Guidelines for the Use of Antiretroviral Agents in Pediatric HIV Infection

December 19, 2024

The Panel on Antiretroviral Therapy and Medical Management of Children Living With HIV has reviewed and updated three sections of the Guidelines for the Use of Antiretroviral Agents in Pediatric HIV Infection that are developed in collaboration with the Panel on Treatment of HIV in Pregnancy and Prevention of Perinatal Transmission (the Panels). These sections have been revised to include new data and publications where relevant. Key updates are summarized below.

Infant Feeding for Individuals With HIV in the United States 

• Although the Guidelines use the term “breastfeeding” to describe feeding a child one’s own milk, the Panels recognize the importance of assessing and using individuals’ preferred terminology; some individuals may prefer using the term “chestfeeding” rather than “breastfeeding.” 
• Bulleted recommendations now include information from the text on counseling about the infant feeding options of formula feeding, use of banked donor milk, or breastfeeding. Recommendations also address clinical management if the breastfeeding parent develops viremia.
  •  In the case of a detectable viral load in a breastfeeding parent, the Panels recommend breastfeeding be stopped temporarily or discontinued and replacement feeding initiated while the viral load is rechecked; causes for the viremia are assessed, and, when applicable, adherence counseling is reinforced (AII). Most experts recommend permanent discontinuation of breastfeeding when HIV RNA is ≥200 copies/mL (CIII). 
  • Depending on the level and persistence of viremia in the breastfeeding parent, next steps may include initiating or modifying infant antiretroviral (ARV) prophylaxis, permanently stopping breastfeeding, and considering the need for additional infant HIV testing. 
  • If the repeat parental viral load is undetectable, a joint decision should be made by the parent and providers about whether breastfeeding may resume (AIII). 

Diagnosis of HIV Infection in Infants and Children 

• Section text and Table 3. Recommended Virologic Testing Schedules for Infants With Perinatal and Breastfeeding Exposure to HIV have been revised to align with changes in Antiretroviral Management of Infants With In Utero, Intrapartum, or Breastfeeding Exposure to HIV. 
• The Panels recommend virologic diagnostic testing at birth using an HIV nucleic acid test, which should generally be performed for all infants with perinatal HIV exposure but is not necessary for infants at low risk of HIV acquisition (defined as being born to a person who had HIV RNA levels <50 copies/mL from 20 weeks of gestation through delivery). Birth testing should be performed in infants at low risk of HIV acquisition if the parent plans to breastfeed or there are concerns about loss to follow-up (BIII). 

Antiretroviral Management of Infants With In Utero, Intrapartum or Breastfeeding Exposure or HIV Infection 

• This section has been extensively revised and the title has been updated to reflect changes in recommendations, associated content about infant ARV management according to risk from in utero and intrapartum HIV exposure, and guidance for infant ARV prophylaxis during breastfeeding. 
• The Panels have added Table 12. Transmission Risk Assessment by HIV RNA Levels and Antenatal Time Period, which summarizes risk of transmission from exposure during three antenatal time periods. Because robust data are not available to define thresholds of risk across pregnancy, the Panels have selected time points balancing available data with implications for clinical management. Transmission risk categories inform ARV choice and management of prophylaxis and presumptive HIV therapy for infants with HIV exposure. 
• Revised criteria for infant risk of HIV infection from in utero or intrapartum exposure and recommended ARV management are summarized in Figure 1. Antiretroviral Management Algorithm for Infants With In Utero or Intrapartum HIV Exposure by Risk of Transmission and Table 13. Antiretroviral Management for Infants With In Utero or Intrapartum Exposure to HIV. The Panels recommend the following:
  •  Infants at high risk of HIV infection from in utero or intrapartum exposure, defined as being born to a pregnant person who had viremia (HIV RNA ≥50 copies/mL) in the 4 weeks prior to delivery, should be provided a three-drug ARV regimen, administered from birth for 2 to 6 weeks, that serves as presumptive HIV therapy or enhanced prophylaxis. If the duration of the three-drug regimen is shorter than 6 weeks, zidovudine (ZDV) should be continued alone to complete a total of 6 weeks of prophylaxis (AII). 
  • Infants at low risk of in utero and intrapartum HIV acquisition, defined as being born to a pregnant person who had HIV RNA levels <50 copies/mL from 20 weeks of gestation through delivery, should receive ZDV alone for a duration of 2 weeks (AII). 
  • Infants not meeting the criteria for high or low risk should have ARV regimens and durations based on case-specific factors related to the level and timing of viremia during the pregnancy (AII). 
• The section now includes updated recommendations and expanded content about ARV prophylaxis for infants who are being breastfed by a parent with HIV. Recommendations of the Panels are summarized in a new table, Table 14. Antiretroviral Management of Infants With Exposure to HIV During Breastfeeding. 
  • For infants with low risk of HIV acquisition during breastfeeding, some Panel members do not recommend extended ARV prophylaxis; however, other Panel members do recommend extended ARV prophylaxis with either nevirapine or lamivudine (CIII). The Panels did not reach consensus. 
  • Infants are considered at low risk of transmission during breastfeeding when (1) the breastfeeding parent is receiving antiretroviral therapy and has had sustained virologic suppression (HIV RNA <50 copies/mL) for at least 3 months prior to delivery and (2) the provider and parent are confident that the breastfeeding parent will maintain ART adherence during breastfeeding (AII). 
  • Bulleted recommendations and associated content have been added to provide guidance about infant ARV prophylaxis or use of presumptive HIV therapy when the breastfeeding parent experiences new viremia or there are concerns about future risk of viremia. 
  • Table 14.1. Antiretroviral Prophylaxis Dosing for Infants Who Are Breastfed has been revised to provide updated dosing information and to address infant ARV management for scenarios when a breastfeeding parent develops viremia or is diagnosed with HIV during breastfeeding.

June 27, 2024

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.