustment See DHHS Guidelines (Appendix B, Table 11) for recommendations for dosing ART in pts with hepatic insufficiency.
= Renal Adjustment (See table)
= See Treatment of Tuberculosis (TB) in Adults with HIV Infection treatment guideline resource for drug interactions. Located at www.seaetc.com/reference
= Dosage in photo, when multiple dosage forms are available
Note: Medication images are NOT actual size, and colors may vary.

Table 1. Regimens for Treatment of HIV-1 in Non-Pregnant Antiretroviral-Naïve Adults/Adolescents Adapted from Table 6 of the Guidelines. Regimens within classes are arranged by evidence rating and then alphabetical order. (/r) indicates low-dose ritonavir and (/c) indicates cobicistat for boosting. See detailed information in this resource and in the Guidelines for dosing and other important points. NOTE: Regimens below assume no baseline resistance. Resistance testing recommended for all pts upon entry into care. Consider repeat testing at the time of ART initiation if treatment is deferred.
Pregnancy & Perinatal Guidelines
For pregnant woman or women with childbearing potential, see the Perinatal Guidelines for managing HIV infection in pregnancy including recommendations for prevention of mother to child transmission.
Recommended Initial Regimens for Most People with HIV Demonstrated durable virologic efficacy, favorable tolerability and toxicity profiles, and ease of use.
INSTI + 2 NRTIs
Bictegravir/tenofovir alafenamide (TAF)/emtricitabine (FTC) (AI)¹
Dolutegravir/abacavir/lamivudine – *Only if HLA-B5701 negative and without hepatitis B virus (HBV) coinfection (AI)**¹
Dolutegravir + tenofovir²/emtricitabine³ (AI)¹
INSTI + 1 NRTI
Dolutegravir/lamivudine (AI)¹ – If HIV RNA < 500,000, no HBV coinfection, and genotype results showing no reverse transcriptase resistance
Recommended Initial Regimens in Certain Clinical Situations Effective/tolerable but have potential disadvantages compared to recommended regimens listed above, have limitations for use in certain patient populations, or have less randomized clinical trial data. May be preferred in some pts. See Table 7 Antiretroviral Regimen Considerations as Initial Therapy based on Specific Clinical Scenarios in the Guidelines for examples.
INSTI + 2 NRTIs
Elvitegravir/cobicistat/tenofovir²/emtricitabine (BI)¹
Boosted PI + 2 NRTIs (Boosted darunavir [DRV] is preferred over boosted atazanavir [ATV])
(Darunavir/c or Darunavir/r) + tenofovir²/emtricitabine³ (AI)¹
(Atazanavir/c or Atazanavir/r) + tenofovir²/emtricitabine³ (BI)¹
(Darunavir/c or Darunavir/r) + abacavir/lamivudine (3TC) – Only if HLA-B*5701 negative and no HBV coinfection (BII)¹
NNRTI + 2 NRTIs
Doravirine/TDF/lamivudine (BI)¹ or Doravirine + TAF²/emtricitabine³ (BIII)¹
Efavirenz (EFV) + tenofovir²/emtricitabine³ (BI for EFV 600 mg/TDF/FTC³ and EFV 400 mg/TDF/3TC, BII for EFV 600 mg + TAF/FTC)¹
Rilpivirine/tenofovir²/emtricitabine (BI) – If HIV RNA < 100,000 copies/mL and CD4 > 200 cells/mm³
Regimens to Consider when Tenofovir² or Abacavir Cannot be Used or Are Not Optimal Two-drug options should not be used in individuals with HBV coinfection or known pre-existing resistance to either ARV in the combination
Dolutegravir/lamivudine (AI)¹ -If HIV RNA < 500,000, no HBV coinfection, and genotype results showing no reverse transcriptase resistance
Darunavir/r once daily + raltegravir twice daily – If HIV RNA < 100,000 copies/mL and CD4 > 200 cells/mm³ (CI)¹
Darunavir/r once daily + lamivudine³ (CI)¹

1. See Table 2 of DHHS Guidelines for rating scheme for strength of recommendations/quality of evidence.
2. Tenofovir alafenamide (TAF) and tenofovir disoproxil fumarate (TDF) are two FDA-approved forms of tenofovir. TAF has fewer bone and kidney toxicities and TDF is associated with lower lipid levels (unknown clinical significance). TAF has been associated with weight gain. Consider safety, cost, and access when choosing between TAF and TDF. If initiating tenofovir without results of renal function tests, our editor recommendation is to use TAF rather than TDF.
3. Emtricitabine (FTC) may replace lamivudine (3TC) and vice versa (co-formulation is major determining factor).
4. Raltegravir can be dosed 400 mg bid (Isentress®) or 1200 mg once daily (two 600 mg tablets, Isentress® HD)

Table 2. Initiation of ART While Awaiting Results of Resistance Testing and Other Labs
ART should be started immediately, or as soon as possible, after diagnosis. If results of labs including renal and resistance tests are not available at the time of ART initiation, providers should consider starting one of the following regimens: Bictegravir/tenofovir alafenamide/emtricitabine (Darunavir/c or Darunavir/r) + tenofovir²/emtricitabine³ Dolutegravir + tenofovir²/emtricitabine³

