Pharmacokinetics of HIV therapies in pregnant patients: an update

ABSTRACT

Introduction

Mother-to-child transmission (MTCT) of HIV is thought to account for over 90% of new pediatric infections, and is associated with poor maternal and fetal outcomes. As such ensuring further reduction in MTCT is a priority in HIV treatment and prevention programs.

Areas covered

This review aims to provide a comprehensive update on the pharmacokinetics of recently approved antiretroviral drugs and novel drug formulations and delivery systems. Alongside recent recommendations for dose adjustments, and an overview of the implications of co-infections on the pharmacokinetics of antiretrovirals relevant to pregnant HIV positive patients. Additionally, potential opportunities to progress pharmacokinetic research of new treatments in this population are highlighted.

Expert opinion

In order to improve our understanding of how to provide safe and effective treatment to HIV positive pregnant women, further work is required to enable their inclusion in early stages of clinical trials. Incentives must be created for this research, in the form of additional investment by key stakeholders and regulatory agencies. Furthermore, as the incidence of MTCT is reduced globally there is a need to conduct long-term pharmacovigilance studies in uninfected children exposed to HIV and antiretrovirals in utero, in order to determine the safest and most effective antiretroviral therapies.

KEYWORDS:

• Pregnancy
• antiretrovirals
• pharmacokinetics
• HIV
• dolutegravir
• efavirenz
• doravine
• co-infection
• long acting injectables

Article highlights

• Pregnancy-based physiological changes can alter the pharmacokinetics of key antiretroviral drugs and this must be considered during novel therapy development

• Dose reduction of efavirenz from 600 mg to 400 mg daily has been shown to appropriate for use in pregnant HIV positive patients

• Dolutegravir has been shown to be non-inferior to efavirenz within pregnant HIV positive populations.

• Further study of the effects of pregnancy on long-acting antiretroviral therapy and the incidence of toxicity is needed given the alterations in pharmacokinetics observed for oral once-daily ART in pregnant women.

• PBPK models have the potential to predict not only ART pharmacokinetics during pregnancy but also prenatal exposure to the maternal drug.

• Future studies should assesse the suitability of PrEP prescription within women of childbearing age and first trimester of pregnancy.

Pharmacovigilance studies are required to further understand the effect of ART exposure in infants exposed to ART and HIV who do not contract HIV.

Declaration of interest

A Olagunju is currently supported by a Wellcome Trust International Training Fellowship at Obafemi Awolowo University (204,776/Z/16/Z) and the University of Liverpool (204,776/A/16/Z). A Owen is the director of Tandem Nano Ltd., the co-inventor of patents related to drug delivery (including LAI atovaqone), has received consultancy fees from Merck, ViiV Healthcare and Gilead and has received grants from Janssen, Merck, ViiV Healthcare and AstraZeneca (to University of Liverpool). M Neary Holds a postdoctoral position on a National Institute of Health funded grant. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

A reviewer of this manuscript discloses being a coordinator of the PANNA network, a European network studying PK of antiretrovirals in pregnancy. Peer reviewers on this manuscript have no other relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded.