2025 HHS Antiretroviral Agents in Pediatric HIV Infection Guideline — Key Highlights

Published: November 10, 2025

Earlier this fall, the United States Department of Health and Human Services (DHHS) updated their guideline on antiretroviral agents in pediatric HIV infection. The 2025 update to the Use of Antiretroviral Agents in Pediatric HIV Infection guideline replaced the previous 2024 version with a selection of key updates, which we outline below.

The update includes new recommendations and changes to the phrasing throughout the guideline on topics involving treatment optimization, toxicity management, unplanned treatment interruptions, recommended therapy regimens, and more.

The following are a selection of key highlights from the many updates made to the guideline in the 2025 update. For a complete view of every change, the full-text version is available wherein the DHHS highlighted every change made for your convenience.

When to Initiate Antiretroviral Treatment in Children with HIV Infection

The guideline panel recommends the initiation of treatment for the opportunistic infection first, before antiretroviral therapy (ART) initiation.

Modifying Antiretroviral Regimens in Children with Sustained Virologic Suppression on Antiretroviral Therapy

This section was updated to better emphasize optimization to integrase strand transfer inhibitor-based regimens for pediatric patients with perinatally acquired HIV.

Examples of Changes in Antiretroviral Regimen Components for Children with Sustained Virologic Suppression (table 18)

The table now includes the addition of Symtuza for children weighing ≥40 kg.

Recognizing and Managing Antiretroviral Treatment Failure

This section received two updated recommendations:

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

This section received updated phrasing and now features supporting references.

Appendix A: Pediatric Antiretroviral Drug Information

Tables 1 and 2 were updated to include the most recent data, dosing, and safety information from the latest FDA approvals of new fixed-dose combinations and formulations:

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.
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.
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.