Update to the Guidelines for the Use of Antiretroviral Agents in Pediatric HIV Infection

Cross-posted from: clinicalinfo.hiv.gov

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 September 30, 2025. Key updates are summarized below. Three sections were developed in collaboration with the Panel on Treatment of HIV During Pregnancy and Prevention of Perinatal Transmission. The Panel has included key knowledge gaps in select sections. In the PDF version of the Guidelines, these changes are highlighted in yellow.

Preventing HIV Transmission During Infant Feeding

• If antiretroviral therapy (ART) is taken consistently and the viral load is maintained at a level of <50 copies/mL (i.e., undetectable viral load) for at least 3 months prior to delivery, the Panels recommend counseling about the options of formula feeding, use of banked donor milk, or breastfeeding.
• The Panel notes there is no evidence that formula supplementation increases the risk of HIV acquisition in the breastfed infant in the context of parental ART and viral suppression.
• The Panel recommends that women with HIV with mastitis or other unilateral breast pathology stop breastfeeding on the affected breast and feed on the contralateral (or unaffected) breast; when symptoms resolve, women can again feed from both breasts.

Diagnosis of HIV Infection in Infants and Children

• Non-subtype B HIV-1 is no longer a diagnostic concern. All recommendations and text referencing non-subtype B HIV-1 have been removed.
• The Panels revised the recommended timing of virologic diagnostic testing for infants with perinatal HIV exposure who are being breastfed. The last test should be performed 3 months after cessation of breastfeeding.
• The HIV RNA Assays subsection has been updated to include a sensitive HIV-1/HIV-2 RNA assay that can be used for infant diagnosis.
• Table 3. Recommended Virologic Testing Schedules for Infants With Perinatal and Breastfeeding Exposure to HIV has been simplified and restructured.

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

• The preferred regimen for initial ART in full-term infants from birth to age <30 days and who weigh ≥2 kg is now the second-generation integrase inhibitor dolutegravir (DTG) in combination with a nucleoside reverse transcriptase inhibitor backbone of zidovudine (ZDV) plus either lamivudine (3TC) or emtricitabine (FTC).
• Studies have established dosing guidelines for DTG pediatric dispersible tablets in neonates.
• The What Not to Start section has been discontinued as a separate document and has been incorporated into this section for brevity and clarity.

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

• Three-drug presumptive treatment for infants with high risk of HIV acquisition now consists of ZDV/3TC plus nevirapine (NVP) or DTG.
• The Panel recommends performing a birth HIV nucleic acid test in all scenarios except for those in which infants are at low risk for HIV acquisition.
• The Panel recommends that extended antiretroviral (ARV) prophylaxis during breastfeeding, when used, be continued until either 4 weeks after the last exposure to breast milk or 4 weeks after concerns about maternal virologic suppression have resolved (BIII). If extended prophylaxis with NVP is planned, it should ideally be initiated from birth, replacing ZDV as the initial prophylaxis; alternatively, extended prophylaxis with 3TC should be initiated after the completion of initial ZDV prophylaxis.
• If a maternal HIV RNA level of ≥200 copies/mL (viremia) develops or there is presumed viremia (e.g., reports of nonadherence to ARVs) during breastfeeding, the Panels recommend cessation of breastfeeding. If the infant had not been receiving ARV prophylaxis, a three-drug ARV regimen should be given for 4 weeks. If the infant had been receiving ARV prophylaxis with 3TC or NVP, the decision to either continue the single-drug prophylaxis or initiate treatment with a three-drug regimen should be based on maternal RNA level and other factors (AII).

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:
  • The FDA approved use of darunavir (DRV) and cobicistat (COBI) (Prezcobix PED) tablets for oral suspension for children aged ≥3 years and weighing ≥15 kg to <25 kg for use in combination with other ARV drugs (see Cobicistat).
  • COBI alone (as Tybost) has been discontinued, and there is no generic standalone tablet formulation of COBI available (see Cobicistat).
  • The Panel supports the use of DTG dispersible tablets (Tivicay PD) in neonates (gestational age ≥37 weeks to age <4 weeks and weighing ≥2 kg) based on available pharmacokinetic (PK) modeling and simulation and clinical trial data; this dosing strategy is not currently approved by the FDA.
  • The Panel supports the use of abacavir (ABC)/DTG/3TC (Triumeq PD) dispersible tablets in children aged ≥4 weeks, HLA-B*5701 negative, and weighing ≥3 kg to <25 kg based on available PK modeling and simulation and clinical trial data; this dosing strategy is not currently approved by the FDA.
• The recent FDA approval of doravirine and islatravir tablets (Idvynso) will be addressed in the next update of the Doravirine section.