Antiretroviral Therapy for Pregnant HIV-Infected Patients 

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]}

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.

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
• All HIV-infected women should be offered ART to reduce perinatal transmission and for their own health
• Elective cesarean section 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 < 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 for women with HIV infection in the United States^[1]

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^[1] (this refers primarily to efavirenz [EFV], which is teratogenic in the first trimester)

• 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)
• Pregnant women with HIV infection who meet standard criteria for initiation of ART should receive combination ART
• If a woman requires immediate initiation of therapy for her own health, initiate treatment as soon as possible, including in the first trimester
• Zidovudine (AZT, ZDV) should be used when feasible; selection of additional ART agents depends on the results of resistance tests and potency, as well as on issues idiosyncratic to pregnancy, such as pharmacokinetics and teratogenicity
• Avoid efavirenz (EFV) in the first trimester and nevirapine (NVP) in women with a CD4 count of >250 cells/mm³
• Preferred regimen includes lopinavir (LPV) 400mg plus  ritonavir (RTV) 100mg PO BID plus lamivudine (3TC) 150mg/AZT 300mg PO BID

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]

Nucleoside reverse transcriptase inhibitor (NRTI) ̶ based regimens

• Zidovudine (AZT, ZDV) is the preferred NRTI for use in combination ART in pregnant women
• Preferred treatment regimen includes lamivudine (3TC) 150mg/AZT 300mg PO BID
• Intrapartum: AZT 2mg/kg IV over 1h, then continuous infusion of 1mg/kg/h from onset of labor to delivery
• Avoid efavirenz (EFV) during the first trimester, and avoid nevirapine (NVP) with a baseline CD4 count of >250 cells/mm³

Non-nucleoside reverse transcriptase inhibitors (NNRTI) ̶ based regimens

• Initial NVP dose is 200mg (immediate-release formulation) PO daily for the first 14d
• Maintenance NVP dose is 200mg PO BID or (extended release) 400 mg PO daily; patients with mild to moderate rash during 14d lead-in period with immediate-release NVP should not have their NVP dose increased until the rash resolves
• NVP should be initiated in patients with CD4 counts of >250 cells/mm³ because of increased risk of hepatotoxicity in women with high CD4 counts

Protease inhibitor ̶ based regimens

• Lopinavir (LPV) 400mg plus ritonavir (RTV) 100mg PO BID
• Some experts administer LPV/RTV standard dosing (2 tablets BID) throughout pregnancy and monitor virologic response and LPV drug levels, if available
• Other experts may increase LPV/RTV dose (based on capsule formulation) during the third trimester (from 2 to 3 tablets BID), returning to standard dosing post partum
• Once-daily LPV/RTV dosing is not recommended during pregnancy, because there are no data to address whether drug levels are adequate with such administration^[1]

Alternative regimens are designated as alternatives for initial therapy in pregnant women when clinical trial data in adults show efficacy but 1 or more of the following conditions apply: there is limited experience in pregnancy, there is a lack of data on teratogenic effects on the fetus, and/or there are dosing, formulation, administration, or interaction issues for that drug or regimen.^[1]

Nucleoside reverse transcriptase inhibitor (NRTI) ̶ based regimens

• Abacavir (ABC) 600mg/lamivudine (3TC) 300mg PO daily or
• ABC 300mg/3TC 150mg/zidovudine (AZT, ZDV) 300mg PO BID or
• Didanosine (ddl; delayed-release capsule): ≥60kg, give 400mg PO daily; 25kg to < 60kg, give 250mg PO daily; 20kg to < 25kg, give 200mg PO daily or
• ddl (powder for oral solution): ≥60kg, give 200mg PO BID or 400mg PO daily; < 60kg, give 125mg PO BID or 250mg PO daily or
• Stavudine (d4T): ≥60kg, give 40mg PO q12h; < 60kg, give 30mg PO q12h or
• Emtricitabine (FTC): (capsules) 200mg PO daily; (oral solution) 240mg (24mL) PO daily

Protease inhibitor ̶ based regimens

• Atazanavir (ATV) is recommended to be combined with low-dose ritonavir (RTV) boosting (ATV/RTV): ATV 300mg plus  RTV 100mg PO daily as a single daily dose or
• Indinavir (IDV) is recommended to be combined with low-dose RTV boosting (IDV/RTV): IDV 400 mg PO plus  RTV 100mg PO BID or
• Nelfinavir (NFV) 1250mg PO BID or
• Saquinavir (SQV) is recommended to be combined with low-dose RTV boosting (SQV/RTV): 1000mg PO BID plus RTV 100mg PO BID