Table 2. Initiation of ART While Awaiting Results of Resistance Testing and Other Labs

ART should be started immediately, or as soon as possible, after diagnosis. If results of labs including renal and resistance tests are not available at the time of ART initiation, providers should consider starting one of the following regimens:

Bictegravir/tenofovir alafenamide/emtricitabine
(Darunavir/c or Darunavir/r) + tenofovir²/emtricitabine³
Dolutegravir + tenofovir²/emtricitabine³

Table 3. Antiretroviral Drugs, Regimens, or Components Not Recommended at Any Time
Agent(s)	Comments
Antiretroviral Drugs Not Recommended
Delavirdine (DLV) Didanosine (ddI) Indinavir (IDV) Nelfinavir (NFV) Stavudine (d4T)	Suboptimal potency, unacceptable toxicities, high pill burden, pharmacologic concerns
Antiretroviral Regimens Not Recommended
Monotherapy (AI)	NRTI monotherapy inferior to dual-NRTI therapy; PI monotherapy inferior to combination ART; INSTI monotherapy has resulted in virologic rebound and INSTI resistance
Dual-NRTI Regimens (AI)	Inferior to triple-drug combination regimens
Triple-NRTI Regimens (AI)	Suboptimal virologic activity, lack of data
Antiretroviral Components Not Recommended
ATV + IDV (AIII)	Potential for additive adverse effects (including hyperbilirubinemia and jaundice)
COBI + RTV as pharmacokinetic enhancers	Additive CYP3A4 enzyme inhibition and ↑ concentrations of ARVs or other concomitant medications
ddI + d4T (AII)	Peripheral neuropathy, pancreatitis, lactic acidosis, implicated in deaths of several pregnant women
ddI + TDF (AII)	↑ ddI levels, toxicities, immunologic nonresponse, early virologic failure, resistance
Two NNRTI Combinations (AI)	Excess clinical adverse events and treatment discontinuation; EFV and NVP are enzyme inducers and can ↓ ETR and RPV levels
FTC + 3TC (AIII)	Similar resistance profiles, minimal additive antiviral activity
ETR + unboosted PI (AII)	ETR may induce metabolism and ↓ unboosted PI levels
ETR + FPV/r (AII)	ETR may alter FPV concentration; appropriate doses not established
ETR + TPV/r (AII)	↓ ETR levels
NVP in ART-naïve ♀ with CD4 > 250 cells/mm3 or ♂ with CD4 > 400 cells/mm3 (BI)	↑ symptomatic, sometimes life-threatening, hepatic events
RTV as sole PI⁵	Pill burden, GI intolerance, metabolic toxicities
Unboosted DRV, SQV, or TPV (AII)	Should only be used with low-dose RTV or COBI (DRV)
d4T + ZDV (AII)	Both thymidine analogs; antagonistic
TAF + TDF	No data supporting combination

5. The Guidelines list as “not recommended as part of initial therapy” but the editors of this resource do not recommend at any time.

Table 4. Renal Dose Adjustments⁶
Renal dosage adjustments are required for didanosine and stavudine. The clinician is encouraged to consider alternative regimen options in any pts on either of these agents. See prescribing information if renal dosing is necessary.
Agent(s)	Dose Adjustment
NRTIs
Emtricitabine	CrCL 30-49: 200 mg cap every 48 hours; CrCL 15-29: 200 mg cap every 72 hours; CrCL < 15: 200 mg cap every 96 hours HD⁷: 200 mg every 24 hours See guidelines for oral soln dosing
Lamivudine	CrCL 30-49: 150 mg every 24 hours; CrCL 15-29: 150 mg x 1 then 100 mg every 24 hours; CrCL 5-14: 150 mg x 1 then 50 mg every 24 hours; CrCL < 5 or HD⁷: 50 mg x 1 then 25 mg every 24 hours
Tenofovir alafenamide⁸	CrCL < 15 and not on HD: Not recommended On HD⁷: One tablet once daily
Tenofovir disoproxil fumarate⁹	CrCL 30-49: 300 mg every 48 hours; CrCL 10-29: 300 mg twice weekly every 72-96 hours; CrCL < 10 and not on HD: no recommendation; HD7: 300 mg every week (assumes 3 HD sessions per week of approximately 4 hours each)
NNRTIs
Rilpivirine¹⁰	Severe renal impairment or HD: use with caution and monitor for adverse effects
PIs
Atazanavir (ATV)	ART-naïve on HD: ATV 300 mg + RTV 100 mg once daily; ART-experienced (exp) on HD: ATV not recommended (unboosted or boosted)
INSTI
Dolutegravir¹¹	Use with caution in INSTI-exp pts with severe renal impairment and certain INSTI resistance mutations or suspected resistance as DTG levels may be decreased
Pharmacokinetic Enhancers
Cobicistat	CrCL < 70: ATV/c or DRV/c use with TDF not recommended

6. No renal dose adj for abacavir, PIs (except ATV, lopinavir/r), NNRTIs, dolutegravir, raltegravir, or T20.
7. Dose after hemodialysis (HD) on HD days.
8. CAUTION: consider tenofovir alafenamide (TAF) as a possible cause for renal dysfunction. TAF as a single agent is available as Vemlidy and is approved for HBV infection. Vemlidy [package insert]. Foster City, CA: Gilead Sciences, Inc; Revised March 2021.
9. CAUTION: consider tenofovir disoproxil fumarate (TDF) or TAF as possible cause for renal dysfunction.
10. Edurant [package insert]. Titusville, NJ: Janssen Pharmaceuticals, Inc.; Revised Jauary 2021.
11. Tivicay [package insert]. Research Triangle Park, NC: ViiV Healthcare; Revised March 2021.

