The Effect of Pregnancy on the Pharmacokinetics of Total and Unbound Dolutegravir and Its Main Metabolite in Women Living With Human Immunodeficiency Virus

2020 ◽  
Author(s):  
Pauline Bollen ◽  
Jolien Freriksen ◽  
Deborah Konopnicki ◽  
Katharina Weizsäcker ◽  
Carmen Hidalgo Tenorio ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Pregnant Women ◽  
Geometric Mean ◽  
Polymerase Chain Reaction Test ◽  
Third Trimester ◽  
Once Daily ◽  
Antiretroviral Agents ◽  
The Third ◽  
Immunodeficiency Virus ◽  
Pharmacologically Active

Abstract Background Pharmacokinetic and efficacy data on dolutegravir in pregnant women living with human immunodeficiency virus (HIV) are still limited but needed to support its use as one of the preferred antiretroviral agents. Methods Within the multicenter Pharmacokinetics of ANtiretroviral agents in HIV-infected pregNAnt women (PANNA) study, pregnant women living with HIV and using dolutegravir once daily (50 mg, with food) underwent 24-hour pharmacokinetic profiling in their third trimester and postpartum. Dolutegravir exposure in the third trimester was considered adequate if geometric mean unbound, pharmacologically active, minimal plasma concentrations (Cmin, unbound) and ≥90% of individual Cmin, unbound levels were >0.85 µg/L, the proposed 90% inhibitory concentration for unbound dolutegravir. Geometric mean ratios (GMRs) with 90% confidence intervals (CIs) for comparison of total and unbound pharmacokinetic parameters in the third trimester and postpartum were calculated, including the metabolic ratio for dolutegravir-glucuronide. Safety and virological data were collected. Results Seventeen women (76% black) were enrolled (25 evaluable pharmacokinetic profiles; 15 in the third trimester, 10 in postpartum). In the third trimester, geometric mean (coefficient of variation, %) Cmin, unbound was 2.87 (87) µg/L and 93% of individual Cmin, unbound levels were >0.85 µg/L. The GMR (90% CI) in the third trimester vs postpartum was 0.86 (.68–1.10) for area under the curve (AUC0-24h), and for Cmax, 0.93 (.77–1.13). GMR (90% CI) for the trough concentrations was 0.71 (.49–1.02), based on total dolutegravir concentrations. Four serious adverse events were reported, unlikely related to dolutegravir. The HIV polymerase chain reaction test was negative in 14/17 infants (result unknown for 3 infants). Conclusions Pharmacokinetic changes for dolutegravir in late pregnancy are not clinically relevant and support the use of dolutegravir 50 mg once daily with food in pregnancy. Clinical Trials Registration NCT00825929.

scholarly journals Clinically Significant Lower Elvitegravir Exposure During the Third Trimester of Pregnant Patients Living With Human Immunodeficiency Virus: Data From the Pharmacokinetics of ANtiretroviral agents in HIV-infected pregNAnt women (PANNA) Network

2020 ◽  
Vol 71 (10) ◽  
pp. e714-e717 ◽  
Author(s):  
Vera Bukkems ◽  
Coca Necsoi ◽  
Carmen Hidalgo Tenorio ◽  
Coral Garcia ◽  
Jürgen Rockstroh ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Clinical Trials ◽  
Pregnant Women ◽  
Effective Concentration ◽  
Third Trimester ◽  
Dosing Interval ◽  
The Third ◽  
Immunodeficiency Virus ◽  
Clinically Significant

Abstract This phase 4 study investigated the influence of pregnancy on the pharmacokinetics of elvitegravir/cobicistat in 14 women with human immunodeficiency virus type 1. The results support the recommendation against elvitegravir/cobicistat use during pregnancy, as the elvitegravir concentration at the end of the dosing interval (Ctrough) was reduced by 77%, with 85% of pregnant women having a Ctrough below the effective concentration (EC90). Clinical Trials Registration. NCT00825929.

scholarly journals Antiretroviral Therapy with a Twice-Daily Regimen Containing 400 Milligrams of Indinavir and 100 Milligrams of Ritonavir in Human Immunodeficiency Virus Type 1-Infected Women during Pregnancy

