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Lower Tenofovir Levels in Pregnant Women Taking a Boosted PI
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ICAAC 2015, September 17-21, 2015, San Diego
Mark Mascolini
Because of higher tenofovir clearance during pregnancy in women taking tenofovir with a ritonavir-boosted protease inhibitor (PI), tenofovir concentrations may be lower than normal in pregnant women, according to results of a US study [1]. Early gestational age and lower serum creatinine predicted higher tenofovir clearance in this 46-woman analysis.
IMPAACT P1026s researchers who conducted this study noted that tenofovir has become a frequent component of regimens taken by pregnant women to control HIV infection and prevent mother-to-infant transmission. But pregnancy can lead to physiologic changes that affect drug concentrations, such as weight gain, altered gastrointestinal function, and rising glomerular filtration rate. Other antiretrovirals taken by a pregnant woman, such as ritonavir, may alter tenofovir pharmacokinetics (PKs). To explore the impact of pregnancy on tenofovir levels during pregnancy and after delivery, the IMPAACT team conducted this study.
Data came from women in IMPAACT P1026S, an ongoing PK analysis of women taking antiretrovirals. Researchers collected steady-state PK profiles during pregnancy then 2 to 12 weeks postpartum. The investigators used univariate and multivariate analyses to assess the impact of variables that may affect tenofovir apparent clearance (CL/F), including age, gestational age, pregnancy stage, weight gain, serum creatinine and albumin, and concomitant drugs.
The analysis involved 650 plasma concentrations from 46 women, including 7 women in the second trimester, 41 in the third trimester, and 38 postpartum. Women had a median age of 30.9 years at their first visit (range 13.5 to 44.9). About one third of women were Hispanic, one third African American, and one fifth white. Median third trimester weight stood at 80.1 kg and median third-trimester weight gain measured 6.85 kg. Thirty-nine women (85%) were taking a ritonavir-boosted PI, including 24 (52%) taking atazanavir and 12 (26%) taking lopinavir.
Median tenofovir clearance (CL/F) fell significantly from the third trimester to the postpartum period (55.37 to 48.05 L/h, P = 0.046). Tenofovir area under the concentration-time curve rose significantly from the third trimester to the postpartum period (2.45 to 2.82 ug x h/mL, P = 0.046). Median serum creatinine fell significantly from the third trimester to the postpartum period (0.55 to 0.70 mg/dL, P < 0.001), while median serum albumin rose significantly (3.2 to 3.9 g/dL, P < 0.001).
In the final statistical model, two factors were independently associated with higher tenofovir clearance (CL/F) after accounting for weight gain and other variables--early gestational age (change in objective function 12.74) and lower serum creatinine (change in objective function 45.77).
The IMPAACT team concluded that "pregnancy can lead to lower tenofovir exposure in [women] receiving ritonavir-boosted protease inhibitors."
Reference
1. Shoji K, Best BM, Mirochnick M, et al. Population pharmacokinetic assessment of factors associated with tenofovir clearance in pregnant and postpartum women with HIV infection in IMPAACT P1026s. ICAAC 2015, September 17-21, 2015, San Diego.
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