Not Found
Locations

Find information on medical topics, symptoms, drugs, procedures, news and more, written for the health care professional.

Antiretroviral Drug Therapy in Children

By Geoffrey A. Weinberg, MD, Professor of Pediatrics; Director, Clinical Pediatric Infectious Diseases and Pediatric HIV Program, University of Rochester School of Medicine and Dentistry; Golisano Children’s Hospital

Click here for
Patient Education

There are > 2 dozen antiretroviral (ARV) drugs (see Table: Dosage and Administration of Selected Antiretroviral Drugs for Children*), including multidrug combination products, available in the US, each of which may have adverse effects and drug interactions with other ARV drugs or commonly used antibiotics, anticonvulsants, and sedatives. New ARV drugs, immunomodulators, and vaccines are under evaluation.

Clinical and laboratory monitoring are important for identifying drug toxicity and therapeutic failure.

Because expert opinions on therapeutic strategies change rapidly, consultation with experts is strongly advised. Tablets containing fixed-dose combinations of ≥ 3 drugs are now widely used in older children and adolescents to simplify regimens and improve adherence; for young children, such combinations are unavailable in the US or are difficult to use. The standard treatment for children is similar to that for adults: combination ART to maximize viral suppression and minimize selection of drug-resistant strains. Preferred regimens vary somewhat by age (see Table Selected Antiretroviral (ARV) Regimens for Initial Therapy of HIV Infection in Children*).

For current information on dosing, adverse effects, and drug interactions, see guidelines for the use of antiretroviral agents in pediatric HIV infection and guidelines for adults and adolescents available at www.aidsinfo.nih.gov. Useful treatment information is also available at www.hivguidelines.org and www.unaids.org/en/. Consultation regarding ART, especially for issues surrounding HIV postexposure prophylaxis and prevention of HIV mother to child transmission, are also available through the National HIV/AIDS Clinicians' Consultation Center located at the University of California San Francisco, available at www.nccc.ucsf.edu.

Selected Antiretroviral (ARV) Regimens for Initial Therapy of HIV Infection in Children*

Age Group

NRTI Backbone Component

NNRTI, PI, or INSTI Component

Infants and children

Infants birth to < 14 days

Zidovudine plus lamivudine (or emtricitabine)

Nevirapine

Children ≥ 14 days to < 2 yr

Zidovudine plus lamivudine (or emtricitabine)

Lopinavir-ritonavir

Children ≥ 2 yr to < 3 yr

Zidovudine (or abacavir) plus lamivudine (or emtricitabine)

Lopinavir-ritonavir or raltegravir

Children ≥ 3 yr to < 6 yr

Abacavir (or zidovudine) plus lamivudine (or emtricitabine)

Atazanavir-ritonavir or raltegravir

Children ≥ 6 yr to < 12 yr

Abacavir (or zidovudine) plus lamivudine (or emtricitabine)

Atazanavir-ritonavir or dolutegravir

Adolescents ≥ 12 yr (one of the following regimens [includes fixed-dose combination tablets])

Tenofovir plus emtricitabine

Atazanavir-ritonavir

Tenofovir plus emtricitabine

Elvitegravir-cobicistat

Abacavir plus lamivudine

Dolutegravir

INSTI = integrase strand transfer inhibitor; NNRTI = nonnucleoside reverse transcriptase inhibitor; NRTI = nucleoside reverse transcriptase inhibitor; PI = protease inhibitor.

*Each regimen is designed to contain 2 NRTI ARV drugs plus either an NNRTI, PI, or INSTI component. Several alternative ARV regimens exist; consultation with an expert in pediatric HIV medicine is advised. For information on adverse effects, other doses (especially for information on fixed-dose combination products), and drug interactions, see the continually updated Department of Health and Human Services Panel on Antiretroviral Therapy and Medical Management of HIV-Infected Children, a Working Group of the Office of AIDS Research Council. Guidelines for the use of antiretroviral agents in pediatric HIV infection, April 27, 2017. Available at www.aidsinfo.nih.gov.

