Updated Reviewed

What to Start

Antiretroviral Treatment Regimens Recommended for Initial Therapy in Infants and Children with HIV

Criteria Used for Recommendations

In general, the recommendations of the Panel on Antiretroviral Therapy and Medical Management of Children Living with HIV (the Panel) are based on reviews of pediatric and adult clinical trial data published in peer-reviewed journals, data prepared by manufacturers for U.S. Food and Drug Administration (FDA) review, and data presented in abstract format at major scientific meetings. Few randomized, Phase 3 clinical trials of antiretroviral treatment (ART) regimens in pediatric patients have directly compared different treatment regimens. Most pediatric drug data come from Phase 1/2 safety and pharmacokinetic (PK) trials and nonrandomized, open-label studies. In general, even in studies of adults, assessment of drug efficacy and potency is primarily based on surrogate marker endpoints, such as viral load (plasma HIV RNA concentration) and CD4 T lymphocyte (CD4) cell count. The Panel modifies recommendations on optimal initial therapy for children as new data become available, new therapies or drug formulations are developed, and additional toxicities are recognized.

When developing recommendations for specific antiretroviral (ARV) drugs or regimens, the Panel considers the following information:

  • Data demonstrating durable viral suppression, immunologic improvement, and clinical improvement (when available) with the drug or regimen, preferably in children. However, if pediatric data are lacking, evidence in adolescents and adults is considered.
  • The extent of pediatric experience with a specific drug or regimen.
  • The incidence and types of short-term and long-term drug toxicity in people who are taking the drug or regimen, focusing on toxicities that are reported in children.
  • The availability and acceptability of formulations that are appropriate for pediatric use, including ease of administration, formulation options (e.g., syrups, powders, or granules vs. chewable tablets vs. pediatric dispersible tablets), palatability, pill size, and number of pills or volume of oral solution needed for an appropriate dose.
  • Dosing frequency and food and fluid requirements.
  • The potential for drug interactions with other medications.

ART regimens recommended for use in children with HIV should generally consist of a backbone of two nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs) plus a third active anchor drug from one of the following classes: an integrase strand transfer inhibitor (INSTI), a non-nucleoside reverse transcriptase inhibitor (NNRTI), or a protease inhibitor (PI) with a PK enhancer (also known as a booster; the two drugs used for this purpose are cobicistat [COBI or c] and ritonavir [RTV or r]).

The Panel classifies recommended ARV drugs or ART regimens for initial treatment of HIV infection in infants and children into one of two categories:

Preferred: ARV drugs or drug combinations are designated as Preferred for initial ART in ART-naive infants and children when clinical trial data in children or, more often, in adults have demonstrated optimal and durable efficacy and when pediatric studies using surrogate markers have demonstrated safety and appropriate drug exposure. Age and weight requirements, formulations, dosing frequency, potential drug interactions, and other factors are also considered when designating ARV drugs or ART regimens as Preferred.

Alternative: Drugs or drug combinations are designated as Alternative for initial therapy when clinical trial data in children or adults show efficacy but the drugs or drug combinations have disadvantages when compared with Preferred regimens. Drugs or drug combinations may be classified as Alternative for use in initial ART regimens in children if they are less effective or durable than a Preferred regimen in children or adults; if specific concerns exist about toxicity, dosing, formulation, administration, or interaction; or if experience with the use of these drugs or drug combinations in children is limited.

ARV drugs or regimens that are not recommended for initial ART in children are discussed in What Not to Start: Regimens Not Recommended for Initial Antiretroviral Therapy in Children. For detailed pediatric information on each drug, see Appendix A. Pediatric Antiretroviral Drug Information.

Factors to Consider When Selecting an Initial ART Regimen

ART regimens for infants and children should contain three fully active drugs for durable and potent virologic suppression. When possible, the initial treatment should reflect an option that only requires once-daily dosing and minimizes the number of liquid formulations, dispersible tablets, or pills that must be administered. Therefore, Panel recommendations reflect once-daily ARV regimens and single-tablet regimens whenever feasible.

Panel recommendations about ARV drugs and drug combinations for initial ART regimens in infants and children are influenced by the availability of FDA-approved drugs. FDA drug approvals of pediatric formulations and approvals for the use of adult formulations in children are based on weight but include age limitations for some drugs. Although age can be used as an initial guide when selecting ARV drugs for use in infants and children, body weight is the preferred determinant for drug selection and drug dosing in infants and children. Gestational age at birth and postnatal age must also be considered in the selection of some drugs for infants. Many drugs that are recommended for use in young infants do not have dosing recommendations for infants born prior to 37 weeks of gestational age (i.e., born preterm).

When making recommendations, the Panel considers efficacy and factors affecting the efficacy of a regimen, age and weight requirements, potential toxicity, tolerability, and drug or regimen characteristics that affect administration and adherence (e.g., formulations, pill size, dosing frequency). Table A below summarizes factors to consider when selecting an ART regimen for infants and children. Details about ARV formulations, fixed-dose combinations, dosing, and administration to infants and children are provided in Appendix A. Pediatric Antiretroviral Drug Information. Advantages and disadvantages of ARV components recommended for initial therapy in infants and children are summarized in Table B and Table 9 below. Additional information is provided in the Adult and Adolescent Antiretroviral Guidelines (see Table B. Advantages and Disadvantages of Antiretroviral Components Recommended as Initial Antiretroviral Therapy).

The Panel recommends rapid initiation of ART (defined as initiating ART immediately or within days of diagnosis), accompanied by a discussion about the importance of adherence and provision of adherence support for all children with HIV (see When to Initiate Antiretroviral Treatment in Children with HIV Infection and Adherence to Antiretroviral Therapy in Children and Adolescents with HIV).

Panel Recommendations for Initial ART Regimens in Infants and Children

The following subsections group Panel recommendations for initial ART regimens for children, including prepubertal adolescents, with HIV infection according to a child’s age (birth to <30 days, ≥30 days to <2 years, ≥2 to <12 years, and ≥12 years). These guidelines provide recommendations for prepubertal children and adolescents (i.e., those with sexual maturity ratings [SMR] of 1 to 3).1 The Adult and Adolescent Guidelines2 address recommendations for postpubertal adolescents (i.e., those with an SMR of 4 and 5); see What to Start. It is important to point out that pediatric approvals for most drugs are now based on specific weight parameters and that weight, rather than SMR, is a key determinant in ARV drug selection.

Preferred regimens for initial ART in infants aged <30 days with HIV-1 infection include an NRTI backbone of two NRTIs plus an INSTI (raltegravir [RAL]) or an NNRTI (nevirapine [NVP]) as the anchor drug. INSTI-based regimens (INSTI plus two NRTIs) are Preferred for initial ART in infants and children aged ≥30 days with HIV-1 infection whenever possible. Preferred anchor drugs, by age and weight, are listed below with Alternative options discussed in subsections by age group:

  • Newborns and infants aged <30 days: NVP, regardless of weight, or RAL if weight ≥2 kg; see Table 8 below regarding gestational age considerations.
  • Infants and children aged ≥30 days and weighing ≥3 kg: dolutegravir (DTG)
  • Children aged ≥2 years and weighing ≥14 kg: DTG or bictegravir (BIC). BIC is available only as a component of the fixed-dose combination (FDC) tablet BIC/emtricitabine (FTC)/tenofovir alafenamide (TAF).

INSTI-based regimens have become the Preferred option for initial ART regimens in infants and children (and adults) whenever possible due to their virologic efficacy, lack of drug interactions, and favorable toxicity profile.3-6 This pediatric recommendation is consistent with recommendations for initial ART in adults and adolescents (see the What to Start: Initial Combination Antiretroviral Regimens for People with HIV section of the Adult and Adolescent Antiretroviral Guidelines). Adult comparative trials have shown that INSTI-containing regimens have superior efficacy compared with PI-containing and NNRTI-containing regimens,7,8 and an increasing number of studies have evaluated the PK, safety, tolerability, and efficacy of these drugs in infants, children, and adolescents (see the Raltegravir, Dolutegravir, and Bictegravir sections).

RAL is a first-generation INSTI and is the only INSTI option FDA approved for use in infants aged <30 days. INSTI-based regimens using second-generation INSTIs that have greater efficacy and a higher barrier to resistance than RAL (i.e., DTG or BIC depending on age and weight), are recommended for initial therapy in children.

Planning for Transitions in ART Regimens

When initiating treatment in infants and children, it is recognized that there may be more potent drug options, options with lower administration burden on a caregiver, and options with lower liquid volume requirements or pill burden as an infant or child gains weight or increases in age and develops the ability to swallow pills. This section briefly addresses planning regimen transitions. Information and recommendations about the sequence and selection of ARV drugs after initial therapy are provided in other Guidelines sections. Modifying Antiretroviral Regimens in Children with Sustained Viral Suppression on Antiretroviral Therapy discusses modifications to simplify or optimize treatment or to manage a specific toxicity. Recognizing and Managing Treatment Failure discusses situations where viral suppression has not been reached on initial ARV therapy. Management of Medication Toxicity or Intolerance provides an overview of management with links to toxicity tables (e.g., Lipodystrophies and Weight Gain, Dyslipidemia) that address specific issues.

Selection of Dual–Nucleoside Reverse Transcriptase Inhibitor Backbone as Part of Initial Antiretroviral Therapy Regimens

Dual-NRTI combinations form the backbone of ART regimens for the treatment of HIV in both adults and children and are used in combination with an anchor drug from one of the following ARV classes: INSTIs, PIs, or NNRTIs. Dual-NRTI backbones recommended by the Panel as part of Preferred or Alternative ART regimens for children or for use in special circumstances are listed below, with links to sections in Appendix A. Pediatric Antiretroviral Drug Information that provide detailed information about the formulations, dosing, safety, and use of each drug in infants and children.

Dual-NRTI selection is influenced by a child’s weight and age, as well as the availability of FDCs for NRTI combinations or FDCs for complete ART regimens. The advantages and disadvantages of the different dual-NRTI backbone options that are recommended for initial therapy in children are shown in Table 9 and discussed briefly below.

ZDV has been shown to be safe and effective as part of ART regimens for infants and children; however, hematologic toxicity (anemia, neutropenia, and/or thrombocytopenia) may affect its use in some children.9,10     Twice-daily dosing of ZDV is required for all ages. Other NRTIs that require only once-daily dosing in children are available (e.g., ABC [for some age groups], FTC, TAF). Hematological toxicity and twice-daily dosing requirements limit the long-term use of ZDV in children. 

ABC is only approved by the FDA for use in children aged ≥3 months, but the Panel recommends use of ABC from birth in full-term infants (see Abacavir).11,12 The Panel supports ABC dosing in neonates that is based on PK simulation models and has been endorsed by the World Health Organization. A negative test for the HLA-B*5701 allele must be obtained prior to use of ABC.

