Antiretroviral Therapy for Pregnant HIV-Infected Patients

Updated: Apr 23, 2015
  • Author: Madhu Chhanda Choudhary, MD; Chief Editor: John Bartlett, MD  more...
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Overview

Overview

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

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%. [2, 3, 1] 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 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 antiretroviral treatment, 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
  • In the United States, addition of single-dose intrapartum/newborn nevirapine (NVP) to the standard antepartum combination antiretroviral regimens used for prophylaxis or treatment in pregnant women is not recommended, because it does not provide additional efficacy in reducing transmission and may be associated with NVP resistance
  • Breastfeeding is not recommended in women with HIV infection in the United States [1]
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Factors in Antiretroviral Therapy Selection

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

  • Comorbidities
  • Patient adherence and convenience of therapy
  • Potential for adverse drug effects on the mother and drug interactions
  • Results of genotypic resistance testing
  • Pharmacokinetic changes in pregnancy
  • Potential teratogenic effects on the fetus and other adverse effects on the fetus or newborn (this refers primarily to efavirenz [EFV], which is potentially teratogenic in the first 8 weeks of pregnancy [1] )
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Recommendations for Treatment-Naive Patients

HIV antiretroviral drug resistance testing should be performed prior to initiating antiretroviral prophylaxis or therapy 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.

If a woman requires immediate initiation of therapy for her own health, initiate treatment as soon as possible, including in the first trimester; delay until second trimester may be considered based on maternal CD4, GI tolerability, and potential fetal risk of first trimester exposure.

A backbone of dual nucleoside analogue reverse transcriptase inhibitors (NRTI) with either a non-nucleoside reverse transcriptase inhibitor (NNRTI) or low-dose ritonavir-boosted protease inhibitor (PI) is the preferred initial regimen in pregnancy.

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Preferred Treatment Regimens

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–non-nucleoside reverse transcriptase inhibitor backbone

Regimens include the following:

  • Zidovudine with lamivudine (300 mg ZDV/150 mg 3TC) PO BID (combination with most experience in pregnancy; can cause hematological toxicity) or
  • Tenofovir with emtricitabine (TDF/FTC) or lamivudine (3TC) once daily (use with caution in renal insufficiency) or
  • Abacavir with lamivudine (ABC/3TC) once daily (only if HLA-B5701–negative)

Non-nucleoside reverse transcriptase inhibitors ̶ based regimen

After the first 8 weeks of pregnancy, efavirenz (EFV) alone is used. 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]

Protease inhibitor ̶ based regimens

Regimens include the following:

  • Lopinavir (LPV) 400 mg plus  ritonavir (RTV) 100 mg PO BID if no lopinavir-associated resistance substitutions (pharmacokinetic study demonstrated 40% decrease in C12h during second and third trimester but not considered significant [8] ); insufficient data for any dosage recommendations in the presence of any lopinavir-associated resistance substitution; once-daily LPV/RTV dosing is not recommended during pregnancy; oral solution should be avoided in pregnancy due to high alcohol content; or
  • Atazanavir (ATV) is recommended to be combined with low-dose ritonavir (RTV) boosting (ATV/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
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Alternative Treatment Regimens

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

Protease inhibitor ̶ based regimens

These include the following:

  • Darunavir (DRV) 800 mg combined with 100 mg RTV daily or
  • Saquinavir (SQV) is recommended to be combined with low-dose RTV boosting (SQV/RTV): 1000 mg PO BID plus  RTV 100 mg PO BID after baseline ECG for potential PR and QT prolongation [9]

Non-nucleoside reverse transcriptase inhibitors ̶ based regimen

Nevirapine (NVP): The initial NVP dose is 200 mg (immediate-release formulation) PO daily for the first 14 days. The maintenance NVP dose is 200 mg PO BID or extended release 400 mg PO daily. Patients with mild to moderate rash during the 14-day lead-in period with immediate-release NVP should not have their NVP dose increased until the rash resolves. NVP should not be initiated in patients with CD4 counts exceeding 250 cells/µL because of increased risk of hepatotoxicity in women with high CD4 counts.

Integrase inhibitors

Raltegravir (RAL) 400 mg BID can be considered in selected circumstances such as GI intolerability to PI or drug-drug interactions.

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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. [10]

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 patients 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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Recommendations for Pregnant HIV-Infected Women Receiving Antiretroviral Therapy

Women who are receiving ART for HIV infection should continue the same regimen during pregnancy in general if it is well tolerated and they have effective HIV virologic suppression.

Efavirenz should be avoided in women of childbearing age. Consideration can be given to continuing efavirenz if pregnancy occurs on an efavirenz-based regimen if it is well tolerated with virologic suppression, as risk of potential neural tube defect has already occurred by the time pregnancy is recognized. In addition, there may be risk of viral escape with regimen change. [11]

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