Table 5: Renal Dosing for Combo Products
Agent(s)	Dose Adjustment
EFV/FTC/TDF (Atripla)⁹	CrCl < 50: not recommended. See dosing for individual agents
3TC/TDF (Cimduo, Temixys)⁹
ZDV/3TC (Combivir)
RPV/FTC/TDF (Complera)⁹
ABC/3TC (Epzicom)
DOR/3TC/TDF (Delstrigo)⁹
DTG/3TC (Dovato)
EFV/3TC/TDF (Symfi and Symfi Lo)⁹
DTG/ABC/3TC (Triumeq)
FTC/TDF (Truvada)⁹	CrCl 30-49: one tablet every 48 hours CrCl < 30: not recommended See dosing for individual agents
ATV/c (Evotaz)	CrCL < 70: Use with TDF not recommended ART-exp on HD: ATV/c not recommended
DRV/c (Prezcobix)	CrCl < 70: Use with TDF not recommended
DTG/RPV (Juluca)	No dose adjustment necessary CrCl < 30: monitor closely for adverse effects
EVG/c/TAF/FTC (Genvoya)⁹ RPV/FTC/TAF (Odefsey)⁹ DRV/c/FTC/TAF (Symtuza)⁹ BIC/FTC/TAF (Biktarvy)⁹ TAF/FTC (Descovy)⁹	CrCl < 30 not on HD: not recommended HD7: one tablet daily.
EVG/c/FTC/TDF (Stribild)⁹	CrCl < 70 do not initiate CrCl < 50 not recommended

Table 6. Statin Interactions with ART¹²
Protease Inhibitor (PI) Interactions
NOTE: Interactions with indinavir, fosamprenavir, nelfinavir , saquinavir, and tipranavir are not included since these are rarely used
Statin	Interactive PI(s)	Prescribing Recommendation
Atorvastatin	ATV, ATV/r	Titrate atorvastatin dose carefully (editors of this resource usually would not exceed 20 mg daily)
	ATV/c	Do not combine
	DRV/c, DRV/r, LPV/r	Titrate atorvastatin dose carefully (not to exceed 20 mg daily)
Fluvastatin	All HIV PIs	No data available
Lovastatin Simvastatin	All HIV PIs	CONTRAINDICATED
Pitavastatin	All HIV PIs	No dosage adjustments necessary
Pravastatin	ATV/c, ATV/r, DRV/c or DRV/r	Titrate pravastatin dose carefully while monitoring for toxicities
Pravastatin	LPV/r	No dosage adjustments necessary
Rosuvastatin	ATV/r, ATV/c LPV/r	Titrate rosuvastatin dose carefully (not to exceed 10 mg daily)
Rosuvastatin	DRV/c, DRV/r	Titrate rosuvastatin dose carefully (not to exceed 20 mg daily)
Stribild (EVG/c/TDF/FTC) & Genvoya (EVG/c/TAF/FTC) Interactions
Statin	Interacting Agent	Prescribing Recommendation
Atorvastatin	cobicistat	Titrate atorvastatin dose carefully (not to exceed 20 mg daily)
Fluvastatin Pitavastatin Pravastatin	cobicistat	No data or dosage recommendation
Lovastatin Simvastatin	cobicistat	CONTRAINDICATED
Rosuvastatin	cobicistat	Titrate rosuvastatin dose carefully (editors of this resource usually would not exceed 20 mg daily)

12. See DHHS Guidelines Drug-Drug Interactions section and www.hiv-druginteractions.org for additional information including statin interactions with NNRTIs. Generally no dosage adjustments needed but there may be decreased statin response depending on agents used.

Table 7. Oral Rilpivirine Interactions with Acid-reducing Agents (ARAs)
ARA	Oral Rilpivirine Dosing Recommendation
Antacids (e.g., Al, Mg, Ca)	Take antacids ≥ 2 hours before or ≥ 4 hours after RPV
H2-Receptor Antagonists	Take H2-Receptor antagonists ≥ 12 hours before or ≥ 4 hours after RPV
Proton Pump Inhibitors	Do not combine-contraindicated

Table 8. Atazanavir Dosing with Acid-reducing Agents
Acid-reducing Agents	ART-naïve	ART-exp
Antacids or buffered medications	ATV, ATV/c, ATV/r: Give ≥ 2 hours before or 1 to 2 hours after antacid or buffered medication
H2 Receptor Antagonists(H2RAs)	ART-naïve with or without TDF	ART-exp without TDF
	ATV: Give ≥ 2 hours before or 10 hours after H2RA. Max dose of famotidine 20 mg bid (not to exceed 20 mg in single dose) [or equivalent]. ATV/r or ATV/c: Give simultaneously with or ≥ 10 hours after H2RA. Max dose of famotidine 40 mg bid [or equivalent].	ATV/r or ATV/c: Give simultaneously with or ≥ 10 hours after H2RA. Max dose of famotidine 20 mg bid [or equivalent].
		ART-exp with TDF
		ATV/r (400/100 mg) or ATV/c (400/150 mg): Give simultaneously with or ≥ 10 hours after H2RA. Max dose of famotidine 20 mg bid [or equivalent].
Proton Pump Inhibitors (PPIs)	ATV: not recommended ATV/r or ATV/c: Max dose of omeprazole 20 mg once daily [or equivalent] taken ≥ 12 hours prior to ATV/r	ATV/r or ATV/c: not recommended

