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

Drugs or drug combinations are designated as Preferred for therapy during pregnancy when clinical trial data in adults have demonstrated efficacy and durability with acceptable toxicity and ease of use, and pregnancy-specific PK data are available to guide dosing. In addition, the available data must suggest a favorable risk-benefit balance for the drug or drug combination compared with other ARV drug options; the assessment of risks and benefits should incorporate maternal, pregnancy, fetal, and infant outcomes. Some Preferred drugs or regimens may have minimal toxicity or teratogenicity risks that are offset by other advantages for people with HIV who are pregnant or who are trying to conceive. Therefore, it is important to read all the information on each drug in the Perinatal Guidelines before administering any of these medications to patients (see Appendix B: Supplement: Safety and Toxicity of Individual Antiretroviral Agents in Pregnancy).

• Once-daily dosing
• Available as an FDC
• Well-tolerated during pregnancy
• Reassuring PK data during pregnancy

• Requires HLA-B*5701 testing before use. ABC should not be used in patients who test positive for HLA-B*5701 because of the risk of developing a hypersensitivity reaction. Requires education about hypersensitivity reactions.
• Not able to be used for Hepatitis B Virus/HIV Coinfection
• ABC/3TC administered with ATV/r or EFV is not recommended if pretreatment HIV RNA is >100,000 copies/mL.
• ABC is not recommended as part of regimens for initial treatment of early (acute or recent) HIV infection since it requires HLA-B*5701 testing before use. When results of HLA-B*5701 testing are not available, use of TDF or TAF rather than ABC will avoid delays in initiating ART.

• Once-daily dosing
• Available as an FDC
• Reassuring PK data and extensive use during pregnancy; no dose adjustment required in pregnancy
• Activity against HBV
• Minimal toxicity compared to ZDV/3TC
• When combined with DTG, the efficacy and toxicity of TAF/FTC and TDF/FTC for treatment of pregnant patients are similar, but TAF/FTC is associated with fewer adverse birth outcomes and less risk of insufficient weight gain in pregnancy.

• When combined with DTG, TAF/FTC is associated with more treatment-emergent obesity in nonpregnant adult women compared to TDF/FTC. (Notably, the impact on weight gain in pregnancy may be beneficial, as noted in the Advantages column.)

• Once-daily dosing
• Available as an FDC
• Reassuring PK data during pregnancy; no dose adjustment required in pregnancy
• Activity against HBV
• When combined with DTG, the efficacy and toxicity of TAF/FTC and TDF/FTC for treatment of pregnant patients are similar.

• Potential concerns about fetal bone and early-life growth abnormalities with TDF, although clinical findings are reassuring to date
• TDF has potential renal toxicity; thus, TDF-based, dual-NRTI combinations should be used with caution in patients with renal insufficiency.

• Once-daily dosing
• DTG/ABC/3TC is available as an FDC.
• Sufficient data about PK, efficacy, and safety of DTG in pregnancy
• High rates of viral suppression
• Dose adjustments during pregnancy are not needed.
• May be particularly useful when drug interactions or the potential for preterm delivery with a PI-based regimen are a concern.
• DTG has been shown to rapidly decrease viral load in ARV-naive pregnant women who present to care later in pregnancy. In nonpregnant adults, DTG is associated with lower rates of INSTI resistance than RAL, and DTG allows for once-daily dosing; for these reasons, DTG is particularly useful for pregnant people presenting late in pregnancy.
• DTG with a NRTI backbone of TAF or TDF with 3TC or FTC is the Preferred regimen for initial treatment in people with early (acute or recent) HIV infection in people without a history of CAB exposure for PrEP, see Early (Acute or Recent) HIV Infection.

• Potential concerns about excess weight gain with DTG
• DTC/ABC/3TC requires HLA-B*5701 testing before use (see ABC/3TC above).
• Specific timing and/or fasting recommendations apply if DTG is taken with calcium or iron (e.g., in prenatal vitamins; see Table 14. Antiretroviral Drug Use in Pregnant People With HIV: Pharmacokinetic and Toxicity Data in Human Pregnancy and Recommendations for Use in Pregnancy).
• DTG is not Preferred for initial treatment in people with early (acute or recent) HIV infection and a history of CAB exposure for PrEP due to concerns about INSTI resistance mutations; DRV/r is Preferred in this situation.

• When a PI-based regimen is indicated, ATV or DRV is recommended over LPV/r.
• DRV/r with a NRTI backbone of TAF or TDF with 3TC or FTC is the Preferred regimen for initial treatment in people with early (acute or recent) HIV infection and a history of CAB exposure for PrEP, see Early (Acute or Recent) HIV Infection.

• Not available as an FDC
• Requires twice-daily dosing during pregnancy
• Requires administration with food
• PIs may increase the risk of preterm birth.

