Antiretroviral Therapy (ART) in Pregnant Women With HIV Infection Overview of HIV Antiretroviral Therapy (ART) in Pregnancy

Updated: Jul 31, 2017
  • Author: Madhu Chhanda Choudhary, MD; Chief Editor: John Bartlett, MD  more...
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Overview of HIV Antiretroviral Therapy (ART) in Pregnancy

Overview of HIV Antiretroviral Therapy (ART) in Pregnancy

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, 3]

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Clinical Data on HIV Antiretroviral Therapy (ART) in Pregnancy

The Pediatric AIDS Clinical Trials Group 076 (PACTG 076) clinical trial showed that the administration of zidovudine (AZT, ZDV) to a pregnant woman and her infant could reduce the risk of perinatal transmission by nearly 70%. [4] Subsequent trials and observational studies have shown combination antiretroviral prophylaxis administered to the mother 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. [5, 6]

These clinical trials have provided the following guiding principles:

  • The probability of HIV transmission is directly correlated with the viral load, especially the viral load at the time of delivery.
  • Regardless of HIV viral load and CD4 count, all HIV-infected pregnant women should be offered antiretroviral therapy (ART) to reduce perinatal transmission.
  • Elective cesarean delivery reduces the risk of perinatal transmission and should be offered at week 38 if the viral load is likely to exceed 1000 copies/mL at delivery; there is no benefit if the viral load is less than 1000 copies/mL or when the procedure is done after rupture of membranes.
  • Combination ART is more effective than a single-drug regimen in reducing perinatal transmission.
  • Longer duration of antepartum antiretroviral prophylaxis is more effective than shorter duration.
  • Antiretroviral drugs reduce perinatal transmission by several methods, accounting for the recommendation for a combination antepartum, intrapartum, and infant ART.
  • In women who are already receiving ART, the regimen needs to be reviewed for its adequacy in controlling HIV, its teratogenic potential, its pharmacologic effects, and patient tolerance during pregnancy.
  • In the absence of antepartum ART, intrapartum antiretroviral drugs should be administered in combination with infant antiretroviral prophylaxis to reduce the risk of perinatal transmission.
  • Four weeks of zidovudine prophylaxis should be given to infants born to mothers with suppressed viremia during pregnancy. Six weeks of combination ART should be administered to infants born to mothers who did not receive antepartum care or did not have a sustained viral response during pregnancy.
  • Breastfeeding is not recommended in women with HIV infection in the United States. [1]
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Factors for HIV Antiretroviral Therapy (ART) Selection in Pregnancy

Antiretroviral therapy (ART) should be selected based on specific factors, including the following:

  • Comorbidities, especially hepatitis B coinfection
  • Patient adherence and convenience of therapy
  • Potential for adverse drug effects on the mother and drug interactions
  • Results of genotypic resistance testing
  • Safety and pharmacokinetic data in pregnancy
  • Potential teratogenic effects on the fetus and other adverse effects on the fetus or newborn: This refers primarily to efavirenz [EFV], which has potential teratogenicity in the first 8 weeks of pregnancy. 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 women who become pregnant while receiving an efavirenz-containing regimen for viral suppression. [7]
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Recommendations for HIV Antiretroviral Therapy (ART) in Pregnant Treatment-Naive Patients

HIV antiretroviral drug resistance testing should be performed prior to initiating antiretroviral therapy (ART) and should be performed if the woman is receiving ART with virologic failure (viral load >500-1000 copies/mL).

If a woman 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 a low-dose ritonavir-boosted protease inhibitor (PI) or an integrase Inhibitor.

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Preferred Regimens for HIV Antiretroviral Therapy (ART) in Pregnancy

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 mother, fetus, or newborn are present. [1]

Two-NRTI backbone

Regimens include the following:

  • Tenofovir disoproxil fumarate with emtricitabine (TDF/FTC co-formulated) or tenofovir disoproxil fumarate with lamivudine (3TC) once daily (use with caution in renal insufficiency) or
  • Abacavir with lamivudine (ABC/3TC) once daily (only if HLA-B5701–negative); avoid combination with ritonavir-boosted atazanavir if the pretreatment HIV viral load exceeds 100,000 copies/mL. [3]

Protease inhibitor ̶ based regimens

Regimens include the following:

  • Atazanavir (ATV) is recommended to be combined with low-dose ritonavir (RTV): ATV 300 mg plus  RTV 100 mg PO daily as a single daily dose; some experts increase ATV/RTV dose to 400/100 mg daily during second and third trimester; manufacturer recommends dose increase in pregnancy if combined with tenofovir or H2 blocker in treatment-experienced patients and with efavirenz in treatment-naive patients [8] or
  • Darunavir (DRV) 600 mg combined with 100 mg RTV twice daily [9] : Once-daily dosing achieves low trough in pregnancy and should not be used, especially in treatment-experienced patients.

Integrase inhibitor regimen

Raltegravir (RAL) 400 mg twice daily [10] : No data on use of once-daily raltegravir 600-mg HD formulation in pregnancy; rapid reduction in viral load potentially useful if present late in pregnancy; hepatic enzyme elevation has occurred when used in late pregnancy

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Alternative Regimens for HIV Antiretroviral Therapy (ART) in Pregnancy

Alternative regimens are designated as alternatives for initial therapy in pregnant women when clinical trial data in adults show efficacy but one or more of the following conditions apply: [1]

  • Limited experience in pregnancy
  • Lack of data on teratogenic effects on the fetus
  • Dosing, formulation, administration, or interaction issues for that drug or regimen

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 inhibitor ̶ based  regimen

Lopinavir (LPV) 400 mg plus  ritonavir (RTV) 100 mg PO BID if no lopinavir-associated mutations: Insufficient data for any dosage recommendations in the presence of any lopinavir-associated resistance substitution; [11] some authors 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 inhibitors ̶ based regimen

Regimens include the following:

  • Efavirenz (EFV) 600 mg PO daily: Although there are concerns of potential neural tube defects in women of childbearing age before pregnancy is detected, increasing data in pregnancy are reassuring [7] or
  • Rilpivirine (RPV) 25 mg PO daily if pretreatment HIV viral load is less than 100,000 copies/mL and CD4 exceeds 200 cells/µL: Limited pregnancy data with highly variable pharmacokinetics.
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Recommendations for Pregnant HIV-Infected Women Receiving Antiretroviral Therapy (ART)

In general, women 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. [12]

If the regimen contains stavudine, didanosine, or full-dose ritonavir, a regimen change should be considered.

No data are available on the use of cobicistat or tenofovir alafenamide in pregnancy.

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Intrapartum Care

Intrapartum AZT should be administered to pregnant HIV-infected women if the HIV viral load is 1000 or more copies/mL or unknown at time of delivery, irrespective of mode of delivery. [13]

AZT 2 mg/kg IV is administered over 1 hour, then 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.

IV AZT is not required if the patient is receiving combination therapy and the HIV viral load is consistently less than 1000 copies/mL near time of delivery and adherence is reliable.

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