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Antiretroviral Drug Therapy in Children

By

Geoffrey A. Weinberg

, MD, University of Rochester School of Medicine and Dentistry

Last full review/revision Jul 2020| Content last modified Jul 2020
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There are > 30 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, antiseizure drugs, 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 (termed single-tablet regimens; one tablet once a day) 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 antiretroviral therapy (ART) to maximize viral suppression and minimize selection of drug-resistant strains. Preferred regimens vary somewhat by age but typically contain 2 nucleoside reverse transcriptase inhibitors (NRTI) plus either a nonnucleoside reverse transcriptase inhibitor (NNRTI), protease inhibitor (PI), or integrase strand transfer inhibitor (INSTI) (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 the use of antiretroviral agents in adults and adolescents with HIV. Useful treatment information is also available at New York State Department of Health AIDS Institute and UNAIDS. Consultation regarding ART, especially for issues surrounding HIV postexposure prophylaxis and prevention of HIV mother-to-child transmission (MTCT), is also available through the National Clinician Consultation Center.

Table
icon

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

Age Group

NRTI Backbone Component (Use 2)

NNRTI, PI, or INSTI Component (Use 1)

Infants birth to < 14 days

Zidovudine plus lamivudine (or emtricitabine)

Nevirapine or

Weight ≥ 2 kg: Raltegravir

Children ≥ 14 days to < 3 years

Zidovudine (or abacavir if ≥ 3 months) plus lamivudine (or emtricitabine)

Lopinavir-ritonavir or

Weight ≥ 2 kg: Raltegravir

Children ≥ 3 years, weight < 25 kg

Abacavir (or zidovudine) plus lamivudine (or emtricitabine)

Atazanavir-ritonavir or

Raltegravir

Children ≥ 3 years, weight ≥ 25 kg

Abacavir (or zidovudine) plus lamivudine (or emtricitabine)

Dolutegravir or

Elvitegravir-cobicistat

Adolescents > 12 years, weight ≥ 25 kg

Emtricitabine plus tenofovir alafenamide

Bictegravir

* Each regimen is designed to contain 2 NRTI antiretroviral (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 14, 2020. Available at AIDSinfo.

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

Table
icon

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)

Oral syrup: 20 mg/mL

Tablet: 300 mg (scored)

Also available in fixed-dose combination (FDC) tablets

3 months–18 years: 8 mg/kg twice daily (up to a maximum of 300 mg twice daily; may give 600 mg once a day 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 weeks 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

Also available in fixed-dose combination tablets

0 to < 3 months: 3 mg/kg once a day

≥ 3 months–18 years: 6 mg/kg once a day (maximum oral solution 240 mg once a day; maximum capsule 200 mg once a day)

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 if FTC suddenly discontinued

FTC may be given without regard to food.

Lamivudine (3TC)

Oral solution: 10 mg/mL, 5 mg/mL

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

Also available in fixed dose combination tablets

0–1 month: 2 mg/kg twice daily

> 1 month to < 3 months: 5 mg/kg twice daily

> 3 months–18 years: 5 mg/kg twice daily (up to 150 mg twice daily)

Children ≥ 3 years of age and weighing ≥ 25 kg who have an undetectable HIV plasma viral load, a stable CD4+ lymphocyte count, and good adherence for a 36-week period: May switch to a dose of 10 mg/kg once a day (not to exceed 300 mg/day)

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

  • Neutropenia, lactic acidosis

  • Severe exacerbation of hepatitis in patients coinfected with hepatitis B 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

Both TDF and TAF are available in fixed-dose combination tablets.

< 2 years: Not recommended

2–12 years: 8 mg/kg once a day up to 300 mg once a day as follows:

  • 10–11 kg: 2 scoops powder once a day

  • 12–13 kg: 2.5 scoops powder once a day

  • 14–16 kg: 3 scoops powder once a day

  • 17–18 kg: 3.5 scoops powder or 1 x 150-mg tablet once a day

  • 19–21 kg: 4 scoops powder or 1 x 150-mg tablet once a day

  • 22–23 kg: 4.5 scoops powder or 1 x 200-mg tablet once a day

  • 24–26 kg: 5 scoops powder or 1 x 200-mg tablet once a day

  • 27–28 kg: 5.5 scoops powder or 1 x 250-mg tablet once a day

  • 29–31 kg: 6 scoops powder or 1 x 250-mg tablet once a day

  • 32–33 kg: 6.5 scoops powder or 1 x 250-mg tablet once a day

  • 34 kg: 7 scoops powder or 1 x 250-mg tablet once a day

  • ≥ 35 kg: 7.5 scoops powder or 1 x 300-mg tablet once a day

12 years and ≥ 35 kg: 1 x 300-mg tablet once a day

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

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 years 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

