A randomized trial to study first-line combination therapy with or without a protease inhibitor in HIV-1-infected patients.
OBJECTIVE
To compare one protease inhibitor (PI)-based and two PI-sparing antiretroviral therapy regimens.


METHODS
International, open label, randomized study of antiretroviral drug-naive patients, with CD4 lymphocyte counts >/= 200 x 106 cells/l and plasma HIV-1 RNA levels > 500 copies/ml. Treatment assignment to stavudine and didanosine plus indinavir or nevirapine or lamivudine. Primary study endpoint was the percentage of patients with plasma HIV-1 RNA levels < 500 copies/ml after 48 weeks in the intention-to-treat analysis (ITT).


RESULTS
In total, 298 patients were enrolled. After 48 weeks, the percentage of patients in the indinavir, nevirapine and lamivudine arms with HIV-1 RNA < 500 copies/ml was 57.0%, 58.4% and 58.7%, respectively, in an ITT analysis. After 96 weeks of follow-up, these percentages were 50.0%, 59.6% and 45.0%, respectively. The percentage of patients with HIV-1 RNA < 50 copies/ml was significantly less for those allocated to lamivudine in an on-treatment analysis after 48 and 96 weeks of follow-up. Patients in the nevirapine arm experienced a smaller increase in the absolute number of CD4 T lymphocytes. There were no significant differences in the incidence of serious adverse events.


CONCLUSIONS
A comparable virological response can be achieved with first-line PI-base and PI-sparing regimens. The triple nucleoside regimen utilized may be less likely to result in viral suppression to < 50 copies/ml, while the nevirapine-based regimen is associated with a lower increase in CD4 T lymphocytes.
van Leeuwen
Remko
R
International Antiviral Therapy Evaluation Center, Academic Medical Center, Amsterdam, The Netherlands.
Katlama
Christine
C
Murphy
Robert L
RL
Squires
Kathleen
K
Gatell
José
J
Horban
Andrej
A
Clotet
Bonaventura
B
Staszewski
Shlomo
S
van Eeden
Arne
A
Clumeck
Nathan
N
Moroni
Mauro
M
Pavia
Andrew T
AT
Schmidt
Reinhold E
RE
Gonzalez-Lahoz
Juan
J
Montaner
Julio
J
Antunes
Francisco
F
Gulick
Robert
R
Bánhegyi
Dénes
D
van der Valk
Marc
M
Reiss
Peter
P
van Weert
Liesbeth
L
van Leth
Frank
F
Johnson
Victoria A
VA
Sommadossi
Jean-Pierre
JP
Lange
Joep M
JM
D000293:Adolescent; D000328:Adult; D000368:Aged; D023241:Antiretroviral Therapy, Highly Active; D018791:CD4 Lymphocyte Count; D005260:Female; D015658:HIV Infections / Q000097:blood / Q000188:drug therapy*; D017320:HIV Protease Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D015497:HIV-1; D006801:Humans; D019469:Indinavir / Q000009:adverse effects / Q000627:therapeutic use*; D019259:Lamivudine / Q000009:adverse effects / Q000627:therapeutic use*; D008055:Lipids / Q000097:blood; D008297:Male; D008875:Middle Aged; D019829:Nevirapine / Q000009:adverse effects / Q000627:therapeutic use*; D016896:Treatment Outcome
D017320:HIV Protease Inhibitors; D008055:Lipids; D019259:Lamivudine; D019469:Indinavir; D019829:Nevirapine