Free and total plasma concentrations of elvitegravir/cobicistat during pregnancy and postpartum: a case report

Marzolini, Catia; Décosterd, Laurent A.; Winterfeld, Ursula; Tissot, F; Francini, Katyuska; Buclin, Thierry; Livio, Françoise

doi:10.1111/bcp.13310

Cited by 15 publications

(16 citation statements)

References 10 publications

(12 reference statements)

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“…Elvitegravir plasma levels are boosted with cobicistat, a potent CYP3A4 inhibitor; however, the pharmacokinetics of elvitegravir in combination with cobicistat have not yet been extensively evaluated during pregnancy. A conference report of a prospective study ( n = 16 patients in the second trimester, n = 20 patients in the third trimester, and n = 15 patients postpartum) by Best [ 11 ], as well as case reports of Marzolini et al [ 48 ] and Schalkwijk et al [ 49 ] have described the pharmacokinetics of elvitegravir in HIV-infected pregnant women. In this review, we mainly focus on the study of Best [ 11 ].…”

Section: Resultsmentioning

confidence: 99%

“…In this study, elvitegravir C max was below the steady-state mean C max (1.7 mg/L) in non-pregnant patients (see Table 2 ) [ 50 ]. Additionally, case reports observed no effect on elvitegravir C max and reduced cobicistat C max [ 48 , 49 ] during the third trimester compared with postpartum.…”

Section: Resultsmentioning

confidence: 99%

“…Elvitegravir shows extensive protein binding to albumin of approximately 98–99% [ 30 , 51 ]; cobicistat also highly binds to albumin (97–98% bound) [ 30 , 51 ]. Marzolini et al [ 48 ] measured the fraction unbound ( f u ) of elvitegravir and cobicistat in one patient and found that the f u of elvitegravir was unchanged ( f u = 0.3%) when comparing the third trimester with postpartum. Moreover, the f u of cobicistat was minimally increased during the third trimester, with an f u of 2.1 versus 1.8%.…”

Section: Resultsmentioning

confidence: 99%

“…Best [ 11 ] found a median elvitegravir C trough of 0.0249 mg/L (interquartile range [IQR] 0.0173–0.0807) and 0.0570 mg/L (IQR 0.0147–0.0940) during the second and third trimesters of pregnancy, respectively. Additionally, the case reports of Marzolini et al [ 48 ] and Schalkwijk et al [ 49 ] found a total elvitegravir C trough below the target of elvitegravir (0.018 and 0.06 mg/L, respectively). The results of these studies imply inadequate exposure to elvitegravir during pregnancy and hence an increased risk of virological failure.…”

Section: Resultsmentioning

confidence: 99%

“…Knowledge on the pharmacokinetics of these drugs in pregnancy is very relevant and can be used to inform perinatal guidelines. To illustrate this, elvitegravir/cobicistat is not recommended for pregnant women [ 7 ] because of inadequate exposure during pregnancy [ 11 , 48 , 49 ]. We do not know whether adequate exposure to, and viral suppression of, raltegravir 1200 mg once daily, dolutegravir 50 mg twice daily, and bictegravir and cabotegravir can be reached using standard dosing regimens in pregnant women.…”

Section: Discussion and Knowledge Gapsmentioning

confidence: 99%

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Pharmacokinetics of HIV-Integrase Inhibitors During Pregnancy: Mechanisms, Clinical Implications and Knowledge Gaps

et al. 2018

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Prevention of mother-to-child transmission of HIV and optimal maternal treatment are the most important goals of antiretroviral therapy in pregnant women with HIV. These goals may be at risk due to possible reduced exposure during pregnancy caused by physiological changes. Limited information is available on the impact of these physiological changes. This is especially true for HIV-integrase inhibitors, a relatively new class of drugs, recommended first-line agents and hence used by a large proportion of HIV-infected patients. Therefore, the objective of this review is to provide a detailed overview of the pharmacokinetics of HIV-integrase inhibitors in pregnancy. Second, this review defines potential causes for the change in pharmacokinetics of HIV-integrase inhibitors during pregnancy. Despite increased clearance, for raltegravir 400 mg twice daily and dolutegravir 50 mg once daily, exposure during pregnancy seems adequate; however, for elvitegravir, the proposed minimal effective concentration is not reached during pregnancy. Lower exposure to these drugs may be caused by increased hormone levels and, subsequently, enhanced drug metabolism during pregnancy. The pharmacokinetics of bictegravir and cabotegravir, which are under development, have not yet been evaluated in pregnant women. New studies need to prospectively assess whether adequate exposure is reached in pregnant women using these new HIV-integrase inhibitors. To further optimize antiretroviral treatment in pregnant women, studies need to unravel the underlying mechanisms behind the changes in the pharmacokinetics of HIV-integrase inhibitors during pregnancy. More knowledge on altered pharmacokinetics during pregnancy and the underlying mechanisms contribute to the development of effective and safe antiretroviral therapy for HIV-infected pregnant women.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Discussion and Knowledge Gapsmentioning

confidence: 99%

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Pharmacokinetics of HIV-Integrase Inhibitors During Pregnancy: Mechanisms, Clinical Implications and Knowledge Gaps

et al. 2018

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State‐of‐the‐Art Review of HIV‐TB Coinfection in Special Populations

Weld

Dooley

2018

Clin Pharma and Therapeutics

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Children and pregnant and postpartum women experience an undue burden of HIV-associated tuberculosis (TB), but data are lacking on key aspects of their complex management. Often excluded from clinical trials, they are left with limited options for HIV-TB cotreatment. This review will focus on pharmacologic aspects of the treatment of HIV-TB coinfection in the special populations of children and pregnant and postpartum women. Pharmacogenomic considerations, rational dosing, drug-drug interactions, safety, immune reconstitution inflammatory syndrome, and ethical and policy aspects of the inclusion of special populations in research will be surveyed. Considerations related to the treatment of both HIV-associated TB disease and HIV-associated latent TB infection will be summarized. Relevant knowledge gaps and research priorities in special populations will be outlined.

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Pharmacokinetic Enhancement of HIV Antiretroviral Therapy During Pregnancy

Salama

Eke

Best

et al. 2020

The Journal of Clinical Pharma

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Pharmacokinetic boosting of antiretroviral (ARV) therapies with either ritonavir or cobicistat is used to achieve target drug exposure, lower pill burden, and provide simplified dosing schedules. Several ARVs require boosting, including the integrase inhibitor elvitegravir as well as protease inhibitors such as darunavir, atazanavir, and lopinavir. The use of boosted regimens in pregnant women living with HIV has been studied for a variety of ARVs; however, a recent recommendation by the US Food and Drug Administration advised against cobicistat-boosted regimens in pregnancy due to substantially lower drug exposures observed in clinical pharmacokinetic studies. The objectives of this article are to review pharmacokinetic enhancement of ARVs with ritonavir and cobicistat during pregnancy and postpartum, describe clinical implications, and provide recommendations for future research.

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Free and total plasma concentrations of elvitegravir/cobicistat during pregnancy and postpartum: a case report

Cited by 15 publications

References 10 publications

Pharmacokinetics of HIV-Integrase Inhibitors During Pregnancy: Mechanisms, Clinical Implications and Knowledge Gaps

Pharmacokinetics of HIV-Integrase Inhibitors During Pregnancy: Mechanisms, Clinical Implications and Knowledge Gaps

State‐of‐the‐Art Review of HIV‐TB Coinfection in Special Populations

Pharmacokinetic Enhancement of HIV Antiretroviral Therapy During Pregnancy

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