Also available in fixed-dose combination tablets

0 to 4 weeks: 4 mg/kg twice daily

≥ 4 weeks weight-based dosing:

  • 4 to < 9 kg: 12 mg/kg twice daily

  • 9 to < 30 kg: 9 mg/kg twice daily

  • 30 kg: 300 mg twice daily

Alternative body surface area dosing: 180–240 mg/m2 twice daily (not to exceed 300 mg twice daily)

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)

Oral suspension: 10 mg/mL

Tablet: 200 mg

Extended-release tablets: 100 and 400 mg

Therapy initiation: Age-appropriate dose given once a day for 14 days then increased to 2 times a day if tolerated (to lessen incidence of adverse reactions). Some experts believe that this step is unnecessary for children < 2 years of age.

Birth to < 4 weeks if gestational age at birth ≥ 37 weeks (investigational dose, not approved by U.S. Food and Drug Administration): No lead-in, 6 mg/kg twice daily

≥ 4 weeks–8 years: 200 mg/m2 twice daily after lead-in

8 years: 120–150 mg/m2 twice daily (up to 200 mg twice daily or, if using extended-release tablets, 400 mg once a day) after lead-in

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 weeks 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 weeks 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 > 14 days, it should be restarted with once-daily age-appropriate lead-in dosing for 14 days  then advanced to age-appropriate twice-daily dosing.

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

Also available in fixed-dose combination tablets

< 3 months: Not approved

≥ 3 months–6 years, weight-based dosing of powder (not interchangeable with capsules):

  • 5 to < 15 kg: ATV 200 mg (4 packets) + RTV 80 mg (1 mL oral solution) once a day with food

  • 15 to < 25 kg: ATV 250 mg (5 packets) + RTV 80 mg (1 mL oral solution) once a day with food

≥ 6 years to < 18 years, weight-based dosing of capsules (not interchangeable with powder):

  • 15 to < 35 kg: ATV 200 mg + RTV 100 mg once a day with food

  • > 35 kg: ATV 200 mg + RTV 100 mg once a day with food

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.

Darunavir (DRV)

Oral suspension: 100 mg/mL

Tablets: 75, 150, 600, and 800 mg

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

Also available in fixed-dose combination tablets with cobicistat (COBI; another pharmacokinetic booster)

< 3 years: Not approved for infants, not recommended for children < 10 kg

≥ 3 years to < 12 years, ≥ 10 kg weight-based dosing:

  • 10 to < 11 kg: DRV 200 mg + RTV 32 mg twice daily

  • 11 to < 12 kg: DRV 220 mg + RTV 32 mg twice daily

  • 12 to < 13 kg: DRV 240 mg + RTV 40 mg twice daily

  • 13 to < 14 kg: DRV 260 mg + RTV 40 mg twice daily

  • 14 to < 15 kg: DRV 280 mg + RTV 48 mg twice daily

  • 15 to < 30 kg: DRV 375 mg + RTV 48 mg twice daily

  • 30 to < 40 kg: DRV 450 mg + RTV 100 mg twice daily

  • 40 kg: DRV 600 mg + RTV 100 mg twice daily

≥ 12 years and ≥ 40 kg: May use DRV 800 mg + 100 mg RTV once a day or in fixed-dose combination with COBI (DRV 800 mg + COBI 150 mg once a day)

DRV may cause the following:

DRV should be given with food to enhance absorption.

Lopinavir/ritonavir (LPV/RTV)

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

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

< 2 weeks: Do not use

2 weeks–12 months: 300 mg (of LPV component) per m2 of body surface area twice daily

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

18 years: LPV 400 mg twice daily

LPV/RTV may cause the following:

  • Gastrointestinal 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 weeks 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 powder: 100 mg/packet

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

Tablet: 100 mg

Used only as a pharmacokinetic booster: 80–100 mg once or twice a day

RTV may cause the following:

  • Gastrointestinal 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 gastrointestinal 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.

Integrase inhibitor

Bictegravir (BIC)

Available only as fixed-dose combination tablet with FTC and TAF

See fixed-dose combination products below

BIC may cause the following:

  • Diarrhea, nausea

Dolutegravir (DTG)

Tablets: 10, 25, and 50 mg

Also available in fixed-dose combination tablets

Infants and children < 30 kg: Not recommended

Children 30–39 kg: 35 mg once a day

Children and adolescents 40 kg: 50 mg once a day (may need to give twice daily 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 hours before or 6 hours after divalent cation-containing oral antacids, laxatives, sucralfate, iron supplements, calcium 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 if coformulation containing FTC or TDF is discontinued suddenly

EVG is coformulated with COBI, a pharmacokinetic booster.

