Pharmacokinetics and safety of single-dose tenofovir disoproxil fumarate and emtricitabine in HIV-1-infected pregnant women and their infants.

Abstract

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 Jr, Amanda Cotter, Murli Purswani, PACTG 394 Study Team
• Journal: Antimicrobial agents and chemotherapy (Antimicrob Agents Chemother) Vol. 55 Issue 12 Pg. 5914-22 (Dec 2011) ISSN: 1098-6596 [Electronic] United States
• PMID: 21896911 (Publication Type: Clinical Trial, Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• Anti-HIV Agents
• Organophosphonates
• Reverse Transcriptase Inhibitors
• Deoxycytidine
• Tenofovir
• Emtricitabine
• Adenine

Topics

• 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
• Emtricitabine
• 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)
• Tenofovir
• Treatment Outcome
• Young Adult