Dosage and Administration of Selected Antiretroviral Drugs for Children*

Drug

Preparations

Recommended Dosage (Oral)

Selected Adverse Effects and Comments

Nucleoside reverse transcriptase inhibitors (NRTIs)

Abacavir (ABC)

Syrup: 20 mg/mL

Tablet: 300 mg (scored)

3 mo–18yr: 8 mg/kg q 12 h (up to a maximum of 300 mg q 12 h; may give 600 mg q 24 h if ≥ 25 kg

ABC may cause the following:

  • Possibly fatal hypersensitivity reaction—symptoms may include rash, nausea and vomiting, sore throat, cough, or shortness of breath

The incidence of hypersensitivity reaction is about 5%. The reaction mostly occurs during the first 6 wk of use and primarily among patients with the HLA-B*5701 genotype (who should not receive ABC).

There is risk of hypotension or death with rechallenge after a hypersensitivity reaction.

Before prescribing ABC, clinicians should test for the HLA-B*5701 allele.

ABC may be given without regard to food.

Emtricitabine (FTC)

Oral solution: 10 mg/mL

Capsules: 200 mg

0 to < 3 mo: 3 mg/kg q 24 h

≥ 3 mo–18 yr: 6 mg/kg q 24 h (maximum oral solution 240 mg q 24 h; maximum capsule 200 mg q 24 h)

FTC is well-tolerated; however, it may rarely cause the following:

  • Neutropenia, hyperpigmentation, lactic acidosis

  • Severe exacerbation of hepatitis in patients coinfected with hepatitis B infection if FTC suddenly discontinued

FTC may be given without regard to food.

Lamivudine (3TC)

Oral solution: 10 mg/mL

Tablets: 100, 150 (scored), and 300 mg

0–1 mo: 2 mg/kg q 12 h

≥ 1 mo–18 yr: 4 mg/kg q 12 h (up to 150 mg q 12 h)

Children ≥ 3 yr of age and weighing ≥ 25 kg who have an undetectable viral load, a stable CD4 lymphocyte count, and good adherence: May switch to a dose of 8 to 10 mg/kg q 24 h (not to exceed 300 mg/day)

3TC is well-tolerated; however, it may rarely cause the following:

  • Neutropenia, hyperpigmentation, lactic acidosis

  • Severe exacerbation of hepatitis in patients coinfected with hepatitis B infection if 3TC suddenly discontinued

3TC may be given without regard to food.

Tenofovir disoproxil fumarate (TDF) (see fixed-dose combination products below for tenofovir alafenamide [TAF])

Oral powder: 40 mg/1 level scoop

Tablets: 150, 200, 250, and 300 mg

< 2 yr: Not recommended

2–12 yr: 8 mg/kg q 24 h up to 300 mg q 24 h as follows:

10–11 kg: 2 scoops powder q 24 h

12–13 kg: 2.5 scoops powder q 24 h

14–16 kg: 3 scoops powder q 24 h

17–18 kg: 3.5 scoops powder or 1 x 150-mg tablet q 24 h

19–21 kg: 4 scoops powder or 1 x 150-mg tablet q 24 h

22–23 kg: 4.5 scoops powder or 1 x 200-mg tablet q 24 h

24–26 kg: 5 scoops powder or 1 x 200-mg tablet q 24 h

27–28 kg: 5.5 scoops powder or 1 x 250-mg tablet q 24 h

29–31 kg: 6 scoops powder or 1 x 250-mg tablet q 24 h

32–33 kg: 6.5 scoops powder or 1 x 250-mg tablet q 24 h

34 kg: 7 scoops powder or 1 x 250-mg tablet q 24 h

≥ 35 kg: 7.5 scoops powder or 1 x 300-mg tablet q 24 h

12 yr and ≥ 35 kg: 1 x 300-mg tablet q 24 h

TDF is usually well-tolerated; however, it may cause the following:

  • Occasional asthenia, headache, diarrhea, nausea, vomiting

  • Renal insufficiency (proximal tubular dysfunction including Fanconi syndrome)

  • Decreased bone mineral density

  • Severe exacerbation of hepatitis in patients coinfected with hepatitis B infection if TDF is discontinued

The powder preparation is bitter and insoluble and should be given in soft food such as applesauce or yogurt rather than liquid.

TDF may be given without regard to food.

TDF powder should be measured only with the supplied 1-g scoop.