EVG should be given with food.

Raltegravir (RAL)

Chewable tablets: 25 and 100 mg

Film-coated tablet: 400 mg

High-dose film-coated tablet: 600 mg

Granules for oral suspension: Packet of 100 mg to be added to 10 mL of water to make 10 mg/mL

Infants and children ≥ 4 weeks and weighing ≥ 3 kg–20 kg: Oral suspension 6 mg/kg twice daily (see package insert)

Children ≥ 11 kg, chewables as follows:

  • 11–13 kg: 75 mg twice daily (3 x 25-mg chewables)

  • 14–19 kg: 100 mg twice daily (1 x 100-mg chewable)

  • 20–27 kg: 150 mg twice daily (1.5 x 100-mg chewables)

  • 28–39 kg: 200 mg twice daily (2 x 100-mg chewables)

  • ≥ 40 kg: 300 mg twice daily (3 x 100-mg chewables)

Children 25 kg: May take either the above dosage of chewable tablets or may take 1 400-mg film-coated tablet twice daily

Children and adolescents ≥ 40 kg:  May take 1 400-mg film-coated tablet twice daily or may take 2 high-dose 600-mg tablets (1200 mg total) once a day

RAL may cause the following:

Oral suspension, chewable tablet, film-coated tablet, and high-dose film-coated tablet dosing is not interchangeable because of differences in bioavailability.

RAL may be given without regard to food.

Selected fixed-dose combination products

ZDV/3TC (Combivir®; also generic)

Combination tablets: ZDV 300 mg + 3TC 150 mg

30 kg: 1 tablet twice daily

See individual drugs

3TC/ABC (Epzicom®; also generic)

Combination tablets: 3TC 300 mg + ABC 600 mg

≥ 25 kg: 1 tablet once a day

See individual drugs

FTC/TDF (Truvada®)

Combination tablets: FTC 200 mg + TDF 300 mg

≥ 35 kg: 1 tablet once a day

See individual drugs

FTC/TAF (Descovy®)

Combination tablets: FTC 200 mg + TAF 25 mg

≥ 25 kg: 1 tablet once a day

See individual drugs

3TC/TDF (Cimduo®, Temixys®)

Combination tablets: 3TC 300 mg + TDF 300 mg

≥ 35 kg: 1 tablet once a day

See individual drugs

ABC/DTG/3TC (Triumeq®

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

≥ 25 kg: 1 tablet once a day

See individual drugs

FTC/TDF/EVG/COBI (Stribild®)

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

≥ 35 kg: 1 tablet once a day

See individual drugs

FTC/TAF/EVG/COBI (Genvoya®

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

≥ 25 kg: 1 tablet once a day

See individual drugs

FTC/TAF/BIC (Biktarvy®

Combination tablets: FTC 200 mg + TAF 25 mg + BIC 50 mg

≥ 25 kg: 1 tablet once a day

See individual drugs

* 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 14, 2020. Available at AIDSinfo.

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 weeks 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 14, 2020. Available at AIDSinfo.

§ This FDC is preferred for children who weigh ≥ 25 kg.

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

ARV = antiretroviral; FDC = fixed-dose combination.

More Information

The following are some English-language resources that may be useful. Please note that THE MANUAL is not responsible for the content of these resources.

See the following continually updated government site for information on drug treatment, including adverse effects, dosing (especially for information on fixed-dose combination products), and drug interactions, educational materials, and quick links to related topics:

The following resources provide information about various other prevention, treatment, and education aspects of HIV/AIDS:

  • New York State Department of Health AIDS Institute HIV Clinical Guidelines Program: Disseminates practical, evidence-based clinical guidelines that promote quality medical care for people in New York who are living with and/or are at risk of acquiring HIV and certain other illnesses

  • UNAIDS: Comprehensive information on how the organization directs, advocates, coordinates, and provides technical support needed to connect leadership from governments, the private sector, and communities to deliver life-saving HIV services

  • National Clinician Consultation Center: Up-to-date HIV/AIDS guidelines and key treatment protocols for HIV/AIDS treatment, prevention, and exposure

  • Perinatal HIV Consultation and Referral Services Hotline 1-888-HIV-8765 (1-888-448-8765): Free 24-hour clinical consultation and advice on treating HIV-infected pregnant women and their infants

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