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

Ann Pharmacother. 2019 Aug;53(8):833-844. doi: 10.1177/1060028019830788. Epub 2019 Feb 10.

Abstract

Objective: To synthesize data on the pharmacokinetics and safety of dolutegravir and elvitegravir in pregnant women living with HIV. Data Sources: A PubMed, EMBASE, Web of Science, and Google Scholar literature search (January 2010 to December 2018) was performed using the search terms dolutegravir, elvitegravir, women, pregnant*, and HIV. Additional reports were identified from conference abstracts and review of reference lists. Study Selection and Data Extraction: English-language studies reporting pharmacokinetic and/or safety data in pregnant women receiving dolutegravir or elvitegravir/cobicistat were included. Data Synthesis: A total of 17 studies were selected. Studies demonstrated a modest decrease in dolutegravir concentrations in pregnancy. Preliminary data suggest an increased risk of neural tube defects when dolutegravir is used at the time of conception. Available pharmacokinetic data in pregnant women showed significantly reduced plasma concentrations of elvitegravir/cobicistat which may increase the risk of virological failure. Current guidelines recommend that dolutegravir should not be initiated in women who have the potential to become pregnant or women in their first trimester of pregnancy and elvitegravir/cobicistat should be avoided during pregnancy. Relevance to Patient Care and Clinical Practice: This review highlights pharmacokinetic and safety data for dolutegravir and elvitegravir/cobicistat in pregnant women. Clinicians need to be aware of these data to convey the risks and benefits of using these agents in women of child-bearing potential. Conclusions: Changes in guideline recommendations reflect emerging data regarding the use of dolutegravir and elvitegravir/cobicistat in pregnancy. Until further information is available, raltegravir or other first-line agents are recommended for women with HIV planning to become pregnant.

Keywords: HIV; dolutegravir; elvitegravir; pharmacokinetics; pregnancy.

Publication types

  • Review

MeSH terms

  • Female
  • Guidelines as Topic
  • HIV Infections / drug therapy*
  • HIV Infections / virology
  • HIV Integrase Inhibitors* / adverse effects
  • HIV Integrase Inhibitors* / pharmacokinetics
  • HIV Integrase Inhibitors* / therapeutic use
  • Heterocyclic Compounds, 3-Ring* / adverse effects
  • Heterocyclic Compounds, 3-Ring* / pharmacokinetics
  • Heterocyclic Compounds, 3-Ring* / therapeutic use
  • Humans
  • Oxazines
  • Piperazines
  • Pregnancy
  • Pregnancy Complications, Infectious / drug therapy*
  • Pregnancy Complications, Infectious / virology
  • Pyridones
  • Quinolones* / adverse effects
  • Quinolones* / pharmacokinetics
  • Quinolones* / therapeutic use

Substances

  • HIV Integrase Inhibitors
  • Heterocyclic Compounds, 3-Ring
  • Oxazines
  • Piperazines
  • Pyridones
  • Quinolones
  • elvitegravir
  • dolutegravir