Pediatric HIV Infection Medication

Updated: Jun 25, 2019
  • Author: Delia M Rivera, MD; Chief Editor: Russell W Steele, MD  more...
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Medication

Medication Summary

Antiretroviral (ART) drugs are used for the treatment of human immunodeficiency virus (HIV) infection and for postexposure prophylaxis (PEP). ART monotherapy does not produce sustained clinical benefits, such as improved survival. This failure is partly due to the development of drug-resistant variants of HIV. Resistance develops rapidly during monotherapy, and cross-resistance among related drugs is common.

Combination therapy with ARTs (a strategy analogous to the treatment of TB and other infectious diseases) has improved efficacy, minimized toxicity, and delayed drug resistance.

Classes of ARTs include the following:

  • Nucleoside or nucleotide reverse transcriptase inhibitors (NRTIs)

  • Nonnucleoside reverse transcriptase inhibitors (NNRTIs)

  • Protease inhibitors (PIs)

  • Integrase inhibitors (IIs)

  • Fusion inhibitors (FIs)

  • Chemokine receptor antagonists (CRAs)

  • Entry inhibitors (CD4-directed post-attachment inhibitors)

Initial therapy should be started with a combination of 3 ARTs, including a backbone of 2 NRTIs plus  an NNRTI, or 2 NRTIs plus  a protease inhibitor. [3]

Numerous ARTs have been approved for pediatric usage and many are available as a pediatric formulation or capsule/tablet.

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Nucleoside or Nucleotide Reverse Transcriptase Inhibitors

Class Summary

NRTIs are nucleoside or nucleotide reverse transcriptase inhibitor analogs with antiretroviral activity. They are indicated for the treatment of HIV infection, and they delay the progression of the disease.

Abacavir (ABC, Ziagen)

Patients and parents must be cautioned about the risk of serious hypersensitivity reaction (HSR). Provide a medication guide and warning card. Test patients for the HLA-B*5701 allele before starting therapy to predict risk of HSR. Indicated for children aged 3 months or older.

Didanosine (ddI, dideoxyinosine, Videx, Videx EC)

This agent is a purine nucleoside analog with antiviral activity. Indicated for children (including neonates aged 2 week or older); however, because of significant toxicity (eg, peripheral neuropathy, lactic acidosis, hepatomegaly), it is not typically prescribed since there are safer agents available.

Lamivudine (3TC, Epivir, Epivir HBV)

Lamivudine is a dideoxynucleoside analog with antiretroviral activity. In combination with oral zidovudine, it produces substantial and sustained increases in CD4+ counts and decreases in viral load in HIV-infected patients. It is approved by the FDA for children aged ≥ 3 months for HIV and is a common component of most nucleoside backbone regimens. It is also approved to treat hepatitis B.

Stavudine (d4T, Zerit)

Stavudine is a synthetic thymidine nucleoside analog active against HIV-1. Although stavudine is approved by the FDA for use in infants and children, it is not typically prescribed because it carries a higher risk of adverse effects associated with mitochondrial toxicity and a higher incidence of lipoatrophy than other NRTIs.

Zidovudine (ZDV, AZT, Retrovir)

This agent is a thymidine analog that inhibits viral replication. It inhibits activity of HIV reverse transcriptase by competing with natural substrate for use by and incorporation into viral DNA. Frequent choice of NRTI backbone for ART. It has extensive experience in pediatrics including treatment and prevention of perinatal transmission.

Emtricitabine (Emtriva)

A synthetic nucleoside cytosine analog, emtricitabine competes with deoxycytidine-5'-triphosphate and incorporates into viral DNA, causing chain termination. It is approved by the FDA in children (starting at birth). It has minimal toxicity and is administered once daily as part of a dual-NRTI backbone.

Tenofovir DF (TDF, Viread)

This antiretroviral agent used in treatment of AIDS inhibits activity of HIV reverse transcriptase by competing with natural substrate deoxyadenosine 5'-triphosphate and, after incorporation into DNA, by causing DNA chain termination. It is administered as prodrug bis-isopropoxycarbonyloxymethyl ester derivative of tenofovir, which is converted, in various enzymatic processes, to tenofovir, an acyclic nucleoside phosphonate (nucleotide) analog of adenosine 5'-monophosphate.

Administration with a high-fat meal enhances bioavailability. Prolonged intracellular levels allows for once-daily dosing. It is approved by the FDA for children aged 2 years or older.

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Nonnucleoside Reverse Transcriptase Inhibitors

Class Summary

NNRTIs inhibit both DNA-directed and RNA-directed polymerase functions of HIV-1 reverse transcriptase. The different sites of action of nonnucleoside and nucleoside inhibitors suggest potential synergistic effects of these agents and their potential activity against nucleoside-resistant HIV strains.

