Guidelines for the Use of Antiretroviral Agents in Adults and Adolescents With HIV

Al, Mg,

+/–

Ca-Containing Antacids

Please refer to the Miscellaneous Drugs section of this table for recommendations on use with other polyvalent cation products (e.g., Fe and Ca supplements, multivitamins).

Al/Mg Hydroxide Antacid

• ↔ BIC AUC if antacid is administered 2 hours after BIC and under fasting conditions
• BIC AUC ↓ 52% if antacid is administered 2 hours before BIC
• BIC AUC ↓ 47% to 79% if administered simultaneously with antacid

CaCO₃ Antacid

• ↔ BIC AUC if administered with food
• BIC AUC ↓ 33% if administered under fasting conditions

With Antacids That Contain Al/Mg

• Administer antacids that contain Al/Mg at least 2 hours after or 6 hours before BIC.

With Antacids That Contain Ca

• Administer BIC and antacids that contain Ca together with food.
• Do not coadminister BIC simultaneously with antacids that contain Ca on an empty stomach.

With Antacids That Contain Polyvalent Cations (Al, Mg, or Ca)

• Administer antacid products at least 2 hours before or 4 hours after taking CAB PO.

DTG AUC ↓ 74% if administered simultaneously with antacid

DTG AUC ↓ 26% if administered 2 hours before antacid

EVG AUC ↓ 40% to 50% if administered simultaneously with antacid

EVG AUC ↓ 15% to 20% if administered 2 hours before or after antacid; ↔ with a 4‑hour interval

Al/Mg Hydroxide Antacid

• RAL C_min ↓ 49% to 63%

CaCO₃ Antacid

• RAL 400 mg twice daily: C_min ↓ 32%
• RAL 1,200 mg once daily: C_min ↓ 48% to 57%

Do not coadminister RAL and Al/Mg hydroxide antacids. Use alternative acid-reducing agent.

With CaCO₃ Antacids

• RAL 1,200 mg once daily: Do not coadminister.
• RAL 400 mg twice daily: No dose adjustment or separation needed

Rifabutin 300 mg Once Daily

• BIC AUC ↓ 38% and C_min ↓ 56%

CAB PO AUC ↓ 23% and C_min ↓ 26%

↔ rifabutin

↓ CAB IM and RPV expected

↔ rifabutin expected

Rifabutin 300 mg Once Daily

• ↔ DTG AUC and C_min ↓ 30%

Rifabutin 150 mg Every Other Day With EVG/c Once Daily Compared to Rifabutin 300 mg Once Daily Alone

• ↔ rifabutin AUC
• 25-O-desacetyl-rifabutin AUC ↑ 625%
• EVG AUC ↓ 21% and C_min ↓ 67%

Rifampin With DTG 50 mg Twice Daily Compared to DTG 50 mg Twice Daily Alone

• DTG AUC ↓ 54% and C_min ↓ 72%

Rifampin With DTG 50 mg Twice Daily Compared to DTG 50 mg Once Daily Alone

• DTG AUC ↑ 33% and C_min ↑ 22%

Use DTG 50 mg twice daily (instead of DTG 50 mg once daily) in patients without suspected or documented INSTI-associated resistance mutations.

Consider an alternative to rifampin, such as rifabutin, in patients with certain suspected or documented INSTI-associated resistance mutations.

RAL 400 mg

• RAL AUC ↓ 40% and C_min ↓ 61%

Rifampin With RAL 800 mg Twice Daily Compared to RAL 400 mg Twice Daily Alone

• RAL AUC ↑ 27% and C_min ↓ 53%

Use RAL 800 mg twice daily instead of 400 mg twice daily.

Do not coadminister RAL 1,200 mg once daily with rifampin.

Monitor closely for virologic response or consider using rifabutin as an alternative rifamycin.

Rifapentine 900 mg Once Weekly

• DTG AUC ↓ 26% and C_min ↓ 47%

Rifapentine 600 mg Once Daily With DTG 50 mg Twice Daily vs DTG 50 mg Once Daily Alone

• ↔ DTG AUC and C_min

With once-weekly rifapentine, DTG 50 mg daily may be used in patients with viral suppression on daily DTG. Monitor for virologic efficacy. Do not coadminister in patients who require twice-daily DTG.

With once-daily rifapentine for 4 weeks (1HP), use DTG 50 mg twice daily. See Tuberculosis/HIV Coinfection for more on rifapentine and DTG use.

Rifapentine 900 mg Once Weekly

• RAL AUC ↑ 71% and C_min ↓ 12%

Rifapentine 600 mg Once Daily

• RAL C_min ↓ 41%

For once-weekly rifapentine and RAL 400 mg twice daily, no dose adjustment is needed.

Do not coadminister with once-daily rifapentine.