3TC and FTC are considered interchangeable as part of ART regimens; both are well tolerated and are associated with few adverse effects (AEs). FTC can be substituted for 3TC as one component of a Preferred dual-NRTI backbone (i.e., FTC plus ABC, TDF, or ZDV). Both 3TC and FTC select for the M184V resistance mutation, which is associated with high-level resistance to both drugs, a modest decrease in susceptibility to ABC, and improved susceptibility to ZDV and TDF as a result of possible decreased viral fitness.13,14

TDF-containing regimens are efficacious and well tolerated. However, reductions in bone mineral density can manifest in children and adults soon after initiating TDF, the clinical significance of which is unknown.15-20 This reduction in bone density is reversible with drug discontinuation. Although TDF is associated with a decline in glomerular filtration rate, the effect is generally small, and severe glomerular toxicity is rare.21,22 Irreversible renal failure is very rare, but cases have been reported.23 With long-term use of TDF, renal toxicity can occur at the site of the proximal convoluted tubules, with clinical manifestations ranging from asymptomatic proteinuria to progressively declining glomerular filtration rates.21,24 Before starting treatment, clinicians should consider whether the benefits of using TDF outweigh the potential risks described above. The combination of TDF with atazanavir (ATV)/r, darunavir (DRV)/r, or lopinavir (LPV)/r increases plasma tenofovir concentrations and the risk of TDF-associated toxicity.25

TAF is only available in FDC tablets that must be swallowed. With TAF, the active drug tenofovir (TFV) achieves higher intracellular concentrations and lower plasma concentrations than TDF. Bone and renal toxicity associated with TDF is linked to higher plasma concentrations of TFV, which may explain why these toxicities do not occur with TAF. Use of COBI- or RTV-boosted PIs in combination with TAF/FTC is not recommended in children weighing <35 kg because these drugs can increase TAF exposure, and no data are available on the use of this combination. In children and adolescents weighing ≥35 kg, boosted PIs can be used with TAF/FTC.

Weight gain and increased risk for clinical obesity have been reported in adults with the use of TAF- and INSTI-containing regimens,26,27 but these side effects have not been clearly demonstrated in children.28-30 Furthermore, use of TAF-containing regimens has also been associated with increased levels of total and low-density lipoprotein cholesterol and triglycerides. When these concerns arise, regimens containing TDF may be preferable. However, providers must consider the risks of proximal renal tubular injury, rare irreversible renal failure, and decreased bone mineral density that can occur when TDF is used.

NRTI Backbone Selection with Hepatitis B Virus Coinfection

When selecting the NRTI backbone for an initial ART regimen, FTC, 3TC, TDF, and TAF have antiviral activity and efficacy against hepatitis B virus (HBV) and should be considered for use in children with HBV/HIV coinfection. For a comprehensive review, see the Hepatitis B Virus, Hepatitis C Virus, and Mycobacterium tuberculosis (TB) sections of the Pediatric Opportunistic Infection Guidelines.

Recommended Initial ART Regimens for Infants From Birth to <30 Days of Age

Panel recommendations for the anchor drugs for Preferred and Alternative initial ART regimens in infants aged <30 days (i.e., RAL, NVP, and LPV/r) reflect FDA approval by current weight and the infant’s postmenstrual age (calculated as gestational age at birth plus postnatal age) at the time the ARV regimen or specific ARV drug is initiated.

Preferred Regimens
  • Term infants (≥37 weeks gestation) or preterm infants with a postmenstrual age ≥37 weeks at the time of treatment initiation:
  • Preterm infants with a postmenstrual age ≥32 weeks to <37 weeks at the time of treatment initiation:
  • Preterm infants with a postmenstrual age <32 weeks at the time of treatment initiation:
Rationale

The Panel recommends RAL or NVP administered with an NRTI backbone of ZDV plus 3TC as an initial regimen for the treatment of HIV-1 infection in infants. These regimens consist of ARV drugs that are FDA approved, with extensive data on the safety and efficacy of their use in infants and children.31-37 The selection of anchor drug and regimen will depend on several factors, such as ARV resistance in the birthing parent, the infant’s gestational age at birth, current postmenstrual age, weight at treatment initiation, the caregiver’s perceived ease of preparing and dosing, availability of appropriate formulations, and availability of medications in the outpatient setting. These have been summarized in Table B. Advantages and Disadvantages of ARVs Recommended for Initial Antiretroviral Therapy in Infants From Birth to <30 Days of Age below. Resistance testing should be performed at the time of HIV diagnosis and before initiation of ART but should not delay treatment initiation. Initial ART regimens can be modified if needed based on results (see Clinical and Laboratory Monitoring of Pediatric HIV Infection).

At the time of HIV diagnosis, some infants at high risk for HIV acquisition may have initiated presumptive HIV therapy. The regimens recommended for presumptive HIV therapy are addressed in Antiretroviral Management of Newborns with Perinatal HIV or Breastfeeding Exposure or HIV Infection and are the same as the ARV regimens recommended for treatment of HIV infection in neonates. Therefore, once the diagnosis of HIV-1 is established in the neonate, the regimen for presumptive HIV therapy can be continued—now as definitive ART—with virologic monitoring to establish successful viral suppression (see Clinical and Laboratory Monitoring of Pediatric HIV Infection).

At the time of HIV diagnosis, some infants at low risk for HIV acquisition might be receiving ZDV alone as prophylaxis. If the infant has a positive HIV nucleic acid test, a complete ART regimen should be initiated without waiting for the results of a confirmatory test. In this case, ZDV may be continued with the addition of a second NRTI and either RAL or NVP. If RAL or NVP is not an option, a LPV/r-based regimen appropriate for the infant’s age and weight can be used (see Alternative Regimens below). If confirmatory testing indicates the infant does not have HIV infection, ART can be discontinued.

Alternative Regimens
Alternative Anchor Drug
  • Infants with a postmenstrual age ≥42 weeks and a postnatal age of ≥14 days

LPV/r: The Panel recommends LPV/r oral solution in combination with the NRTI backbone recommended in Preferred Regimens above as an Alternative anchor drug for infants with a postmenstrual age of ≥42 weeks of gestation and a postnatal age of >14 days. LPV/r oral solution contains 42.4% (volume/volume) alcohol and 15.3% (weight/volume) propylene glycol. Use of this drug in infants before 42 weeks postmenstrual age and before a postnatal age of 14 days, at a time when hepatic metabolic function and kidney excretory function are maturing, can lead to accumulation of LPV, alcohol, and propylene glycol, resulting in serious cardiac, renal, metabolic, or respiratory problems. For more information about LPV/r use in newborns, refer to the Lopinavir/Ritonavir section in Appendix A. Pediatric Antiretroviral Drug Information.

Alternative NRTI Backbone
  • Term infants (≥37 weeks gestation)

ABC: A negative test for the HLA-B*5701 allele must be obtained prior to use of ABC. Although ABC is not FDA approved for use in infants aged <3 months, the Panel recommends ABC as part of an Alternative NRTI backbone for full-term infants from birth (see Abacavir). An ABC dosing recommendation using PK simulation models has been endorsed by the World Health Organization using weight-band dosing for full-term neonates. A recent study of infants with HIV in a South African cohort, stratified by age (<28 days and ≥28 days) and weight (<3 kg and ≥3 kg), demonstrated the safety and effectiveness of ABC in infants aged <3 months and in neonates weighing <3 kg.11,12,38

Practical and Clinical Considerations

The clinician should provide the infant’s caregiver with information about prescribed medications, including names, doses, dose times, potential side effects, and how to properly administer the medications. Appropriately sized oral syringes should be dispensed, and liquid medications should include bottle adapter plugs to minimize wastage. Practice preparing and administering the medications should be completed and documented in the medical record. This is especially important when RAL is prescribed because there is a multistep process to prepare the infant dose using the oral granules for suspension (see Raltegravir). ARV availability and complexity of preparation and administration may affect decisions about the use of NVP versus RAL. It is recommended that a medication calendar be provided and that the caregiver be involved in deciding the most convenient times for the medications to be administered. Clinicians should ensure that insurance covers the prescribed ART regimen and that the infant’s local pharmacy stocks all components of the regimen. For neonates who are initiating ART while still in the hospital, clinicians should provide caregivers with the appropriate information and an initial supply of medications before discharge.

At each clinic visit, the clinician and caregiver should review the process of preparing the different liquid formulations of the medications to ensure that correct volumes and doses are being administered. When appropriate, weight-band dosing should be used and doses should be adjusted based on weight gain and age. This is particularly important during the first weeks of life, when changes to drug metabolism and renal function occur that impact appropriate dosing recommendations (see Appendix A. Pediatric Antiretroviral Drug Information). Refills should be arranged with pharmacies that stock the ARV drugs.

Special Situations
  • ARV Drug Resistance: Infants can acquire HIV infection with drug-resistant virus. Transmitted drug resistance has been demonstrated with NNRTIs, NRTIs, PIs, and INSTIs, although transmitted resistance to INSTIs is very rare.39 Therefore, when a birthing parent has not achieved viral suppression during pregnancy and drug resistance is suspected, the birthing parent’s ARV resistance data should be reviewed, if available, and consultation with a pediatric HIV expert is recommended. In neonates, a Preferred ART regimen should be commenced immediately; this may later be changed or modified based on the results of baseline infant HIV genotyping (see Clinical and Laboratory Monitoring of Pediatric HIV Infection).
  • HIV-2 Infection: ART regimens for infants with HIV-2 infection only or infants with HIV-2 and HIV-1 coinfection should include ARVs that are active against HIV-2. Because NNRTIs are not active against HIV-2, NVP should not be used. A RAL-based regimen is recommended for infants with HIV-2 or with HIV-2 and HIV-1 coinfection: RAL (for full-term infants weighing ≥2 kg) plus ZDV plus (3TC or FTC). Consultation with a pediatric HIV expert or the National Perinatal HIV/AIDS Hotline (1-­888-­448­8765) is recommended for the care of infants weighing <2 kg or with a gestational age <37 weeks.
Planning ARV Transitions

Although the ARV regimen started in the first 29 days of life can be continued, the Panel recommends that consideration be given to changing the regimen to a DTG-containing regimen after the infant reaches the appropriate age and weight; see Preferred Regimens for Children Aged ≥30 Days to <2 Years below. This change should be considered because DTG has greater efficacy and durability than RAL or NVP,40 DTG dispersible tablets are easier to prepare and administer than RAL granules, and DTG is available in a FDC formulation.

Recommended Initial ART Regimens for Infants and Children Aged ≥30 Days to <2 Years

Preferred Regimens
  • Aged ≥30 days to <2 years and weighing ≥3 kga
  • Aged ≥3 months to <2 years and weighing ≥6 kg to <25 kg
    • DTG plus ABC plus 3TC as a FDC (Triumeq PD) if HLA-B*5701 negative

a For infants aged ≥30 days who weigh <3 kg, therapy should be initiated using one of the regimens described in Recommended Initial ART Regimens for Infants from Birth to <30 Days of Age above (e.g., NVP or RAL). Transition to a DTG-based regimen should be considered when the infant’s weight is ≥3 kg.

Rationale

It is assumed that all children in this age group are unable to swallow pills and will require treatment with ARVs in liquid, dispersible tablet, powder packet, or chewable tablet formulations.

For infants and children weighing ≥3 kg who are starting ART at ≥30 days of age, the Panel recommends initiation of an INSTI-based ART regimen using DTG plus two NRTIs. DTG is a second-generation INSTI that has a higher barrier to resistance than RAL and is FDA approved for use in this age group. While there is low potential for development of resistance with DTG, young infants may initially have very high HIV viral loads and continue to have low level viremia during the first year of life. The overall risk of developing resistance with DTG-based ART in young infants is unknown.