Drugs or drug combinations are designated as Alternative options for therapy during pregnancy when clinical trial data in adults show efficacy and the data in pregnant individuals are generally favorable, but limited. Most Alternative drugs or regimens are associated with more PK, dosing, tolerability, formulation, administration, or interaction concerns than those in the Preferred category, but they are acceptable for use in pregnancy. Some Alternative drugs or regimens may have known toxicity or teratogenicity risks that are offset by other advantages for people with HIV who are pregnant or who are trying to conceive. Therefore, it is important to read all the information on each drug in the Perinatal Guidelines before administering any of these medications to patients (see Appendix B: Supplement: Safety and Toxicity of Individual Antiretroviral Agents in Pregnancy).

• Reassuring safety data
• Like DTG, RAL may be particularly useful when drug interactions or the potential for preterm delivery with PI-based regimens are a concern.
• PK data are available for RAL in pregnancy when using the twice-daily formulation (400 mg twice daily).
• Like DTG, RAL has been shown to rapidly decrease viral load in ARV-naive pregnant women who present to care later in pregnancy. In nonpregnant adults, DTG is associated with lower rates of INSTI resistance than RAL, and DTG permits once-daily dosing; for these reasons DTG is Preferred and RAL is Alternative for use during pregnancy.

• Twice-daily dosing in pregnancy is recommended due to low drug level with once-daily dosing during pregnancy.
• Not available as an FDC
• Lower barrier to resistance than DTG; for this reason, RAL is Alternative for use during pregnancy
• PK data are not available for the once-daily 1,200 mg (2 × 600 mg) extended-release formulation (raltegravir HD) in pregnancy.
• Specific timing and/or fasting recommendations apply if RAL is taken with calcium or iron (e.g., in prenatal vitamins; see Table 14. Antiretroviral Drug Use in Pregnant People With HIV: Pharmacokinetic and Toxicity Data in Human Pregnancy and Recommendations for Use in Pregnancy).

• Once-daily dosing
• Extensive experience during pregnancy

• Not available as an FDC
• Associated with increased maternal indirect bilirubin levels, which theoretically may increase the risk of neonatal hyperbilirubinemia. No clinically significant neonatal hyperbilirubinemia or kernicterus reported, but neonatal bilirubin monitoring is recommended.
• Requires increased dosing in the second or third trimester
• Has been associated with small but significant reductions in language and social-emotional scores and late language
• PIs may increase the risk of preterm birth.
• Do not use with PPIs.
• Requires consideration of timing when dosed with H2 blockers, which are commonly used during pregnancy (see Table 14).

• Available as an FDC
• Significant experience during pregnancy

• Requires twice-daily dosing
• Associated with higher rates of side effects, including nausea, headache, and reversible maternal and neonatal anemia and neutropenia
• Other regimens have demonstrated similar or greater efficacy and fewer side effects.

• Once-daily dosing
• Available as an FDC
• Extensive experience in pregnancy
• Not associated with increased risk of NTDs or other congenital anomalies in human studies (although cautionary text based on animal studies remains in the package insert (see Efavirenz and Table 14).
• No dose changes are required during pregnancy.
• Useful for patients who require treatment with drugs that have significant interactions with Preferred agents or who need the convenience of a coformulated, single-tablet, once-daily regimen and are not eligible for DTG

• Overall higher rates of adverse events than some Preferred drugs
• Requires enhanced surveillance for depression and suicidality
• Increased risk of adverse birth outcomes has been observed with EFV/TDF/FTC versus DTG/TAF/FTC started during pregnancy.
• Increased risk of toxicity, including dizziness, fatigue, hepatotoxicity, vivid dreams/nightmares

• Once-daily dosing
• Available as an FDC
• Useful for patients who require treatment with drugs that have significant interactions with Preferred agents or who need the convenience of a coformulated, single-tablet, once-daily regimen and are not eligible for DTG

• Limited use for individuals with high pretreatment HIV RNA. RPV is not recommended in patients with pretreatment HIV RNA >100,000 copies/mL or CD4 counts <200 cells/mm³.
• Requires close viral monitoring in second and third trimesters because PK data suggest lower drug levels. Insufficient data to suggest dosing changes
• Do not use with PPIs.
• Requires consideration of timing when dosed with H2 blockers or PPIs, which are commonly used during pregnancy (see Table 14)
• Requires administration with food

These drugs and drug combinations are approved for use in adults, but pregnancy-specific PK or safety data are too limited to make recommendations for use in pregnant people. When a pregnant person presents to care while virally suppressed on one of these drugs or drug combinations, providers should consider whether to continue their current regimen or switch to a recommended ARV regimen (see People With HIV Who Are Taking Antiretroviral Therapy When They Become Pregnant and Table 7. Situation-Specific Recommendations for Use of Antiretroviral Drugs in Pregnant People and Nonpregnant People Who Are Trying to Conceive). It is critical that providers report exposures to these medications in pregnancy to the Antiretroviral Pregnancy Registry.