2008 ◽  
Vol 52 (4) ◽  
pp. 1542-1544 ◽  
Author(s):  
Jade Ghosn ◽  
Ines De Montgolfier ◽  
Chantal Cornélie ◽  
Stéphanie Dominguez ◽  
Claire Pérot ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Daily Regimen ◽  
Child Transmission ◽  
Third Trimester ◽  
Safety And Efficacy ◽  
Hiv Rna ◽  
The Third ◽  
Immunodeficiency Virus ◽  
Mother To Child

ABSTRACT We evaluated the safety and efficacy of a twice daily regimen containing 400 mg of indinavir and 100 mg of ritonavir in 32 human immunodeficiency virus (HIV)-infected women during pregnancy. The median indinavir trough concentration was 208 ng/ml during the third trimester. At delivery, 26 of 28 women on indinavir-ritonavir had HIV RNA levels of <200 copies/ml. No infant was HIV infected. These data are encouraging for the use of this combination for prevention of mother-to-child transmission of HIV.

scholarly journals Lowered Rilpivirine Exposure During the Third Trimester of Pregnancy in Human Immunodeficiency Virus Type 1–Infected Women

2017 ◽  
Vol 65 (8) ◽  
pp. 1335-1341 ◽  
Author(s):  
Stein Schalkwijk ◽  
Angela Colbers ◽  
Deborah Konopnicki ◽  
Andrea Gingelmaier ◽  
John Lambert ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Human Immunodeficiency Virus Type ◽  
Virus Type ◽  
Third Trimester ◽  
The Third ◽  
Immunodeficiency Virus

Erratum

1996 ◽  
Vol 17 (6) ◽  
pp. 202-202
Keyword(s):  
Human Immunodeficiency Virus ◽  
Hiv Infection ◽  
First Trimester ◽  
Pregnant Mother ◽  
Third Trimester ◽  
The Third ◽  
Immunodeficiency Virus

In the discussion of the "Index of Suspicion" case of human immunodeficiency virus (HIV) infection in an infant in Pediatrics in Review. 1996;17:67 (February), the sentence that reads, "Diagnosis of HIV infection in the pregnant mother should lead to her treatment with zidovudine after the third trimester...." is incorrect. It should read, "treatment with zidovudine after the first trimester."

scholarly journals Effect of Fluconazole on Indinavir Pharmacokinetics in Human Immunodeficiency Virus-Infected Patients

1998 ◽  
Vol 42 (2) ◽  
pp. 223-227
Author(s):  
S. De Wit ◽  
M. Debier ◽  
M. De Smet ◽  
J. McCrea ◽  
J. Stone ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Treatment Period ◽  
Geometric Mean ◽  
Pharmacokinetic Interaction ◽  
Hiv Protease ◽  
Pharmacokinetic Parameters ◽  
Once Daily ◽  
Immunodeficiency Virus ◽  
Clinically Significant ◽  
To Receive

ABSTRACT To evaluate a potential pharmacokinetic interaction of coadministration of fluconazole, and indinavir, a human immunodeficiency virus (HIV) protease inhibitor, 13 patients were enrolled in a multiple-dose, three-period, placebo-controlled, crossover study. Patients were randomly assigned to receive indinavir at 1,000 mg every 8 h for 7 1 3 days (with fluconazole placebo), fluconazole at 400 mg once daily for 8 days (with indinavir placebo), and indinavir with fluconazole in combination. The pharmacokinetics of both drugs were measured on day 8 of each treatment period. The peak concentration in plasma ( C max ) and the time to reach C max were obtained by inspection, and the area under curve (AUC) was calculated for indinavir and fluconazole for each treatment period in which the respective drugs were administered. There was a marginally ( P = 0.08) statistically significant decrease in the AUC from 0 to 8 h (AUC 0–8 ) for indinavir when it was administered with fluconazole. However, the magnitudes of the decreases in C max and the concentration at 8 h postdosing ( C 8 ) were not as great as the decrease in AUC 0–8 . Although the 90% confidence interval for the geometric mean ratio was within the hypothesized limits, the clinical significance is not clear. Indinavir coadministration with fluconazole had no statistically ( P > 0.5) or clinically significant effect on the C max and C 8 of indinavir. Fluconazole coadministration with indinavir had no statistically or clinically significant effect on the pharmacokinetics of fluconazole. One patient was discontinued because of mild to moderate abdominal pain and diarrhea while on indinavir and fluconazole in combination. No serious adverse experience according to the results of laboratory tests was noted. Total bilirubin levels in serum were mildly increased in most patients treated with indinavir. This was not clinically significant and was not affected by the coadministration of fluconazole. Although the values of the pharmacokinetic parameters for indinavir decrease in the presence of fluconazole, indinavir and fluconazole can be administered concomitantly to HIV-infected patients without adjustment of the dose of either drug, and both drugs are generally well tolerated.