INSTIs have better efficacy and safety profiles than NNRTIs or PIs, and DTG has been studied extensively in children.3,5 Importantly, the FDC of DTG/ABC/3TC has proven efficacy and a good safety profile, with weight-band dosing that achieves PK targets.41

For infants aged ≥30 days to ≤6 weeks receiving presumptive HIV therapy with RAL or NVP plus two NRTIs at the time of HIV diagnosis, the Panel recommends changing to one of the DTG-based regimens listed above using DTG dispersible tablets. The liquid formulations of the NRTIs used as part of presumptive HIV therapy (usually ZDV plus 3TC) can be continued; no change in NRTIs is required.

Alternative Regimens
Alternative Anchor Drugs
  • LPV/r: LPV is available as an oral solution coformulated with RTV, and twice-daily dosing is recommended. LPV/r should be administered with food to improve tolerability.34,42,43 Poor taste and palatability of the oral solution may become an issue for young children and limit acceptance of this regimen. LPV/r has a high genetic barrier to drug resistance. However, poor acceptance of formulation, gastrointestinal side effects, and poor weight gain may limit its use in this age group.44
  • ATV/r: ATV/r can be considered an Alternative to LPV/r in children weighing ≥15 kg.45 ATV and RTV are available as separate powder packets that are mixed with either soft food or formula and administered once daily. The powder formulation of ATV can be used in children weighing ≥15 kg to < 25 kg. The powder formulations have poor palatability and may be difficult to tolerate in this age group.
  • NNRTIs: NVP could be considered if there is resistance or intolerance to both PIs and INSTIs. However, NVP is generally not recommended as an initial treatment in this age group as the low genetic barrier to resistance during a time of significant viremia may lead to drug resistance to all members of the NNRTI class of drugs.35 Efavirenz (EFV) is not recommended for children <3 years of age due to highly variable PK in young children, difficulty in determining an appropriate dose without therapeutic drug monitoring, and side effects (i.e., neurologic toxicity).46
NRTI Backbones in Alternative Regimens
  • Twice-daily dosing: An NRTI backbone of ZDV plus 3TC twice daily or ABC plus 3TC twice daily allows for all medications to be administered at the same time when given in combination with LPV/r or RAL. There is considerable experience with ZDV and 3TC in this age group. ABC is associated with less bone marrow toxicity than ZDV and may be the Preferred NRTI for long-term use.
Practical and Clinical Considerations

DTG plus ZDV plus 3TC can be initiated immediately. However, due to the potential of ABC hypersensitivity, a negative test for the HLA-B*5701 allele must be obtained before initiating a regimen of DTG plus ABC plus 3TC. HLA-B*5701 should be included in the initial work-up for all infants and children with HIV. ABC is not FDA approved for use in infants aged <3 months, but the Panel does recommend use of twice-daily ABC for infants aged ≥30 days. In decisions about selecting ABC as a component of the initial regimen for children aged <2 years, clinicians should consider concerns regarding delays initiating treatment related to HLA-B*5701 testing versus the advantages of using a FDC.

For infants who are aged ≥30 days and ≥3 kg in weight, DTG is available as dispersible tablets that are administered separately, along with the liquid formulations of ZDV and 3TC. For infants and children weighing ≥6 kg to <25 kg who are initiating therapy at 3 months of age, DTG plus ABC plus 3TC is available as dispersible FDC tablets (Triumeq PD) that can be administered once daily and provides a number of advantages:

  • Tablets are mixed in water (volume depends on the number of tablets needed for weight-band dosing; see Dolutegravir for details about dosing and preparation).
  • Once-daily dosing improves adherence to ARVs.
  • Use of the FDC formulation avoids the need to measure and administer liquid ZDV and 3TC separately and minimizes difficulties in accurately measuring the volumes needed.
  • Use of the FDC minimizes the need to adjust doses frequently as the infant or child grows.

When teaching families about preparing the medications, it should be explained that dispersible tablets need to be mixed in water because there is a lack of data about dispersing DTG or DTG/ABC/3TC dispersible tablets in other liquids, such as formula or breast milk. With once-daily dosing, it is particularly important to emphasize the critical importance of not missing any doses.

Special Situations
  • DTG dispersible tablets not available: If DTG dispersible tablets are not available, RAL can be administered using either the oral granules for suspension dispersed in water or as the chewable tablets dispersed in juice or formula/milk.47 RAL oral granules for suspension require a multistep process to prepare each dose, and twice-daily dosing is required. RAL also has a lower genetic barrier to resistance compared to DTG.
  • Identification of viral resistance: If viral resistance is identified in baseline genotype testing, the initial ART regimen may need to be modified.
    • INSTI resistance: If resistance to INSTIs is present, the regimen should consist of the NRTI backbone plus a PI. Use of LPV/r is recommended in this situation, as it is coformulated with ritonavir in a formulation suitable for administration in this age group. If there is multidrug ARV resistance, consultation with a pediatric HIV expert is recommended.
    • Presence of M184V resistance mutation: If the M184V/I mutation associated with FTC and 3TC is present, these medications should be continued if the new regimen contains TDF, TAF, or ZDV. The presence of this mutation may increase susceptibility to these NRTIs.
  • HLA-B*5701 positive: ART regimens with ABC should not be given due to ABC-associated hypersensitivity.
  • Presence of HBV infection: In HIV/HBV coinfection, an ART regimen should include two NRTIs active against HBV (see Selection of Dual–Nucleoside Reverse Transcriptase Inhibitor Backbone as Part of Initial Antiretroviral Therapy Regimens above). However, regimens containing only one active NRTI (3TC or FTC) may be used when children in this age group don’t meet the weight criteria for use of a second NRTI active against HBV. They should be changed to a TAF/FTC-containing regimen as soon as possible after they weigh ≥14 kg.
  • HIV-2 infection: ART regimens for infants and children with HIV-2 infection only or those with HIV-2/HIV-1 coinfection should include ARVs that are active against HIV-2. Consultation with a pediatric HIV expert is recommended for the care of infants and children with HIV-2.
Planning ARV Transitions

For infants aged ≥3 months and weighing ≥6 kg who initiated treatment on DTG plus ZDV plus (3TC or FTC), the Panel recommends changing to a regimen of once-daily DTG plus ABC plus 3TC that is available as dispersible FDC tablets (Triumeq PD) in order to simplify measurement of ARV doses and administration. A negative test for the HLA-B*5701 allele must be obtained prior to initiation of an ABC-containing regimen.

There are additional options for transitioning to other INSTI-containing preparations as children become older and are able to swallow pills, such as the FDC BIC/FTC/TAF (Biktarvy), which can be used in children aged ≥2 years and weighing ≥14 kg (see discussion in Recommended Initial ART Regimens for Children Aged ≥2 Years to <12 Years below). The NRTI backbone FTC/TAF is available in a FDC (Descovy) that can be used in combination with an anchor drug, such as DTG, in children weighing ≥14 kg who are able to swallow pills.

Recommended Initial ART Regimens for Children Aged ≥2 Years to <12 Years

Preferred Regimens

In considering an initial ART regimen for children aged ≥2 years to <12 years, some children, particularly younger children, may not be able to swallow pills, whereas older children may be able to take pills. It is recommended that clinicians counsel families about teaching children how to swallow pills, as this increases the number of ARV options and simplifies regimens.48 Children as young as 4 years of age can be taught how to swallow pills. In addition to age and ability to swallow pills, the weight of the child must also be taken into consideration. Therefore, the Panel recommendations for what regimen to start are presented for children unable to swallow pills and those who are able. FDA-approved pill formulations are based on a child’s weight, followed by recommendations for those who are able to swallow pills and the minimum weight allowed for dosing. Please refer to Appendix A. Pediatric Antiretroviral Drug Information for specific dosing of ARV drugs by weight band.

Preferred Regimens for Children Aged ≥2 Years to ≤12 Years Who Are Not Able to Swallow Pills
  • DTG plus ABC plus 3TC in the dispersible FDC formulation (Triumeq PD) for children weighing 6 kg to <25 kg if HLA-B*5701 negative or
    • DTG film-coated tablets (Tivicay) plus ABC plus (3TC or FTC) in liquid formulations for children weighing ≥25 kg if HLA-B*5701 negative (see Dolutegravir for special instructions about administering DTG tablets to children who are not able to swallow pills)
  • DTG plus FTC plus TAF for children weighing ≥14 kg (see Dolutegravir and Tenofovir Alafenamide for available formulations of DTG [Tivcay, Tivicay PD], dosage strengths of FTC/TAF [Descovy], and special instructions for administering DTG film-coated tablets and FTC/TAF tablets to children who are not able to swallow pills) or
  • DTG in dispersible tablets plus ZDV plus (3TC or FTC) in liquid formulations

The dispersible FDC tablet of DTG/ABC/3TC (Triumeq PD) is a once-daily regimen. A child must have a negative HLA-B*5701 allele screening test prior to initiation of treatment to ensure that the child will not be at risk for a hypersensitivity reaction to ABC.

When the DTG/ABC/3TC dispersible FDC tablet cannot be used (i.e., it is not available or results of HLA-B*5701 testing are unknown or positive) and the child weighs <14 kg at treatment initiation, the Panel recommends initiating a regimen of DTG plus ZDV plus 3TC. DTG is available as dispersible tablets (Tivicay PD) dosed once daily that can be used in children weighing 6 kg to <25 kg. ZDV and 3TC are both available in liquid formulations and require twice-daily dosing. If DTG/ABC/3TC cannot be used and the child weighs ≥14 kg, DTG plus FTC/TAF (Descovy) is recommended by the Panel. FTC/TAF (Descovy) is available in two different-strength tablets, with the lower-strength tablet for children weighing ≥14 kg to <25 kg.

Preferred Regimens for Children Aged ≥2 Years to ≤12 Years Who Are Able to Swallow Pills

For children weighing <14 kg, see regimens listed above for children who are not able to swallow pills.

  • BIC plus FTC plus TAF (FDC BIC/FTC/TAF, Biktarvy) for children weighing ≥14 kg
  • DTG plus FTC plus TAF (DTG, Tivicay, plus the FDC FTC/TAF, Descovy) for children weighing ≥14 kg
  • DTG plus ABC plus 3TC (FDC DTG/ABC/3TC, Triumeq) for children weighing ≥25 kg if HLA‑B*5701 negative
Rationale

The Panel recommends initiating ART with a once-daily, single-tablet regimen of BIC/FTC/TAF (Biktarvy) for children weighing ≥14 kg. Two different strengths of BIC/FTC/TAF tablets are available, with the lower-strength tablet for children weighing ≥14 kg and <25 kg. The product label states that for children who are unable to swallow a whole tablet, the BIC/FTC/TAF tablet can be split and each part taken separately, as long as all parts are ingested within approximately 10 minutes.49

DTG/3TC/ABC (Triumeq) is another Preferred single-tablet regimen option for children weighing ≥25 kg; however, the DTG/3TC/ABC pill is much larger than the BIC/FTC/TAF pill and might be more challenging to swallow, particularly for younger children. If DTG/3TC/ABC is selected, documentation of a negative HLA-B*5701 screening should occur prior to treatment initiation. For children weighing ≥14 kg, the film-coated tablet of DTG (Tivicay) used in conjunction with the FDC tablets of FTC/TAF (Descovy) is also recommended by the Panel.