Efavirenz (DMP-266, EFV, Sustiva)

Efavirenz is used only in combination regimens. It is approved by the FDA for children aged 3 months or older who weigh at least 3.5 kg.

Nevirapine (NVP, Viramune, Viramune XR)

Nevirapine is indicated for use in combination with other ARDs for treatment of HIV-1 infection. It is approved by the FDA in children from infancy (aged ≥ 15 days) onward. The extended-release tablet is approved for use in children aged ≥ 6 years.

Rilpivirine (Edurant)

NNRTI indicated in combination with other ARTs for treatment of HIV-1 infection in treatment-naïve adolescents aged 12-17 years who weigh at least 35 kg with HIV-1 RNA ≤ 100,000 copies/mL.

Etravirine (Intelence)

Indicated in combination with other antiretroviral agents (ART) for treatment of HIV-1 infection in ART-experienced patients with evidence of viral replication and HIV-1 strains resistant to a NNRTIs and other antiretroviral agents in children aged 2 years or older and weigh at least 10 kg.

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Protease Inhibitors

Class Summary

Protease inhibitors inhibit HIV protease, which is required for HIV replication and the formation of mature, infectious viral particles.

Nelfinavir (Viracept, NPV)

Nelfinavir inhibits HIV-1 protease, resulting in the production of an immature and noninfectious virus. It is approved by the FDA in combination with 2 NRTIs in children aged ≥ 2 years and adolescents.

Lopinavir and ritonavir (Kaletra, LVP/r)

Lopinavir inhibits HIV protease and renders enzyme incapable of processing polyprotein precursors, leading to production of noninfectious, immature HIV particles. Ritonavir inhibits CYP3A metabolism of lopinavir, increasing plasma levels. It is approved for children (including infants aged > 14 days), children, and adolescents. This product is available in tablets (200 mg/50 mg LPV/r), pediatric tablets (100 mg/25 mg LPV/r), and PO solution (80 mg/20 mg LPV/r; 42.4% alcohol by volume).

Ritonavir (Norvir, RTV)

Ritonavir is an HIV protease inhibitor used as part of double or triple therapy with nucleosides and other protease inhibitors. It is used as a boosting agent to other ARDs.

Atazanavir (ATV, Reyataz)

Atazanavir is an azapeptide HIV-1 protease inhibitor. It prevents virion maturation by selectively inhibiting Gag and Gag-Pol polyproteins in HIV-1 infected cells. It is approved by the FDA for infants (aged ≥ 3 months who weigh at least 5 kg), children, and adolescents.

Darunavir (DRV, Prezista)

An HIV-1 protease inhibitor, darunavir selectively inhibits HIV-encoded Gag-Pol polyprotein cleavage in infected cells, preventing formation of mature virus particles. It is indicated to treat HIV disease not responding to other ARDs. Coadminister with low-dose ritonavir (ritonavir-boosted therapy decreases elimination and increases darunavir serum concentration).

Darunavir is typically coadministered with other anti-HIV agents (eg, NRTIs). Food increases maximum concentration (Cmax) and area under the concentration-time curve (AUC). Coadministered with ritonavir, it is approved by the FDA as a part of an ART regimen in treatment-naïve and treatment- experienced children aged ≥ 3 years.

Fosamprenavir (f-APV, Lexiva)

A prodrug of amprenavir (inhibitor of HIV protease), fosamprenavir is rapidly converted to amprenavir by cellular phosphatases in vivo. Amprenavir inhibits HIV-1 protease and binds its active site, preventing the processing of viral Gag and Gag-Pol polyprotein precursors and resulting in immature, noninfectious viral particles. Although approved by the FDA in children as young as 4 weeks, the AIDSinfo Panel members recommend use in children aged 6 months or older. The panel also recommends fosamprenavir only be used as boosted therapy, since unboosted fosamprenavir may select for mutations associated with resistance to darunavir.

Tipranavir (TPV, Aptivus)

A nonpeptidic protease inhibitor, tipranavir inhibits HIV replication. It is indicated for combination antiretroviral treatment of HIV-1 infected patients aged 2 years or older who are treatment-experienced and infected with HIV-1 strains resistant to >1 protease inhibitor. This agent must be coadministered with ritonavir 200 mg to attain therapeutic levels. It is ineffective if used alone without ritonavir-boosted levels. Results of genotypic or phenotypic testing and/or treatment history should guide use. It is available as 250 mg caps or as PO solution of 100 mg/mL.

Saquinavir (Invirase)

Saquinavir is an HIV protease inhibitor used as part of double or triple therapy with nucleosides and other protease inhibitors. It must be used in combination with ritonavir as a boosting agent. It is available as a 200-mg hard gel cap or 500-mg film-coated tablet. It is not approved by the FDA for use in children or adolescents aged <16 years. Limited data are available from investigational trials in children aged ≥ 2 years.