Table 9. INSTI Interactions with Acid-reducing Agents and Polyvalent Cations
	Bictegravir (BIC)	Dolutegravir (DTG)	Elvitegravir/cobicistat (EVG/c)	Raltegravir (RAL)	Cabotegravir (CAB) – Oral
Antacids (e.g., Al, Mg, Ca)	Take BIC ≥ 2 hours before or ≥ 6 hours after antacids containing Al or Mg Take BIC with antacids containing Ca with food	Take DTG ≥ 2 hours before or ≥ 6 hours after antacids containing Al, Mg, Ca	Take EVG/c ≥ 2 hours before or ≥ 2 hours after antacids containing Al, Mg, Ca	With calcium carbonate antacids: No dosage adjustment or separation needed with RAL 400 mg bid Do not use once daily RAL HD formulation with calcium carbonate antacids With Al and/or Mg containing antacids: Do not combine	Take oral CAB ≥ 4 hours before or ≥ 2 hours after antacids containing AI, Mg, Ca
Polyvalent cation (e.g., Al, Ca, Fe, Mg, Zn) containing medications including multivitamins, supplements, laxatives, sucralfate and buffered medications	Supplements containing Ca or Fe: Take simultaneously with food or if fasting, take BIC ≥ 2 hours before Other polyvalent cations (editor recommendation): Take BIC ≥ 2 hours before or ≥ 6 hours after	Supplements containing Ca or Fe: Take simultaneously with food or if fasting, take DTG ≥ 2 hours before or ≥ 6 hours after Other polyvalent cations: Take DTG ≥ 2 hours before or ≥ 6 hours after	Take EVG/c ≥ 2 hours before or ≥ 6 hours after polyvalent cation containing supplements	Take RAL ≥ 2 hours before or ≥ 6 hours after polyvalent cation containing supplements	Take CAB ≥ 2 hours before or ≥ 4 hours after supplements that contain polyvalent cations
H2-Receptor Antagonists	No dose adjustment necessary
Proton Pump Inhibitors	No dose adjustment necessary

Table 10. Cabenuva Adult dose: Oral Lead-In and Ventrogluteal Intramuscular (IM) Injection Schedule
Drug	Oral Lead-In ≥ 28 days	IM Initiation Injections (Loading Dose)	IM Continuation Injections (Monthly Dosing)
CAB	30 mg once daily with a meal	600 mg (3 mL)	400 mg (2 mL)
RPV	25 mg once daily with a meal	900 mg (3 mL)	600 mg (2 mL)

Table 11. Antiretrovirals Not Included in This Resource
Detailed information about the drugs listed here is not included in this resource. The user is encouraged to consult the product labeling and other resources.
Drugs Not Recommended
Delavirdine (DLV)	Nelfinavir (NFV)
Didanosine (ddI)	Stavudine (d4T)
Indinavir (IDV)
Drugs Used Less Frequently
Abacavir/lamivudine/zidovudine (ABC/3TC/ZDV)	Lopinavir/ritonavir (LPV/r)
Enfuvirtide (T-20, ENF)	Etravirine (ETR)
Maraviroc (MVC)	Fosamprenavir (FPV)
Nevirapine (NVP)	Fostemsavir (FTR)
Saquinavir (SQV)	Ibalizumab (IBA)
Tipranavir (TPV)	Lamivudine/zidovudine (3TC/ZDV)
Zidovudine (ZDV)

Nucleoside/Nucleoside Reverse Transcriptase Inhibitors (NRTIs)

Class adverse effects: Lactic acidosis and hepatic steatosis

(uh-BACK-ah-veer)

Dosage form: 300 mg tab, 20 mg/mL soln (240 mL/bottle)
- Also available in combination products: Epzicom, Trizivir, Triumeq; see Combination Products or prescribing information for more detail
Adult and adolescent dose (weight ≥ 25 kg):
- 300 mg PO bid or 600 mg PO once daily

NOTE: Perform HLA-B*5701 test prior; only use if negative

Important Points:

Use with caution in pts with ↑ CVD risk. Use with caution if pre-ART viral load >100,000 copies/mL unless combined with dolutegravir.
Alcohol ↑ ABC levels 41%; potential for adverse effects
AEs: Hypersensitivity reaction (2-9%), characterized by sign/symptom from ≥ 2 groups: G1: fever; G2: rash; G3: nausea, vomiting, diarrhea, or abdominal pain; G4: malaise, fatigue, or achiness; G5: dyspnea, cough, or pharyngitis (onset 4-6 weeks). Discontinue drug promptly and DO NOT RECHALLENGE!

