Guidelines for the Use of Antiretroviral Agents in Pediatric HIV Infection

June 27, 2024

The Panel on Antiretroviral Therapy and Medical Management of Children Living with HIV (the Panel) has reviewed and updated text and references of the Guidelines for the Use of Antiretroviral Agents in Pediatric HIV Infection last published on April 11, 2023. Key updates are summarized below. These changes are highlighted in yellow in the PDF version of the guidelines. Some section titles were revised to fit with updated content and the use of people-first language.

Updates to the following sections, shared with the Perinatal Guidelines, are planned for August 2024:

• Infant Feeding for Individuals with HIV in the United States
• Diagnosis of HIV Infection in Infants and Children
• Antiretroviral Management of Newborns with Perinatal HIV Exposure or HIV Infection

Clinical and Laboratory Monitoring of Pediatric HIV Infection

• The section has been updated to address recommended baseline screening tests for coinfections and opportunistic infections (e.g., tuberculosis, hepatitis B virus, hepatitis C virus, cytomegalovirus). See Table 6. Sample Schedule for Clinical and Laboratory Monitoring of Children Before and After Initiation of Antiretroviral Therapy and the Pediatric Opportunistic Infection Guidelines.

When to Initiate Antiretroviral Treatment in Children with HIV Infection

•  If a child with HIV has not initiated antiretroviral treatment (ART), the Panel recommends that ART initiation be discussed and strongly encouraged at every visit. 
• When there are concerns about optimal timing of ART initiation relative to treatment of opportunistic infections (e.g., cryptococcal meningitis, tuberculous meningitis, disseminated Mycobacterium avium complex disease), timing should be discussed with a pediatric HIV specialist. 
• New data provide additional evidence supporting the neurodevelopmental and immune benefits associated with early initiation of ART. 

What to Start: Antiretroviral Treatment Regimens Recommended for Initial Therapy in Infants and Children with HIV 

• The section has been revised to present and discuss Panel recommendations for initial ART regimens by age group (i.e., birth to <30 days, ≥30 days to <2 years, ≥2 to <12 years, and ≥12 years) rather than by antiretroviral (ARV) drug class. Content has been added within new subsections to address practical considerations in ARV drug and regimen selection and implementation of initial ART. Some content is deliberately repeated across the age groups. 
• Two new tables have been added to the section: Table A. Factors to Consider When Selecting an Antiretroviral Treatment Regimen for Children and Table B. Advantages and Disadvantages of Anchor Drugs Recommended for Initial Antiretroviral Therapy Regimens in Infants from Birth to <30 days of Age. Table 8. Antiretroviral Treatment Regimens Recommended for Initial Therapy for HIV Infection in Infants and Children: Birth to <12 Years of Age has been reorganized to present Preferred and Alternative regimens and ARV drugs by age group to follow the revised structure of the section. 
• Nevirapine- and raltegravir-based regimens continue to be recommended as Preferred ART for infants aged <30 days. Lopinavir/ritonavir (LPV/r)-based ART is now recommended as an Alternative regimen for infants in this age group if they have reached a postmenstrual age of 42 weeks and a postnatal age of at least 14 days; LPV/r was previously a Preferred ARV for infants. 
• To avoid delays in initiating treatment in neonates, abacavir (ABC) is now recommended as an Alternative rather than a Preferred nucleoside reverse transcriptase inhibitor for infants aged <30 days who test negative for the HLA-B*5701 allele. 
• The Panel now recommends second-generation integrase strand transfer inhibitor (INSTI)-based regimens with dolutegravir (DTG) or bictegravir (BIC) as the Preferred anchor drugs for initial ART in infants and children aged ≥30 days and weighing ≥3 kg whenever possible. DTG is approved for children aged ≥30 days and weighing ≥3 kg, and BIC is approved for children aged ≥2 years and weighing ≥14 kg. Protease inhibitor (PI)-based regimens are recommended as Alternative options. Non-nucleoside reverse transcriptase inhibitor-based regimens are recommended as Alternative options only if needed for resistance or intolerance to INSTIs and PIs. 

