Triple-nucleoside regimens versus efavirenz-containing regimens for the initial treatment of HIV-1 infection.
BACKGROUND
Regimens containing three nucleoside reverse-transcriptase inhibitors offer an alternative to regimens containing nonnucleoside reverse-transcriptase inhibitors or protease inhibitors for the initial treatment of human immunodeficiency virus type 1 (HIV-1) infection, but data from direct comparisons are limited.


METHODS
This randomized, double-blind study involved three antiretroviral regimens for the initial treatment of subjects infected with HIV-1: zidovudine-lamivudine-abacavir, zidovudine-lamivudine plus efavirenz, and zidovudine-lamivudine-abacavir plus efavirenz.


RESULTS
We enrolled a total of 1147 subjects with a mean baseline HIV-1 RNA level of 4.85 log10 (71,434) copies per milliliter and a mean CD4 cell count of 238 per cubic millimeter were enrolled. A scheduled review by the data and safety monitoring board with the use of prespecified stopping boundaries led to a recommendation to stop the triple-nucleoside group and to present the results in the triple-nucleoside group in comparison with pooled data from the efavirenz groups. After a median follow-up of 32 weeks, 82 of 382 subjects in the triple-nucleoside group (21 percent) and 85 of 765 of those in the combined efavirenz groups (11 percent) had virologic failure; the time to virologic failure was significantly shorter in the triple-nucleoside group (P<0.001). This difference was observed regardless of the pretreatment HIV-1 RNA stratum (at least 100,000 copies per milliliter or below this level; P< or =0.001 for both comparisons). Changes in the CD4 cell count and the incidence of grade 3 or grade 4 adverse events did not differ significantly between the groups.


CONCLUSIONS
In this trial of the initial treatment of HIV-1 infection, the triple-nucleoside combination of abacavir, zidovudine, and lamivudine was virologically inferior to a regimen containing efavirenz and two or three nucleosides.
Gulick
Roy M
RM
Weill Medical College of Cornell University, New York, USA. rgulick@med.cornell.edu
Ribaudo
Heather J
HJ
Shikuma
Cecilia M
CM
Lustgarten
Stephanie
S
Squires
Kathleen E
KE
Meyer
William A
WA
Acosta
Edward P
EP
Schackman
Bruce R
BR
Pilcher
Christopher D
CD
Murphy
Robert L
RL
Maher
William E
WE
Witt
Mallory D
MD
Reichman
Richard C
RC
Snyder
Sally
S
Klingman
Karin L
KL
Kuritzkes
Daniel R
DR
D000328:Adult; D000368:Aged; D000480:Alkynes; D048588:Benzoxazines; D018791:CD4 Lymphocyte Count; D003521:Cyclopropanes; D015224:Dideoxynucleosides / Q000009:adverse effects / Q000627:therapeutic use; D004311:Double-Blind Method; D024882:Drug Resistance, Viral / Q000235:genetics; D004359:Drug Therapy, Combination; D005260:Female; D005500:Follow-Up Studies; D015658:HIV Infections / Q000188:drug therapy*; D015497:HIV-1 / Q000235:genetics; D006801:Humans; D019259:Lamivudine / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D009705:Nucleosides / Q000627:therapeutic use*; D010078:Oxazines / Q000009:adverse effects / Q000627:therapeutic use*; D012367:RNA, Viral / Q000097:blood; D018894:Reverse Transcriptase Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D015215:Zidovudine / Q000009:adverse effects / Q000627:therapeutic use; D000099227:Abacavir
D000480:Alkynes; D048588:Benzoxazines; D003521:Cyclopropanes; D015224:Dideoxynucleosides; D019259:Lamivudine; D009705:Nucleosides; D010078:Oxazines; D012367:RNA, Viral; D018894:Reverse Transcriptase Inhibitors; D015215:Zidovudine; D000099227:Abacavir; C098320:efavirenz