(em-trih-SIGH-ta-been)

Dosage form: 200 mg cap, 10 mg/mL soln (170 mL/bottle)
- Also available in combination products: Biktarvy, Symtuza,Truvada, Atripla, Complera, Descovy, Genvoya, Odefsey, Stribild; see Combination Products or prescribing information for more detail
Adult and adolescent dose (weight ≥ 40 kg):
- 200 mg cap or 240 mg (24 mL) soln PO once daily

Important Points:

Abrupt withdrawal can cause chronic active hep B flares
AEs: Generally well-tolerated, ↑ pigmentation of palms/soles (> in black and Hispanic pts)
Refrigerate soln or room temp if used within 3 months

(la-MI-vue-deen)

Dosage form: 150 mg, 300 mg tab, 10 mg/mL soln (240 mL)
- Also available in combination products: Combivir, Cimduo, Delstrigo, Epzicom, Temixys, Symfi and Symfi Lo, Trizivir, Triumeq; see Combination Products or prescribing information for more detail
Adult and adolescent dose (weight ≥ 25 kg):
- 300 mg PO once daily or 150 mg PO bid

Important Points:

Abrupt withdrawal can cause chronic active hep B flares
AEs: Generally well-tolerated

(ten-OH-foh-veer)

Dosage form: 25 mg tablet (approved for hepatitis B treatment)
- Also available in combination products: Biktarvy, Descovy, Genvoya, Odefsey, Symtuza
Adult dose: 1 tab PO once daily

Important Points:

Document urine glucose and protein at baseline and perform routine monitoring (e.g., at least every 6 months) of eGFR
Monitor serum phosphorus in pts with or at risk for renal impairment
Abrupt withdrawal can cause chronic active hep B flares
AEs: nausea, diarrhea, headache, renal insufficiency, decreased bone density (renal and bone issues less common and increases in cholesterol, LDL, Trigs, HDL more common than with tenofovir disoproxil fumarate), weight gain

¹³

(ten-OH-foh-veer)

Nucleotide RTI

Dosage form: 300 mg tab
- 40 mg/1 g oral powder (60 g multi-use bottle)
- Also available in combination products: Cimduo, Temixys, Symfi and Symfi Lo, Truvada, Atripla, Complera, Delstrigo, Stribild; see Combination Products or prescribing information for more detail
Adult and adolescent¹⁴ dose (weight ≥ 35 kg): 300 mg PO once daily

Important Points:

Take tabs with or without food; take powder with food. Mix powder in ¼ – ½ cup of soft food (e.g., applesauce, baby food, yogurt) and take entire dose ASAP to avoid bad taste.
Interacts with ATV (see ATV for dosing)
Document urine glucose and protein at baseline and perform routine monitoring (at least every 6 months) of eGFR
Monitor serum phosphorus in pts with or at risk for renal impairment
Avoid TDF if concomitant or recent use of nephrotoxic agent
Abrupt withdrawal can cause chronic active hep B flares
Can decrease bone mineral density, consider calcium and vitamin D supplementation
AEs: Flatulence, headache, diarrhea, nausea, vomiting, renal insufficiency, Fanconi Syndrome (rare), ↓ PO4, osteopenia (rare, multifactorial)

13. Tabs are with or without food; powder is with food.
14. See the Guidelines for Use of Antiretroviral Agents in Pediatric HIV Infection for concerns about ↓ bone mineral density especially in pre-pubertal or early puberty (Tanner Stages 1 or 2)

Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTIs)

Class adverse effects: rash (rarely Stevens-Johnson Syndrome), ↑ LFTs, many drug interactions.
See DHHS Guidelines and www.hiv-druginteractions.org.

(Door-Ave-uh-reen)

Dosage form: 100 mg tab
- Also available in combination product: Delstrigo™; see Combination Products for more detail
Adult dose: 100 mg PO once daily

Important Points:

AEs: nausea, dizziness, abnormal dreams

(eh-FAH-vih-rehnz)

Dosage form: 200 mg cap, 600 mg tab
- Also available in combination products: Atripla, Symfi and Symfi Lo; see Combination Products for more detail
Adult and adolescent dose (weight ≥ 40 kg): 600 mg PO once daily at bedtime

Important Points:

Take at bedtime without food to ↓ CNS side effects
False positive cannabinoid or benzodiazepine test (usually on screening, confirmatory test should be negative)
Use with caution in pts with psychiatric illness or using medications with neuropsych effects (CNS AEs more common)
AEs: Drowsiness, dizziness, impaired concentration, insomnia, abnormal dreaming, agitation (Usually resolves in 2-4 weeks), depression, suicidal ideation (rare), hallucinations (rare), ↑ lipids , QT prolongation

(ril-pih-VIGH-reen)

Dosage form: 25 mg tab
- Also available in combination products: Complera, Odefsey and Cabenuva; see Combination Products for more detail
Adult and adolescent dose¹⁵ (weight ≥ 35 kg): 25 mg once daily

Important Points:

Take with a meal (at least 390 kcal)
Interacts with acid-reducing agents. See Table 7.
Caution with drugs that prolong the QT interval
AEs: Depression, insomnia, headache, rash

15. Not recommended in pts with pre-ART HIV RNA > 100,000 copies/mL or CD4 count < 200 cells/mm³ due to ↑ rate of virologic failure

