Recommendations for the Use of Antiretroviral Drugs During Pregnancy and Interventions to Reduce Perinatal HIV Transmission in the United States

December 19, 2024

The Panel on Treatment of HIV in Pregnancy and Prevention of Perinatal Transmission has reviewed and updated three sections of the Recommendations for the Use of Antiretroviral Drugs During Pregnancy and Interventions to Reduce Perinatal HIV Transmission in the United States that are developed in collaboration with the Panel on Antiretroviral Therapy and Medical Management of Children Living With HIV (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 13. 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 10. 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 11. 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 12. 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 12.1. 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.

January 31, 2024 

• Throughout the guidelines, minor changes were made to the HIV RNA threshold for resistance testing to be consistent with the Drug-Resistance Testing section in the Adult and Adolescent Antiretroviral Guidelines. 
• Review of Clinical Trials of Antiretroviral Interventions to Prevent Perinatal HIV Transmission, the former Appendix A that provided information about the historical context of perinatal HIV prevention, has been archived; see Perinatal Archived Guidelines.

Introduction 

• This section has been revised to clarify terms and present recent data about perinatal HIV transmission (i.e., during pregnancy and labor and delivery) and postnatal HIV transmission (i.e., through breastfeeding). 

Pregnancy and Postpartum HIV Testing and Identification of Perinatal and Postnatal HIV Exposure 

• Revisions have been made to the section title and bulleted recommendations and throughout the text to provide added detail, new data, and clarification. 
• The Panel recommends that when acute HIV infection is suspected during pregnancy, the intrapartum period, or while breastfeeding, a plasma HIV RNA assay should be performed in conjunction with an antigen/antibody immunoassay. 

Pre-Exposure Prophylaxis (PrEP) to Prevent HIV During Periconception, Antepartum, and Postpartum Periods 

• Given the lack of data, episodic or non-daily PrEP is not recommended for protection against vaginal exposure to HIV. 
• For people planning to discontinue daily oral PrEP, ongoing use for 7 to 28 days after last HIV exposure is recommended. This timeframe aligns with recommendations for post-exposure prophylaxis. 
• For people who become pregnant while receiving PrEP, including drugs not yet approved for PrEP during pregnancy (e.g., long-acting injectable cabotegravir [CAB-LA], tenofovir alafenamide [TAF]), clinicians are strongly encouraged to register them with the Antiretroviral Pregnancy Registry as early in pregnancy as possible. 
• Efficacy studies evaluating TAF/emtricitabine (FTC) as PrEP in people with vaginal exposure have not been completed. Therefore, the Panel does not recommend TAF/FTC as PrEP for this population, including during pregnancy and postpartum. Additionally, TDF/FTC pharmacokinetic data cannot be readily extrapolated to TAF/FTC.

Reproductive Options When One or Both Partners Have HIV

• Rescreening for genital tract infections while attempting to conceive may be considered based on individual risk and duration of the preconception period. 
• To prevent HIV acquisition, the Panel recommends that health care providers discuss PrEP with all sexually active people without HIV, including individuals who are trying to conceive. PrEP should be offered to those who desire PrEP or have specific indications for PrEP. 

Initial Evaluation and Continued Monitoring of HIV During Pregnancy

• Revisions have been made to clarify recommendations for CD4 T lymphocyte cell count monitoring that align with guidance in the Adult and Adolescent Antiretroviral Guidelines. 

Antiretroviral Therapy for People with HIV Who Are Trying to Conceive 

• Data are not available about the efficacy and safety of injectable cabotegravir (CAB) and rilpivirine (RPV) during pregnancy. For those who are considering switching regimens prior to conception to prevent fetal exposure, it is important to recognize that CAB and RPV injections must be stopped at least 1 year before conception to ensure that these long-acting drugs are fully eliminated. 
• Among those on long-acting injectable antiretroviral therapy (ART) who have a history of poor adherence to oral medications, switching from long-acting injectable CAB and RPV to oral ART to prepare for conception may be associated with increased risk of viral rebound and non-nucleoside reverse transcriptase inhibitor resistance. Shared decision-making should be used when making decisions about changing to an oral regimen. 