• Coformulated as single, once‑daily pill
• High barrier to resistance
• No food requirement

• Limited PK, toxicity, and efficacy data in pregnancy
• May be associated with weight gain
• Specific timing and/or fasting recommendations apply if BIC is taken with calcium or iron (e.g., in prenatal vitamins; see Table 14).

• Coformulated with TDF/FTC
• No food requirement

• Limited PK, toxicity, and efficacy data in pregnancy
• Initial studies suggest potentially lower drug levels in third trimester.

Drugs and drug combinations listed in this category are Not Recommended for use in pregnancy because of inferior virologic efficacy or potentially serious maternal or fetal safety concerns or because they are not recommended for initial therapy in non-pregnant adults. This category includes drugs or drug combinations for which PK data demonstrate low drug levels and risk of viral rebound during pregnancy. Levels of these drugs are often low in late pregnancy (during the second and third trimesters), when risk for perinatal transmission is high if maternal viremia occurs. (see Table 7 and Table 14).

Note: When a pregnant person presents to care while virally suppressed on one of these drugs or drug combinations, providers should consider whether to continue their current regimen with more frequent viral load monitoring or switch to a Preferred ARV regimen (see People With HIV Who Are Taking Antiretroviral Therapy When They Become Pregnant and Table 7).

• Limited existing data suggest insufficient levels of both COBI and ATV in second and third trimesters.
• Changing COBI component to RTV is likely to improve efficacy but will increase pill burden.

• Injectable delivery may be more effective and/or more convenient than oral ART for some patients.
• Approved for nonpregnant adults who have RNA levels <50 copies/mL for at least 3 months on a stable oral ARV regimen, with no history of treatment failure and no known or suspected resistance

• Limited PK, toxicity, and efficacy data during pregnancy
• Not recommended as initial treatment for ARV-naive adults or adolescents (pregnant or nonpregnant)
• Due to the long half-life of injectable CAB and RPV, drug levels may persist up to 12 months after the last dose. Optimal timing of switch to an oral regimen is not known (see Management of the Treatment-Experienced Patient in the Adult and Adolescent Antiretroviral Guidelines).

• Coformulated as single-tablet, once-daily regimen

• Limited existing data suggest insufficient levels of both COBI and ATV in second and third trimesters; viral breakthroughs have been reported.
• Changing COBI component to RTV is likely to improve efficacy but will increase pill burden; in addition to adding RTV as separate pill, both DRV and RTV should be dosed BID.

• Coformulated as single-tablet, once-daily regimen

• Limited existing data suggest insufficient levels of both COBI and EVG in second and third trimesters.
• Viral breakthrough at delivery was identified in 26% of individuals in IMPAACT P1026. Data are insufficient to suggest dosing changes.
• Unlike for DRV/c and ATV/c, there is no option to replace COBI with RTV boosting.
• Specific timing and/or fasting recommendations apply, especially if taken with calcium or iron (e.g., in prenatal vitamins; see Table 14).

• Not recommended in nonpregnant individuals who are ART-naive
• Limited PK, toxicity, and efficacy data during pregnancy

• No data in pregnancy
• Requires IV administration

These drugs are Not Recommended for use in pregnant people who have never received ART. Except for NVP and LPV/r, data on the PKs, safety, and efficacy of these drugs during pregnancy are limited.

Some of these drugs also are categorized as Not Recommended, except in special circumstances, during pregnancy because the Panel recognizes that circumstances may exist in which patients who are ART-experienced may need to initiate or continue these drugs during pregnancy to reach or maintain viral suppression (see Table 7).

• Standard adult dose is appropriate during pregnancy in the special circumstance where ETR is used.

• Not recommended in nonpregnant individuals who are ART-naive
• Limited PK, toxicity, and efficacy data during pregnancy

• Extensive experience during pregnancy

• Requires twice-daily dosing in pregnancy; data suggest that once-daily LPV/r will not achieve sufficient plasma concentrations.
• Some experts recommend increased dosing in the second and third trimesters (see Table 14 and Lopinavir/Ritonavir).
• Associated with nausea and diarrhea
• Associated with increased risk of preterm birth and small-for-gestational-age neonatal status (see Antiretroviral Drug Regimens and Maternal and Neonatal Outcomes)

• Limited data suggest standard adult dose is appropriate during pregnancy.

• Not recommended in nonpregnant individuals who are ART-naive
• Limited PK, toxicity, and efficacy data during pregnancy
• Requires tropism testing before use

• Standard adult dosing is appropriate in pregnancy in the special circumstance where NVP is used.

• Greater potential for adverse effects
• Low barrier to resistance
• Requires complex lead-in dosing
• NVP should be used with caution when initiating ART in women with CD4 counts >250 cells/mm³.
• Use NVP and ABC together with caution; both can cause hypersensitivity reactions in the first few weeks after initiation.

• Limited PK, toxicity, and efficacy data during pregnancy