TAF is used for older children and adolescents ≥ 6 yr of age weighing ≥ 25 kg as part of certain fixed-dose combination products. It is designed to have equivalent antiretroviral efficacy to TDF but fewer renal and bone adverse effects.

Zidovudine (ZDV)

Oral syrup: 10 mg/mL

IV solution: 10 mg/mL

Capsule: 100 mg

Tablet: 300 mg

0–6 wk: 4 mg/kg q 12 h

6 wk–17 yr: 240 mg/m2 q 12 h or weight-based dosing:

4–8 kg: 12 mg/kg q 12 h

9–29 kg: 9 mg/kg q 12 h

30 kg: 300 mg q 12 h

18 yr: 300 mg q 12 h

ZDV may cause the following:

  • Macrocytic anemia, granulocytopenia

  • Headache, malaise, anorexia, nausea, vomiting

  • Nail pigmentation

  • Hyperlipidemia, hyperglycemia

  • Lactic acidosis, hepatomegaly with hepatic steatosis

  • Myopathy

ZDV may be given without regard to food.

Nonnucleoside reverse transcriptase inhibitors (NNRTIs)

Nevirapine (NVP)

Suspension: 10 mg/mL

Tablet: 200 mg

Extended-release tablets: 100 and 400 mg

Therapy initiation: Age-appropriate dose given once/day for 14 days then increased to twice/day if tolerated (to lessen incidence of adverse reactions)

< 4 wk (investigational dose, not FDA-approved): No lead-in, 6 mg/kg q 12 h

≥ 4 wk–8 yr: 200 mg/m2 q 12 h

8 yr: 120–150 mg/m2 q 12 h (up to 200 mg q 12 h or, if using extended-release tablets, 400 mg q 24 h)

If an older child or adolescent has been taking NVP tablets twice daily without adverse effects, the extended-release tablets may be used as follows to convert to once-daily dosing:

0.58–0.83 m2: 200 mg once/day (2 x 100 mg)

0.84–1.16 m2: 300 mg once/day (3 x 100 mg)

≥1.17 m2: 400 mg once/day (1 x 400 mg)

NVP may cause the following:

  • Rash, including Stevens-Johnson syndrome

  • Symptomatic hepatitis, including fatal hepatic necrosis

  • Severe systemic hypersensitivity syndrome with potential for multisystem organ involvement and shock

Rash is most common during first 6 wk of therapy; if rash occurs during 14-day regimen, the dose is not increased until rash resolves.

Hepatic toxicity is most common during first 12 wk of therapy, and frequent clinical and laboratory monitoring should be done during this time and periodically thereafter; if clinical hepatitis is suspected, hepatic transaminase levels are obtained.

If hepatitis or hypersensitivity reaction occurs, no rechallenge is done.

If NVP therapy is interrupted for > 7 days, it should be restarted with a 14-day regimen.

NVP may be given without regard to food.

Protease inhibitors (PIs)

Atazanavir (ATV)

Capsules: 150, 200, and 300 mg

Powder: 50 mg/packet

Given with low-dose ritonavir (RTV) as a pharmacokinetic booster

< 3 mo: Not approved

≥ 3 mo–6 yr, weight-based dosing:

5–14 kg: ATV 200 mg (4 packets) + RTV 80 mg (1 mL oral solution) q 24 h

15–24 kg: ATV 250 mg (5 packets) + RTV 80 mg (1 mL oral solution) q 24 h

≥ 6 yr–17 yr:

15–19 kg: ATV 150 mg + RTV 100 mg q 24 h

20–39 kg: ATV 200 mg + RTV 100 mg q 24 h

40 kg: ATV 300 mg + RTV 100 mg q 24 h

18 yr: ATV 300 mg + RTV 100 mg q 24 h

ATV may cause the following:

  • Asymptomatic indirect hyperbilirubinemia (incidence 30%), jaundice (incidence 10%)

  • Hyperglycemia, hyperlipidemia, fat maldistribution

  • Prolongation of PR interval (see Normal cardiac rhythm) on ECG

  • Nephrolithiasis (rare)

ATV should be given with food to enhance absorption.