↑ clarithromycin expected

↑ COBI possible

Reduce clarithromycin dose by 50% in patients with CrCl 50 to 60 mL/min.

Do not coadminister in patients with CrCl <50 mL/min. Consider alternative ARV or use azithromycin.

↔ INSTI expected

↔ erythromycin expected

↑ erythromycin expected

↑ COBI possible

Do not coadminister in patients who require apixaban 2.5 mg twice daily.

Reduce apixaban dose by 50% in patients who require apixaban 5 mg or 10 mg twice daily.

↑ dabigatran expected

With COBI 150 mg Alone

• Dabigatran AUC ↑ 110% to 127%

Reduction of Risk of Stroke and Systemic Embolism in Nonvalvular Atrial Fibrillation in Adult Patients

• CrCl >30 mL/min: no dose adjustment needed
• CrCl ≤30 mL/min: do not coadminister.

Treatment and Reduction in the Risk of Recurrence of DVT and PE or Prophylaxis of DVT and PE Following Hip Replacement Surgery in Adult Patients

• CrCl ≥50 mL/min: no dose adjustment needed
• CrCl <50 mL/min: do not coadminister.

Stroke Prevention in Nonvalvular Atrial Fibrillation

• No dose adjustment needed

DVT and PE

• Administer edoxaban 30 mg once daily.

Increase DTG dose to 50 mg twice daily in ART-naive or ART-experienced (but INSTI-naive) patients.

Do not coadminister in INSTI-experienced patients with known or suspected INSTI resistance.

Carbamazepine AUC ↑ 43%

EVG AUC ↓ 69% and C_min ↓ >99%

↓ COBI expected

↓ INSTI possible

↓ COBI possible

↓ BIC and DTG possible

↓ or ↔ RAL possible

Tricyclic Antidepressants

(e.g., amitriptyline, desipramine, doxepin, imipramine, nortriptyline)

Selective Serotonin Reuptake Inhibitors

(e.g., citalopram, escitalopram, fluoxetine, fluvoxamine, paroxetine, sertraline, vortioxetine)

Starting Cariprazine in a Patient Who Is Already Receiving EVG/c

• Administer cariprazine 1.5 mg on Day 1 and Day 3, with no dose given on Day 2. From Day 4 onward, administer cariprazine 1.5 mg daily. Dose can be increased to a maximum of cariprazine 3 mg daily. If EVG/c is withdrawn, cariprazine dose may need to be increased.

Starting EVG/c in a Patient Who Is Already Receiving Cariprazine

• For patients receiving cariprazine 3 mg or cariprazine 6 mg daily, reduce the dose by half. For patients receiving cariprazine 4.5 mg daily, reduce dose to cariprazine 1.5 mg or cariprazine 3 mg daily. For patients receiving cariprazine 1.5 mg daily, change to cariprazine 1.5 mg every other day. If EVG/c is withdrawn, cariprazine dose may need to be increased

↔ olanzapine expected

↑ samidorphan possible

Other Antipsychotics

CYP3A4 and/or CYP2D6 substrates (e.g., perphenazine, risperidone, thioridazine)

Starting Quetiapine in a Patient Receiving EVG/c

• Start quetiapine at the lowest dose and titrate up as needed. Monitor for quetiapine efficacy and adverse events.

Starting EVG/c in a Patient Receiving a Stable Dose of Quetiapine

• Reduce quetiapine dose to 1/6 of the current dose. Closely monitor for quetiapine efficacy and adverse events.

↔ atogepant expected

↑ atogepant expected

Chronic migraine: Do not coadminister.

Episodic migraine: Administer atogepant at a dose of 10 mg once daily.

↑ isavuconazole expected

↑ or ↓ EVG and COBI possible

↔ INSTI expected

↔ itraconazole expected

↑ itraconazole expected

↑ EVG and COBI possible

↔ INSTI expected

↔ posaconazole expected

↑ EVG and COBI possible

↑ posaconazole possible

↔ INSTI expected

↔ voriconazole expected

↑ voriconazole expected

↑ EVG and COBI possible

DTG 50 mg Once Daily Plus Metformin 500 mg Twice Daily

• Metformin AUC ↑ 79% and C_max ↑ 66%

DTG 50 mg Twice Daily Plus Metformin 500 mg Twice Daily

• Metformin AUC ↑ 2.4-fold and C_max ↑ 2-fold

Start metformin at the lowest dose and titrate based on glycemic control. Monitor for adverse events of metformin.

When starting/stopping DTG in patients on metformin, dose adjustment of metformin may be necessary to maintain optimal glycemic control and/or minimize adverse events of metformin.

