Antiretroviral Therapy in Adolescents and Young Adults

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The number of cases of human immunodeficiency virus () infection among young adolescents has been increasing over the years. Adolescents and young adults often acquire through sexual activity and are thus excellent candidates for intervention and prevention programs. Many are recently infected or unaware of their HIV infection status, which may increase the risk of transmission. [1] Early intervention, including prevention strategies, counseling, and HIV testing, plays a key role in treating adolescents and young adults. [2]

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] Special consideration may be needed in perinatally infected patients, as they are often more treatment-experienced and may have developed a significant burden of antiretroviral resistance.

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 Sexual Maturity Rating (SMR; also known as Tanner staging) of puberty and not just on age alone. [3, 4]

Adolescents in early puberty (ie, SMR stages III and less) should be on pediatric dosing schedules, whereas those in late puberty (ie, SMR stages IV and 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. Patients should be counseled on options to prevent pregnancy, as well as the potential for with hormonal contraceptives. Guidelines for Use of Antiretroviral Agents in HIV Infected Adults and Adolescents Tables 18a, b, and d provide further information on . [1] Patients should be counseled on the risks and benefits of certain agents, such as efavirenz and dolutegravir, based on the latest guidelines in an evolving field.

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

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.

Emtricitabine (FTC)

Lamivudine (3TC)

Tenofovir disoproxil fumarate (TDF)

Zidovudine (ZDV)

Other combinations

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)

Etravirine (ETR)

Nevirapine (NVP)

Rilpivirine (RPV)

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)

Darunavir (DRV)

Fosamprenavir (FPV)

Indinavir (IDV)

Lopinavir/ritonavir (LPV/RTV)

Nelfinavir (NFV)

Ritonavir (RTV)

Saquinavir (SQV)

Tipranavir (TPV)

Pediatric dose (2-18 years):

Older than 18 years:

Enfuvirtide (ENF)

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

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

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

Raltegravir (RAL)

Dolutegravir (DTG)

Elvitegravir (EVG)

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.

Overview

What increases the risk of HIV infection among adolescents and young adults?

What are antiretroviral therapy considerations in adolescents and young adults with HIV infection?

How is abacavir (ABC) administered in the antiretroviral therapy of HIV infection in adolescents and young adults?

How is emtricitabine (FTC) administered in the antiretroviral therapy of HIV infection in adolescents and young adults?

How is lamivudine (3TC) administered in the antiretroviral therapy of HIV infection in adolescents and young adults?

How is tenofovir disoproxil fumarate (TDF) administered in the antiretroviral therapy of HIV infection in adolescents and young adults?

How is zidovudine (ZDV) administered in the antiretroviral therapy of HIV infection in adolescents and young adults?

How is Stribild administered in the antiretroviral therapy of HIV infection in adolescents and young adults?

How is Genvoya administered in the antiretroviral therapy of HIV infection in adolescents and young adults?

How is efavirenz (EFV) administered in the antiretroviral therapy of HIV infection in adolescents and young adults?

How is etravirine (ETR) administered in the antiretroviral therapy of HIV infection in adolescents and young adults?

How is nevirapine (NVP) administered in the antiretroviral therapy of HIV infection in adolescents and young adults?

How is rilpivirine (RPV) administered in the antiretroviral therapy of HIV infection in adolescents and young adults?

How is atazanavir (ATV) administered in the antiretroviral therapy of HIV infection in adolescents and young adults?

How is darunavir (DRV) administered in the antiretroviral therapy of HIV infection in adolescents and young adults?

How is fosamprenavir (FPV) administered in the antiretroviral therapy of HIV infection in adolescents and young adults?

How is indinavir (IDV) administered in the antiretroviral therapy of HIV infection in adolescents and young adults?

How is lopinavir/ritonavir (LPV/RTV) administered in the antiretroviral therapy of HIV infection in adolescents and young adults?

How is nelfinavir (NFV) administered in the antiretroviral therapy of HIV infection in adolescents and young adults?

How is ritonavir (RTV) administered in the antiretroviral therapy of HIV infection in adolescents and young adults?

How is saquinavir (SQV) administered in the antiretroviral therapy of HIV infection in adolescents and young adults?

How is tipranavir (TPV) administered in the antiretroviral therapy of HIV infection in adolescents and young adults?

