title: Integrase inhibitors in late pregnancy and rapid HIV viral load reduction.
abstract: BACKGROUND
  Minimizing time to HIV viral suppression is critical in pregnancy. Integrase strand transfer inhibitors (INSTIs), like raltegravir, are known to rapidly suppress plasma HIV RNA in nonpregnant adults. There are limited data in pregnant women.
  
  
  OBJECTIVE
  We describe time to clinically relevant reduction in HIV RNA in pregnant women using INSTI-containing and non-INSTI-containing antiretroviral therapy (ART) options.
  
  
  METHODS
  We conducted a retrospective cohort study of pregnant HIV-infected women in the United States from 2009 through 2015. We included women who initiated ART, intensified their regimen, or switched to a new regimen due to detectable viremia (HIV RNA >40 copies/mL) at ≥20 weeks gestation. Among women with a baseline HIV RNA permitting 1-log reduction, we estimated time to 1-log RNA reduction using the Kaplan-Meier estimator comparing women starting/adding an INSTI in their regimen vs other ART. To compare groups with similar follow-up time, we also conducted a subgroup analysis limited to women with ≤14 days between baseline and follow-up RNA data.
  
  
  RESULTS
  This study describes 101 HIV-infected pregnant women from 11 US clinics. In all, 75% (76/101) of women were not taking ART at baseline; 24 were taking non-INSTI containing ART, and 1 received zidovudine monotherapy. In all, 39% (39/101) of women started an INSTI-containing regimen or added an INSTI to their ART regimen. Among 90 women with a baseline HIV RNA permitting 1-log reduction, the median time to 1-log RNA reduction was 8 days (interquartile range [IQR], 7-14) in the INSTI group vs 35 days (IQR, 20-53) in the non-INSTI ART group (P < .01). In a subgroup of 39 women with first and last RNA measurements ≤14 days apart, median time to 1-log reduction was 7 days (IQR, 6-10) in the INSTI group vs 11 days (IQR, 10-14) in the non-INSTI group (P < .01).
  
  
  CONCLUSIONS
  ART that includes INSTIs appears to induce more rapid viral suppression than other ART regimens in pregnancy. Inclusion of an INSTI may play a role in optimal reduction of HIV RNA for HIV-infected pregnant women presenting late to care or failing initial therapy. Larger studies are urgently needed to assess the safety and effectiveness of this approach.
authors.affiliation: Department of Obstetrics and Gynecology, University of North Carolina School of Medicine, Chapel Hill, NC. Electronic address: lisa_rahangdale@med.unc.edu.
authors.forename: Lisa
authors.initials: L
authors.lastname: Rahangdale
authors.affiliation: Department of Epidemiology, University of North Carolina Gillings School of Public Health, Chapel Hill, NC.
authors.forename: Jordan
authors.initials: J
authors.lastname: Cates
authors.affiliation: Department of Obstetrics and Gynecology, Divison of Research, University of Miami Miller School of Medicine, Miami, FL.
authors.forename: JoNell
authors.initials: J
authors.lastname: Potter
authors.affiliation: Department of Gynecology and Obstetrics, Division of Maternal-Fetal Medicine, Emory University, Atlanta, GA.
authors.forename: Martina L
authors.initials: ML
authors.lastname: Badell
authors.affiliation: Department of Obstetrics, Gynecology, and Reproductive Sciences; University of California-San Francisco, San Francisco, CA.
authors.forename: Dominika
authors.initials: D
authors.lastname: Seidman
authors.affiliation: Department of Obstetrics and Gynecology, Division of Maternal Fetal Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL.
authors.forename: Emilly S
authors.initials: ES
authors.lastname: Miller
authors.affiliation: Department of Gynecology and Obstetrics, Johns Hopkins University, Baltimore, MD.
authors.forename: Jenell S
authors.initials: JS
authors.lastname: Coleman
authors.affiliation: Department of Obstetrics and Gynecology, Medical University of South Carolina, Charleston, SC.
authors.forename: Gweneth B
authors.initials: GB
authors.lastname: Lazenby
authors.affiliation: Department of Obstetrics and Gynecology, Baylor College of Medicine, Houston, TX.
authors.forename: Judy
authors.initials: J
authors.lastname: Levison
authors.affiliation: Department of Medicine, University of Pennsylvania Perelmen School of Medicine, Philadelphia, PA (formerly at Sidney Kimmel Medical College at Thomas Jefferson University).
authors.forename: William R
authors.initials: WR
authors.lastname: Short
authors.affiliation: Department of Medicine, Brigham and Women's Hospital, Boston, MA.
authors.forename: Sigal
authors.initials: S
authors.lastname: Yawetz
authors.affiliation: Medical Practice Evaluation Center, Division of Infectious Diseases, Massachusetts General Hospital, Boston, MA.
authors.forename: Andrea
authors.initials: A
authors.lastname: Ciaranello
authors.affiliation: Department of Obstetrics and Gynecology, Duke University, Durham, NC.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Livingston
authors.affiliation: Department of Obstetrics and Gynecology, Divison of Research, University of Miami Miller School of Medicine, Miami, FL.
authors.forename: Lunthita
authors.initials: L
authors.lastname: Duthely
authors.affiliation: Department of Gynecology and Obstetrics, Emory University School of Medicine, Atlanta, GA.
authors.forename: Bassam H
authors.initials: BH
authors.lastname: Rimawi
authors.affiliation: Department of Gynecology and Obstetrics, Johns Hopkins University, Baltimore, MD.
authors.forename: Jean R
authors.initials: JR
authors.lastname: Anderson
authors.affiliation: Department of Obstetrics and Gynecology, University of North Carolina School of Medicine, Chapel Hill, NC.
authors.forename: Elizabeth M
authors.initials: EM
authors.lastname: Stringer
mesh_terms: D000328:Adult; D004359:Drug Therapy, Combination / Q000379:methods; D005260:Female; D005865:Gestational Age; D006678:HIV; D015658:HIV Infections / Q000188:drug therapy*; D019428:HIV Integrase Inhibitors / Q000627:therapeutic use*; D017320:HIV Protease Inhibitors / Q000627:therapeutic use; D006575:Heterocyclic Compounds, 3-Ring / Q000627:therapeutic use; D006801:Humans; D010078:Oxazines; D010879:Piperazines; D011247:Pregnancy; D011251:Pregnancy Complications, Infectious / Q000188:drug therapy* / Q000821:virology; D011262:Pregnancy Trimester, Second; D011263:Pregnancy Trimester, Third; D011728:Pyridones; D012367:RNA, Viral / Q000097:blood*; D012189:Retrospective Studies; D018894:Reverse Transcriptase Inhibitors / Q000627:therapeutic use; D013997:Time Factors; D019562:Viral Load / Q000187:drug effects*; D055815:Young Adult; D000099226:Dolutegravir
chemical_list: D019428:HIV Integrase Inhibitors; D017320:HIV Protease Inhibitors; D006575:Heterocyclic Compounds, 3-Ring; D010078:Oxazines; D010879:Piperazines; D011728:Pyridones; D012367:RNA, Viral; D018894:Reverse Transcriptase Inhibitors; D000099226:Dolutegravir
keywords: HIV; integrase inhibitors; pregnancy