Guidelines for the Use of Antiretroviral Agents in Pediatric HIV Infection

September 30, 2025

The Panel on Antiretroviral Therapy and Medical Management of Children Living With HIV (the Panel) has reviewed and updated the text and references of previous versions of the Guidelines for the Use of Antiretroviral Agents in Pediatric HIV Infection published on June 27, 2024. Key updates are summarized below. In the PDF version of the Guidelines, these changes are highlighted in yellow.

When to Initiate Antiretroviral Treatment in Children With HIV Infection

• In antiretroviral therapy (ART)–naive children and adolescents with cryptococcal meningitis, tuberculous meningitis, and disseminated Mycobacterium avium complex disease, the Panel recommends initiation of treatment for the opportunistic infection first, before ART initiation (see Guidelines for the Prevention and Treatment of Opportunistic Infections in Children With and Exposed to HIV).

Management of Children Receiving Antiretroviral Therapy

• Modifying Antiretroviral Regimens in Children With Sustained Virologic Suppression on Antiretroviral Therapy has been updated to emphasize optimization to integrase strand transfer inhibitor (INSTI)–based regimens for children with perinatally acquired HIV. The Panel recommends the following:
  • INSTI drugs have demonstrated higher efficacy and improved safety profiles compared to non-nucleoside reverse transcriptase inhibitors (NNRTIs) or protease inhibitors (PIs). INSTI-based ART regimens are Preferred initial regimens for infants, children, and adolescents; thus, optimization to an INSTI-based regimen for eligible children and adolescents should be offered.
• Table 18. Examples of Changes in Antiretroviral Regimen Components for Children With Sustained Virologic Suppression has been updated to include the addition of Symtuza for children weighing ≥40 kg.
• Recommendations have been updated in Recognizing and Managing Antiretroviral Treatment Failure:
  • When using a new regimen with only two fully active antiretroviral (ARV) medications, at least one should have a high barrier to resistance (i.e., second-generation INSTI or boosted PI).
  • If two fully active ARV medications are not available, at least one fully active medication with a high barrier to resistance (i.e., second-generation INSTI, boosted PI) should be used plus two partially active nucleos(t)ide reverse transcriptase inhibitors, (i.e., tenofovir disoproxil fumarate or tenofovir alafenamide (TAF) with lamivudine [3TC] or emtricitabine (FTC); abacavir and 3TC). In this case, frequent viral load monitoring is recommended for early detection of virologic failure.

Special Considerations for Antiretroviral Therapy Use in Adolescents With HIV

• New text with supporting references has been added to the section. Without ideal HIV care, models project that adolescents with perinatally acquired HIV have life expectancies 10 to 12 years shorter than youth without HIV, highlighting the importance of specialized care that addresses critical barriers to optimal health outcomes in this population.

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 U.S. Food and Drug Administration (FDA) approvals of new formulations and FDCs. Significant changes are summarized below: 

• In addition to the Dolutegravir updates for 2024 (published in June 2024 with highlighted updates republished in August 2025), the following updates are new for the Pediatric Antiretroviral Drug Appendix A:
  • The FDA approved rilpivirine (RPV) tablets for oral suspension (Edurant PED) for children aged ≥2 years and weighing ≥14 kg to <25 kg for use in combination with other ARV drugs (see Rilpivirine).
  • The FDA approved use of FTC, RPV, and TAF (ODEFSEY) as a complete regimen for the treatment of HIV-1 in pediatric patients weighing ≥25 kg (see Rilpivirine, Tenofovir Alafenamide, and Emtricitabine).
  • The FDA approved use of darunavir and cobicistat (Prezcobix) for children weighing ≥25 kg to ≤40 kg for use in combination with other ARV drugs (see Cobicistat).

December 19, 2024

Preventing HIV Transmission During Infant Feeding

• 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 viremia is identified.
  • In the case of a detectable viral load during breastfeeding, 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 during breastfeeding, next steps may include initiating or modifying infant ARV prophylaxis, permanently stopping breastfeeding, and considering the need for additional infant HIV testing.
  • If the repeat 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 (HIV RNA levels <50 copies/mL from 20 weeks of gestation through delivery put infants at low risk of HIV acquisition). Birth testing should be performed in infants at low risk of HIV acquisition if there is a plan 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:
  • Viremia (HIV RNA ≥50 copies/mL) in the 4 weeks prior to delivery puts infants at higher risk of HIV infection from in utero or intrapartum exposure. Infants in this category 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).
  • HIV RNA levels <50 copies/ml from 20 weeks of gestation through delivery put infants at low risk of in utero and intrapartum HIV acquisition. These infants 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. 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 3TC (CIII). The Panels did not reach consensus.
  • Infants are considered at low risk of transmission during breastfeeding when (1) the breastfeeding woman is receiving ART 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 woman 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 woman 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 woman develops viremia or is diagnosed with HIV during breastfeeding.