Combination therapy with efavirenz, nelfinavir, and nucleoside reverse-transcriptase inhibitors in children infected with human immunodeficiency virus type 1. Pediatric AIDS Clinical Trials Group 382 Team.
BACKGROUND
Consistent long-term viral suppression has been difficult to achieve in children with human immunodeficiency virus type 1 (HIV-1) infection. We tested the safety and antiviral efficacy of a novel combination consisting of efavirenz, nelfinavir, and one or more nucleoside reverse-transcriptase inhibitors in 57 children previously treated with only nucleoside reverse-transcriptase inhibitors.


METHODS
The children were monitored for 48 weeks after the initiation of therapy. We assessed plasma concentrations of efavirenz and nelfinavir, plasma HIV-1 RNA levels, and lymphocyte subpopulations.


RESULTS
At base line, the 57 HIV-1-infected children (age range, 3.8 to 16.8 years) had a median of 699 CD4 cells per cubic millimeter and 10,000 copies of HIV-1 RNA per milliliter of plasma. The most common treatment-related effects of at least moderate severity were rash (in 30 percent of children), diarrhea (in 18 percent), neutropenia (in 12 percent), and biochemical abnormalities (in 12 percent). Serious side effects were uncommon. The mean values for the area under the curve for efavirenz and nelfinavir corresponded to expected values. In an intention-to-treat analysis, 76 percent of children had plasma HIV-1 RNA levels of less than 400 copies per milliliter after 48 weeks of therapy and 63 percent had levels of less than 50 copies per milliliter. A high plasma HIV-1 RNA level at base line significantly decreased the likelihood that plasma levels of HIV-1 RNA would become undetectable during treatment.


CONCLUSIONS
In HIV-1-infected children who were previously treated with nucleoside reverse-transcriptase inhibitors, the combination of efavirenz, nelfinavir, and nucleoside reverse-transcriptase inhibitors was generally well tolerated and had a potent and sustained antiviral effect.
Starr
S E
SE
Division of Immunologic and Infectious Diseases, Children's Hospital of Philadelphia, PA 19104, USA. starr@email.chop.edu
Fletcher
C V
CV
Spector
S A
SA
Yong
F H
FH
Fenton
T
T
Brundage
R C
RC
Manion
D
D
Ruiz
N
N
Gersten
M
M
Becker
M
M
McNamara
J
J
Mofenson
L M
LM
Purdue
L
L
Siminski
S
S
Graham
B
B
Kornhauser
D M
DM
Fiske
W
W
Vincent
C
C
Lischner
H W
HW
Dankner
W M
WM
Flynn
P M
PM
D000293:Adolescent; D000480:Alkynes; D048588:Benzoxazines; D018791:CD4 Lymphocyte Count; D002648:Child; D002675:Child, Preschool; D003521:Cyclopropanes; D004359:Drug Therapy, Combination; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology; D017320:HIV Protease Inhibitors / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D015497:HIV-1 / Q000302:isolation & purification; D006801:Humans; D008297:Male; D019888:Nelfinavir / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D010078:Oxazines / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D012367:RNA, Viral / Q000097:blood; D018894:Reverse Transcriptase Inhibitors / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*
D000480:Alkynes; D048588:Benzoxazines; D003521:Cyclopropanes; D017320:HIV Protease Inhibitors; D010078:Oxazines; D012367:RNA, Viral; D018894:Reverse Transcriptase Inhibitors; D019888:Nelfinavir; C098320:efavirenz