Antiretroviral Therapy in Adolescents and Young Adults

Updated: Oct 04, 2017
  • Author: David J Cennimo, MD, FAAP, FACP, AAHIVS; Chief Editor: Michelle R Salvaggio, MD, FACP  more...
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Overview

Overview

The number of cases of human immunodeficiency virus (HIV) infection among young adolescents has been increasing over the years. Adolescents and young adults acquire HIV through high-risk behaviors. Many of them are recently infected or unaware of their HIV infection status. [1] Early intervention, including prevention strategies, counseling, and HIV testing, plays a key role in treating adolescents and young adults. [2]

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Antiretroviral Therapy Considerations

For postpubertal adolescents, antiretroviral treatment guidelines for adults may be used; postpubertal youth who were perinatally infected may also use the adult antiretroviral treatment guidelines. [1]

Puberty has a direct effect on how a drug is metabolized and on the drugs' pharmacokinetic properties; therefore, dosage of medications for HIV infection should be based on the Tanner staging of puberty and not just on age alone. [3, 4]

Adolescents in early puberty (ie, Tanner stages I and II) should be on pediatric dosing schedules, whereas those in late puberty (ie, Tanner stage V) should follow adult dosing schedules. [1]

Adolescents who are undergoing their growth-spurt period (ie, Tanner stage III in females and Tanner stage IV in males) should follow the adult dosing guidelines.

Puberty may be delayed in children who were perinatally infected with HIV, adding to discrepancies between Tanner stage-based dosing and age-based dosing. [5]

Dosing of antiretroviral medications for adolescents can be unpredictable and is dependent on multiple factors, including body mass and composition and chronologic age. [1]

The possibility of pregnancy should be discussed with all adolescent females; efavirenz should be avoided in women who plan to become pregnant, owing to teratogenic effects in the first trimester; potential interactions between antiretroviral drugs and hormonal contraception must be considered; Guidelines for Use of Antiretroviral Agents in HIV Infected Adults and Adolescents Tables 15a, b, and d provide further information. [1]

Adolescents are at risk of transmitted drug resistance, and baseline genotype data should guide antiretroviral selection. [6]

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Nucleoside/Nucleotide Reverse Transcriptase Inhibitors

The definition of "adolescent" may differ depending on the regimen; for regimens with specific definitions of "adolescent," the definition is provided in parentheses following the regimen.

Abacavir (ABC)

Patients should be tested for HLA-B*5701 prior to initiation. Patients who are positive are at the highest risk of abacavir hypersensitivity.

  • ABC 300 mg PO BID or 600 mg PO once daily (adolescent, ≥16 years); liquid formulation available at 20 mg/mL with the same recommended dose
  • Trizivir: Combination formulation including ABC 300 mg/lamivudine (3TC) 150 mg/zidovudine (ZDV) 300 mg; give 1 tablet PO BID (adolescent, ≥40 kg); not a first-line therapy
  • Epzicom: Combination formulation including ABC 600 mg/3TC 300 mg; give 1 tablet PO once daily (adolescent, >16 years)

Emtricitabine (FTC)

  • Oral solution: 240 mg (24 mL) PO once daily; capsules: 200 mg PO once daily (adolescent, ≥18 years)
  • Truvada: Combination formulation including FTC 200 mg/tenofovir (TDF) 300 mg; 1 tablet PO once daily (adult dose; not recommended for patients <18 years)
  • Atripla: Combination formulation including FTC 200 mg/efavirenz (EFV) 600 mg/TDF 300 mg; 1 tablet PO once daily (adult dose; not recommended for patients <18 years)

Lamivudine (3TC)

  • If ≥50 kg, give 150 mg PO BID or 300 mg PO once daily; if < 50 kg, give 4 mg/kg (up to 150 mg) BID (adolescent, ≥16 years)
  • Combivir: Combination formulation including 3TC 150 mg/ZDV 300 mg; give 1 tablet PO BID (adolescent, ≥30 kg)
  • Trizivir: Combination formulation including ABC 300 mg/3TC 150 mg/ZDV 300 mg; give 1 tablet PO BID (adolescent, ≥ 40 kg)
  • Epzicom: Combination formulation including ABC 600 mg/3TC 300 mg; give 1 tablet PO once daily (adolescent, ≥40 kg)