How is enfuvirtide (ENF) administered in the antiretroviral therapy of HIV infection in adolescents and young adults?

How is maraviroc (MVC) administered in the antiretroviral therapy of HIV infection in adolescents and young adults?

How is maraviroc (MVC) administered in the antiretroviral therapy of HIV infection in children?

How is raltegravir (RAL) administered in the antiretroviral therapy of HIV infection in adolescents and young adults?

How is dolutegravir (DTG) administered in the antiretroviral therapy of HIV infection in adolescents and young adults?

How is elvitegravir (EVG) administered in the antiretroviral therapy of HIV infection in adolescents and young adults?

What is the role of cobicistat (Tybost) in the antiretroviral therapy of HIV infection in adolescents and young adults?

U.S. Department of Health and Human Services. Guidelines for the Use of Antiretroviral Agents in HIV-1-Infected Adults and Adolescents. 2018 May 30. [Full Text].

Kahana SY, Rohan J, Allison S, Frazier TW, Drotar D. A meta-analysis of adherence to antiretroviral therapy and virologic responses in HIV-infected children, adolescents, and young adults. AIDS Behav. 2013 Jan. 17(1):41-60. [Medline].

Pharmacokinetics and pharmacodynamics in adolescents. January 20-21, 1994. Proceedings. J Adolesc Health. 1994 Dec. 15(8):605-78. [Medline].

El-Sadar W, Oleske JM, Agins BD, et al. Evaluation and management of early HIV infection. Clinical Practice Guideline No. 7 (AHCPR Publication No. 94-0572). Rockville, MD: Agency for Health Policy and Research, Public Health Service, US Department of Health and Human Services, 1994.

U.S. Department of Health and Human Services. Guidelines for the Use of Antiretroviral Agents in Pediatric HIV Infection. 2017 Apr 27. [Full Text].

Viani RM, Peralta L, Aldrovandi G, et al. Prevalence of primary HIV-1 drug resistance among recently infected adolescents: a multicenter adolescent trials network for HIV/AIDS interventions study. J Infect Dis. 2006 Dec 1. 194(11):1505-9. [Medline].

Takuva S, Evans D, Zuma K, Okello V, Louwagie G. Comparative durability of nevirapine versus efavirenz in first-line regimens during the first year of initiating antiretroviral therapy among Swaziland HIV-infected adults. Pan Afr Med J. 2013. 15:5. [Medline]. [Full Text].

Loutfy MR, Walmsley SL, Klein MB, Raboud J, Tseng AL, Blitz SL, et al. Factors affecting antiretroviral pharmacokinetics in HIV-infected women with virologic suppression on combination antiretroviral therapy: a cross-sectional study. BMC Infect Dis. 2013 Jun 3. 13:256. [Medline]. [Full Text].

Isentress HD (raltegravir) [package insert]. Whitehouse Station, NJ: Merck & Co, Inc. 2017 May. Available at [Full Text].

David J Cennimo, MD, FAAP, FACP, AAHIVS Assistant Professor of and Pediatrics, Adult and Pediatric Infectious Diseases, Rutgers New Jersey Medical School; Hospital Epidemiologist and Co-Director of Antimicrobial Stewardship, University Hospital

David J Cennimo, MD, FAAP, FACP, AAHIVS is a member of the following medical societies: American Academy of HIV Medicine, American Academy of Pediatrics, American College of Physicians, American Medical Association, HIV Medicine Association, Infectious Diseases Society of America, Medical Society of New Jersey, Pediatric Infectious Diseases Society

Disclosure: Nothing to disclose.

Mary L Windle, PharmD Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Nothing to disclose.

Michelle R Salvaggio, MD, FACP Assistant Professor, Department of Internal Medicine, Section of Infectious Diseases, University of Oklahoma College of Medicine; Medical Director of Infectious Diseases Institute, Director, Clinical Trials Unit, Director, Ryan White Programs, Department of Medicine, University of Oklahoma Health Sciences Center; Attending Physician, Infectious Diseases Consultation Service, Infectious Diseases Institute, OU Medical Center

Michelle R Salvaggio, MD, FACP is a member of the following medical societies: American College of Physicians, Infectious Diseases Society of America

Disclosure: Received honoraria from Merck for speaking and teaching.

Antiretroviral Therapy in Adolescents and Young Adults

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