Tenofovir alafenamide use in pregnant and lactating women living with HIV

ABSTRACT

Introduction: Tenofovir alafenamide (TAF)-containing fixed-dose drug combinations (FDCs) are increasingly being used in managing pregnant women living with HIV. However, TAF is not currently recommended during pregnancy due to limited pharmacokinetic and safety data. TAF, a newer nucleotide phosphonamidate prodrug of tenofovir (TFV), achieves high levels of tenofovir-diphosphate in lymphoid cells and hepatocytes, and 90% lower systemic concentrations of TFV compared to tenofovir disoproxil fumarate (TDF), thereby maximizing TAF’s antiviral efficacy, potency and clinical safety.

Areas covered: This review discusses the currently available information on the pharmacology of TAF in pregnant women living with HIV. Pharmacokinetic studies with TAF during pregnancy have yielded varying results compared to postpartum, but TAF exposures during pregnancy have been within the range of those typically observed in non-pregnant adults. The efficacy and safety of TAF in treatment-naïve pregnant women living with HIV is currently being evaluated in the VESTED study, a phase-III NIH randomized clinical trial.

Expert opinion: Initial pregnancy data suggest that TAF-based FDCs have high efficacy and low risk of adverse effects during pregnancy. TAF is likely to become part of first-line regimens for use in pregnant women living with HIV once additional pregnancy data from phase III trials are available.

KEYWORDS:

• Tenofovir Alafenamide (TAF)
• pregnancy
• postpartum
• Human Immunodeficiency Virus (HIV)

Article Highlights

• There is a unique difference between the site and mechanism of action of cobicistat boosting of TAF and cobicistat boosting of protease and integrase inhibitors. This difference in site and mechanism of action likely explains the difference in effectiveness of cobicistat boosting of TAF in pregnancy compared to protease and integrase inhibitors.

• Plasma TAF exposures during pregnancy are within the typical range of those in non-pregnant adults taking similar doses, but higher than expected plasma exposures of TAF were noted postpartum for unclear reasons.

• TAF has a higher genetic barrier to treatment-emergent resistance mutations such as K65R, Q151M, T69-insertion complex, and multiple thymidine analog resistance mutations (TAMs) in comparison to TDF, owing to the high TFV-DP concentrations attained in PBMCs

• TAF was shown to have a more rapid attainment of protective levels in PBMC and, a longer duration of effect above the EC90 following drug discontinuation in comparison TDF.

• TAF, due to its potency and good safety profile, might form the cornerstone for management of pregnant women living with HIV

This box summarizes key points contained in the article.

Declaration of Interest

M Mirochnick has received research support from Merck, ViiV and Gilead, and has served as a consultant for ViiV and Gilead. 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 receiving research support from Gilead Sciences (paid to institution) for an investigator-initiated study.

Additional information

Funding

This paper was not funded