Tenofovir disoproxil fumarate (TDF)

  • 300 mg PO once daily (adolescent, ≥12 y and >35 kg)
  • Truvada: Combination formulation including 3TC 200 mg/TDF 300 mg; 1 tablet PO once daily
  • Atripla: Combination formulation including EFV 600 mg/FTC 200 mg/TDF 300 mg; 1 tablet PO once daily
  • Although TDF is approved for age >2 years, data pointing to decreased bone mineral density have led to the recommendation to reserve use until later adolescence (Tanner 4 or 5) [5]

Zidovudine (ZDV)

  • 200 mg PO TID or 300 mg PO BID (adolescent, ≥18 years); oral solution 10 mg/mL
  • Combivir: Combination formulation including 3TC 150 mg/ZDV 300 mg; give 1 tablet PO BID (adolescent, ≥30 kg)
  • Trizivir: Combination formulation including ABC 300 mg/3TC 150 mg/ZDV 300 mg; give 1 tablet PO BID (adolescent, ≥40 kg)

Other combinations

  • Stribild: elvitegravir/cobicistat/emtricitabine/tenofovir TD approved for adults and adolescents aged 12 years or older who weigh at least 35 kg. Combination formulation including EVG 150 mg/Cobi 150 mg/emtricitabine (FTC) 200 mg/tenofovir disoproxil fumarate (TDF) 300 mg; take once daily with food
  • Genvoya: Identical to elvitegravir with the exception that it contains 10 mg of tenofovir alafenamide (AF). It is approved for adults and adolescents aged 12 years or older who weigh at least 35 kg
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Non-nucleoside Reverse Transcriptase Inhibitors

The definition of "adolescent" may differ depending on the regimen; for regimens with specific definitions of "adolescent," the definition is provided in parentheses following the regimen.

Efavirenz (EFV)

  • 600 mg PO once daily (adolescent, ≥40 kg) [7]
  • Atripla: Combination formulation including EFV 600 mg/emtricitabine (FTC) 200 mg/ tenofovir disoproxil fumarate (TDF) 300 mg; 1 tablet PO once daily (drug combination should not be used in pediatric patients, <40 kg, in whom the EFV dose would be excessive)

Etravirine (ETR)

  • General adult dosing: 200 mg (one 200-mg tablet or two 100-mg tablets) PO BID following a meal

Nevirapine (NVP)

  • 200 mg PO BID; initiate therapy with 200 mg given once daily for the first 14 days; increase to 200 mg administered BID if there is no rash and if no other adverse effects occur [7] ; avoid in women with CD4 >250 or men with CD4 >400 owing to increased risk of hepatotoxicity; 10 mg/mL oral suspension
  • Dosing recommendations during coadministration with other antiretrovirals: NVP in combination with lopinavir/ritonavir (LPV/RTV) may require a higher dose of LPV/RTV

Rilpivirine (RPV)

  • Indicated in combination with other antiretroviral agents for treatment of HIV-1 infection in treatment-naïve adolescents aged 12-17 years with HIV-1 RNA ≤100,000 copies/mL (approved by FDA for adolescents in August 2015)
  • 25 mg PO once daily; take with food
  • Complera: Combination formulation including RPV 25 mg/emtricitabine (FTC) 200 mg/tenofovir disoproxil fumarate (TDF) 300 mg; take once daily with food
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Protease Inhibitors

The definition of "adolescent" may differ depending on the regimen; for regimens with specific definitions of "adolescent," the definition is provided in parentheses following the regimen.