Lopinavir/ritonavir (LPV/r)

Oral solution: 80/20 mg/mL (contains 43% alcohol and 15% propylene glycol)

Film-coated tablets: 100/25 and 200/50 mg

< 2 wk: Do not use

2 wk–12 mo: 300 mg (of LPV component) per m2 of body surface area q 12 h

1–17 yr: 230–300 mg (of LPV component; many experts prefer the higher dosage) per m2 of body surface area q 12 h (up to maximum of LPV 400 mg q 12 h)

18 yr: LPV 400 mg q 12 h

LPV/r may cause the following:

  • GI intolerance (diarrhea, nausea, vomiting)

  • Hyperglycemia, hyperlipidemia (especially triglycerides), fat maldistribution

  • Possible prolongation of PR and QT intervals

  • Rash, including Stevens-Johnson syndrome

Do not give to premature or young neonates (ie, before 42 wk postmenstrual age or 14 days postnatal age) because of risk of life-threatening cardiotoxicity.

Once-daily dosing is not recommended for children or adolescents because of greater clearance.

A dose increase is required if patients are receiving concomitant NVP, EFV, FPV, or NFV.

LPV/r tablets may be given without regard to food, but the oral solution should be given with food to increase absorption and mask taste (very poor palatability).

Ritonavir (RTV)

Oral solution: 80 mg/mL (contains 43% alcohol by volume)

Tablet: 100 mg

Used only as a pharmacokinetic booster: 80–100 mg q 12–24 h

RTV may cause the following:

  • GI intolerance (diarrhea, nausea, vomiting)

  • Hyperglycemia, hyperlipidemia (especially triglycerides), fat maldistribution

  • Rash, including Stevens-Johnson syndrome

RTV is very rarely used as a primary ARV drug because of GI intolerance at higher doses.

RTV is best absorbed when given with food. Tablets may be more palatable than capsules, but both are superior to liquid, which is poorly palatable. The oral solution may be given with certain foods (eg, chocolate milk, ice cream, peanut butter) to mask its taste.

Entry inhibitor (CCR5 antagonist)

Maraviroc (MVC)

Oral solution: 20 mg/mL

Tablets: 25, 75,150, and 300 mg

Approved for use in children ≥ 2 yr of age weighing ≥ 10 kg; consult pediatric HIV guidelines

MVC may cause the following:

  • Cough, fever, rash, abdominal pain

  • Hepatotoxicity (may be preceded by severe rash and/or significant allergic reaction)

  • Orthostatic hypotension (especially in patients with severe renal insufficiency)

  • Multiple drug interactions

MVC is effective against only CCR5-tropic HIV; an HIV tropism assay is required before use.

MVC should be given with food.

Fusion inhibitor

Enfuvirtide (ENF, T20)

Lyophilized powder for injection: Delivers 90 mg/mL

6–15 yr: 2 mg/kg sc q 12 h (up to 90 mg sc q 12 h)

16 yr: 90 mg sc q 12 h

Not commonly used because of cost, twice daily injections, and local adverse effects.

ENF may cause the following:

  • Local injection site reaction (eg, pain, discomfort, induration, erythema, nodules, ecchymosis) in 88–98% of patients

  • Hypersensitivity reaction (< 1% incidence of fever, malaise, nausea, vomiting, chills, possibly elevated hepatic transaminases)

    If hypersensitivity reaction occurs, no rechallenge is done.

ENF may be given without regard to food.

Integrase inhibitor

Dolutegravir (DTG)

Tablet: 10, 25, and 50 mg

Infants and children <30 kg: Not recommended

Children 30–39 kg: 35 mg q 24 h

Children and adolescents 40 kg: 50 mg q 24 h (may need to give q 12 h with certain UGT1A or CYP3A inducers; package insert should be consulted

DTG may cause the following:

  • Insomnia

  • Headache

DTG may be given without regard to food; however, it should be given 2 h before or 6 h after divalent cation-containing oral antacids, laxatives, sucralfate, iron supplements, Ca supplements, or buffered drugs.

Elvitegravir (EVG)

Available only as fixed-dose combination tablet with FTC, TDF, and cobicistat (COBI) and as fixed-dose combination tablet with FTC, TAF, and COBI

See fixed-dose combination products below

EVG may cause the following:

  • Diarrhea, nausea

  • Renal insufficiency, decreased bone mineral density (see TDF)

  • Severe exacerbation of hepatitis in patients coinfected with hepatitis B infection if coformulation containing FTC or TDF is discontinued suddenly

EVG is coformulated with cobicistat (COBI), a pharmacokinetic booster.

