Pharmacokinetics and Safety of the Integrase Inhibitors Elvitegravir and Dolutegravir in Pregnant Women With HIV

Nguyen, Binh; Foisy, Michelle; Hughes, Christine

doi:10.1177/1060028019830788

Cited by 13 publications

(7 citation statements)

References 26 publications

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“…Peri-conception exposure to RAL is not associated with NTD and therefore remains the only INSTI recommended in high-income countries for women during the peri-conceptional period or during pregnancy (DHHS (USA), the European AIDS Clinical Society [] and Canadian guidelines [74]). Further trials on efficacy and tolerability are needed on the use of RAL QD 1200 mg in this population [69].…”

Section: Instis and Pregnancymentioning

confidence: 99%

Update on Adverse Effects of HIV Integrase Inhibitors

Kołakowska

Maresca

Collins

et al. 2019

Curr Treat Options Infect Dis

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Keywords HIV integrase inhibitors I Drug-related side effects and adverse reactions I Raltegravir I Elvitegravir I Dolutegravir Abstract Purpose of review The goal of this paper is to provide an up-to-date review of adverse events related to the class of integrase strand transfer inhibitors (INSTIs), which became the class of choice in few years. We sought answers specifically to issues pertaining to neuropsychiatric adverse events, as well as weight gain, which were the two most important categories of adverse events raised in recent studies based on real-life experience. The primary focus of this paper is on adults with a brief summary on pregnant women and children/adolescents. Recent findings Dolutegravir (DTG) bears the heaviest burden of neuropsychiatric side effects. Weight gain was reported with all INSTIs, although there are methodological caveats in the analyses and the findings need to be interpreted with caution. Moreover, due to recent findings on neural tube defects in infants exposed to dolutegravir during their peri-conception period, its use is not recommended for women of childbearing age without proper birth control method, while raltegravir remains the only drug which may be prescribed without caution. Given the importance of cognitive and metabolic comorbidities in people living with HIV in regard to their quality of life, future research needs to focus on long-term effects of INSTIs in relation to these adverse events. Pharmacogenetics seems to be a promising tool. Safety during pregnancy is also another important issue to further clarify. Summary INSTIs are a generally well-tolerated class of antiretrovirals (ARV), and has a

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Section: Instis and Pregnancymentioning

confidence: 99%

Update on Adverse Effects of HIV Integrase Inhibitors

Kołakowska

Maresca

Collins

et al. 2019

Curr Treat Options Infect Dis

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“…This study demonstrates that standard elvitegravir and cobicistat dosing during pregnancy results in significantly lower exposure, which may increase the risk of virologic failure and mother‐to‐child transmission. (Table 3) Several case studies have also shown significantly decreased elvitegravir exposure in pregnant women 62,63 . Importantly, elvitegravir C min values observed during pregnancy (16.8 and 18.3 ng/mL) are well below the concentration that inhibits 95% of viral replication of 45 ng/mL.…”

Section: Pharmacokinetics Of Cobicistat‐boosted Regimens In Pregnancymentioning

confidence: 98%

“…(Table 3) Several case studies have also shown significantly decreased elvitegravir exposure in pregnant women. 62,63 Importantly, elvitegravir C min values observed during pregnancy (16.8 and 18.3 ng/mL) are well below the concentration that inhibits 95% of viral replication of 45 ng/mL. Due to the current evidence demonstrating significantly reduced and likely subtherapeutic plasma concentrations of elvitegravir/cobicistat, the FDA currently discourages the use of elvitegravir/cobicistat during pregnancy.…”

Section: Pharmacokinetics Of Cobicistat-boosted Regimens In Pregnancymentioning

confidence: 99%

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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“…reduced exposure to antiretroviral agents of pregnant women living with HIV has been recently reported for darunavir, rilpivirine, cobicistat, elvitegravir, and dolutegravir. [85][86][87] Additionally, the understanding of antiretroviral placental and breastmilk transfer may offer additional insight into the potential role in preventing HIV transmission in utero and ensuring safety of in utero and breastmilk antiretroviral exposures in infants; furthermore, it may also have implications regarding viral resistance in cases where transmission does occur (reviewed in 88 ).…”

Section: A C C E P T E Dmentioning

confidence: 99%

“…In our case, the newborn-to-mother ratio for dolutegravir was 4-fold higher than the data reported in literature. 86,87 Similarly, great inter-individual variations in the newborn/mother drug ratio have…”

Section: A C C E P T E Dmentioning

confidence: 99%

Impact of Therapeutic Drug Monitoring of Antiretroviral Drugs in Routine Clinical Management of People Living With HIV: A Narrative Review

Cattaneo

Baldelli

Cozzi

et al. 2020

Therapeutic Drug Monitoring

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Purpose:The treatment of human immunodeficiency virus (HIV) infection has evolved significantly since the advent of highly active antiretroviral therapy. As a result, a response rate of 90-95 % now represents a realistically achievable target. Given this background, it is difficult to imagine the additional benefits that therapeutic drug monitoring (TDM) could provide in the management of HIV infection.Methods: This article is not intended to provide a systematic literature review on TDM of antiretroviral agents; rather, the authors aim to discuss the potential added value of TDM in the optimal management of people living with HIV (PLWH) in selected real-life clinical scenarios based on data collected over 10 years by their TDM service.Results: Some clinical situations, in which the selection of the optimal antiretroviral therapy is challenging, have been identified. These include poorly compliant patients, sub-optimal antiretroviral therapies (in terms of both efficacy and toxicity), polypharmacy with a high risk of drug-drug interactions (DDIs), and different patient populations, such as pregnant women. Conclusions:The transformation of HIV infection from a near universally fatal illness to a lifelong chronic disease has resulted in an HIV population that is growing and aging, placing new and increasing demands on public programs and health services. Increasingly, the management of comorbidities, polypharmacy, and DDIs and their impact on antiretroviral therapy will have to be undertaken. These clinical settings represent some of the new frontiers for the use of TDM with the goal of achieving optimal prescription and outcome for PLWH.

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Pharmacokinetics and Safety of the Integrase Inhibitors Elvitegravir and Dolutegravir in Pregnant Women With HIV

Cited by 13 publications

References 26 publications

Update on Adverse Effects of HIV Integrase Inhibitors

Update on Adverse Effects of HIV Integrase Inhibitors

Pharmacokinetic Enhancement of HIV Antiretroviral Therapy During Pregnancy

Impact of Therapeutic Drug Monitoring of Antiretroviral Drugs in Routine Clinical Management of People Living With HIV: A Narrative Review

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