scholarly journals Early Postpartum Pharmacokinetics of Lopinavir Initiated Intrapartum in Thai Women

2009 ◽  
Vol 53 (5) ◽  
pp. 2189-2191 ◽  
Author(s):  
Tim R. Cressey ◽  
Russell Van Dyke ◽  
Gonzague Jourdain ◽  
Thanyawee Puthanakit ◽  
Anuvat Roongpisuthipong ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Third Trimester ◽  
Serious Adverse Events ◽  
Time Curve ◽  
Thai Women ◽  
The Third ◽  
Early Postpartum Period ◽  
Concentration Time ◽  
Early Postpartum ◽  
Immunodeficiency Virus

ABSTRACT Lopinavir (LPV) exposure is reduced during the third trimester of pregnancy. We report the pharmacokinetics of standard LPV-ritonavir dosing (400/100 mg twice daily) in the immediate and early postpartum period when initiated during labor. In 16 human immunodeficiency virus-infected Thai women, the median (range) LPV area under the concentration-time curve and maximum and minimum concentrations in plasma were 99.7 (66.1 to 180.5) μg·h/ml, 11.2 (8.0 to 17.5) μg/ml, and 4.6 (1.7 to 12.5) μg/ml, respectively, at 41 (12 to 74) h after delivery. All of the women attained adequate LPV levels through 30 days postpartum. No serious adverse events were reported.

scholarly journals Tenofovir alafenamide plasma concentrations are reduced in pregnant women living with HIV: data from the PANNA Network

2021 ◽  
Author(s):  
Vera E Bukkems ◽  
Coca Necsoi ◽  
Carmen Hidalgo Tenorio ◽  
Coral Garcia ◽  
Irene Alba Alejandre ◽  
...  
Keyword(s):  
Pregnant Women ◽  
Geometric Mean ◽  
Plasma Concentrations ◽  
Pharmacokinetic Parameters ◽  
Third Trimester ◽  
Safety Outcome ◽  
The Third ◽  
Women Living With Hiv ◽  
Tenofovir Alafenamide ◽  
Living With Hiv

Abstract Background Tenofovir alafenamide (TAF), a prodrug of tenofovir (TFV), is included in the majority of the recommended first-line antiretroviral regimens for patients living with HIV, but there are limited data on TAF use in pregnant women. We aimed to examine the plasma pharmacokinetics of TAF and TFV in pregnant women from Europe. Methods Pregnant women living with HIV were included from treatment centers across Europe, and intensive pharmacokinetic sampling in the third trimester and postpartum was performed. Pharmacokinetic parameters of TAF and TFV were determined with noncompartmental analysis. The proportion of women with a TAF AUCtau below the target of 53.1 ng*h/mL was determined. Clinical efficacy and safety outcome parameters were reported. Results In total, 20 pregnant women living with HIV were included. At the third trimester, geometric mean TAF AUClast and Cmax were decreased by 46% and 52%, respectively, compared with postpartum. TFV AUC0-24h, Cmax, and Ctrough decreased by 33%, 30% and 34%, respectively. The proportion of women with a TAF AUClast &lt;53.1 ng*h/mL was 6% at third trimester and 0% postpartum. One out of 20 women had a viral load &gt;50 copies/mL at third trimester and no mother-to-child transmission occurred. Conclusions TAF plasma concentrations were reduced by about half in women living with HIV during third trimester of pregnancy, but remained above the predefined efficacy target in the majority of the pregnant women. TFV concentrations were reduced by approximately 30% during third trimester. Despite the observed exposure decrease, high virologic efficacy was observed in this study.

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