Pharmacokinetic (PK) Enhancers

(koe-BIK-i-stat)

Dosage form: 150 mg tab
- Mostly in combination products: Evotaz, Prezcobix, Symtuza, Stribild, and Genvoya see Combination Products for more detail

16

(rih-TAH-nuh-veer)

Dosage form: 100 mg tab, 100 mg oral powder packet, 80 mg/mL soln (240 mL/bottle)
- Used only at low doses with other PIs (see primary PI for dosing, food requirements and adverse effects)

Important Points:

Store tabs at room temp; do not refrigerate soln

16. Food requirements depend on concomitant PI. See information in PI section of resource.

Protease Inhibitors (PIs)

Class adverse effects: ↑ glucose, ↑ lipids (less with ATV and DRV), lipodystrophy, ↑ LFTs, nausea, vomiting, diarrhea (more common with LPV/r compared to DRV or ATV) ↑ bleeding in hemophiliacs. All undergo hepatic metabolism mostly via CYP3A4 – Many drug interactions. See DHHS Guidelines and www.hiv-druginteractions.org.

(ah-ta-ZA-na-veer)

Dosage form: 200, 300 mg cap
- Also available in combination product: Evotaz; see Combination Products for more detail
Adult and adolescent dose (weight ≥ 40 kg):
- – 400 mg PO once daily (ART-naïve only) or
- – 300 mg + (COBI 150 mg or RTV 100 mg) PO once daily (naïve, exp, or with TDF)

Important Points:

Take with food
Interacts with acid reducing agents. See Table 8.
AEs: ↑ unconjugated bilirubin (common), jaundice or scleral icterus (less common); rash; prolonged PR interval, asymptomatic 1st degree AV block (rare); nephrolithiasis (rare), cholelithiasis

(da-ROO-nuh-veer)

Dosage form: 600, 800 mg tab, 100 mg/mL susp (200 mL/bottle)
- Also available in combination products: Prezcobix and Symtuza; see Combination Products for more detail
Adult and adolescent dose (weight ≥ 40 kg):
- – 800 mg + (COBI 150 mg or RTV 100 mg) PO once daily (ART-naïve or ART-exp if no DRV mutations [V11I, V32I, L33F, I47V, I50V, I54L, I54M, T74P, L76V, I84V, L89V])²⁴ or
- – 600 mg + RTV 100 mg PO bid (ART-naïve or ART-exp)

Important Points:

Take with food
AEs: Rash (10%), abdominal pain, headache, hepatotoxicity, caution with sulfa allergy (not contraindicated)

17. Prezista [package insert]. Titusville, NJ: Janssen Pharmaceuticals, Inc.; Revised February 2021.

Integrase Strand Transfer Inhibitors (INSTIs)

Class adverse effects: Insomnia, depression and suicidal ideation reported infrequently, more common in pts with pre-existing psychiatric conditions, weight gain. See DHHS Guidelines and www.hiv-druginteractions.org.

(bik-TAR-vee)

Each tab contains: 50 mg bictegravir (BIC) + 200 mg FTC + 25 mg TAF
Adult dose: 1 tab PO once daily
- See Full Regimen Combinations for important points

(Doe-loo-teg’-ra-vir)

Dosage form: 50 mg tab
- Also available in combination products: Juluca and Triumeq; see Combination Products for more detail
Adult and adolescent dose¹⁹ (weight ≥ 40 kg):
- 50 mg PO once daily (ART-naïve or exp but INSTI-naïve) or
- 50 mg PO bid (ART-naïve or exp but INSTI-naïve when given with potent UGT1A/CYP3A inducers [e.g., EFV, FPV/r, TPV/r, carbamazepine, or rifampin]) or
- 50 mg PO bid (pts with clinically suspected INSTI resistance or INSTI mutations)

See the Viking-3 trial data in the Tivicay® Prescribing Information for predicted efficacy response in the setting of certain INSTI resistance mutations.

Refer to: https://hivdb.stanford.edu/DR/INIResiNote.html for a complete list of INSTI mutations. In the setting of suspected or known INSTI resistance, consider a regimen that does not include metabolic inducers.

Important Points:

Interacts with polyvalent cations. See Table 9.
AEs: Headache and insomnia most common. Hypersensitivity reaction including rash, constitutional symptoms and organ dysfunction (e.g. liver injury) have been reported.
Increase in SCr (without a decrease in glomerular function).

18. Tivicay [package insert]. Research Triangle Park, NC: ViiV Healthcare; Revised July 2021.
19. Do not combine with NVP. Do not combine with ETR unless ATV/r, DRV/r, or LPV/r included in regimen as ETR may ↓ DTG levels. Note: DHHS Guidelines do not recommend combining ETR with ATV (± RTV).

