Safety and pharmacokinetics of nelfinavir during the second and third trimesters of pregnancy and postpartum.
OBJECTIVE
Evaluate the safety, tolerability, and pharmacokinetics (PK) of nelfinavir during pregnancy and postpartum in HIV-infected women.


METHODS
Phase IV, non-randomized, open-label study of nelfinavir 625 mg tablets (1250 mg) in combination with lamivudine/zidovudine twice daily. Primary endpoint was treatment-related or possibly treatment-related gastrointestinal or hepatic adverse events (AEs). Selected maternal and infant outcomes were recorded. Frequent plasma samples were collected for PK studies during the 2nd and 3rd trimesters, and 6 weeks postpartum, to analyze total and free nelfinavir and M8 concentrations.


RESULTS
Sixteen HIV+ pregnant women were enrolled. Six mild treatment-related AEs and 3 serious AEs occurred; 1 serious AE (elevated AST) met the primary endpoint. Compared with 6 weeks postpartum, levels of total nelfinavir were reduced by 44% and 46%, total M8 by 82% and 83%, free nelfinavir by 48% and 39%, and free M8 by 83% and 79% in the 2nd and 3rd trimesters, respectively. At 6 weeks postpartum, 75% and 50% of subjects maintained HIV-1 RNA levels <400 and <50 copies/mL, respectively. All pregnancies resulted in live births without transmission in 15 infants.


CONCLUSIONS
Nelfinavir in combination with lamivudine/zidovudine was generally well tolerated. Total and free nelfinavir and M8 exposure were reduced in late pregnancy.
Pfizer Inc, New York, New York 10017, USA.
A
A
Fang
S R
SR
Valluri
M-J
MJ
O'Sullivan
R
R
Maupin
T
T
Jones
I
I
Delke
P
P
Clax
D000328:Adult; D018791:CD4 Lymphocyte Count; D005260:Female; D015658:HIV Infections / Q000188:drug therapy*; D017320:HIV Protease Inhibitors / Q000009:adverse effects*; D015497:HIV-1 / Q000235:genetics / Q000302:isolation & purification; D006801:Humans; D019888:Nelfinavir / Q000009:adverse effects* / Q000493:pharmacokinetics; D049590:Postpartum Period; D011247:Pregnancy; D011251:Pregnancy Complications, Infectious / Q000188:drug therapy*; D011262:Pregnancy Trimester, Second; D011263:Pregnancy Trimester, Third; D012367:RNA, Viral / Q000097:blood
D017320:HIV Protease Inhibitors; D012367:RNA, Viral; D019888:Nelfinavir