The FDC of BIC/FTC/TAF (Biktarvy) has been studied in adolescents aged 12 years to <18 years and weighing ≥35 kg (Cohort 1), children aged 6 years to <12 years and weighing ≥25 kg (Cohort 2), and children aged ≥2 years and weighing ≥14 kg to <25 kg (Cohort 3). All participants had maintained viral loads <50 copies/mL for ≥6 months. Cohorts 1 and 2 received the adult formulation of BIC/FTC/TAF. Children in Cohort 3 received BIC 30 mg/FTC 120 mg/TAF 15 mg. Overall, the drug was well tolerated in all participants in all cohorts. Drug exposure in all cohorts was similar to the exposure observed in adults. At 24 weeks, all 50 adolescents (Cohort 1) and 50 children (Cohort 2) maintained viral suppression, and at Week 48, 49 of 50 participants in each cohort maintained suppression.50 Among children in Cohort 3, after 24 weeks, all 12 participants maintained viral suppression.

DTG, studied in the multinational open-label IMPAACT 1093 study3,51,52 and ODYSSEY4,10,53 has been demonstrated to be safe, efficacious, and well tolerated in children. The dispersible tablet formulation of the FDC ABC 60 mg/DTG 5 mg/3TC 30 mg (Triumeq PD) has been studied in IMPAACT P2019 to confirm dosing of the three-drug FDC in pediatric patients aged <12 years (NCT03760458). In IMPAACT P2019, children are being dosed in five weight bands aligned with WHO-preferred weight bands. Results of the initial PK and safety assessments for 35 participants in weight bands ≥6 kg demonstrated acceptable PK parameters and tolerability for all cohorts and confirmed dosing according to World Health Organization weight bands.41

Alternative Regimens
Anchor Drugs

When concern for INSTI resistance exists, the following anchor drugs represent Alternative treatment options when paired with two fully active NRTIs.

  • ATV plus RTV or COBI: ATV is available as a powder packet that should be mixed with solid food and administered once daily. ATV powder should be coadministered with RTV once daily for a child aged ≥2 years and weighing ≥15 kg to ≤25 kg. RTV is also available in powder packets; the powder formulation has poor palatability and may be difficult to tolerate. For a child weighing ≥15 kg who is able to swallow pills, the capsule formulation of ATV can be dosed once daily with the RTV tablets (i.e., ATV/r). Boosting ATV with COBI is only an option if the child weighs ≥35 kg and is able to swallow pills. The FDC of COBI-boosted ATV (ATV/c) can be administered once daily.
  • DRV plus RTV or COBI: DRV, dosed twice daily, is an option for children aged ≥3 years to <12 years and weighing ≥20 kg. However, DRV requires a PK enhancer or boosting agent, such as RTV or COBI. DRV is available as a solution or tablet that can be administered with a RTV powder packet or tablet. Boosting DRV with COBI is only an option if the child weighs ≥40 kg. COBI-boosted DRV (DRV/c) is available in a once-daily FDC (Prezcobix).
  • NNRTIs: An NNRTI-based regimen using NVP, EFV, or doravirine (DOR) could be considered if there is resistance or intolerance to both PIs and INSTIs. EFV is not recommended by the Panel for use in children aged <3 years due to highly variable PK in young children, difficulty in determining an appropriate dose without therapeutic drug monitoring, and side effects (i.e., neurologic toxicity) (see Efavirenz). DOR is approved for use in children weighing ≥35 kg, and recent data found that once-daily dosing of DOR/3TC/TDF was safe and well tolerated for maintaining viral suppression through 96 weeks in adolescents.54
Practical and Clinical Considerations

The availability of FDC formulations and method of administration are important considerations in the selection of a Preferred initial regimen.

  • BIC/FTC/TAF (Biktarvy) is a single-tablet regimen for children weighing ≥14 kg. The tablet may not be crushed or dissolved; however, it can be split in half prior to dosing for ease of swallowing. BIC/FTC/TAF is available in two formulations for children able to swallow pills, including BIC 30 mg/FTC 120 mg/TAF 15 mg for children weighing ≥14 kg to <25 kg and BIC 50 mg/FTC 200 mg/TAF 25 mg for children weighing ≥25 kg.
  • ABC/DTG/3TC (Triumeq PD) are dispersible tablets that can be used in children weighing <25 kg and should be dissolved in water. Each tablet contains all three drugs. The number of tablets per dose is based on a child’s weight.
  • ABC/DTG/3TC (Triumeq) is a nondispersible, single-tablet regimen option for children weighing ≥25 kg who are able to swallow whole pills. However, a disadvantage is the larger pill size, which can make swallowing challenging compared with the other recommended options.
  • DTG plus FTC/TAF is dosed once daily. DTG is available as dispersible tablets (Tivicay PD) and as a film-coated tablet (Tivicay). FTC/TAF (Descovy) is available in two different strengths as a single tablet to be swallowed. See Dolutegravir and Tenofovir Alafenamide for specific weight parameters and for special instructions about administering these ARVs to children who are not able to swallow pills.
Special Situations
  • Identification of viral resistance: If viral resistance is identified in baseline genotypic testing, the initial ART regimen may need to be modified.
    • INSTI resistance: If resistance to INSTIs is present, the regimen should consist of the NRTI backbone plus a boosted PI. PI options include ATV or DRV, both of which should be boosted with either RTV or COBI. See Alternative Regimens Anchor Drugs above for age and weight restrictions for each PI in conjunction with its formulation and its boosting agent. If there is multidrug ARV resistance, consultation with a pediatric HIV expert is recommended.
    • Presence of M184V resistance mutation: Regimens should contain at least two, but preferably three, fully active drugs for durable and potent virologic suppression. If the M184V/I mutation associated with FTC and 3TC is present, these medications should be continued if the regimen contains TDF, TAF, or ZDV. The presence of this mutation may increase susceptibility to these NRTIs.
  • HLA-B*5701 positive: ARV regimens with ABC should be avoided due to ABC-associated hypersensitivity.
  • Presence of HBV infection: The ART regimen should include two NRTIs active against HBV (see Selection of Dual–Nucleoside Reverse Transcriptase Inhibitor Backbone as Part of Initial Antiretroviral Therapy Regimens above). The Panel recommends the FDC FTC/TAF (Descovy) as the NRTI backbone for children with HIV/HBV coinfection.
  • HIV-2 infection: ART regimens for children with HIV-2 infection only or those with HIV-2/HIV-1 coinfection should include ARVs that are active against HIV-2. Consultation with a pediatric HIV expert is recommended for the care of infants and children with HIV-2.
Planning ARV Transitions

Among children aged ≥2 years to <12 years who initiated treatment when they were unable to swallow pills or whose weight precluded use of a pill option, once children can swallow pills and are of an appropriate age, the Panel recommends transitioning to the once-daily FDC of BIC/FTC/TAF (Biktarvy), so long as there are no contraindications.

Recommended Regimens for Children and Adolescents Aged ≥12 Years

Recommendations for initial ART regimens for adolescents are also addressed in What to Start in the Guidelines for the Use of Antiretroviral Agents in Adults and Adolescents with HIV (see Adolescents and Young Adults with HIV), with an overview provided here.

Pubertal changes during adolescence encompass increased growth velocity, changes in body composition, and development of secondary sexual characteristics. It is recognized that these changes can affect the PK and pharmacodynamics of drugs. Adolescents with perinatal HIV infection are more likely to have delayed puberty and growth compared to their uninfected peers.55 However, regimens recommended for initial ART in the Adult and Adolescent Guidelines provide adequate drug exposure and are effective and safe when used for people with HIV infection in this age bracket above a minimum weight, regardless of pubertal stage.

Preferred Regimens

For adolescents aged ≥12 years who do not have a history of using long-acting cabotegravir (CAB-LA) for HIV preexposure prophylaxis (PrEP), Preferred ART regimens are listed below.

DRV-based regimens are recommended for initial therapy in adolescents who previously received CAB-LA for PrEP (see Alternative Regimens below).

In the unlikely event that some adolescents aged ≥12 years are not able to swallow pills or weigh <25 kg, please refer to the Preferred regimens in the 2- to 12-year age group above and Table 8 below.

Rationale

The Preferred regimens (BIC/FTC/TAF and DTG/ABC/3TC) are consistent with the Panel’s recommendations for the 2- to 12-year age group and are available as FDC single-tablet regimens that contain the appropriate dose of the three drugs for the specified weight. These FDC regimens are also the same as those recommended for use in adults and adolescents without delay in pubertal onset, allowing for the continuation of the same initial Preferred regimen as patients transition through puberty in adolescence to adulthood. The third regimen, DTG plus FTC plus TAF, is not a single-tablet regimen and has the disadvantage of requiring use of two tablets for each dose.

The Adult and Adolescent Guidelines also recommend the two-drug regimen DTG/3TC as an option for initial ART in some individuals (see What to Start). However, the Panel does not recommend a DTG/3TC regimen for initial therapy in adolescents because data are limited about its use for this age group and there are concerns about the efficacy and durability of two-drug ART regimens related to gaps or lapses in ARV adherence common in adolescents.

Alternative Regimens
  • DRV/c plus TAF plus FTC (FDC DRV/c/TAF/FTC, Symtuza) for adolescents weighing ≥40 kg
  • DRV/c (FDC, Prezcobix) plus TDF/FTC (FDC, Truvada) for adolescents weighing ≥40 kg

Boosted DRV regimens are approved for use in adolescents and can be used if there are concerns about INSTI resistance (e.g., adolescents diagnosed with HIV who have a history of CAB-LA use for PrEP). These Alternative regimens give the provider a choice between using a TAF-containing regimen as a single daily  FDC tablet (first option) or a TDF-containing regimen consisting of two daily tablets (second option). These alternate choices will be driven by concern for renal and bone disease in the patient (i.e., the need to avoid TDF) or adverse weight or lipid issues in the patient (i.e., the need to avoid TAF).

Practical and Clinical Considerations

Clinicians should provide the education and support that caregivers and adolescents need in order to administer or take ARVs correctly and adhere to the ART regimen (see Adherence to Antiretroviral Therapy in Children and Adolescents with HIV). Adolescents may have difficulty adhering to daily oral medications. Among many other factors, the number of pills and the pill size are important considerations. Additionally, in considering the optimal regimen for initiation, the clinician should understand whether the adolescent will be supervised to take treatment or is expected to take their treatment independently. Preferred initial therapy with a single tablet dosed once daily helps maintain adherence and viral suppression. Biktarvy is one of the smallest FDC single-tablet regimens currently available (see Appendix A, Table 2. Antiretroviral Fixed-Dose Combination Tablets and Co-packaged Formulations: Minimum Body Weights and Considerations for Use in Children and Adolescents).

Several other issues unique to adolescents need to be addressed when initiating HIV treatment. Some may be living with caregivers who are not aware of their diagnosis and may still be accessing care under their parent or caregiver’s health insurance plan. Communications between health insurance companies and caregivers can compromise confidentiality and result in accidental disclosure. Clinicians and social workers need to work around this issue, and in some instances, assist the patient in establishing their own access to HIV drugs and/or health insurance. Some adolescents may be emancipated and living on their own, but need access to affordable health insurance. In other instances, adolescents with HIV have been rejected by their families and are homeless. Rapid initiation of HIV treatment, though desirable, may have to be deferred until social barriers to adherence are addressed. Adolescents can have other comorbidities, such as depression and increased risk for suicide. These are heightened in adolescents who are sexual and gender minorities. Food insecurity and other social determinants of health that can affect an adolescent’s ability to safely initiate and adhere to HIV treatment should be evaluated and available support offered, if possible. Finally, use of gender-affirming language can be beneficial in establishing and maintaining rapport with adolescents, facilitating sustained engagement in care. For additional information, see Special Considerations for Antiretroviral Therapy Use in Adolescents with HIV and Adolescents and Young Adults with HIV in the Adult and Adolescent Antiretroviral Guidelines.

