Approach

Optimising the management of maternal HIV infection improves maternal health and helps to prevent perinatal and secondary sexual transmission. All pregnant women with HIV should receive antiretroviral therapy (ART) to prevent perinatal transmission. ART reduces perinatal transmission by decreasing maternal viral load in the blood and genital secretions. ART should be initiated as early as possible in the pregnancy, regardless of CD4 count or viral load, and should be administered during the antepartum, intrapartum, and postnatal periods, as well as neonatal prophylaxis for the infant. The goal of ART is to achieve and maintain viral suppression to undetectable levels (i.e., HIV RNA <50 copies/mL).[7] An infectious diseases consultation is strongly recommended early in pregnancy.

Antiretroviral therapy in pregnant women

Women with HIV who are receiving ART and have achieved virological suppression should continue their ART during pregnancy provided that it is safe, effective in suppressing viral replication, and well tolerated. Discontinuation of ART may lead to viral rebound and increased risk of intrauterine HIV transmission. However, certain antiretroviral drugs are not recommended in pregnancy due to a high risk of toxicity, and some of the newer ART regimens lack significant experience in pregnancy and/or may need additional dosing or therapeutic drug level monitoring secondary to decreased plasma concentrations in the second and third trimesters. Switching to drug regimens that are recommended in pregnancy should be considered in these situations; however, this should only be done under specialist guidance to ensure continued viral suppression and tolerability. (See Antepartum antiretroviral therapy section.) Resistance testing is recommended before switching regimens if HIV RNA is above the threshold for standard genotypic drug resistance testing (see Investigations). If the regimen is modified during pregnancy, viral load should be monitored more frequently (e.g., every 1-2 months) until stable viral suppression occurs.[7]

Women who are not currently taking ART should be started on a regimen as soon as HIV is a feasible diagnosis regardless of CD4 count or viral load; earlier viral suppression is associated with a lower risk of perinatal transmission. (See Antepartum antiretroviral therapy section.) Treatment should not be delayed due to concerns about teratogenicity with first-trimester exposure. Resistance testing should be performed to help guide selection of drugs, but initiation of ART should be started empirically and not delayed for results of resistance testing (see Investigations). Regimens can be modified once results of resistance testing are available.[7]

Women who present for pregnancy care during the early first trimester should be counselled on the risks (e.g., potential teratogenic effects, maternal adverse effects, increased risk of preterm delivery) and benefits (e.g., improved maternal health, reduced risk of perinatal transmission) of ART during early pregnancy. Multiple studies indicate no difference in rates of total birth defects for first-trimester exposure compared with later drug exposures and national birth defect registry data. However, data on the risks of birth defects for many newer drugs are limited and evolving.[7] All cases of ART drug exposure during pregnancy should be reported to the Antiretroviral Pregnancy Registry. Antiretroviral Pregnancy Registry Opens in new window There are mixed data regarding the increased risk of preterm delivery and low birth weight/small for gestational age with ART. Given the clear benefits of ART in pregnancy for both the health of the mother and prevention of perinatal transmission, ART should not be withheld due to concerns for potential adverse pregnancy outcomes. However, patients should be counselled regarding the potential risks.[7][79][80][81][82][83][84][85][86]​ See Complications.

If an ART drug regimen must be stopped during pregnancy (e.g., for severe toxicity), all drugs should be stopped simultaneously. A complete, effective ART regimen should be reinitiated as soon as possible. Women should continue taking antepartum ART during labour and delivery as prescribed.[7]

A specialist should be consulted for the management of special populations including pregnant women with hepatitis B or C co-infection, renal or hepatic impairment, perinatally acquired infection, or HIV-2 infection; pregnant women who present to care and who are already on ART (or have been in the past); and non-pregnant women who are trying to conceive. These patient groups are beyond the scope of this topic.

Antepartum antiretroviral therapy

Pregnancy should not preclude the use of drug regimens that would be chosen for non-pregnant people, unless the risks outweigh the benefits or adequate drug levels are not likely to be attained during pregnancy. Shared decision-making following discussion of the potential risks and benefits to the patient and fetus is important when choosing drug regimens, acknowledging the limited data available.[7]

Regimens are complex, and consultation with an infectious diseases specialist is recommended. The US National Institutes of Health guidelines suggest the following principles:[7]

  • In general, the same regimens as recommended for treatment of non-pregnant adults should be used in pregnant women unless there are known adverse effects for women, fetuses, or infants that outweigh benefits

  • Multiple factors must be considered when choosing a regimen for a pregnant woman including comorbidities, convenience, adverse effects, drug interactions, resistance testing results, pharmacokinetics, and experience with use in pregnancy

  • Pharmacokinetic changes in pregnancy may lead to lower plasma levels of drugs and necessitate increased dosages, more frequent dosing, or boosting, especially of protease inhibitors.

