Lopinavir/ritonavir in pregnancy: results from a systematic review

Pharmacokinetic studies suggesting that pregnant women experience declines in lopinavir/r levels in the third trimester have led to differing dosing guidelines.

BHIVA do not recommend increasing the standard 400/100 mg twice daily dosing in the third trimester, whereas US DHHS guidelines recommend a dose increase.

Marisol Martinez from Abbvie (the pharmaceutical company formerly know as Abbott) showed findings from a systematic review undertaken by the company to assess maternal and infant clinical and safety outcomes in pregnant women treated with lopinavir/r containing regimens. The investigators searched PubMed, EMBASE, and HIV conferences for studies published through May 31, 2012. Studies were selected if they included HIV positive pregnant women receiving regimens containing this boosted protease inhibitor (regardless of dose) and reported maternal and infant outcomes as a primary objective.

They indentified 13 publications/presentations describing nine studies. The studies included 2675 women treated with lopinavir/r: 1618 were dosed at 400/100 mg twice daily, 70 received >800/200 mg/day with dosing interval not specified and 987 received an unknown lopinavir/r dose.

Overall >80% of women (64 – 97%) achieved viral suppression according to the threshold in the study in which they enrolled (200 – 1000 copies/mL). There was no significant difference in the proportion of women with viral load >1000 copies/mL in the one study that looked at both standard and high doses of lopinavir/r.

There were increases in maternal CD4 counts in four studies that reported this at enrollment and at or near delivery.

Vertical transmission rates ranged from 0 – 2.8%. The rate was respectively 0.6% (1/164) and 0.0% (0/70) in the one trial that compared standard to higher-dose.

Rates of preterm delivery <37 weeks ranged from 8.7 – 22.6%, low birth weight from 11.5 – 20.3%, still births from 0.3 – 3% and infant mortality from 0 – 5.8%.

No maternal deaths were attributed to lopinavir/r. Maternal SAEs including obstetrical and post-partum complications were reported in 4 studies (n=1011) and occurred in 0 – 36.1% of women.

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Of note with this analysis is the large variation in study settings. The analysis does not appear to support routine dose increase of lopinavir/r in the third trimester of pregnancy.

Pasley M et al. Systematic review of the safety and efficacy of Lopinavir/ritonavir-based antiretroviral therapy in pregnant women. 3rd International Workshop on HIV & Women, 14-15 January 2013, Toronto, Canada. Oral abstract O_15.
http://regist2.virology-education.com/2013/3hw/docs/24_Martinez.pdf