Special Situations

Where weight gain and increased risk for clinical obesity is a concern, or the adolescent has a high-risk lipid profile, a TAF-containing regimen may not be appropriate as a component of a preferred initial regimen (see Selection of Dual–Nucleoside Reverse Transcriptase Inhibitor Backbone as Part of Initial Antiretroviral Therapy Regimens above). A FDC single-tablet regimen containing the NNRTI DOR with a backbone of TDF/FTC can be considered when initiating treatment in adolescents with these concerns.54 However, providers must take into account the risks of proximal tubular injury, rare irreversible renal failure, and decreased bone mineral density that can occur when TDF is used.

Planning ARV Transitions

Adherence to daily oral medications is particularly challenging for adolescents,56,57 with lower rates of virologic suppression compared to adults.58 CAB and RPV (Cabenuva) is a two-drug long-acting ART regimen administered as two intramuscular injections on a bimonthly schedule that is approved for adolescents weighing ≥35 kg and adults with HIV who are virologically suppressed on an oral regimen.

Although it is not an option for initial therapy, it provides an option for adolescents who wish to maintain viral suppression without the need for daily oral medications. In select circumstances, some adolescents experiencing difficulties with adherence to an oral ART regimen could receive intensive adherence support to achieve viral suppression on their initial regimen as a bridge to switching to long-acting injectable CAB and RPV (see Management of Children Receiving Antiretroviral Therapy: Modifying Antiretroviral Regimens in Children with Sustained Virologic Suppression on Antiretroviral Therapy).59

Table 8. Antiretroviral Treatment Regimens Recommended for Initial Therapy for HIV Infection in Infants and Children: Birth to <12 Years of Age

The Panel on Antiretroviral Therapy and Medical Management of Children Living with HIV (the Panel) designates regimens as Preferred based on efficacy, ease of administration, acceptable toxicity, and other considerations. Alternative regimens also have demonstrated efficacy, but clinical experience with these regimens is limited, or these regimens are more difficult to administer than Preferred regimens. Regimens should be tailored to the individual patient by weighing the advantages and disadvantages of each combination (see Table A. Factors to Consider When Selecting an Antiretroviral Treatment Regimen for Infants, Children and Adolescents and Table 9. Advantages and Disadvantages of Antiretroviral Components Recommended for Initial Therapy in Infants and Children).

Many agents have multiple formulations and age and weight recommendations. Refer to Appendix A. Pediatric Antiretroviral Drug Information for additional information and recommended doses and formulations. In addition, many drugs that are recommended for use in newborns do not have dosing recommendations for premature infants. Additional information regarding dosing recommendations in this population can be found in Antiretroviral Management of Newborns with Perinatal HIV Exposure or HIV Infection.

Children who are receiving effective and tolerable antiretroviral regimens can continue using those regimens as they age, even if the combinations they are receiving are no longer Preferred regimens. Refer to the Management of Children Receiving Antiretroviral Therapy sections for additional guidance about transitioning children to other regimens as they grow.

Panel recommendations for children and adolescents aged ≥12 years are not included in this table; see Recommended Regimens for Children and Adolescents Aged ≥12 Years in the text.

See the Adult and Adolescent Antiretroviral Guidelines for recommendations about initial antiretroviral therapy for adolescents.

Preferred Initial Regimens and ARV Drugs Based on Age and Weight at Time of Treatment Initiation
8A. Infants from Birth to <30 Days of Age
Panel Recommendationa,bRegimen or ARV DrugAge and/or Weight RestrictioncFormulations and Commentsc
Preferred ART regimens for infants ≥37 weeks of gestation and aged <30 days and preterm infants with a postmenstrual age of ≥37 weeks at treatment initiation

NNRTI (NVP) or INSTI (RAL) plus two NRTIs

None

≥2 kg (RAL)

All oral solutions

RAL granules for oral suspension plus oral solutions for ZDV plus (3TC or FTC)

Preferred ART regimen for preterm infants ≥32 to <37 weeks of gestation

NNRTI (NVP) plus two NRTIs

NoneAll oral Solutions
Preferred ART regimens for preterm infant <32 weeks of gestationConsultation with a pediatric HIV expert or the National Perinatal HIV/AIDS Hotline (1-888-448-8765) is recommended
Alternative ART regimens for infants 

PI (LPV/r) plus two NRTIs

Postmenstrual age ≥42 weeks and a postnatal age of >14 days (LPV/r)All oral solutions
Alternative NRTI backbone for infants≥37 weeks of gestation

All oral solutions

Use of ABCd requires negative HLA-B*5701 testing.

Preferred Initial Regimens and ARV Drugs Based on Age and Weight at Time of Treatment Initiation
8B. Infants and Children Aged ≥30 Days to <2 Years
Panel Recommendationa,bRegimen or ARV DrugAge and/or Weight RestrictioncFormulations and Commentsc
Preferred ART regimens for infants and children aged ≥30 days to <2 years

INSTI (DTG)e,f plus two NRTIs

DTG ≥30 days and ≥3 kg to <25 kg

DTG ≥30 days and ≥3 kg to <25 kg

≥3 months and ≥6 kg to <25 kg (Triumeq PD)

≥25 kg (Triumeq)

DTG dispersible tablets plus oral solutions (ABCd, ZDV, 3TC, or FTC)

DTG/ABC/3TC in FDC dispersible tablets (Triumeq PD)

DTG/ABC/3TC FDC tablets if ≥25 kg (Triumeq). See Dolutegravir for special instructions if a child is unable to swallow pills.

Alternative anchor drugs to replace DTG in an ART regimen with a Preferred NRTI backbone for infants and children aged ≥30 days to <2 years

Postmenstrual age ≥42 weeks and postnatal age >14 days

ATV  ≥15 kg to <25 kg

<3 years

LPV/r oral solution

ATV is available in powder packets; RTV is available in 100 mg tablets and 100 mg powder packets.

NVP solution

Preferred Initial Regimens and ARV Drugs Based on Age and Weight at Time of Treatment Initiation
8C. Children Aged ≥2 Years to <12 Years
Panel Recommendationa,bRegimen or ARV DrugAge and/or Weight RestrictioncFormulations and Commentsc
Preferred ART regimens for children aged ≥2 years to <12 years who are unable to swallow pills

INSTI (DTG) plus two NRTIs

≥3 months and 3 kg to <25 kg (Triumeq PD)

≥30 days and ≥3 kg (DTG)

≥30 days and ≥3 kg (DTG)

≥14 kg to <25 kg (FTC/TAF)

For children who are unable to swallow pills

DTG/ABC/3TC in FDC dispersible tablets (Triumeq PD)

DTG dispersible tablets plus oral solutions (ZDV, 3TC, or FTC)

TAF available as FTC/TAF in FDC (Descovy) only; not available as an individual drug. See Tenofovir Alafenamide for special instructions about administering FTC/TAF to children who are not able to swallow pills.

For children who are ≥25 kg and unable to swallow pills, see Dolutegravir and Tenofovir Alafenamide for special instructions about administering DTG 50 mg and FTC/TAF (200 mg FTC/25 mg TAF).

Preferred ART regimens for children aged ≥2 years to <12 years who are able to swallow pills

INSTI (BIC or DTG) plus two NRTIs

Aged ≥2 years and ≥14 kg to <25 kg (BIC 30 mg/FTC 120 mg/TAF 15 mg)

≥25 kg (BIC 50 mg/FTC 200 mg/TAF 25 mg)

≥14 kg (DTG tablets, Tivicay)

≥25 kg

Aged ≥30 days and ≥3 kg (DTG)

≥14 kg (FTC/TAF)

For children who are able to swallow pills

BIC is only available in the FDC BIC/FTC/TAF.

The product label states that for children who are unable to swallow a whole tablet, the BIC/FTC/TAF tablet can be split and each part taken separately, as long as all parts are ingested within approximately 10 minutes; see Bictegravir.

DTG/ABC/3TC in FDC tablets (Triumeq)

TAF available as FTC/TAF in FDC (Descovy) only; not available as an individual drug. See Tenofovir Alafenamide.

Alternative anchor drugs in an ART regimen with a Preferred NRTI backbone for children aged ≥2 years to <12 yearsi 
  • ATV powder plus RTV powder (boosted PI)
  • ATV capsules plus RTV tablets (boosted PI)
  • ATV plus COBI in FDC tablet (ATV/c, boosted PI)

≥15 kg to ≤ 25 kg

≥15 kg

≥35 kg

ATV is available in 50 mg powder packets; RTV is available in 100 mg powder packets.

ATV and RTV powder can be mixed with soft food or liquid.

  • DRV plus RTV (boosted PI)
  • DRV plus COBI in FDC tablet (DRV/c, boosted PI)

≥20 kg

≥40 kg

DRV is available in an oral solution or tablets to be taken with RTV powder or tablets.

None

Aged ≥6 years

NVP solution or immediate release tablets
Aged ≥3 years and ≥10 kgEFV capsules can be opened and used as a sprinkle formulation for children who are unable to swallow pills.
≥35 kgAvailable as a single tablet regimen (DOR/3TC/TDF)
a Panel recommendations summarized in this table are for children with HIV-1 infection.

b Recommendations for ARV drugs or ART regimens to be used in special circumstances are addressed in the text (e.g., ARV resistance, HBV coinfection).

c Additional information about FDCs is available in Appendix A. Pediatric Antiretroviral Drug Information, Appendix A, Table 1. Antiretrovirals Available in Fixed-Dose Combination Tablets or as a Co-packaged Formulation, by Drug Class and Appendix A, Table 2. Antiretroviral Fixed-Dose Combination Tablets and Co-packaged Formulations: Minimum Body Weights and Considerations for Use in Children and Adolescents.

d ABC is not approved by the U.S. Food and Drug Administration (FDA) for use in full-term neonates and infants aged <3 months. Recent data from the IMPAACT P1106 trial and two observational cohorts provide reassuring data on the safety of ABC in infants when initiated at the age of <3 months (see Abacavir). Before ABC administration, a negative HLA-B*5701 allele test result should be available. An FDC tablet that contains ABC/3TC (Epzicom and generic) is available for use in children weighing ≥25 kg.

e If DTG dispersible tablets are not available, RAL can be administered using either the oral granules for suspension dispersed in water or as the chewable tablets dispersed in juice, formula, or milk.

f An NRTI backbone of ZDV plus 3TC twice daily or ABC plus 3TC twice daily allows for all medications to be administered at the same time when given in combination with LPV/r or RAL. There is considerable experience with ZDV and 3TC in this age group. ABC is associated with less bone marrow toxicity than ZDV and may be the preferred NRTI for long-term use.

g There are two different strengths of BIC/FTC/TAF tablets, with the lower-strength tablet for children weighing ≥14 kg and <25 kg.

h The product label for BIC/FTC/TAF (Biktarvy) states that for children who are unable to swallow a whole tablet, the BIC/FTC/TAF tablet can be split and each part taken separately, as long as all parts are ingested within approximately 10 minutes.

i FTC plus TAF is recommended as a Preferred NRTI combination for children and adolescents weighing ≥14 kg when used with an INSTI or NNRTI; an FDC tablet that contains FTC/TAF (Descovy) is available in two strengths, with dosage determined by a child’s weight (see Tenofovir Alafenamide). FTC/TAF is approved by the FDA for children weighing ≥14 kg when used in the regimen BIC/FTC/TAF, which is also available in two strengths, with dosage determined by a child’s weight. EVG/c/FTC/TAF is approved for use in children weighing ≥25 kg. FTC/TAF is a Preferred NRTI combination for children and adolescents weighing ≥35 kg when used with a boosted PI; FTC/TAF is not approved or recommended for use with a boosted PI in children weighing <35 kg.

