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

Consolidated ARV guidelines, June 2013

Rationale and supporting evidence: Alternative regimens for toxicity, intolerance or lack of availability of recommended regimens

AZT is recommended as the alternative NRTI for non-pregnant women who cannot tolerate or receive TDF. Given the extensive safety and efficacy data on AZT in pregnant and breastfeeding women, AZT is also the recommended alternative NRTI for pregnant and breastfeeding women.

For non-pregnant women who cannot tolerate or receive EFV, the recommended alternative NNRTI is NVP. However, because ART (triple ARV drugs) is now recommended for pregnant and breastfeeding women regardless of CD4 cell count, concerns remain regarding the use of NVP in women with higher CD4 counts.

Although the 2010 guidelines (2,82) stated that the benefit of NVP outweighed the risk for women with CD4 counts of 250 to 350 cells/ mm3, data on safety in women with CD4 counts ≥350 cells/mm3 are limited, and the finding of life-threatening hepatic toxicity when NVP was used for occupational post-exposure prophylaxis in individuals without HIV infection raises concerns regarding its use for individuals with higher CD4 count. However, a recent systematic review of the risk of NVP-associated toxicity in pregnant women (134) (Web Annex) suggests that the frequency of adverse events is no higher than that in the general adult population.

Further, data on the association between NVP toxicity and elevated CD4 cell counts are conflicting, and the risk of significant hepatic toxicity in most studies is about 3% (121). Data suggest that switching to NVP for individuals who have been treated and had virological suppression is not associated with elevated toxicity even where the immune system has reconstituted.

Finally, the alternative to substituting NVP for EFV toxicity would be a PI, which is the recommended second-line therapy and is more expensive than NNRTI drugs. On balance, the Guidelines Development Group held that the overall benefit of substituting NVP for pregnant or breastfeeding women in the rare circumstances that EFV is not tolerated outweighs the potential risks.