First-line ART for pregnant and breastfeeding women and ARV drugs for their infants

Consolidated ARV guidelines, June 2013

Clinical considerations and key research gaps

Clinical considerations

Maintaining the drug supply chain and ensuring uninterrupted delivery of maternal ART and infant ARV drugs during pregnancy and breastfeeding are critical for PMTCT. All antenatal care and maternal and child health sites providing PMTCT services should have the capacity to initiate, support and monitor ongoing maternal ART and infant ARV drugs.

Key research gaps

Surveillance of ARV drug toxicity. Research is needed to continue to evaluate both the short- and long-term effects of EFV, TDF and other ARV drugs on pregnant and breastfeeding women, fetuses and children, including monitoring for birth defects and other adverse pregnancy outcomes and evaluating the renal and bone effects of TDF on both the woman and HIV-exposed infant.

Acceptability of EFV as first-line ART. The level of intolerance to EFV and whether switching to an alternative first-line regimen is necessary needs to be studied further, as do ways to support alternative first-line regimens in programme settings for pregnant and breastfeeding women.

Infant prophylaxis. Better data are needed on the optimal duration of infant prophylaxis when mothers receive ART, especially if the mother starts ART late in pregnancy or during the postpartum period and hence is not virally suppressed at the time of delivery or when breastfeeding begins. NVP formulations that are improved and easier to administer are needed to facilitate drug administration to neonates and infants.

Optimal management of infants identified as HIV exposed during breastfeeding. It is important to determine the extent to which perinatal HIV exposure is missed antenatally and the extent of maternal seroconversion, appropriate strategies for postpartum screening of infants for HIV exposure and optimal testing and prophylaxis strategies.

Stopping NNRTI-based ART (use of a “tail”). Because of the prolonged half-life of EFV (and NVP), suddenly stopping an NNRTI-based regimen risks developing NNRTI resistance. For women who choose to or must stop EFV-based ART because of toxicity or other conditions, more data are needed to determine whether an NRTI “tail” coverage is needed to reduce this risk. Pharmacokinetic modelling reviewed for the guidelines suggests that, if the NRTI backbone included TDF, such a tail may not be needed, but if the NRTI backbone included AZT, a two-week tail is advisable (EFV has a longer half-life than NVP).