Key: 3TC = lamivudine; ABC = abacavir; ARV = antiretroviral; ART = antiretroviral therapy; ATV = atazanavir; BIC = bictegravir; DOR = doravirine; DRV = darunavir; DTG = dolutegravir; EFV = efavirenz; FTC = emtricitabine; INSTI = integrase strand transfer inhibitor; HBV = hepatitis B virus; LPV/r = lopinavir/ritonavir; NNRTI = non-nucleoside reverse transcriptase inhibitor; NRTI = nucleoside reverse transcriptase inhibitor; NVP = nevirapine; PI = protease inhibitor; RAL = raltegravir; TAF = tenofovir alafenamide; TDF = tenofovir disoproxil fumarate; ZDV = zidovudine

Table 9. Advantages and Disadvantages of Antiretroviral Components Recommended for Initial Therapy in Infants and Children

See Appendix A. Pediatric Antiretroviral Drug Information and Table 7. Antiretroviral Regimen Considerations for Initial Therapy Based on Specific Clinical Scenarios in the Adult and Adolescent Antiretroviral Guidelines for more information. For detailed information about drug interactions, see Drug–Drug Interactions and ARV class-specific tables 24a-24g and 25a-25b in Adult and Adolescent Antiretroviral Guidelines, the HIV Drug Interaction Checker, and updated prescribing information.

Note: Drugs within each ARV class are listed in alphabetical order.

ARV Class/ Agent(s)AdvantagesDisadvantages
All INSTIs

INSTI Class Advantages

  • Well tolerated

INSTI Class Disadvantages

  • Possible weight gain in adults, especially Black/African American women
  • Potential for multiple drug interactions due to metabolism via hepatic enzymes (e.g., CYP3A4, UGT1A1). Information about drug interactions is available in the Adult and Adolescent Antiretroviral Guidelines and the HIV Drug Interaction Checker.
  • Oral absorption can be reduced by simultaneous administration with drugs or supplements containing polyvalent cations.
BIC
  • The FDC tablet is not recommended for patients with hepatic impairment or an estimated CrCl <30 mL/min.
  • CNS side effects, particularly sleep disturbances. Depression and suicidal ideation (rare; usually in patients with preexisting psychiatric conditions).
  • CYP3A4 and UGT1A1 substrate (but not a CYP3A4 inducer or inhibitor); potential for drug–drug interactions
  • Inhibits tubular secretion of creatinine resulting in an increase in serum creatinine without affecting glomerular function. This is generally benign but can be misinterpreted by clinicians not aware of this side effect. Added follow-up may be required in patients with underlying renal disease.
DTG
  • UGT1A1 substrate; potential for drug–drug interactions.
  • CNS side effects, particularly sleep disturbances. Depression and suicidal ideation (rare; usually in patients with preexisting psychiatric conditions).
  • Inhibits tubular secretion of creatinine resulting in an increase of serum creatinine without affecting glomerular function. This is generally benign but can be misinterpreted by clinicians not aware of this side effect. Added follow-up may be required in patients with underlying renal disease.
RAL
  • No food requirement
  • Available in tablet, chewable tablet, and oral granules for suspension formulations
  • Chewable tablets can be crushed and mixed with various liquids for infants aged ≥4 weeks who weigh ≥3 kg.
  • Favorable lipid profile
  • Lower barrier to resistance than boosted PI-, BIC-, or DTG-based regimens
  • Oral absorption of RAL can be reduced by simultaneous administration with drugs or supplements containing polyvalent cations.
  • UGT1A1 substrate; potential for drug interaction
  • Depression and suicidal ideation (rare; usually in patients with preexisting psychiatric conditions)
  • Increases in creatine kinase, myopathy, and rhabdomyolysis have been reported.
  • Potential for rare systemic allergic reaction or hepatitis
  • Granule formulation requires a multistep preparation before administration; caregiver must be taught how to properly prepare this formulation.
  • Higher pill burden than other INSTI-based regimens. No FDC formulation.
All NNRTIs

NNRTI Class Advantages

  • Long half-life allows for once daily dosing of DOR, EFV, and RPV.
  • Lower risk of dyslipidemia and fat maldistribution than PIs
  • PI-sparing
  • Lower pill burden than PIs for children taking the solid formulation; easier to use and adhere to than PI-based regimens.

NNRTI Class Disadvantages

  • Prevalence of NNRTI-resistant viral strains in ART-naive patients and the drugs’ low barrier for the development of resistance. A single mutation can confer resistance, with cross-resistance between EFV and NVP.
  • Rare, but serious and potentially life-threatening, cases of skin rash (including SJS) and hepatic toxicity. All NNRTIs pose this risk, but the risk is greatest with NVP; these toxic effects have not been reported in neonates.
  • Potential for multiple drug interactions due to metabolism via hepatic enzymes (e.g., CYP3A4). Information about drug interactions is available in the Adult and Adolescent Antiretroviral Guidelines and the HIV Drug Interaction Checker.
DOR
  • Neuropsychiatric AEs, but fewer than reported for EFV
  • DOR is contraindicated when coadministered with drugs that are strong cytochrome P450 (CYP)3A enzyme inducers (see Doravirine).
  • Potential for CYP3A4 drug interactions
  • Treatment-emergent DOR resistance mutations may confer resistance to certain NNRTIs.
EFV
  • CNS side effects, including dizziness, abnormal dreams, headache, depression, suicidality, insomnia, somnolence. Bedtime dosing is recommended to reduce CNS effects.
  • Rash (generally mild); QTc prolongation, dyslipidemia
  • Potential for CYP3A4 drug interactions
  • No commercially available liquid formulation
  • Limited data on dosing for children aged <3 years
  • No data on dosing for children aged <3 months
NVP
  • Liquid formulation is available.
  • Dosing information for young infants is available.
  • No food requirement
  • Extended-release formulation that allows once-daily dosing in older children is available.
  • Reduced virologic efficacy in young infants, regardless of exposure to NVP as part of a peripartum preventive regimen
  • Higher incidence of rash/HSR than other NNRTIs
  • Higher rates of serious hepatic toxicity than EFV
  • Decreased virologic response compared with EFV
  • Twice-daily dosing necessary in children with BSA <0.58 m2
  • Low barrier to resistance
RPV
  • Should not use in patients with viral loads >100,000 copies/mL
  • Food requirement. Must be taken with a ≥500 kcal meal at a consistent time each day; this may affect adherence.
  • Potential for CYP3A4 drug interactions
  • RPV oral absorption is reduced with increased gastric pH. Use of RPV with PPIs is contraindicated; see Adult Drug–Drug Interactions for dosing recommendations when RPV is coadministered with H2 blocker or antacids.
  • Low barrier to resistance
  • Side effects include depression, headache, skin rash, and QTc prolongation.
All PIs

PI Class Advantages

  • NNRTI-sparing
  • Clinical, virologic, and immunologic efficacy are well-documented.
  • Higher barrier to resistance than NNRTIs and RAL. Resistance to PIs requires multiple mutations.
  • When combined with a dual-NRTI backbone, a regimen that contains a PI targets HIV at two steps of viral replication by inhibiting the activity of viral reverse transcriptase and protease enzymes.

PI Class Disadvantages

  • Metabolic complications, including dyslipidemia, fat maldistribution, and insulin resistance.
  • Potential for multiple drug interactions because of metabolism via hepatic enzymes (e.g., CYP3A4)
    Information about drug interactions is available in the Adult and Adolescent Antiretroviral Guidelines and the HIV Drug Interaction Checker.
  • Higher pill burden than NRTI-based or NNRTI-based regimens for patients taking solid formulations.
  • Poor palatability of liquid preparations, which may affect adherence.
  • Most PIs require RTV or COBI boosting, resulting in drug–drug interactions that are associated with RTV or COBI.

ATV/r and ATV/c

Unboosted ATV

  • Once-daily dosing
  • Powder formulation is available for young children.
  • ATV has less effect on TG and total cholesterol levels than other PIs (but RTV boosting may be associated with elevations in these parameters).
  • No liquid formulation
  • Food requirement
  • Indirect hyperbilirubinemia is common but asymptomatic. Scleral icterus may be distressing to the patient, which may affect adherence. Other side effects include cholelithiasis, nephrolithiasis, and PR interval prolongation.
  • Must be used with caution in patients with preexisting conduction system defects (can prolong the PR interval of an ECG)
  • ATV boosted with RTV or COBI is recommended. Both RTV and COBI are associated with a large number of drug–drug interactions. CYP3A4 substrate and inhibitor.
  • ATV absorption is reduced when ATV is given with acid-lowering therapies.
  • COBI inhibits active tubular secretion of creatinine and can increase serum creatinine without affecting renal glomerular function. This is generally benign but can be misinterpreted by clinicians not aware of this side effect. Added follow-up may be required in patients with underlying renal disease.
DRV/c or DRV/r
  • Pediatric pill burden high with current tablet dose formulations
  • Food requirement
  • Must be boosted with RTV or COBI to achieve adequate plasma concentrations.
  • Contains sulfa moiety. The potential for cross-sensitivity between DRV and other drugs in sulfonamide class is unknown. Other side effects include hyperlipidemia and increase in transaminases.
  • RTV and COBI are associated with a large number of potential drug–drug interactions.
  • COBI inhibits active tubular secretion of creatinine and can increase serum creatinine without affecting renal glomerular function. This is generally benign but can be misinterpreted by clinicians not aware of this side effect. Added follow-up may be required in patients with underlying renal disease.
  • Can be used only once daily in the absence of certain PI-associated resistance mutations.
LPV/r
  • LPV is only available coformulated with RTV in liquid and tablet formulations.
  • Tablets can be given without food, but they may be better tolerated when taken with a meal or snack.
  • Poor palatability of liquid formulation (bitter taste)
  • Liquid formulation should be administered with food.
  • RTV is associated with a large number of drug–drug interactions.
  • Should not be administered to neonates before a postmenstrual age of 42 weeks (the span of time between the first day of the mother’s last menstrual period and birth, plus the time elapsed after birth) and a postnatal age ≥14 days
  • Must be used with caution in patients with pre-existing conduction system defects (can prolong PR and QT interval of an ECG)
ABC plus (3TC or FTC)
  • Risk of ABC HSR; perform HLA-B*5701 screening before initiating ABC.
  • ABC use has been associated with CV disease and cardiac events in some, but not all, observational studies conducted in adults.
FTC/TAF for children aged ≥6 years
  • Limited data on the safety and efficacy of this combination in children
  • Increased lipid levels
TDF plus (3TC or FTC)
  • Once-daily dosing for TDF
  • Resistance is slow to develop.
  • Lower risk of mitochondrial toxicity than other NRTIs
  • No food requirement
  • TDF is available as reduced-strength tablets and oral powder for use in younger children
  • Available in FDC tablets (see Appendix A, Table 1. Antiretrovirals Available in Fixed-Dose Combination Tablets)
  • Active against HBV; a recommended dual-NRTI option for patients with HBV/HIV coinfection.
  • Limited pediatric experience
  • Potential bone and renal toxicity.
ZDV plus (3TC or FTC)
  • Extensive pediatric experience
  • Coformulations of ZDV and 3TC are available for children weighing ≥30 kg.
  • Palatable liquid formulations
  • No food requirement
  • FTC is available as a palatable liquid formulation that can be administered once daily.
  • Bone marrow suppression and lipoatrophy with ZDV
  • ZDV requires twice-daily dosing.
Key: 3TC = lamivudine; ABC = abacavir; AE = adverse event; ATV = atazanavir; BIC = bictegravir; BSA = body surface area; CNS = central nervous system; COBI = cobicistat; CrCl = creatinine clearance; CYP = cytochrome P450; DOR = doravirine; DRV = darunavir; DTG = dolutegravir; ECG = electrocardiogram; EFV = efavirenz; FDC = fixed-dose combination; FTC = emtricitabine; HSR = hypersensitivity reaction; INSTI = integrase strand transfer inhibitor; LPV = lopinavir; LPV/r = lopinavir/ritonavir; NNRTI = non nucleoside reverse transcriptase inhibitor; NRTI = nucleoside reverse transcriptase inhibitor; NVP = nevirapine; PI = protease inhibitor; RAL = raltegravir; RPV = rilpivirine; RTV = ritonavir; SJS = Stevens-Johnson Syndrome; TAF = tenofovir alafenamide; TDF = tenofovir disoproxil fumarate; TFV = tenofovir; TG = triglyceride; ZDV = zidovudine