↔ DTG

↔ elbasvir

↔ grazoprevir

↑ elbasvir expected

↑ grazoprevir expected

↔ RAL with elbasvir

RAL AUC ↑ 43% with grazoprevir

↔ elbasvir

↔ grazoprevir

No significant effect

RAL AUC ↑ 47%

Glecaprevir AUC ↑ 3-fold

Pibrentasvir AUC ↑ 57%

EVG AUC ↑ 47%

No dose adjustment needed.

If coadministered with TDF, monitor for TDF-related adverse events. Consider monitoring for hepatotoxicity if coadministered with TDF or TAF.

↑ TDF expected

↑ ledipasvir expected

↔ INSTI expected

↔ sofosbuvir expected

↔ CAB expected

↔ sofosbuvir and velpatasvir expected

↔ EVG/c/TAF/FTC

Velpatasvir AUC ↑ 50%

When Administered With Sofosbuvir/
Velpatasvir/
Voxilaprevir (400 mg/100 mg/100 mg) plus Voxilaprevir 100 mg

• ↔ BIC, sofosbuvir, velpatasvir, voxilaprevir

When Administered With Sofosbuvir/
Velpatasvir/
Voxilaprevir (400 mg/100 mg/100 mg) plus Voxilaprevir 100 mg

• Sofosbuvir AUC ↑ 22%
• ↔ velpatasvir
• Voxilaprevir AUC ↑ 2-fold

↔ INSTI expected

↔ sofosbuvir, velpatasvir, and voxilaprevir expected

↑ brincidofovir possible

↑ EVG possible

↔ INSTI expected

↔ cidofovir expected

No dose adjustment needed.

Do not initiate CAB/RPV IM during or within 2 weeks after tecovirimat treatment. (Refer to Table 24b for interaction with RPV.)

↑ TAF possible

↔ ritonavir-boosted nirmatrelvir expected

↔ INSTI expected

↔ amiodarone expected

↑ BIC possible with diltiazem

↔ expected for all other CCBs

↔ INSTI expected

↔ CCB expected

In Patients on EVG/c ≥10 Days

• Start bosentan at 62.5 mg once daily or every other day based on individual tolerability.

In Patients on Bosentan Who Require EVG/c

• Stop bosentan ≥36 hours before EVG/c initiation. At least 10 days after initiation of EVG/c, resume bosentan at 62.5 mg once daily or every other day based on individual tolerability.

Beclomethasone

Inhaled or intranasal

Budesonide, Ciclesonide, Fluticasone, Mometasone

Inhaled or intranasal

Betamethasone, Budesonide

Systemic

↔ INSTI expected

 ↔ glucocorticoid expected

↑ glucocorticoid possible

↓ EVG possible

Dexamethasone

Systemic

Prednisone, Prednisolone

Systemic

Betamethasone, Methylprednisolone,

Prednisolone, Triamcinolone

Local injections, including intra-articular, epidural, or intra-orbital

Injectable Contraceptives

Depot MPA

Oral Contraceptives

(e.g., desogestrel, drospirenone, ethinyl estradiol, levonorgestrel, norethindrone, norgestimate) 

↔ ethinyl estradiol and norgestimate with DTG 

↔ ethinyl estradiol and levonorgestrel with CAB PO 

↔ ethinyl estradiol and norgestimate expected with BIC, RAL 

↔ norgestimate expected with CAB PO and IM 

↔ levonorgestrel expected 

↔ drospirenone expected 

↔ norethindrone expected 

Norgestimate AUC, C_max, and C_min ↑ > 2-fold 

Ethinyl estradiol AUC ↓ 25% and C_min ↓ 44% 

↑ drospirenone possible 

The effects of increases in progestin (norgestimate) are not fully known and may include insulin resistance, dyslipidemia, acne, and venous thrombosis. Decreased ethinyl estradiol may lead to more intermenstrual bleeding. Weigh the risks and benefits of using the drug and consider using an alternative ARV or contraceptive method.

Clinical monitoring is recommended due to the potential for hyperkalemia. Consider using alternative ARV or contraceptive method.

↑ levonorgestrel possible

↑ norethindrone expected

Subdermal Implant Contraceptives

(e.g., etonogestrel, levonorgestrel)

Etonogestrel ↑ 27% with DTG

↔ etonogestrel or levonorgestrel expected with BIC, CAB, RAL

↑ etonogestrel expected

↑ levonorgestrel expected

Transdermal Contraceptives

(e.g., ethinyl estradiol/norelgestromin, ethinyl estradiol/levonorgestrel)  

↑ progestin possible 

↓ ethinyl estradiol possible 

Vaginal Ring Contraceptives

(e.g., etonogestrel/ethinyl estradiol, segesterone/ethinyl estradiol) 

↑ progestin possible 

↓ ethinyl estradiol possible 

Emergency Contraceptives

Levonorgestrel (PO)