For antiretroviral-naive women without resistance, a combination regimen including 2 nucleoside reverse transcriptase inhibitors (NRTIs), known as an NRTI backbone, and either a protease inhibitor (PI) with low-dose ritonavir boosting or an integrase strand transfer inhibitor (INSTI), is preferred. A non-nucleoside reverse transcriptase inhibitor (NNRTI) may be used as an alternative option to a PI or INSTI. Based on the US National Institutes of Health guidelines, recommended preferred and alternative options for ART in pregnant women (and those trying to conceive) include:[7]

NRTIs

  • Preferred options: abacavir/lamivudine; emtricitabine/tenofovir disoproxil; emtricitabine/tenofovir alafenamide; lamivudine/tenofovir disoproxil; lamivudine plus tenofovir alafenamide

  • Alternative option: lamivudine/zidovudine

INSTIs

  • Preferred option: dolutegravir

  • Alternative options: raltegravir, bictegravir

PIs

  • Preferred option: there are no preferred options for use in treatment-naive pregnant women

  • Alternative options: ritonavir-boosted atazanavir; ritonavir-boosted darunavir (may be a preferred option in certain circumstances - for example, people with a history of cabotegravir exposure for pre-exposure prophylaxis [PrEP])

NNRTIs

  • Preferred options: there are no preferred options for use in treatment-naive pregnant women

  • Alternative options: efavirenz; rilpivirine

The preferred initial regimen for treatment-naive pregnant women (and those trying to conceive) is dolutegravir plus a dual NRTI backbone.[7] Other regimens may be recommended in special circumstances and specific situations: a detailed discussion of all recommended ART regimens is beyond the scope of this topic. Local guidelines should be consulted.

In pregnant women with early (acute and recent) HIV infection, the recommended regimen depends on whether the patient has a prior history of long-acting cabotegravir use as PrEP.[7]

  • History of prior use of long-acting cabotegravir as PrEP: ritonavir-boosted darunavir plus tenofovir disoproxil (or tenofovir alafenamide) plus emtricitabine or lamivudine is the preferred regimen, pending results of genotype testing for INSTI resistance mutations

  • Other regimens may be recommended during the postnatal period.

The World Health Organization supports the use of dolutegravir plus tenofovir disoproxil plus emtricitabine or lamivudine as a preferred first-line option for all adults, including pregnant women and women of childbearing age. Lamivudine plus tenofovir disoproxil plus efavirenz (low dose) is an alternative first-line option.[87]

There are no data about the use of two-drug regimens in pregnancy. However, pregnant women who present to care on a two-drug regimen and have successfully maintained viral suppression may continue the regimen with more frequent viral load monitoring (e.g., every 1-2 months) throughout pregnancy.[7]

Preliminary data from a birth outcomes surveillance study in Botswana raised concern of an increased risk of neural tube defects (0.9%) in infants born to women who were receiving dolutegravir at the time of conception. However, updated results from the study have shown that the prevalence of neural tube defects in infants who were exposed to dolutegravir at the time of conception is not significantly different from those on non-dolutegravir-based regimens.[7]​ In one US cohort study, no clear differences in birth outcomes were reported with dolutegravir-based regimens compared with non-dolutegravir-based regimens; however, sample sizes were small.[88]

There are insufficient pharmacokinetic and safety data to recommend newer drugs such as cabotegravir, cabotegravir/rilpivirine, doravirine, enfuvirtide, etravirine, fostemsavir, ibalizumab, lenacapavir, and maraviroc in pregnant women at this time. However, some drugs may be recommended in special circumstances (e.g., extensive treatment experience, resistance). Patients who present to care and who are on long-acting injectable cabotegravir/rilpivirine should be counselled about the extremely limited and insufficient data with this regimen, and either continue the regimen with frequent viral load monitoring or switch to one of the preferred or alternative three-drug regimens, using a shared decision-making process. Cabotegravir and rilpivirine must be stopped 1 year before conception in patients considering switching regimens prior to conception to prevent fetal exposure to these drugs. Cobicistat-based regimens are not generally recommended in pregnant women due to pharmacokinetic changes in the second and third trimesters, which may cause lower drug exposures and subsequent virological failure. However, some women may choose to continue this drug with frequent viral load monitoring and possible dose adjustments, rather than switching to a preferred or alternative regimen.[7]

Scheduled caesarean delivery

A scheduled caesarean delivery at 38 weeks' gestation (compared with 39 weeks for most other indications) is recommended for pregnant women with HIV who have HIV RNA levels >1000 copies/mL or unknown viral load near the time of delivery, in order to reduce the risk of perinatal transmission.[7] In non-virally suppressed patients who present in labour prior to their scheduled caesarean delivery date, an emergency caesarean delivery should be performed. However, there are insufficient data to address the question of how long after the onset of labour or rupture of membranes the benefit of caesarean delivery for prevention of perinatal transmission is lost. Urgent consultation with a perinatal HIV specialist is recommended.

cheduled caesarean delivery is not routinely recommended for women on ART who have HIV RNA levels ≤1000 copies/mL because of the low rate of perinatal transmission in these patients, as well as limited or no known evidence of benefit, and an increased risk of infection, surgical trauma, hospital deaths, and prolonged hospitalisation associated with caesarean delivery.[7][14][89]​​ If scheduled caesarean delivery or induction is indicated in these patients, it should be performed at the standard time for obstetric indications.