 

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What to Start

Regimens Recommended for Initial Therapy of Antiretroviral-Naive Children

Factors to Consider When Selecting an Initial ART Regimen

Table 8. Antiretroviral Treatment Regimens Recommended for Initial Therapy for HIV Infection in Infants and Children: Birth to <12 Years of Age

Preferred Initial Regimens and ARV Drugs Based on Age and Weight at Time of Treatment Initiation
8A. Infants from Birth to <30 Days of Age
Panel Recommendationa,bRegimen or ARV DrugAge and/or Weight RestrictioncFormulations and Commentsc
Preferred ART regimens for infants ≥37 weeks of gestation and aged <30 days and preterm infants with a postmenstrual age of ≥37 weeks at treatment initiation

NNRTI (NVP) or INSTI (RAL) plus two NRTIs

None

≥2 kg (RAL)

All oral solutions

RAL granules for oral suspension plus oral solutions for ZDV plus (3TC or FTC)

Preferred ART regimen for preterm infants ≥32 to <37 weeks of gestation

NNRTI (NVP) plus two NRTIs

NoneAll oral Solutions
Preferred ART regimens for preterm infant <32 weeks of gestationConsultation with a pediatric HIV expert or the National Perinatal HIV/AIDS Hotline (1-888-448-8765) is recommended
Alternative ART regimens for infants 

PI (LPV/r) plus two NRTIs

Postmenstrual age ≥42 weeks and a postnatal age of >14 days (LPV/r)All oral solutions
Alternative NRTI backbone for infants≥37 weeks of gestation

All oral solutions

Use of ABCd requires negative HLA-B*5701 testing.

Preferred Initial Regimens and ARV Drugs Based on Age and Weight at Time of Treatment Initiation
8B. Infants and Children Aged ≥30 Days to <2 Years
Panel Recommendationa,bRegimen or ARV DrugAge and/or Weight RestrictioncFormulations and Commentsc
Preferred ART regimens for infants and children aged ≥30 days to <2 years

INSTI (DTG)e,f plus two NRTIs

DTG ≥30 days and ≥3 kg to <25 kg

DTG ≥30 days and ≥3 kg to <25 kg

≥3 months and ≥6 kg to <25 kg (Triumeq PD)

≥25 kg (Triumeq)

DTG dispersible tablets plus oral solutions (ABCd, ZDV, 3TC, or FTC)

DTG/ABC/3TC in FDC dispersible tablets (Triumeq PD)

DTG/ABC/3TC FDC tablets if ≥25 kg (Triumeq). See Dolutegravir for special instructions if a child is unable to swallow pills.

Alternative anchor drugs to replace DTG in an ART regimen with a Preferred NRTI backbone for infants and children aged ≥30 days to <2 years

Postmenstrual age ≥42 weeks and postnatal age >14 days

ATV  ≥15 kg to <25 kg

<3 years

LPV/r oral solution

ATV is available in powder packets; RTV is available in 100 mg tablets and 100 mg powder packets.

NVP solution

Preferred Initial Regimens and ARV Drugs Based on Age and Weight at Time of Treatment Initiation
8C. Children Aged ≥2 Years to <12 Years
Panel Recommendationa,bRegimen or ARV DrugAge and/or Weight RestrictioncFormulations and Commentsc
Preferred ART regimens for children aged ≥2 years to <12 years who are unable to swallow pills

INSTI (DTG) plus two NRTIs

≥3 months and 3 kg to <25 kg (Triumeq PD)

≥30 days and ≥3 kg (DTG)

≥30 days and ≥3 kg (DTG)

≥14 kg to <25 kg (FTC/TAF)

For children who are unable to swallow pills

DTG/ABC/3TC in FDC dispersible tablets (Triumeq PD)

DTG dispersible tablets plus oral solutions (ZDV, 3TC, or FTC)

TAF available as FTC/TAF in FDC (Descovy) only; not available as an individual drug. See Tenofovir Alafenamide for special instructions about administering FTC/TAF to children who are not able to swallow pills.

For children who are ≥25 kg and unable to swallow pills, see Dolutegravir and Tenofovir Alafenamide for special instructions about administering DTG 50 mg and FTC/TAF (200 mg FTC/25 mg TAF).

Preferred ART regimens for children aged ≥2 years to <12 years who are able to swallow pills

INSTI (BIC or DTG) plus two NRTIs

Aged ≥2 years and ≥14 kg to <25 kg (BIC 30 mg/FTC 120 mg/TAF 15 mg)

≥25 kg (BIC 50 mg/FTC 200 mg/TAF 25 mg)

≥14 kg (DTG tablets, Tivicay)

≥25 kg

Aged ≥30 days and ≥3 kg (DTG)

≥14 kg (FTC/TAF)

For children who are able to swallow pills

BIC is only available in the FDC BIC/FTC/TAF.

The product label states that for children who are unable to swallow a whole tablet, the BIC/FTC/TAF tablet can be split and each part taken separately, as long as all parts are ingested within approximately 10 minutes; see Bictegravir.

DTG/ABC/3TC in FDC tablets (Triumeq)

TAF available as FTC/TAF in FDC (Descovy) only; not available as an individual drug. See Tenofovir Alafenamide.

Alternative anchor drugs in an ART regimen with a Preferred NRTI backbone for children aged ≥2 years to <12 yearsi 
  • ATV powder plus RTV powder (boosted PI)
  • ATV capsules plus RTV tablets (boosted PI)
  • ATV plus COBI in FDC tablet (ATV/c, boosted PI)

≥15 kg to ≤ 25 kg

≥15 kg

≥35 kg

ATV is available in 50 mg powder packets; RTV is available in 100 mg powder packets.

ATV and RTV powder can be mixed with soft food or liquid.

  • DRV plus RTV (boosted PI)
  • DRV plus COBI in FDC tablet (DRV/c, boosted PI)

≥20 kg

≥40 kg

DRV is available in an oral solution or tablets to be taken with RTV powder or tablets.

None

Aged ≥6 years

NVP solution or immediate release tablets
Aged ≥3 years and ≥10 kgEFV capsules can be opened and used as a sprinkle formulation for children who are unable to swallow pills.
≥35 kgAvailable as a single tablet regimen (DOR/3TC/TDF)
a Panel recommendations summarized in this table are for children with HIV-1 infection.

b Recommendations for ARV drugs or ART regimens to be used in special circumstances are addressed in the text (e.g., ARV resistance, HBV coinfection).

c Additional information about FDCs is available in Appendix A. Pediatric Antiretroviral Drug Information, Appendix A, Table 1. Antiretrovirals Available in Fixed-Dose Combination Tablets or as a Co-packaged Formulation, by Drug Class and Appendix A, Table 2. Antiretroviral Fixed-Dose Combination Tablets and Co-packaged Formulations: Minimum Body Weights and Considerations for Use in Children and Adolescents.

d ABC is not approved by the U.S. Food and Drug Administration (FDA) for use in full-term neonates and infants aged <3 months. Recent data from the IMPAACT P1106 trial and two observational cohorts provide reassuring data on the safety of ABC in infants when initiated at the age of <3 months (see Abacavir). Before ABC administration, a negative HLA-B*5701 allele test result should be available. An FDC tablet that contains ABC/3TC (Epzicom and generic) is available for use in children weighing ≥25 kg.

e If DTG dispersible tablets are not available, RAL can be administered using either the oral granules for suspension dispersed in water or as the chewable tablets dispersed in juice, formula, or milk.

f An NRTI backbone of ZDV plus 3TC twice daily or ABC plus 3TC twice daily allows for all medications to be administered at the same time when given in combination with LPV/r or RAL. There is considerable experience with ZDV and 3TC in this age group. ABC is associated with less bone marrow toxicity than ZDV and may be the preferred NRTI for long-term use.

g There are two different strengths of BIC/FTC/TAF tablets, with the lower-strength tablet for children weighing ≥14 kg and <25 kg.

h The product label for BIC/FTC/TAF (Biktarvy) states that for children who are unable to swallow a whole tablet, the BIC/FTC/TAF tablet can be split and each part taken separately, as long as all parts are ingested within approximately 10 minutes.

i FTC plus TAF is recommended as a Preferred NRTI combination for children and adolescents weighing ≥14 kg when used with an INSTI or NNRTI; an FDC tablet that contains FTC/TAF (Descovy) is available in two strengths, with dosage determined by a child’s weight (see Tenofovir Alafenamide). FTC/TAF is approved by the FDA for children weighing ≥14 kg when used in the regimen BIC/FTC/TAF, which is also available in two strengths, with dosage determined by a child’s weight. EVG/c/FTC/TAF is approved for use in children weighing ≥25 kg. FTC/TAF is a Preferred NRTI combination for children and adolescents weighing ≥35 kg when used with a boosted PI; FTC/TAF is not approved or recommended for use with a boosted PI in children weighing <35 kg.

