Trough concentrations of lopinavir, nelfinavir, and nevirapine with standard dosing in human immunodeficiency virus-infected pregnant women receiving 3-drug combination regimens.
The objective of this study was to evaluate the plasma drug concentrations in human immunodeficiency virus (HIV)-infected pregnant women receiving highly active antiretroviral therapy (HAART) and to define the rate of occurrence of subtherapeutic concentrations for some commonly used antiretroviral drugs during pregnancy. We evaluated HIV-infected women (n = 68) in the third trimester of pregnancy in steady-state treatment with an HAART regimen administrated on a twice a day basis, which included 2 nucleoside reverse transcriptase inhibitors plus nelfinavir (NFV), lopinavir/ritonavir (LPV/r), or nevirapine (NVP). Blood samples were collected at predose (C(trough)). The following thresholds were used to define therapeutic drug concentrations-NFV: 0.8 microg/mL; LPV: 4.0 microg/mL/1.0 microg/mL (experienced/naive); and NVP: 3.1 microg/mL. At predose sampling, adequate drug concentrations were found in a higher proportion of women receiving NFV (70.8%) and LPV (75.0%) than NVP (55.6%). Median C(trough) plasma concentrations were 1.2 microg/mL for NFV, 5.5 microg/mL for LPV, and 3.1 microg/mL for NVP. Women receiving lopinavir/ritonavir had the lowest rates of detectable (>50 copies/mL) HIV RNA (15.4%) compared with rates of 22.2% and 41.7% among women receiving NVP and NFV, respectively. Genotypic resistance was detected in 50% of women with detectable HIV RNA for whom samples were available for testing. Subtherapeutic predose concentrations among HIV-infected pregnant women were more commonly found with NVP than with protease inhibitors. LPV administration was associated with the best viral load suppression.
Baroncelli
Silvia
S
Department of Therapeutic Research and Medicines Evaluation, Istituto Superiore di Sanità, Viale Regina Elena 299, Rome, Italy.
Villani
Paola
P
Floridia
Marco
M
Pirillo
Maria F
MF
Galluzzo
Clementina M
CM
Cusato
Maria
M
Amici
Roberta
R
Pinnetti
Carmela
C
Sabbatini
Francesca
F
Molinari
Atim
A
Tamburrini
Enrica
E
Regazzi
Mario
M
D000293:Adolescent; D000328:Adult; D023241:Antiretroviral Therapy, Highly Active / Q000592:standards; D015331:Cohort Studies; D004359:Drug Therapy, Combination; D005260:Female; D015658:HIV Infections / Q000097:blood* / Q000150:complications / Q000188:drug therapy*; D006801:Humans; D061466:Lopinavir; D019888:Nelfinavir / Q000008:administration & dosage / Q000097:blood* / Q000592:standards; D019829:Nevirapine / Q000008:administration & dosage / Q000097:blood* / Q000592:standards; D011247:Pregnancy; D011251:Pregnancy Complications, Infectious / Q000097:blood* / Q000188:drug therapy* / Q000821:virology; D011744:Pyrimidinones / Q000008:administration & dosage / Q000097:blood* / Q000592:standards; D019562:Viral Load / Q000502:physiology; D055815:Young Adult
D011744:Pyrimidinones; D061466:Lopinavir; D019829:Nevirapine; D019888:Nelfinavir