(ral-TEG-ra-veer)

Dosage form: 400 mg tab, 600 mg tab (HD)
Adult and adolescent dose (weight ≥ 25 kg) for RAL: 400 mg PO bid
Adult and adolescent dose (weight ≥ 40 kg) for RAL HD: 1200 mg PO once daily

Important Points:

Interacts with polyvalent cations. See Table 9.
AEs: Diarrhea, nausea, headache; ↑ ALT, AST, CPK; myopathy and rhabdomyolysis have been reported, rare severe skin reactions (SJS/TEN) and systemic HSR with rash and constitutional symptoms +/- hepatitis

Combination Products

See individual drug components for important points

Full Regimen Combinations

(bik-TAR-vee)

Each tab contains: 50 mg bictegravir (BIC) + 200 mg FTC + 25 mg TAF
Adult dose: 1 tab PO once daily

Important points:

Interacts with polyvalent cations. See Table 9.
AEs: BIC: diarrhea, nausea, headache

²⁰

(kab’ en ue vah)

Injectable suspensions:

CAB extended release 600 mg/3 mL co-packaged with RPV extended release 900 mg/3mL
CAB extended release 400 mg/2 mL co-packaged with RPV extended release 600 mg/2mL

Oral tablets (not co-packaged):

Cabotegravir (Vocabria) 30 mg
Rilpivirine (Edurant) 50 mg

See Table 10 for dosing.

Important points:

Not intended for ART-naïve pts. Cabenuva is recommended for use in pts who are virologicallly-suppressed on a stable ART regimen (HIV-1 RNA < 50 copies/mL for at least 3 months), without history of treatment failure, with no known or suspected resistance to CAB or RPV, no active HBV infection (unless receiving an oral HBV active regimen), not pregnant or planning pregnancy, not receiving medications with significant drug interactions with CAB or RPV
Start initiation injection on last day of oral lead-in dosing
Take oral RPV and CAB with a meal (at least 390 kcal)
Oral RPV interacts with acid reducing agents. See Table 7.
Oral CAB interacts with polyvalent cations. See Table 9.
Go to https://cabenuvahcp.com for detailed information including prescribing information, management of planned and unplanned missed doses, injection education, patient enrollment forms, and ViiVConnect Portal.
Residual concentrations of CAB and RPV can remain in the body for ≥ 12 months. If discontinuing Cabenuva, an alternative fully-suppressive ART regimen should be started within 1 month of last Cabenuva injection.
AEs: injection site reactions, pyrexia, fatigue, headache, musculoskeletal pain, nausea, sleep disturbances, dizziness, rash

20. Injection is with or without food. Oral dosing should be taken with a meal

(sim toó zah)

Each tab contains: 800 mg DRV + 150 mg COBI + 200 mg FTC +10 mg TAF
Adult dose: 1 tab PO once daily

Important Points: Take with food

(TRI-u-meck)

Each tab contains: 50 mg DTG + 600 mg ABC + 300 mg 3TC
Adult and adolescent dose (weight ≥ 40 kg): 1 tab PO once daily

NOTE: Perform HLA-B*5701 test prior; only use if negative and pt not co-infected with hepatitis B virus

Each tab contains: 50 mg DTG and 300 mg 3TC
Adult dose: 1 tab PO once daily

Important points:

Interacts with polyvalent cations. See Table 9.
Only for adults with no antiretroviral treatment history, HIV RNA < 500,00 copies/mL, no HBV coinfection and with no resistance mutations to the individual components

(Jah-LOO-kah)

Each tab contains: 50 mg DTG + 25 mg RPV
Adult dose: 1 tab PO once daily

Important Points:

Take with a meal (at least 390 kcal)
Interacts with polyvalent cations. See Table 9.
Not intended for ART-naive pts. Juluca can be used in pts who are virologically suppressed (HIV-1 RNA <50 copies/mL) on a stable antiretroviral regimen for ≥6 months with no history of treatment failure and no known resistance mutations to the individual components of Juluca.

(del-STREE-go)

Each tab contains: 100 mg DOR + 300 mg 3TC + 300 mg TDF
Adult dose: 1 tab PO once daily

(uh-TRIP-luh)

Each tab contains: 600 mg EFV + 200 mg FTC + 300 mg TDF
Adult and adolescent dose (weight ≥ 40 kg): 1 tab PO once daily at bedtime

Important Points: Take at bedtime without food to ↓ CNS side effects

(SIM-fee & SIM-fee LOW)

Each tab contains: 600 mg EFV + 300 mg 3TC + 300 mg TDF (Symfi)
400 mg EFV + 300 mg 3TC + 300 mg TDF (Symfi Lo)
Adult and Adolescent dose (weight ≥ 35 kg): 1 tab PO once daily

Important Points: Take at bedtime without food to ↓ CNS side effects

(jen-VOY-uh)

Each tab contains: 150 mg EVG + 150 mg COBI + 200 mg FTC + 10 mg TAF
Adult and adolescent dose (age ≥ 12 years and weight ≥ 35 kg): 1 tab PO once daily

Important Points:

Take with food
Interacts with polyvalent cations. See Table 9.
AEs: EVG/COBI: diarrhea, nausea

(STRY-bild)

Each tab contains: 150 mg EVG + 150 mg COBI + 200 mg FTC + 300 mg TDF
Adult and adolescent dose (weight > 35 kg and Tanner stage 4 or 5): 1 tab PO once daily

Important Points:

Take with food
Do not initiate in pts with CrCL < 70
Interacts with polyvalent cations. See Table 9.
AEs: EVG/COBI: diarrhea, nausea

(oh-DEF-see)

Each tab contains: RPV 25 mg + 200 mg FTC + 25 mg TAF
Adult and adolescent dose (weight ≥ 35 kg): 1 tab PO once daily

Important Points:

Take with a meal (at least 390 kcal)
Interacts with acid reducing agents. See Table 7.