Atazanavir (ATV)

  • Age 16-21 years: For antiretroviral-naive patients, give ATV 300 mg PO plus ritonavir (RTV) 100 mg PO with food or ATV 400 mg PO once daily with food [8]
  • Antiretroviral-experienced patients: ATV 300 mg PO plus RTV 100 mg PO, both once daily with food
  • Dosing recommendations during coadministration with other antiretrovirals: ATV in combination with EFV in therapy-naive patients only (adult dose): ATV 400 mg plus RTV 100 mg PO plus EFV 600 mg PO, all once daily but at separate times (ATV + RTV with food, EFV without food)
  • ATV in combination with TDF (adult dose): ATV 300 mg PO plus RTV 100 mg PO plus TDF 300m g PO, all once daily with food
  • Only RTV-boosted ATV should be used in combination with TDF, because TDF decreases ATV exposure

Darunavir (DRV)

  • Treatment naive: Adolescent (≥18 years)/adult dose: DRV 800 mg PO plus RTV 100 mg PO, both once daily with food
  • Treatment experienced: Adolescent (≥18 years)/adult dose: DRV 600 mg PO plus RTV 100 mg PO, both twice daily with food

Fosamprenavir (FPV)

  • Antiretroviral-naive patients: Adolescent (>18 years)/adult dose: For unboosted (without RTV) twice-daily regimen, give FPV 1400 mg PO BID; for boosted (with RTV) twice-daily regimen, give FPV 700 mg PO plus ritonavir 100 mg PO, both BID
  • Boosted (with RTV) once-daily regimen: FPV 1400 mg PO plus RTV 200 mg PO, both once daily or FPV 1400 mg PO plus RTV 100 mg PO, both once daily
  • Protease inhibitor-experienced patients: FPV 700 mg PO plus RTV 100 mg PO, both BID
  • Once-daily administration of FPV plus RTV is not recommended in protease inhibitor-experienced patients
  • Only FPV boosted with RTV should be used in combination with EFV

Indinavir (IDV)

  • Adolescents: 800 mg PO q8h
  • IDV in combination with RTV: IDV 800 mg PO plus RTV 100 mg or 200 mg BID

Lopinavir/ritonavir (LPV/RTV)

  • LPV 400 mg/RTV 100 mg per dose BID (adolescent, ≥40 kg)
  • Pediatric dose (>6 mo - 18 years): For individuals receiving concomitant nelfinavir (NFV), NVP, EFV, or FPV (these drugs induce LPV metabolism and reduce LPV plasma levels), increased LPV/RTV dosing is required with concomitant administration of these drugs and/or in treatment-experienced patients in whom reduced susceptibility to LPV is suspected (such as those with prior treatment with other protease inhibitors)
  • Once-daily dosing is not recommended in adolescents

Nelfinavir (NFV)

  • Adolescents: 1250 mg (five 250-mg tablets or two 625-mg tablets) BID or 750-mg (three 250-mg tablets) TID
  • Some adolescents require higher doses than adults to achieve equivalent drug exposures; monitor patients carefully to guide appropriate dosing

Ritonavir (RTV)

  • RTV as a pharmacokinetic enhancer: Major use of RTV is as a pharmacokinetic enhancer of other protease inhibitors; dose of RTV recommended varies with the different protease inhibitors

Saquinavir (SQV)

  • SQV 1000 mg plus RTV 100 mg, both BID; should be taken within 2 hours after a full meal; SQV should only be used in combination with RTV or LPV/RTV (never unboosted) (adolescents, ≥16 years)

Tipranavir (TPV)

Pediatric dose (2-18 years):

  • Body-surface-area dosing: TPV 375 mg/m 2 plus RTV 150 mg/m 2, both BID; maximum dose is TPV 500 mg plus RTV 200 mg, both BID
  • Weight-based dosing: TPV 14 mg/kg plus RTV 6 mg/kg, both BID; maximum dose is TPV 500 mg plus RTV 200 mg, both BID

Older than 18 years:

  • TPV 500 mg plus RTV 200 mg, both BID
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Fusion Inhibitors

Enfuvirtide (ENF)

  • 90 mg (1 mL) injected SC BID into the upper arm, anterior thigh, or abdomen (adolescent defined as >16 years):
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Cellular Chemokine Receptor (CCR5) Antagonists

Maraviroc (MVC)

Indicated in combination with other antiretrovirals for the treatment of only CCR5-tropic HIV-1 infection in patients aged ≥2 years who weigh at least 10 kg

It is imperative to test all patients for CCR5 tropism using a highly sensitive tropism assay before initiating the drug

Outgrowth of pre-existing low-level CXCR4- or dual/mixed-tropic HIV-1 not detected by tropism testing at screening has been associated with virologic failure on maraviroc