Indinavir (Crixivan, IDV)

This agent prevents formation of protein precursors necessary for HIV infection of uninfected cells and viral replication. Indinavir has not been approved by the FDA for use in the pediatric population. Although indinavir was one of the first protease inhibitors to be studied in children, its use in pediatrics has never been common and is currently very rare. Indinavir is not recommended by the AIDSinfo Panel members for use in children because of its unfavorable toxicity profile, limited efficacy data, and uncertain pharmacokinetics.

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Integrase Inhibitors

Class Summary

HIV integrase is responsible for the transport and attachment of proviral DNA to host-cell chromosomes, allowing transcription of viral proteins.

Raltegravir (RAL, Isentress)

Raltegravir is an HIV-1integrase strand transfer inhibitor (INSTI). It is indicated for use in combination therapy regimens for the treatment of HIV infection in children who weigh at least 30 kg.

Dolutegravir (DTG, Tivicay)

Dolutegravir is an integrase strand transfer inhibitor (INSTI) that inhibits catalytic activity of HIV-1 integrase, an HIV encoded enzyme required for viral replication. It is approved for use in children aged ≥ 12 years who weigh at least 40 kg.

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Fusion Inhibitors

Class Summary

These agents disrupt HIV binding and, ultimately, fusion with host cells. Entry inhibitors bind to CCR5 chemokines coreceptors. Fusion inhibitors bind to the HR1 region of gp41.

Enfuvirtide (T-20, Fuzeon)

Enfuvirtide is a fusion inhibitor. It blocks entry of HIV into human immune cells by inhibiting gp41 protein, disrupting viral structural rearrangement to fuse with healthy immune cells and preventing HIV replication. In clinical trials, selected patients with multidrug resistance were twice as likely to achieve undetectable HIV-1 plasma levels (< 40 copies/mL) when enfuvirtide was added to optimized antiretroviral regimens. It is approved for children aged 6 years or older.

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Chemokine Receptor Antagonists

Class Summary

Selectively antagonizes the interaction between human CCR5 and HIV-1 gp120. Blocking this interaction prevents CCR5-tropic HIV-1 entry into cells.

Maraviroc (MVC, Selzentry)

Maraviroc is a selective chemokine receptor antagonist (CRA). 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. It blocks viral entry via CCR5 co-receptor into host cells, reduces viral load, and increases T-cell counts in CCR5-tropic HIV-1 (ie, R5 virus). This agent is indicated for combination treatment with optimized background therapy in treatment-experienced adults infected with only R5 virus who have evidence of viral replication and have HIV-1 strains resistant to multiple antiretroviral agents. It is approved for children as young as 2 years old.

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Complete Regimen Combinations

Class Summary

Complete fixed-dose regimens assist with medication adherence. Three- and four-drug combination products are available to decrease pill burden and administration frequency.

Emtricitabine/tenofovir/efavirenz (Atripla)

Contains emtricitabine and tenofovir (NRTIs), plus efavirenz (NNRTI). Indicated for use alone as a complete regimen or in combination with other antiretroviral agents for the treatment of HIV-1 infection in adults and pediatric patients aged ≥ 12 years who weigh at least 40 kg.

Elvitegravir/cobicistat/emtricitabine/tenofovir AF (Genvoya)

Four-drug antiretroviral (ART) combination of elvitegravir (integrase strand transfer inhibitor [INSTI]), cobicistat (CYP3A inhibitor), and emtricitabine and tenofovir alafenamide (TAF), both nucleoside analog reverse transcriptase inhibitors (NRTIs). It is indicated as a complete treatment regimen for HIV-1 infection in adults and children aged ≥ 12 y (weight ≥ 25 kg) who are ART-naïve or to replace the current ART regimen in those who are virologically suppressed (HIV-1 RNA < 50 copies/mL) on a stable ART regimen for at least 6 months with no history of treatment failure and no known substitutions associated with resistance to the individual components.

Elvitegravir/cobicistat/emtricitabine/tenofovir DF (Stribild)

Combination integrase inhibitor, CYP3A4 inhibitor (boosted therapy), and 2 NRTIs as a complete regimen for treatment of HIV infection in treatment-naive pediatric patients aged ≥ 12 y who weigh at least 35 kg. It is also indicated as replacement of the current antiretroviral regimen in patients who are virologically-suppressed (HIV-1 RNA < 50 copies/mL) on a stable ART regimen for at least 6 months with no history of treatment failure and no known substitutions associated with resistance to the individual components of Stribild.