Pregnant People with HIV Who Have Never Received Antiretroviral Drugs (Antiretroviral-Naive)

•  The following dolutegravir (DTG)-based regimens are Preferred as initial ART for pregnant people who have never received antiretroviral (ARV) drugs: 
  • DTG plus (tenofovir disoproxil fumarate [TDF] or TAF) plus (FTC or lamivudine [3TC]) or 
  • DTG plus abacavir (ABC) plus 3TC—only for individuals who are HLA-B*5701 negative and without chronic hepatitis B virus (HBV) coinfection
•  However, in people with a history of CAB exposure for PrEP, the following ritonavir-boosted darunavir (DRV/r)–based regimens are Preferred for initial ART due to concerns about integrase strand transfer inhibitor (INSTI) resistance mutations: 
  • DRV/r plus (TDF or TAF) plus (FTC or 3TC) or 
  • DRV/r plus ABC plus 3TC—only for individuals who are HLA-B*5701 negative and without HBV coinfection 
• In other situations, DRV/r is now recommended as an Alternative rather than a Preferred ARV for use in pregnancy; see Table 7. Situation-Specific Recommendations for Use of Antiretroviral Drugs in Pregnant People and Nonpregnant People Who Are Trying to Conceive.
•  Table 6. What to Start: Initial Antiretroviral Regimens During Pregnancy for People Who Are Antiretroviral-Naive has been revised to reflect updated Panel recommendations for persons who are ARV naive and list the advantages and disadvantages of ARV combinations and regimens. 

Pregnant People Who Have Not Achieved Viral Suppression on Antiretroviral Therapy

• Revisions were made to update bulleted recommendations and text on the definition, evaluation, and management of lack of viral suppression and virologic failure. 
• The Panel does not recommend adding a single ARV drug to a virologically failing regimen. The Adult and Adolescent Antiretroviral Guidelines discuss specific regimen modifications for situations in which viral suppression has not been achieved or where there has been a rebound of viral load (see Virologic Failure) that can be considered in conjunction with Table 7. Situation-Specific Recommendations for Use of Antiretroviral Drugs in Pregnant People and Nonpregnant People Who Are Trying to Conceive. 

Table 7. Situation-Specific Recommendations for Use of Antiretroviral Drugs in Pregnant People and Nonpregnant People Who Are Trying to Conceive 

• Based on new data about pharmacokinetics in pregnancy and updated information in the Antiretroviral Pregnancy Registry, bictegravir (BIC) is now recommended as an Alternative ARV for use in pregnancy and for people who are trying to conceive; it was previously categorized as Insufficient Data to Recommend use in pregnancy. Data are still limited, but no safety concerns have been observed. 
• DRV/r is now recommended as an Alternative rather than a Preferred ARV for use in pregnancy and for people who are trying to conceive. However, in pregnant people with a history of CAB exposure for PrEP, DRV/r is a Preferred ARV for initial ART regimens due to concerns about INSTI resistance mutations. 
• DRV/r, rather than ritonavir-boosted atazanavir (ATV/r), is recommended as an option for initial ART in nonpregnant adults. However, DRV/r requires twice-daily dosing in pregnancy, and dosing frequency affects ARV adherence. For this reason, when a protease inhibitor–based regimen is indicated in pregnancy, some Panel members would use ATV/r rather than DRV/r.
• Panel recommendations for fostemsavir and ibalizumab (IBA) have been revised from Not Recommended to Not Recommended Except in Special Circumstances since they may be needed for some pregnant people with extensive treatment experience.
• Appendix C. Antiretroviral Counseling Guide for Health Care Providers has been updated to incorporate changes in the tables and text sections that address recommendations regarding the use of specific ARV drugs in pregnancy. 

HIV-2 Infection and Pregnancy

• BIC was added to the ARV drugs that are recommended for treating HIV-¬2 infection during pregnancy and for people who are trying to conceive.
  • For patients with multidrug-resistant virus, IBA and lenacapavir (LEN) demonstrate in vitro potency against HIV-2 and may be considered; these drugs are Not Recommended Except in Special Circumstances for use in pregnancy. 

Early (Acute and Recent) HIV Infection 

• Based on changes to Panel recommendations on the use of BIC in pregnancy, BIC plus TAF plus FTC is now recommended as an Alternative ART regimen for pregnant people with early infection and without a history of prior use of CAB-LA as PrEP.

Initial Postnatal Management of the Neonate Exposed to HIV 

• Information about recommended testing for viral coinfections in the infants with perinatal HIV exposure (e.g., congenital cytomegalovirus, hepatitis C virus, HBV) with links to resources about testing and care has been added.

Appendix B: Safety and Toxicity of Individual Antiretroviral Agents in Pregnancy 

• Table 14: Antiretroviral Drug Use in Pregnant People with HIV: Pharmacokinetic and Toxicity Data in Human Pregnancy and Recommendations for Use in Pregnancy and the individual drug sections have been reviewed and updated. A new drug section was added for LEN. Although limited data in animals have not identified reproductive safety concerns, no data in humans are available about the use of LEN in pregnancy.