EVG should be given with food.

Raltegravir (RAL)

Chewable tablets: 25 and 100 mg

Film-coated tablet: 400 mg

Granules for oral suspension: Packet of 100 mg to be added to 5 mL of water to make 20 mg/mL

Infants and children ≥ 4 wk and weighing ≥ 3 kg–20 kg: Oral suspension 6 mg/kg q 12 h (see package insert)

Children ≥ 11 kg, chewables as follows:

11–13 kg: 75 mg q 12 h (3 x 25-mg chewables)

14–19 kg: 100 mg q 12 h (1 x 100-mg chewable)

20–27 kg: 150 mg q 12 h (1.5 x 100-mg chewables)

28–39 kg: 200 mg q 12 h (2 x 100-mg chewables)

≥ 40 kg: 300 mg q 12 h (3 x 100-mg chewables)

12 yr: 400 mg q 12 h (1 x 400-mg film-coated)

RAL may cause the following:

  • Nausea, headache, diarrhea, fatigue

  • Rash, including Stevens-Johnson syndrome

  • Creatine phosphokinase elevation; rarely, rhabdomyolysis

Chewable tablets may be chewed or swallowed whole but are not interchangeable with film-coated tablets or the oral suspension because of different bioavailability.

RAL may be given without regard to food.

Some fixed-dose combination products

ZDV/3TC (Combivir®)

Combination tablets: ZDV 300 mg + 3TC 150 mg

30 kg: 1 tablet q 12 h

See individual drugs

3TC/ABC (Epzicom®)

Combination tablets: 3TC 300 mg + ABC 600 mg

≥ 25 kg: 1 tablet q 24 h

See individual drugs

FTC/TDF (Truvada®)

Combination tablets: FTC 200 mg + TDF 300 mg

12 yr and ≥ 35 kg: 1 tablet q 24 h

See individual drugs

ABC/DTG/3TC (Triumeq®)

Combination tablets: ABC 600 mg + DTG 50 mg + 3TC 300 mg

≥ 40 kg: 1 tablet q 24 h

See individual drugs

FTC/TDF/EVG/COBI (Stribild®)

Combination tablets: FTC 200 mg + TDF 300 mg + EVG 150 mg + COBI 150 mg

≥ 12 yr and ≥ 35 kg: 1 tablet q 24 h

See individual drugs

FTC/TAF/EVG/COBI (Genvoya®)

Combination tablets: FTC 200 mg + TAF 10 mg + EVG 150 mg + COBI 150 mg

≥ 6 yr and ≥ 25 kg: 1 tablet q 24 h

See individual drugs

TAF is used for older children and adolescents ≥ 6 yr of age weighing ≥ 25 kg as part of certain fixed-dose combination products. It is designed to have equivalent antiretroviral efficacy to TDF but fewer renal and bone adverse effects.

*Several alternative ARV drugs are not included here; consultation with an expert in pediatric HIV medicine is advised. For information on adverse effects, other doses (especially for information on fixed-dose combination products), and drug interactions, see the continually updated Department of Health and Human Services Panel on Antiretroviral Therapy and Medical Management of HIV-Infected Children, a Working Group of the Office of AIDS Research Council. Guidelines for the use of antiretroviral agents in pediatric HIV infection, April 27, 2017. Available at www.aidsinfo.nih.gov.

Tenofovir disoproxil fumarate and tenofovir alafenamide are functionally grouped within the NRTIs but are actually nucleotide reverse transcriptase inhibitors by chemical structure.

The dosing for zidovudine should be reduced for premature infants < 35 wk gestation; see Department of Health and Human Services Panel on Antiretroviral Therapy and Medical Management of HIV-Infected Children, a Working Group of the Office of AIDS Research Council. Guidelines for the use of antiretroviral agents in pediatric HIV infection, April 27, 2017. Available at www.aidsinfo.nih.gov.

Clinicians also can call the Perinatal HIV Consultation and Referral Services Hotline: 1-888-HIV-8765 (1-888-448-8765) for questions regarding interventions to decrease vertical HIV transmission and neonatal diagnosis.

ARV = antiretroviral.

Resources In This Article