Key: 3TC = lamivudine; ABC = abacavir; ARV = antiretroviral; ART = antiretroviral therapy; ATV = atazanavir; BIC = bictegravir; DOR = doravirine; DRV = darunavir; DTG = dolutegravir; EFV = efavirenz; FTC = emtricitabine; INSTI = integrase strand transfer inhibitor; HBV = hepatitis B virus; LPV/r = lopinavir/ritonavir; NNRTI = non-nucleoside reverse transcriptase inhibitor; NRTI = nucleoside reverse transcriptase inhibitor; NVP = nevirapine; PI = protease inhibitor; RAL = raltegravir; TAF = tenofovir alafenamide; TDF = tenofovir disoproxil fumarate; ZDV = zidovudine

Table 9. Advantages and Disadvantages of Antiretroviral Components Recommended for Initial Therapy in Infants and

ARV Class/ Agent(s)AdvantagesDisadvantages
All INSTIs

INSTI Class Advantages

  • Well tolerated

INSTI Class Disadvantages

  • Possible weight gain in adults, especially Black/African American women
  • Potential for multiple drug interactions due to metabolism via hepatic enzymes (e.g., CYP3A4, UGT1A1). Information about drug interactions is available in the Adult and Adolescent Antiretroviral Guidelines and the HIV Drug Interaction Checker.
  • Oral absorption can be reduced by simultaneous administration with drugs or supplements containing polyvalent cations.
BIC
  • The FDC tablet is not recommended for patients with hepatic impairment or an estimated CrCl <30 mL/min.
  • CNS side effects, particularly sleep disturbances. Depression and suicidal ideation (rare; usually in patients with preexisting psychiatric conditions).
  • CYP3A4 and UGT1A1 substrate (but not a CYP3A4 inducer or inhibitor); potential for drug–drug interactions
  • Inhibits tubular secretion of creatinine resulting in an increase in serum creatinine without affecting glomerular function. This is generally benign but can be misinterpreted by clinicians not aware of this side effect. Added follow-up may be required in patients with underlying renal disease.
DTG
  • UGT1A1 substrate; potential for drug–drug interactions.
  • CNS side effects, particularly sleep disturbances. Depression and suicidal ideation (rare; usually in patients with preexisting psychiatric conditions).
  • Inhibits tubular secretion of creatinine resulting in an increase of serum creatinine without affecting glomerular function. This is generally benign but can be misinterpreted by clinicians not aware of this side effect. Added follow-up may be required in patients with underlying renal disease.
RAL
  • No food requirement
  • Available in tablet, chewable tablet, and oral granules for suspension formulations
  • Chewable tablets can be crushed and mixed with various liquids for infants aged ≥4 weeks who weigh ≥3 kg.
  • Favorable lipid profile
  • Lower barrier to resistance than boosted PI-, BIC-, or DTG-based regimens
  • Oral absorption of RAL can be reduced by simultaneous administration with drugs or supplements containing polyvalent cations.
  • UGT1A1 substrate; potential for drug interaction
  • Depression and suicidal ideation (rare; usually in patients with preexisting psychiatric conditions)
  • Increases in creatine kinase, myopathy, and rhabdomyolysis have been reported.
  • Potential for rare systemic allergic reaction or hepatitis
  • Granule formulation requires a multistep preparation before administration; caregiver must be taught how to properly prepare this formulation.
  • Higher pill burden than other INSTI-based regimens. No FDC formulation.
All NNRTIs

NNRTI Class Advantages

  • Long half-life allows for once daily dosing of DOR, EFV, and RPV.
  • Lower risk of dyslipidemia and fat maldistribution than PIs
  • PI-sparing
  • Lower pill burden than PIs for children taking the solid formulation; easier to use and adhere to than PI-based regimens.

NNRTI Class Disadvantages

  • Prevalence of NNRTI-resistant viral strains in ART-naive patients and the drugs’ low barrier for the development of resistance. A single mutation can confer resistance, with cross-resistance between EFV and NVP.
  • Rare, but serious and potentially life-threatening, cases of skin rash (including SJS) and hepatic toxicity. All NNRTIs pose this risk, but the risk is greatest with NVP; these toxic effects have not been reported in neonates.
  • Potential for multiple drug interactions due to metabolism via hepatic enzymes (e.g., CYP3A4). Information about drug interactions is available in the Adult and Adolescent Antiretroviral Guidelines and the HIV Drug Interaction Checker.
DOR
  • Neuropsychiatric AEs, but fewer than reported for EFV
  • DOR is contraindicated when coadministered with drugs that are strong cytochrome P450 (CYP)3A enzyme inducers (see Doravirine).
  • Potential for CYP3A4 drug interactions
  • Treatment-emergent DOR resistance mutations may confer resistance to certain NNRTIs.
EFV
  • CNS side effects, including dizziness, abnormal dreams, headache, depression, suicidality, insomnia, somnolence. Bedtime dosing is recommended to reduce CNS effects.
  • Rash (generally mild); QTc prolongation, dyslipidemia
  • Potential for CYP3A4 drug interactions
  • No commercially available liquid formulation
  • Limited data on dosing for children aged <3 years
  • No data on dosing for children aged <3 months
NVP
  • Liquid formulation is available.
  • Dosing information for young infants is available.
  • No food requirement
  • Extended-release formulation that allows once-daily dosing in older children is available.
  • Reduced virologic efficacy in young infants, regardless of exposure to NVP as part of a peripartum preventive regimen
  • Higher incidence of rash/HSR than other NNRTIs
  • Higher rates of serious hepatic toxicity than EFV
  • Decreased virologic response compared with EFV
  • Twice-daily dosing necessary in children with BSA <0.58 m2
  • Low barrier to resistance
RPV
  • Should not use in patients with viral loads >100,000 copies/mL
  • Food requirement. Must be taken with a ≥500 kcal meal at a consistent time each day; this may affect adherence.
  • Potential for CYP3A4 drug interactions
  • RPV oral absorption is reduced with increased gastric pH. Use of RPV with PPIs is contraindicated; see Adult Drug–Drug Interactions for dosing recommendations when RPV is coadministered with H2 blocker or antacids.
  • Low barrier to resistance
  • Side effects include depression, headache, skin rash, and QTc prolongation.
All PIs

PI Class Advantages

  • NNRTI-sparing
  • Clinical, virologic, and immunologic efficacy are well-documented.
  • Higher barrier to resistance than NNRTIs and RAL. Resistance to PIs requires multiple mutations.
  • When combined with a dual-NRTI backbone, a regimen that contains a PI targets HIV at two steps of viral replication by inhibiting the activity of viral reverse transcriptase and protease enzymes.

PI Class Disadvantages

  • Metabolic complications, including dyslipidemia, fat maldistribution, and insulin resistance.
  • Potential for multiple drug interactions because of metabolism via hepatic enzymes (e.g., CYP3A4)
    Information about drug interactions is available in the Adult and Adolescent Antiretroviral Guidelines and the HIV Drug Interaction Checker.
  • Higher pill burden than NRTI-based or NNRTI-based regimens for patients taking solid formulations.
  • Poor palatability of liquid preparations, which may affect adherence.
  • Most PIs require RTV or COBI boosting, resulting in drug–drug interactions that are associated with RTV or COBI.

ATV/r and ATV/c

Unboosted ATV

  • Once-daily dosing
  • Powder formulation is available for young children.
  • ATV has less effect on TG and total cholesterol levels than other PIs (but RTV boosting may be associated with elevations in these parameters).
  • No liquid formulation
  • Food requirement
  • Indirect hyperbilirubinemia is common but asymptomatic. Scleral icterus may be distressing to the patient, which may affect adherence. Other side effects include cholelithiasis, nephrolithiasis, and PR interval prolongation.
  • Must be used with caution in patients with preexisting conduction system defects (can prolong the PR interval of an ECG)
  • ATV boosted with RTV or COBI is recommended. Both RTV and COBI are associated with a large number of drug–drug interactions. CYP3A4 substrate and inhibitor.
  • ATV absorption is reduced when ATV is given with acid-lowering therapies.
  • COBI inhibits active tubular secretion of creatinine and can increase serum creatinine without affecting renal glomerular function. This is generally benign but can be misinterpreted by clinicians not aware of this side effect. Added follow-up may be required in patients with underlying renal disease.
DRV/c or DRV/r
  • Pediatric pill burden high with current tablet dose formulations
  • Food requirement
  • Must be boosted with RTV or COBI to achieve adequate plasma concentrations.
  • Contains sulfa moiety. The potential for cross-sensitivity between DRV and other drugs in sulfonamide class is unknown. Other side effects include hyperlipidemia and increase in transaminases.
  • RTV and COBI are associated with a large number of potential drug–drug interactions.
  • COBI inhibits active tubular secretion of creatinine and can increase serum creatinine without affecting renal glomerular function. This is generally benign but can be misinterpreted by clinicians not aware of this side effect. Added follow-up may be required in patients with underlying renal disease.
  • Can be used only once daily in the absence of certain PI-associated resistance mutations.
LPV/r
  • LPV is only available coformulated with RTV in liquid and tablet formulations.
  • Tablets can be given without food, but they may be better tolerated when taken with a meal or snack.
  • Poor palatability of liquid formulation (bitter taste)
  • Liquid formulation should be administered with food.
  • RTV is associated with a large number of drug–drug interactions.
  • Should not be administered to neonates before a postmenstrual age of 42 weeks (the span of time between the first day of the mother’s last menstrual period and birth, plus the time elapsed after birth) and a postnatal age ≥14 days
  • Must be used with caution in patients with pre-existing conduction system defects (can prolong PR and QT interval of an ECG)
ABC plus (3TC or FTC)
  • Risk of ABC HSR; perform HLA-B*5701 screening before initiating ABC.
  • ABC use has been associated with CV disease and cardiac events in some, but not all, observational studies conducted in adults.
FTC/TAF for children aged ≥6 years
  • Limited data on the safety and efficacy of this combination in children
  • Increased lipid levels
TDF plus (3TC or FTC)
  • Once-daily dosing for TDF
  • Resistance is slow to develop.
  • Lower risk of mitochondrial toxicity than other NRTIs
  • No food requirement
  • TDF is available as reduced-strength tablets and oral powder for use in younger children
  • Available in FDC tablets (see Appendix A, Table 1. Antiretrovirals Available in Fixed-Dose Combination Tablets)
  • Active against HBV; a recommended dual-NRTI option for patients with HBV/HIV coinfection.
  • Limited pediatric experience
  • Potential bone and renal toxicity.
ZDV plus (3TC or FTC)
  • Extensive pediatric experience
  • Coformulations of ZDV and 3TC are available for children weighing ≥30 kg.
  • Palatable liquid formulations
  • No food requirement
  • FTC is available as a palatable liquid formulation that can be administered once daily.
  • Bone marrow suppression and lipoatrophy with ZDV
  • ZDV requires twice-daily dosing.
Key: 3TC = lamivudine; ABC = abacavir; AE = adverse event; ATV = atazanavir; BIC = bictegravir; BSA = body surface area; CNS = central nervous system; COBI = cobicistat; CrCl = creatinine clearance; CYP = cytochrome P450; DOR = doravirine; DRV = darunavir; DTG = dolutegravir; ECG = electrocardiogram; EFV = efavirenz; FDC = fixed-dose combination; FTC = emtricitabine; HSR = hypersensitivity reaction; INSTI = integrase strand transfer inhibitor; LPV = lopinavir; LPV/r = lopinavir/ritonavir; NNRTI = non nucleoside reverse transcriptase inhibitor; NRTI = nucleoside reverse transcriptase inhibitor; NVP = nevirapine; PI = protease inhibitor; RAL = raltegravir; RPV = rilpivirine; RTV = ritonavir; SJS = Stevens-Johnson Syndrome; TAF = tenofovir alafenamide; TDF = tenofovir disoproxil fumarate; TFV = tenofovir; TG = triglyceride; ZDV = zidovudine

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