Document Detail


Pharmacokinetics and safety of single-dose tenofovir disoproxil fumarate and emtricitabine in HIV-1-infected pregnant women and their infants.
MedLine Citation:
PMID:  21896911     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Tenofovir (TFV) is effective in preventing simian immunodeficiency virus (SIV) transmission in a macaque model, is available as the oral agent tenofovir disoproxil fumarate (TDF), and may be useful in the prevention of mother-to-child transmission of human immunodeficiency virus (HIV). We conducted a trial of TDF and TDF-emtricitabine (FTC) in HIV-infected pregnant women and their infants. Women received a single dose of either 600 mg TDF, 900 mg TDF, or 900 mg TDF-600 mg FTC at labor onset or prior to a cesarean section. Infants received no drug or a single dose of TDF at 4 mg/kg of body weight or of TDF at 4 mg/kg plus FTC at 3 mg/kg as soon as possible after birth. All regimens were safe and well tolerated. Maternal areas under the serum concentration-time curve (AUC) and concentrations at the end of sampling after 24 h (C(24)) were similar between the two doses of TDF; the maximum concentrations of the drugs in serum (C(max)) and cord blood concentrations were higher in women delivering via cesarean section than in those who delivered vaginally (P = 0.04 and 0.046, respectively). The median ratio of the TFV concentration in cord blood to that in the maternal plasma at delivery was 0.73 (range, 0.26 to 1.95). Without TDF administration, infants had a median TFV concentration of 12 ng/ml 12 h after birth. Following administration of a single dose of TDF at 4 mg/kg, infant TFV concentrations fell below the targeted level, 50 ng/ml, by 24 h postdose. In HIV-infected pregnant women and their infants, 600 mg of TDF is acceptable as a single dose during labor. Low concentrations at birth support infant dosing as soon after birth as possible. Rapidly decreasing TFV levels in infants suggest that multiple or higher doses of TDF will be necessary to maintain concentrations that are effective for viral suppression.
Authors:
Patricia M Flynn; Mark Mirochnick; David E Shapiro; Arlene Bardeguez; John Rodman; Brian Robbins; Sharon Huang; Susan A Fiscus; Koen K A Van Rompay; James F Rooney; Brian Kearney; Lynne M Mofenson; D Heather Watts; Patrick Jean-Philippe; Barbara Heckman; Edwin Thorpe; Amanda Cotter; Murli Purswani;
Publication Detail:
Type:  Clinical Trial; Journal Article; Research Support, N.I.H., Extramural     Date:  2011-09-06
Journal Detail:
Title:  Antimicrobial agents and chemotherapy     Volume:  55     ISSN:  1098-6596     ISO Abbreviation:  Antimicrob. Agents Chemother.     Publication Date:  2011 Dec 
Date Detail:
Created Date:  2011-11-14     Completed Date:  2012-03-29     Revised Date:  2013-06-27    
Medline Journal Info:
Nlm Unique ID:  0315061     Medline TA:  Antimicrob Agents Chemother     Country:  United States    
Other Details:
Languages:  eng     Pagination:  5914-22     Citation Subset:  IM    
Affiliation:
St Jude Children’s Research Hospital, Memphis, Tennessee 138105-2794, USA. pat.flynn@stjude.org
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MeSH Terms
Descriptor/Qualifier:
Adenine / administration & dosage,  adverse effects,  analogs & derivatives*,  pharmacokinetics
Adult
Anti-HIV Agents* / administration & dosage,  adverse effects,  pharmacokinetics
Deoxycytidine / administration & dosage,  adverse effects,  analogs & derivatives*,  pharmacokinetics
Dose-Response Relationship, Drug
Drug Therapy, Combination
Female
HIV Infections / drug therapy*,  transmission,  virology
HIV-1 / drug effects
Humans
Infant
Infectious Disease Transmission, Vertical / prevention & control*
Organophosphonates* / administration & dosage,  adverse effects,  pharmacokinetics
Pregnancy
Pregnancy Complications, Infectious / drug therapy*,  virology
Reverse Transcriptase Inhibitors* / administration & dosage,  adverse effects,  pharmacokinetics
Treatment Outcome
Young Adult
Grant Support
ID/Acronym/Agency:
1 U01 AI068616/AI/NIAID NIH HHS; 5 U01 AI41110/AI/NIAID NIH HHS; AI068632/AI/NIAID NIH HHS; N01-DK-9-001/HHSN267200800001C/DK/NIDDK NIH HHS; U01AI068632/AI/NIAID NIH HHS
Chemical
Reg. No./Substance:
0/Anti-HIV Agents; 0/Organophosphonates; 0/Reverse Transcriptase Inhibitors; 0/emtricitabine; 0/tenofovir disoproxil; 73-24-5/Adenine; 951-77-9/Deoxycytidine
Investigator
Investigator/Affiliation:
Elvia Perez-Hernandez / ; Antonio Rodriguez-Mimoso / ; Midnela Acevedo-Flores / ; Luis Marquez-Babilonia / ; M Thorpe / ; Nina K Sublette / ; Arry Dieudonne / ; Charmane Calilap-Bernardo / ; Juliette Johnson / ; Lisa Monti / ; Nehali Patel / ; Jill Utech / ; Sandra J Boyd / ; Ernestine Brown / ; Tamika Watson / ; Theodore B Jones / ; Mavis Dummitt / ; Stefan Hagmann / ; Murli Purswani / ; Amanda Cotter / ; Gwendolyn B Scott / ; Erika Lopez / ; Sergio Jordan /
Comments/Corrections

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