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Elvitegravir pharmacokinetics during pregnancy and postpartum
Low elvitegravir troughs in third trimester confirm caution in pregnancy
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19th International Workshop on Clinical Pharmacology of Antiviral Therapy
Mark Mascolini
Five of 7 women had subtherapeutic elvitegravir troughs in the third trimester of pregnancy, compared with 1 of 6 woman after delivery, according to results of a multicenter European study [1]. One woman taking elvitegravir had a detectable viral load near delivery, but no infants became infected.
Authorities recommend the integrase inhibitor elvitegravir coformulated with cobicistat, tenofovir, and emtricitabine as one first-line option for nonpregnant people. But because prior research showed much lower elvitegravir exposure during pregnancy than postpartum [2], US perinatal guidelines do not recommend cobicistat-boosted elvitegravir for initial use during pregnancy [3]. European PANNA network investigators conducted this study to collect more data on elvitegravir concentrations during pregnancy.
PANNA researchers selected HIV-infected women taking a once-daily regimen including elvitegravir/cobicistat (150/150 mg) plus 2 nucleos(t)ides during pregnancy. Study participants had steady-state 24-hour drug-level monitoring in the third trimester of pregnancy and after delivery. The investigators defined the minimum effective concentration of elvitegravir as 0.13 mg/L.
The analysis included 7 women, 5 black and 2 white, with a median age of 32 years (range 25 to 40). One woman switched from elvitegravir late in the third trimester because of resistant virus and so did not contribute postpartum samples to the analysis. Median gestational age stood at 39 weeks at delivery (range 36 to 40) and median birth weight at 3140 g (range 2240 to 4480).
Geometric mean elvitegravir 24-hour area under the concentration-time curve (and coefficient of variation) was 11 mg*h/L (37%) in the third trimester and 16 mg*h/L (36%) after delivery to yield a geometric mean ratio of 0.67 (90% confidence interval [CI] 0.47 to 0.96). Geometric mean elvitegravir trough was 0.06 mg/L (113%) in the third trimester and 0.17 mg/L (58%) postpartum to yield a geometric mean ratio of 0.35 (90% CI 0.16 to 0.76). Maximum concentration was also lower in the third trimester at 1.1 mg/L (31%) than postpartum at 1.4 mg/L (33%) (geometric mean ratio 0.79, 90% CI 0.61 to 1.02).
Five of 7 women had a subtherapeutic elvitegravir trough in the third trimester, compared with 1 of 6 women after delivery. One of 7 women had a detectable viral load in the weeks before delivery (6363 copies 6 weeks before delivery). No children were born with HIV infection. In 4 women-infant pairs, median cord-to-maternal blood elvitegravir ratio was 0.87 (range 0.3 to 1.2), a finding showing substantial fetal exposure to elvitegravir around delivery.
The PANNA investigators cautioned that their findings must be confirmed in a larger group, but these preliminary results support earlier results [2] informing the recommendation to avoid starting elvitegravir during pregnancy [3].
References
1. Colbers A, Schalkwijk S, Konopnicki D, Rockstroh J, Burger D. Elvitegravir pharmacokinetics during pregnancy and postpartum. 19th International Workshop on Clinical Pharmacology of Antiviral Therapy. May 22-24, 2018. Baltimore. Abstract 17.
2. Best B, Capparelli E, Stek A, et al. Elvitegravir/cobicistat pharmacokinetics in pregnancy and postpartum. Conference on Retroviruses and Opportunistic Infections (CROI). February 13-16, 2017, Seattle. Abstract 755. www.croiconference.org/sites/default/files/posters-2017/755_Best.pdf
3. US Department of Health and Human Services. Recommendations for the use of antiretroviral drugs in pregnant women with HIV infection and interventions to reduce perinatal HIV transmission in the United States. March 2018. https://aidsinfo.nih.gov/guidelines/html/3/perinatal-guidelines/0
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