What Not to Start: Regimens Not Recommended for Initial Antiretroviral Therapy in Infants and Children 

• Because elvitegravir (EVG) has a lower genetic barrier to the development of resistance compared to second-generation INSTIs (i.e., DTG, BIC), the Panel no longer recommends EVG as an Alternative ARV for initial ART regimens in children. 
• Lenacapavir (LEN), a capsid inhibitor, has been added to this section. LEN is U.S. Food and Drug Administration (FDA) approved for use in heavily treatment-experienced adults with multidrug-resistant HIV-1; it is not approved for initial ART or for use in children. 

Special Considerations for Antiretroviral Therapy Use in Adolescents with HIV 

• Trauma experience is high among people with HIV generally and among youth with perinatally acquired HIV. Interest in the adoption of trauma-informed care (TIC) practices for people with HIV is emerging; however, research evaluating TIC interventions is limited, and efficacy is mixed. Providers may consider utilizing TIC principles for youth who have experienced trauma. 

Adherence to Antiretroviral Therapy in Children and Adolescents with HIV 

• The Panel recommends discussing the option of long-acting injectable ART to facilitate and support adherence with eligible patients and their caregivers. 

Management of Children Receiving Antiretroviral Therapy 

• Modifying Antiretroviral Regimens in Children with Sustained Virologic Suppression on Antiretroviral Therapy and Table 18. Examples of Changes in Antiretroviral Regimen Components for Children with Sustained Virologic Suppression have been updated to incorporate the most recent switch options in line with pediatric ARV drug approvals and Panel recommendations.
• Recognizing and Managing Antiretroviral Treatment Failure and Table 20. Options for Regimens with at Least Two Fully Active Agents to Achieve Virologic Suppression in Patients with Virologic Failure and Evidence of Viral Resistance have been updated to incorporate new data and recommendations for ARV options in the context of treatment failure. 
• Boxed recommendations in Antiretroviral Treatment Interruption in Children with HIV have been updated to underscore that treatment interruption is not recommended as a strategy to confirm diagnosis or to assess remission or cure in clinical settings. 
  • The section has been updated to expand content about mitigating unplanned interruptions in treatment (e.g., by clinicians working closely with families and providing anticipatory guidance around potential short-term interruptions from such events as vacation, travel, or summer camps). 
  • Guidance for Non-HIV-Specialized Providers Caring for People with HIV Who Have Been Displaced by Disasters (Such as a Hurricane) addresses the care of children when unforeseeable events, such as natural disasters, displace them from their primary HIV care programs. 

Appendix A: Pediatric Antiretroviral Drug Information 

Drug sections and fixed-dose combination (FDC) tables, Table 1. Antiretrovirals Available in Fixed-Dose Combination Tablets or as a Co-packaged Formulation, by Drug Class and Table 2. Antiretroviral Fixed-Dose Combination Tablets and Co-packaged Formulations: Minimum Body Weights and Considerations for Use in Children and Adolescents, in this appendix were reviewed and updated to include recent pediatric data, dosing and safety information, and FDA approvals of new formulations and FDCs. Significant changes are summarized below: 

• The dispersible FDC ABC/DTG/emtricitabine (Triumeq PD) now has FDA-approved dosing for use in infants and children aged ≥3 months and weighing ≥6 kg to <25 kg (see Dolutegravir, Abacavir, and Emtricitabine). 
• Information about DTG dispersible tablet (Tivicay) dosing for infants and children with first-generation INSTI resistance has been added to the Dolutegravir section. 
• Based on available data, cautions about the use of DTG in pregnancy due to concerns about neural defects have been removed from the package inserts for products containing DTG. 
• Ritonavir (RTV) oral solution has been discontinued, but the pediatric formulation of 100-mg powder packets is still available for children who are not able to swallow pills (see Ritonavir). 
• • Because the minimum dose of the powdered formulation of RTV is now 100 mg, doses of RTV-boosted atazanavir (ATV/r) and RTV-boosted darunavir (DRV/r) requiring <100 mg RTV have been removed or updated. Dosing for ATV/r is available for children weighing ≥15 kg. Dosing for DRV/r is available for children weighing ≥20 kg. See Atazanavir and Darunavir. 
• A new drug section has been added for the capsid inhibitor lenacapavir. LEN is FDA approved for use in adults with multidrug-resistant HIV infection who are heavily treatment experienced. 
• The recent FDA approval of rilpivirine tablets for oral suspension (Edurant PED) will be addressed in the next update of the Rilpivirine section.