Antiretroviral therapy (ART) during pregnancy should focus on the reduction of perinatal transmission and the treatment of maternal human immunodeficiency virus (HIV) disease.[1] ART can reduce perinatal transmission by several mechanisms, including lowering maternal antepartum viral load and preexposure and postexposure prophylaxis of the infant. Therefore, for prevention of perinatal transmission of HIV, combined antepartum, intrapartum, and infant antiretroviral prophylaxis is recommended.[1] Combination drug regimens are considered the standard of care for treatment of HIV infection and for prevention of perinatal HIV transmission.[2]
The Pediatric AIDS Clinical Trials Group 076 (PACTG 076) clinical trial showed that the administration of zidovudine (AZT, ZDV) to a pregnant person and their infant could reduce the risk for perinatal transmission by nearly 70%.[3] Subsequent trials and observational studies have shown combination antiretroviral prophylaxis administered to the pregnant individual antenatally is associated with reduced perinatal transmission rates of less than 2%.[1, 2] Additional trials have also identified simple regimens that are effective in reducing perinatal transmission in resource-limited countries. From these study results, we can better understand the use of antiretroviral drugs in resource-limited and resource-rich countries.[4, 5]
These clinical trials have provided the following guiding principles:
Antiretroviral therapy (ART) should be selected based on specific factors, including the following:
HIV antiretroviral drug resistance testing should be performed prior to initiating antiretroviral therapy (ART) and should be performed if the pregnant person is receiving ART with virologic failure (defined as an HIV viral load >200 copies/mL but may be unsuccessful with an HIV viral load from 200-1000 copies/mL).
If an individual with HIV infection presents late in pregnancy, ART should be initiated immediately, before availability of resistance testing.
Initiate treatment as soon as possible, including in the first trimester.
The preferred initial regimen in pregnancy is a backbone of dual nucleoside analogue reverse transcriptase inhibitors (NRTI) with either ritonavir-boosted protease inhibitor (PI) or an integrase Inhibitor.
Three-drug ART has reduced maternal-fetal HIV transmission rate to less than 2%. However, the safest and most efficacious combination is not yet clear.[6]
Preferred regimens have demonstrated optimal efficacy and durability with acceptable toxicity and ease of use. No evidence of teratogenic effects on the fetus or established association with teratogenic or clinically significant adverse outcomes for the pregnant person, fetus, or newborn are present.[1]
Two-NRTI backbone
Regimens include the following:
Protease inhibitor-based regimens
Regimens include the following:
Integrase inhibitor regimen
Alternative regimens are designated as alternatives for initial therapy in pregnant people when clinical trial data in adults show efficacy but one or more of the following conditions apply:[1]
NRTI backbone
Zidovudine with lamivudine (300 mg ZDV/150 mg 3TC) twice a day: Combination with most experience in pregnancy; can cause hematological toxicity
Protease inhibitor̶based regimen
Lopinavir (LPV) 400 mg plus ritonavir (RTV) 100 mg PO twice a day if no lopinavir-associated mutations: Insufficient data for any dosage recommendations in the presence of any lopinavir-associated resistance substitution[15] ; some clinicians increase dose to 600 mg/150 mg twice a day in second and third trimester of pregnancy; once-daily LPV/RTV dosing is not recommended during pregnancy; oral solution should not be used in pregnancy because of its high alcohol content
Non-nucleoside reverse transcriptase inhibitors̶based regimen
Regimens include the following:
In general, people who are receiving ART for HIV infection should continue the same regimen during pregnancy, if it is well tolerated and yields effective HIV virologic suppression.[17] Bictegravir and Doravirine containing regimens have limited information in pregnancy but can be continued with more frequent viral load monitoring if well tolerated and suppressed on the regimen.
The following regimens require changes during pregnancy:
Efavirenz (EFV)
There had been concerns of neural tube defect due to efavirenz exposure during conception and first trimester. However, the risk of neural tube defect associated with efavirenz appears to be similar to that in the general population; therefore, efavirenz should be continued in those who become pregnant while receiving an efavirenz-containing regimen for viral suppression.[16] The TSEPAMO study in Botswana redemonstrated the safety of efavirenz in pregnancy, with the occurrence of only one case of skeletal dysplasia in an efavirenz-exposed infant among 395 individuals with first-trimester exposure to efavirenz-based ART.[11]
However, the SMARTT observational cohort of HIV exposed and uninfected children found that in utero exposure to an efavirenz-containing regimen was associated with an increased risk for microcephaly. This association was more pronounced when efavirenz was combined with zidovudine as opposed to tenofovir-containing regimen.[20] In another analysis of HIV-exposed but uninfected children exposed to specific antiretrovirals in utero, a higher risk of neurological disease with efavirenz exposure was redemonstrated.[21] Efavirenz remains a recommended alternate regimen for treatment initiation during pregnancy with shared decision making with patient and should be continued during pregnancy if the patient is already on it and virally suppressed.
Dolutegravir (DTG)
Dolutegravir (DTG) appears to be safe if started in pregnancy; however, there were concerns of preconception safety signal. The TSEPAMO study in Botswana reported neural tube defects in 4 of 426 (0.9%) babies born to people who were taking dolutegravir at the time they became pregnant, compared with a 0.1% occurrence in babies born to those who were not taking dolutegravir.[22] In an updated analysis of the TSEPAMO study, among the 1,683 deliveries in which the pregnant person was taking dolutegravir-based ART at conception, five neural-tube defects were found (0.30% of deliveries; 95% CI, 0.13 to 0.69), compared with 15 defects among 14,792 deliveries (0.10%; 95% CI, 0.06 to 0.17) in those receiving non-dolutegravir ART at conception.[23] Zero neural tube defects were reported in 2,812 infants (95% CI: 0 to 0.13) born to those who started DTG during pregnancy.[11] In an updated analysis, the risk for infant neural tube defect was not significantly elevated when compared with non DTG based regimen exposure around the time of conception[28] ; therefore, a dolutegravir-based regimen is now preferred for ART initiation during pregnancy and in people of childbearing potential.[1]
Intrapartum AZT should be administered to pregnant HIV-infected individuals during labor if the HIV viral load is 1000 or more copies/mL or unknown at time of delivery, irrespective of the mode of delivery.[24] If the HIV viral load is between 50 to 1000 copies/ml at 34-36 weeks of pregnancy or 4-6 weeks before delivery, intrapartum AZT may be considered.
AZT 2 mg/kg IV is administered over 1 hour, then as a continuous infusion of 1 mg/kg/h from onset of labor to delivery.
Oral AZT, if part of the combination regimen, should be stopped while IV AZT is administered.
Overview
What are the goals of antiretroviral therapy (ART) for HIV infection during pregnancy?
What is the efficacy of antiretroviral therapy (ART) for HIV infection during pregnancy?
When is antiretroviral therapy (ART) initiated in pregnant women with HIV infection?
What is the initial antiretroviral therapy (ART) regimen for pregnant women with HIV infection?
What are the preferred antiretroviral therapy (ART) regimens for pregnant women with HIV infection?
What is the two-NRIT antiretroviral therapy (ART) regimen for pregnant women with HIV infection?
What is included in intrapartum antiretroviral therapy (ART) for pregnant women with HIV infection?