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Review of the Efficacy, Safety, and Pharmacokinetics of Raltegravir in Pregnancy
Maliakkal A et al.
J Acquir Immune Defic Syndr. 2016 Jun 1;72(2):153-61

16th September 2016, by Pr François Raffi

Raltegravir was previously considered an alternative antiretroviral in pregnancy because of limited data, but recent pregnancy guidelines (DHSS) recommend raltegravir as a preferred integrase treatment option. Data from published articles and preliminary meeting reports between 2001 and July 2015 are reviewed, including 3 prospective PK studies, 8 retrospective studies, and 15 case reports. The literature includes a total of 278 maternal–infant pairs who received raltegravir during pregnancy.

Zidovudine infusion at delivery was administered in 83% of the 147 cases in which its use was reported. Delivery was by cesarean section in 79% of the 182 cases in which mode of delivery was reported.

The standard raltegravir dose seems safe and effective in preventing mother-to-child transmission in late pregnancy presenters with unknown or unsuppressed viral load, or in multidrug resistance. Viral decay was rapid allowing most women to deliver at undetectable viral levels.

Multiple physiological changes during pregnancy can account for highly variable but overall reduced maternal plasma RAL levels, but given the inherent PK variability of this drug, these changes do not seem to affect viral suppression, and dose adjustments have not been recommended. RAL is highly transferred across the placenta and has prolonged elimination in the neonate, two properties that support its efficacy in preventing MTCT.

Raltegravir was well tolerated, with the exception of a few cases of reversible transient increases in maternal transaminases. No infant adverse effect was consistently reported, except for 1 study observing 14% of infants being small for gestational age, but the relationship to RAL was unclear. The Antiretroviral Pregnancy Registry (APR) reported 6 defects out of 180 live births and 6 defects out of 173 live births, when RAL was first exposed in the first trimester and second/third trimester, respectively.

Existing data support the use of raltegravir in antiretroviral-naive and experienced pregnant women. If integrase inhibitor-based therapy was initiated later in pregnancy, it may enable more pregnant women to achieve suppressed viral loads at the time of delivery and enable more opportunities for vaginal delivery.

     
     
     
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