Comparative studies of two-times-daily versus three-times-daily indinavir in combination with zidovudine and lamivudine.
OBJECTIVE
To compare the efficacy and safety of two-times-daily versus three-times-daily indinavir in combination with zidovudine and lamivudine.


METHODS
Two multicenter, open-label, randomized 24-week studies.


METHODS
Adults HIV-1 infection, HIV-1 RNA greater than 10000 copies/ml, and no prior lamivudine or protease inhibitor therapy were eligible. In a pilot study (Study A), patients received indinavir at 800 mg every 8 h, 1000 mg every 12 h, or 1200 mg every 12 h. In a subsequent study (Study B), patients received indinavir at 800 mg every 8 h or 1200 mg every 12 h. All subjects received zidovudine (300 mg) and lamivudine (150 mg) every 12 h. An intent-to-treat analysis was used.


RESULTS
In Study A, which enrolled 88 patients, neither HIV-1 RNA nor CD4 cell responses differed significantly between treatment groups at 24 weeks when corrected for multiple comparisons. Study B enrolled 433 patients, but was prematurely discontinued when interim analysis suggested greater efficacy of three-times-daily indinavir. Of the first 87 patients reaching week 24, HIV-1 RNA was less than 400 copies/ml in 91% receiving three-times-daily versus 64% receiving two-times-daily indinavir (P < 0.01).


CONCLUSIONS
Three-times-daily indinavir appears more efficacious than two-times-daily dosing when administered with zidovudine and lamivudine. Two-times-daily indinavir dosing should only be considered in situations characterized by favorable pharmacokinetic drug-drug interactions.
Haas
D W
DW
Vanderbilt University School of Medicine, Nashville, Tennessee 37212, USA. david.w.haas@vanderbilt.edu
Arathoon
E
E
Thompson
M A
MA
de Jesus Pedro
R
R
Gallant
J E
JE
Uip
D E
DE
Currier
J
J
Noriega
L M
LM
Lewi
D S
DS
Uribe
P
P
Benetucci
L
L
Cahn
P
P
Paar
D
D
White
A C
AC
Collier
A C
AC
Ramirez-Ronda
C H
CH
Harvey
C
C
Chung
M O
MO
Mehrotra
D
D
Chodakewitz
J
J
Nguyen
B Y
BY
D000328:Adult; D019380:Anti-HIV Agents / Q000009:adverse effects / Q000627:therapeutic use*; D023241:Antiretroviral Therapy, Highly Active; D018791:CD4 Lymphocyte Count; D004334:Drug Administration Schedule; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology; D015497:HIV-1 / Q000302:isolation & purification / Q000502:physiology; D006801:Humans; D019469:Indinavir / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D019259:Lamivudine / Q000009:adverse effects / Q000627:therapeutic use*; D010865:Pilot Projects; D012367:RNA, Viral / Q000097:blood; D018894:Reverse Transcriptase Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D016896:Treatment Outcome; D019562:Viral Load; D015215:Zidovudine / Q000009:adverse effects / Q000627:therapeutic use*
D019380:Anti-HIV Agents; D012367:RNA, Viral; D018894:Reverse Transcriptase Inhibitors; D019259:Lamivudine; D015215:Zidovudine; D019469:Indinavir