Cohorts of HIV-positive pregnant women given ART (specifically, AZT and 3TC) have demonstrated little in the way of maternal or fetal toxicity. However, several antiretroviral agents and combinations should be avoided or used with caution during pregnancy. The use of EFV in pregnant monkeys has been associated with abnormalities in their offspring;¹¹¹ a single case of myelomeningocele has also been reported in a human infant exposed to EFV in utero.^112,113 Generally, pregnant women and women of childbearing age who are not using contraception should not be given EFV. If a woman becomes pregnant while receiving an EFV-containing regimen, NVP or a PI should be substituted. While this particular use has not been studied, efavirenz may possibly be given in the third trimester, as the development of the infant’s neural tube occurs during the first trimester.

NVP has been associated with an increased risk of hepatotoxicity in women with a CD4 count above 250 cells/mm³; thus, a regimen containing AZT, 3TC, and NVP may not always be recommended for pMTCT in women with high CD4 counts.^114–117 However, NVP is the most widely available nonteratogenic third agent in resource-poor settings and in ZL clinics is used in the first-line regimen for ART and pMTCT regardless of maternal CD4. A recent study from Brazil demonstrated minimal toxicity from this approach.¹¹⁸ When NVP-based triple therapy is given to women with a CD4 count above 250 cells/mm³, close monitoring of liver function tests—one week after the initiation of ART and then every two weeks subsequently or if symptoms develop—is strongly recommended. Another reasonable alternative is to initiate AZT at the 28^th week of gestation, with the addition of maternal NVP at labor and after birth for the infant.¹¹⁹

The use of d4T and didanosine (ddI) in combination is associated with increased mitochondrial toxicity during pregnancy and should be avoided.^120–122 In addition, tenofovir (TDF) should not be used during pregnancy, due to concerns about osteopenia in infants and a general lack of safety data. ¹²³