Early experience of dolutegravir pharmacokinetics in pregnancy: high maternal levels and significant foetal exposure with twice-daily dosing

impact of tenofovir disoproxil fumarate on kidney function: four-year data from the HIV-infected outpatient cohort. Systematic review and meta-analysis: renal safety of tenofovir disoproxil fumarate in HIV-infected patients. renal failure after initiation of tenofovir disoproxil fumarate. et al. Tenofovir-related nephrotoxicity in human immunodefi-ciency virus-infected patients: three cases of renal failure, Fanconi syndrome, and nephrogenic diabetes insipidus. Acute renal failure and Fanconi syndrome in an AIDS patient on tenofovir treatment: case report and review of literature. Fanconi syndrome associated with use of tenofovir in HIV-infected patients: a case report and review of the literature. et al. Proximal tubular dysfunction and kidney injury associated with tenofovir in HIV patients: a case series. Derwarker R, et al. Tenofovir DF plus lamivudine or emtrici-tabine for nonoccupational postexposure prophylaxis (NPEP) in a Boston Community Health Center. et al. Tolerability of HIV postexposure prophy-laxis with tenofovir/emtricitabine and lopinavir/ritonavir tablet formulation. et al. Tenofovir plasma concentrations according to companion drugs: a cross-sectional study of HIV-positive patients with normal renal function. Severe acute renal failure in an HIV-infected patient after only 2 weeks of tenofovir-based antiretroviral therapy. Tenofovir alafenamide versus tenofovir disoproxil fumarate, coformulated with elvitegravir, cobicistat, and emtricitabine, for initial treatment of HIV-1 infection: two randomised, double-blind, phase 3, noninferiority trials. Early experience of dolutegravir pharmacokinetics in pregnancy: high maternal levels and significant foetal exposure with twice-daily dosing Dolutegravir is licenced for use in both adults and children over 12 years of age, although data are limited on its use in pregnant women. The manufacturer suggests that dolutegravir should be used in pregnancy only if the benefits outweigh the risks [1]. UK and US guidelines state that there are insufficient data to make recommendations on its use in pregnancy [2,3]. Nevertheless there are sporadic case reports of successful use in pregnant women [4,5] with significant placental transfer suggested by ex-vivo models [6] and a case report in vivo [5]. However, the effect of pregnancy on dolutegravir pharmacokinetics and optimal dosing during pregnancy is unknown. Here, we present our early experience of dolutegravir pharmacokinetics in two pregnant women, including the first published report of truncated 8-h pharmacokinetic profiles of dolutegravir in the first and third trimesters, in addition to measurement of foetal dolutegravir levels in umbilical cord blood. Our unit has treated two pregnant women with dolutegravir, in both cases with extensive drug resistance where dolutegravir was justified to prevent onward transmission. The first was a 23-year-old woman …