Dosing for patients older than 16 years

  • When given with potent CYP3A inhibitors (with or without CYP3A inducers), including protease inhibitors (except TPV/RTV): 150 mg PO BID
  • When given with nucleoside reverse transcriptase inhibitors, ENF, TPV/RTV, NVP, raltegravir (RAL), and drugs that are not potent CYP3A inhibitors or inducers: 300 mg PO BID
  • When given with potent CYP3A inducers, including EFV and ETR (without a strong CYP3A inhibitor): 600 mg PO BID
  • Additional dose adjustment required with renal impairment

Dosing for children

Recommended dosage differs based on concomitant medications owing to drug interactions; examples are listed below (ie, not an exhaustive list)

Noninteracting concomitant medications

<30 kg: Not recommended

≥30 kg: 300 mg PO BID

Noninteracting drugs include tipranavir/ritonavir, nevirapine, raltegravir, all NRTIs, and enfuvirtide

Also, all other medications that are not potent CYP3A inhibitors or inducers

Potent CYP3A inhibitors (with or without a potent CYP3A inducer)

10 kg to <20 kg: 50 mg PO BID

20 kg to <30 kg: 75 mg (tablet) or 80 mg (oral solution) PO BID

30 kg to <40 kg: 100 mg PO BID

≥40 kg: 150 mg PO BID

Potent CYP3A inhibitors include protease inhibitors (except tipranavir/ritonavir), delavirdine, elvitegravir/ritonavir, ketoconazole, itraconazole, clarithromycin, and other potent CYP3A inhibitors (eg, nefazodone, telithromycin)

Potent CYP3A inducers (without a potent CYP3A inhibitor)

Maraviroc is NOT recommended for children taking potent CYP3A inducers

Potent CYP3A inducers include efavirenz, rifampin, etravirine, carbamazepine, phenobarbital, and phenytoin

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Integrase Inhibitors

Raltegravir (RAL)

  • Isentress 400-mg tab: 400 mg PO BID (adults and children who weigh ≥25 kg)
  • Isentress HD 600-mg tab: 1200 mg PO once daily (adults and adolescents who weigh ≥40 kg) [9]

Dolutegravir (DTG)

  • 50 mg PO once daily (adolescents ≥12 y)

Elvitegravir (EVG)

  • Vitekta: 85 mg or 150 mg used in combination with an HIV protease inhibitor (ie, atazanavir, lopinavir, darunavir, fosamprenavir, or tipranavir) and coadministered with ritonavir plus other antiretroviral drug(s) as indicated for the treatment of HIV-1 infection in antiretroviral treatment–experienced adults; limited data (off-label) available for adolescents aged 12-17 y
  • Stribild: Elvitegravir is a component of the FDA-approved “quad” pill, elvitegravir/cobicistat/emtricitabine/tenofovir TD (Stribild) approved for adults and adolescents aged 12 y or older who weigh at least 35 kg. Combination formulation including EVG 150 mg/Cobi 150 mg/emtricitabine (FTC) 200 mg/tenofovir disoproxil fumarate (TDF) 300 mg; take once daily with food
  • Genvoya: Identical to elvitegravir with the exception that it contains 10 mg of tenofovir alafenamide (AF). It is approved for adults and adolescents aged 12 y or older who weigh at least 35 kg.
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Boosting Agents

Cobicistat (Tybost) is a CYP3A inhibitor. As a single agent, it is indicated to increase systemic exposure of atazanavir or darunavir (once-daily dosing regimen) in combination with other antiretroviral agents. It is also a component of elvitegravir/cobicistat/emtricitabine/tenofovir TD (Stribild), elvitegravir/cobicistat/emtricitabine/tenofovir AF (Genvoya), darunavir/cobicistat (Prezcobix), and atazanavir/cobicistat (Evotaz).

Cobicistat may be used for treatment-naïve or treatment-experienced patients (without darunavir resistance–associated substitutions). The dosage is 150 mg PO once daily plus atazanavir 300 mg PO once daily or darunavir 800 mg PO once daily.

Use in patients aged 12 years or older has been approved for the combination products elvitegravir/cobicistat/emtricitabine/tenofovir (Stribild, Genvoya), but safety and efficacy are not established in adolescents for cobicistat when added to other regimens.

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