↑ or ↓ estradiol possible

↑ cyproterone, dutasteride, and finasteride possible

↔ estrogen expected with estradiol or conjugated estrogen (equine and synthetic)

↔ drospirenone, MPA, and micronized progesterone expected

↓ or ↑ estrogen possible

↑ drospirenone possible

↑ oral MPA possible

↑ oral micronized progesterone possible

Buprenorphine

Sublingual, buccal, or implant

Buprenorphine AUC ↑ 35% and C_min ↑ 66%

Norbuprenorphine (active metabolite) AUC ↑ 42% and C_min ↑ 57%

↔ buprenorphine and norbuprenorphine (active metabolite) (sublingual)

↔ buprenorphine or norbuprenorphine (active metabolite) expected (implant)

↑ tramadol expected

↓ M1 (active metabolite) possible

For Treatment of Erectile Dysfunction

• Start with sildenafil 25 mg every 48 hours and monitor for sildenafil-related adverse events.

Contraindicated for treatment of PAH.

For Treatment of Erectile Dysfunction

• Start with tadalafil 5 mg. Do not exceed a single dose of tadalafil 10 mg every 72 hours. Monitor for tadalafil-related adverse events.

For Treatment of PAH

In Patients on EVG/c >7 Days

• Start with tadalafil 20 mg once daily. Increase to tadalafil 40 mg once daily based on tolerability.

In Patients on Tadalafil who Require EVG/c

• Stop tadalafil ≥24 hours before EVG/c initiation. Seven days after EVG/c initiation, restart tadalafil at 20 mg once daily and increase to tadalafil 40 mg once daily based on tolerability.

Dose reduction of benzodiazepine may be necessary. Initiate with a low dose and monitor for benzodiazepine-related adverse events.

Consider using an alternative benzodiazepine, such as lorazepam, oxazepam, or temazepam.

With DTG 25 mg

• ↔ midazolam AUC

↑ midazolam expected

↑ triazolam expected

Contraindicated

Do not coadminister triazolam or oral midazolam and EVG/c.

Parenteral midazolam can be administered in a closely monitored setting. Consider dose reduction, especially if >1 dose is administered.

Do not coadminister in patients with hepatic or renal impairment.

For Treatment of Gout Flares

• Administer a single dose of colchicine 0.6 mg, followed by colchicine 0.3 mg 1 hour later. Do not repeat dose for at least 3 days.

For Prophylaxis of Gout Flares

• If original dose was colchicine 0.6 mg twice daily, decrease to colchicine 0.3 mg once daily. If dose was 0.6 mg once daily, decrease to 0.3 mg every other day.

For Treatment of Familial Mediterranean Fever

• Do not exceed colchicine 0.6 mg once daily or 0.3 mg twice daily.

Polyvalent Cation Supplements

Mg, Al, Fe, Ca, Zn, including multivitamins with minerals

Note: Please refer to the Acid Reducers section in this table for recommendations on use with Al-, Mg-, and Ca-containing antacids.

↔ BIC AUC if administered simultaneously with Fe or Ca and food

BIC AUC ↓ 33% if administered simultaneously with CaCO₃ under fasting conditions

BIC AUC ↓ 63% if administered simultaneously with Fe under fasting conditions

With Supplements That Contain Ca or Fe

• Administer BIC and supplements that contain Ca or Fe together with food.

Do not coadminister BIC under fasting conditions simultaneously with, or 2 hours after, supplements that contain Ca or Fe.

If coadministration is necessary, administer INSTI at least 2 hours before or at least 4 hours after supplements that contain polyvalent cations, including but not limited to the following products: cation-containing laxatives; Fe, Ca, or Mg supplements; and sucralfate. Monitor for virologic response.

Many oral multivitamins also contain varying amounts of polyvalent cations; the extent and significance of chelation is unknown.

DTG AUC ↓ 39% if administered simultaneously with CaCO₃ under fasting conditions

DTG AUC ↓ 54% if administered simultaneously with Fe under fasting conditions

↔ DTG when administered with Ca or Fe supplement simultaneously with food

With Supplements That Contain Ca or Fe

• Administer DTG and supplements that contain Ca or Fe together with food, or administer DTG at least 2 hours before or at least 6 hours after supplement.

Do not coadminister DTG under fasting conditions simultaneously with, or 2 hours after, supplements that contain Ca or Fe.

If coadministration is necessary, administer INSTI at least 2 hours before or at least 6 hours after supplements that contain polyvalent cations, including but not limited to the following products: cation-containing laxatives; Fe, Ca, or Mg supplements; and sucralfate. Monitor for virologic response.

Many oral multivitamins also contain varying amounts of polyvalent cations; the extent and significance of chelation is unknown.