(com-PLAIR-uh)

Each tab contains: 25 mg RPV + 200 mg FTC + 300 mg TDF
Adult and adolescent dose (weight ≥ 35 kg): 1 tab PO once daily

Important Points:

Take with a meal (at least 390 kcal)
Interacts with acid reducing agents. See Table 7.

NRTI Combinations

(sim-DEW-oh)

Each tab contains: 300 mg 3TC + 300 mg TDF
Adult and Adolescent dose (weight ≥ 35 kg): 1 tab PO once daily

( des-KOH-vee)

Each tab contains: 200 mg FTC + 25 mg TAF
Adult and adolescent dose (weight > 35 kg): 1 tab PO once daily

(EP-zih-com)

Each tab contains: 600 mg ABC + 300 mg 3TC
Adult and adolescent dose (weight ≥ 25 kg): 1 tab PO once daily

NOTE: Perform HLA-B*5701 test prior; only use if negative

(true-VAH-duh)

Each tab contains: 200 mg FTC + 300 mg TDF
Adult and adolescent dose (weight ≥ 35 kg): 1 tab (200 mg FTC/300 mg TDF) PO once daily

Also available in pediatric dosing formulations: 100 mg FTC + 150 mg TDF, 133 mg FTC + 200 mg TDF and 167 mg FTC + 250 mg TDF

PI Combinations

(EV-oh-taz)

Each tab contains: 300 mg ATV + 150 mg COBI
Adult dose: 1 tab PO once daily

(prez-koe-bix)

Each tab contains: 800 mg DRV + 150 mg COBI
Adult dose: 1 tab PO once daily

ART in Adults & Adolescents

Table of Contents

Editors:

Defintion of Symbols

Table 1. Regimens for Treatment of HIV-1 in Non-Pregnant Antiretroviral-Naïve Adults/Adolescents

Pregnancy & Perinatal Guidelines

Recommended Initial Regimens for Most People with HIV

INSTI + 2 NRTIs

INSTI + 1 NRTI

Recommended Initial Regimens in Certain Clinical Situations

INSTI + 2 NRTIs

Boosted PI + 2 NRTIs (Boosted darunavir [DRV] is preferred over boosted atazanavir [ATV])

NNRTI + 2 NRTIs

Regimens to Consider when Tenofovir2 or Abacavir Cannot be Used or Are Not Optimal

Table 2. Initiation of ART While Awaiting Results of Resistance Testing and Other Labs

Table 3. Antiretroviral Drugs, Regimens, or Components Not Recommended at Any Time

Agent(s)

Comments

Antiretroviral Drugs Not Recommended

Antiretroviral Regimens Not Recommended

Antiretroviral Components Not Recommended

Table 4. Renal Dose Adjustments6

Agent(s)

Dose Adjustment

NRTIs

NNRTIs

PIs

INSTI

Pharmacokinetic Enhancers

Table 5: Renal Dosing for Combo Products

Agent(s)

Dose Adjustment

Table 6. Statin Interactions with ART12

Protease Inhibitor (PI) Interactions

Statin

Interactive PI(s)

Prescribing Recommendation

Stribild (EVG/c/TDF/FTC) & Genvoya (EVG/c/TAF/FTC) Interactions

Statin

Interacting Agent

Prescribing Recommendation

Table 7. Oral Rilpivirine Interactions with Acid-reducing Agents (ARAs)

ARA

Oral Rilpivirine Dosing Recommendation

Table 8. Atazanavir Dosing with Acid-reducing Agents

Acid-reducing

Agents

ART-naïve

ART-exp

ART-naïve with or without TDF

ART-exp without TDF

ART-exp with TDF

Table 9. INSTI Interactions with Acid-reducing Agents and Polyvalent Cations

Bictegravir

(BIC)

Dolutegravir (DTG)

Elvitegravir/cobicistat (EVG/c)

Raltegravir

(RAL)

Cabotegravir (CAB) – Oral

Table 10. Cabenuva Adult dose: Oral Lead-Inand VentroglutealIntramuscular (IM) Injection Schedule

Drug

Oral Lead-In≥ 28 days

IM Initiation Injections (Loading Dose)

IMContinuation Injections(MonthlyDosing)

Table 11. Antiretrovirals Not Included in This Resource

Drugs Not Recommended

Drugs Used Less Frequently

Nucleoside/Nucleoside Reverse Transcriptase Inhibitors (NRTIs)

Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTIs)

Pharmacokinetic (PK) Enhancers

Protease Inhibitors (PIs)

Integrase Strand Transfer Inhibitors (INSTIs)

Combination Products

Full Regimen Combinations

NRTI Combinations

PI Combinations

Regimens to Consider when Tenofovir² or Abacavir Cannot be Used or Are Not Optimal

Table 4. Renal Dose Adjustments⁶

Table 6. Statin Interactions with ART¹²

Table 10. Cabenuva Adult dose: Oral Lead-In
and Ventrogluteal
Intramuscular (IM) Injection Schedule

Oral Lead-In
≥ 28 days

IM
Continuation Injections
(Monthly
Dosing)