Emtricitabine/rilpivirine/tenofovir DF (Complera)

Indicated as complete regimen for treatment of HIV-1 infection in treatment-naïve adults and adolescents aged 12 years or older (weight ≥ 35 kg) with HIV-1 RNA > 100,000 copies/mL, and in certain virologically-suppressed (HIV-1 RNA < 50 copies/mL) patients on a stable ART regimen at start of therapy in order to replace their current ART regimen. Combination consists of 2 NRTIs (ie, emtricitabine and tenofovir) and 1 NNRTI (ie, rilpivirine).

Emtricitabine/rilpivirine/tenofovir AF (Odefsey)

Indicated as complete regimen for treatment of HIV-1 infection in treatment-naïve adults and adolescents aged 12 years or older (weight ≥ 35 kg) with HIV-1 RNA > 100,000 copies/mL, and in certain virologically-suppressed (HIV-1 RNA < 50 copies/mL) patients on a stable ART regimen at start of therapy in order to replace their current ART regimen. Combination consists of 2 NRTIs (ie, emtricitabine and tenofovir) and 1 NNRTI (ie, rilpivirine).

Efavirenz/lamivudine/tenofovir DF (Symfi, Symfi Lo)

Three-drug combination of a non-nucleoside reverse transcriptase inhibitor, and two nucleo(t)side reverse transcriptase inhibitors and is indicated as a complete regimen for the treatment of human immunodeficiency virus type 1 (HIV-1) infection in adults and children who weigh at least 35 kg (Symfi Lo) or 40 kg (Symfi).

Bictegravir/emtricitabine/tenofovir AF (Biktarvy)

Three-drug combination of bictegravir (BIC), an HIV-1 integrase strand transfer inhibitor (INSTI), and emtricitabine (FTC) and tenofovir alafenamide (TAF), both HIV-1 nucleoside analog reverse transcriptase inhibitors (NRTIs). Indicated as a complete regimen for treatment of HIV-1 infection in adults and pediatric patients weighing ≥25 kg who are ART-naïve or replacing current antiretroviral regimen in those who are virologically-suppressed (HIV-1 RNA

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HIV, ART Combos

Class Summary

Combination ARTs are helpful to promote compliance with complex medication regimens.

Emtricitabine/tenofovir AF (Descovy)

NRTI combination product. Indicated in combination with other ART agents (eg, NNRTIs, PIs) for the treatment of HIV-1 infection in adults and pediatric patients aged ≥ 12 y (weight ≥ 35 kg). It is also indicated, in combination with other ARTs other than protease inhibitors that require a CYP3A inhibitor, for the treatment of HIV-1 infection in children weighing 25-35 kg. Tenofovir alafenamide (AF) is a more targeted form of tenofovir that has demonstrated high antiviral efficacy at a dose that is 10 times lower than tenofovir DF, as well as an improved renal and bone safety profile.

Additionally, it is indicated for HIV-1 preexposure prophylaxis (PrEP) for at-risk adults and adolescents to reduce the risk of HIV-1 infection from sex, excluding those who have receptive vaginal sex.

Emtricitabine/tenofovir DF (Truvada)

Indicated, in combination with other antiretroviral agents (eg, NNRTIs, PIs), for the treatment of HIV-1 infection in adults and pediatric patients who weigh at least 17 kg and can swallow the tablet whole.

Additionally, it is also indicated in combination with safer sex practices for preexposure prophylaxis (PrEP) to reduce the risk of sexually acquired HIV-1 in adults and adolescents at high risk. 

Lamivudine/zidovudine (3tc/zdv, Combivir)

Combination of 2 NRTIs. It is indicated in combination with other antiretroviral agents for the treatment of HIV-1 infection in children who weigh at least 30 kg, adolescents, and adults.

Lamivudine/zidovudine/abacavir (Trizivir)

Abacavir is a nucleoside reverse transcriptase inhibitor, which interferes with HIV viral RNA dependent DNA polymerase and inhibits viral replication. Lamivudine and zidovudine are thymidine analogs that inhibit viral replication. Indicated in combination with other ARTs for HIV infection in adults and children aged ≥ 12 years who weigh at least 40 kg.

Lamivudine/abacavir (Epzicom)

Abacavir is a nucleoside reverse transcriptase inhibitor, which interferes with HIV viral RNA dependent DNA polymerase and inhibits viral replication. Lamivudine is a thymidine analog that inhibit viral replication. Indicated in combination with other ARTs for HIV infection in adults and children who weigh at least 25 kg.

Abacavir/dolutegravir/lamivudine (Triumeq)

Indicated for human immunodeficiency virus type 1 (HIV-1) infection in combination with other ARTs in adults and children weighing ≥ 40 kg.

Lamivudine/tenofovir DF (Cimduo)

Combination contains 2 NRTIs (lamivudine 300 mg and tenofovir disoproxil fumarate 300 mg) that is indicated in combination with other ARTs for HIV-1 infection in adults and children who weigh at least 35 kg.

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