Intrapartum antiretroviral therapy

Intravenous zidovudine (started at least 3 hours before scheduled delivery) is recommended in women with HIV RNA >1000 copies/mL or unknown viral load near delivery (within 4 weeks of delivery). It is not recommended in women receiving ART with HIV RNA ≤50 copies/mL during late pregnancy and near delivery, provided there are no concerns about adherence to ART. Intravenous zidovudine may be considered in women with HIV RNA between 50 and ≤1000 copies/mL within 4 weeks of delivery; however, there are inadequate data to determine whether this provides additional protection against perinatal transmission in this group.[7] Women should continue taking ART during labour and before delivery.

Postnatal antiretroviral therapy

All infants who have been perinatally exposed to HIV should receive postnatal ART to reduce the risk of perinatal transmission. ART should be started as close to the time of delivery as possible, preferably within 6 hours.[7]​ The ART regimen depends on whether the infant is at low or high risk of perinatal transmission. Consultation with, and management by, a paediatric infectious disease specialist is recommended.[7]

Infants at low risk of perinatal transmission

  • A 2-week course of zidovudine is recommended, provided the newborn is ≥37 weeks’ gestation and is born to a mother who meets all of the following criteria:[7]

    • Currently receiving ART and has received at least 10 consecutive weeks of treatment during pregnancy

    • Achieved and/or maintained viral suppression for the duration of pregnancy (defined as at least 2 consecutive tests with <50 copies/mL obtained at least 4 weeks apart)

    • Viral load is <50 copies/mL at or after 36 weeks’ gestation

    • Did not have acute HIV infection during pregnancy

    • Has good ART adherence.

  • Infants who do not meet the above criteria, but who have a viral load <50 copies/mL at, or after, 36 weeks’ gestation should receive a 4- to 6-week course of zidovudine. All premature infants <37 weeks’ gestation should receive a 4- to 6-week course of zidovudine.[7]

Infants at high risk of perinatal transmission

  • Presumptive HIV therapy with a 3-drug regimen (i.e., zidovudine plus lamivudine plus nevirapine [treatment dose], or zidovudine plus lamivudine plus raltegravir) administered from birth for 2-6 weeks is recommended in infants born to a mother who:[7]

    • Has not received antepartum ART, or

    • Has received only intrapartum ART, or

    • Has received antepartum ART but did not achieve viral suppression within 4 weeks of delivery, or

    • Had primary or acute HIV infection during pregnancy.

  • If the duration of treatment is shorter than 6 weeks, zidovudine monotherapy should be continued to complete a 6-week treatment course.[7]

  • Infants born to mothers who have primary or acute HIV infection during breastfeeding should be managed as per infants at high risk of perinatal transmission.[7]

In some situations, a two-drug prophylaxis regimen (zidovudine for 6 weeks plus 3 prophylactic doses of nevirapine within 48 hours of birth, 48 hours after first dose, and 96 hours after second dose) may be considered in infants aged ≥32 weeks gestation at birth who weigh ≥1.5 kg. However, this decision depends on the likelihood of HIV transmission and should be made by a specialist.[7]

The selection of ART for newborns with presumed or confirmed HIV infection is beyond the scope of this topic.

Breastfeeding

Several studies in low‐resource settings with exclusive breastfeeding in women with HIV demonstrated next to no perinatal HIV transmission with maternal viral suppression on ART.[37][90][91]​​ However, while suppressive ART significantly reduces the risk of perinatal HIV transmission through breastfeeding, it does not completely eliminate the risk (estimated to be 3/1000).[7]

US guidelines recommend that patients should receive patient-centred, evidence-based counselling to support shared decision-making about infant feeding, including breastfeeding. Replacement feeding is recommended to eliminate the risk of HIV transmission via breastfeeding when people with HIV are not on ART and/or do not have a suppressed viral load during pregnancy (at a minimum throughout the third trimester) and at delivery. However, patients who are on ART with a sustained undetectable viral load should be supported if they choose to breastfeed.[7]

Measures to minimise risk of HIV transmission (e.g., exclusive breastfeeding for the first 6 months, gradual weaning, immediate treatment of maternal mastitis and infant thrush, infant monitoring) are recommended in women who choose to breastfeed.[7]

The American Academy of Pediatrics (AAP) supports a harm reduction approach in people on ART with sustained viral suppression <50 copies/mL, but recommends counselling people against breastfeeding if they are not on ART or are on ART without viral suppression.[92]

Transgender and gender diverse people assigned female sex at birth

It is generally appropriate to extrapolate the recommendations above to all people assigned female sex at birth, including transgender and gender diverse people, with modification when indicated (e.g., drug interactions with gender-affirming hormones). Some patients may experience the onset or worsening of gender dysphoria and associated symptoms (e.g., depression) during prepregnancy, antepartum, and postnatal periods, and should be monitored appropriately.[7]​ This topic currently uses gender-specific terms; however, the topic is intended to be inclusive of all birthing parents, regardless of gender identity.

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