Class-sparing regimens for initial treatment of HIV-1 infection.
BACKGROUND
The use of either efavirenz or lopinavir-ritonavir plus two nucleoside reverse-transcriptase inhibitors (NRTIs) is recommended for initial therapy for patients with human immunodeficiency virus type 1 (HIV-1) infection, but which of the two regimens has greater efficacy is not known. The alternative regimen of lopinavir-ritonavir plus efavirenz may prevent toxic effects associated with NRTIs.


METHODS
In an open-label study, we compared three regimens for initial therapy: efavirenz plus two NRTIs (efavirenz group), lopinavir-ritonavir plus two NRTIs (lopinavir-ritonavir group), and lopinavir-ritonavir plus efavirenz (NRTI-sparing group). We randomly assigned 757 patients with a median CD4 count of 191 cells per cubic millimeter and a median HIV-1 RNA level of 4.8 log10 copies per milliliter to the three groups.


RESULTS
At a median follow-up of 112 weeks, the time to virologic failure was longer in the efavirenz group than in the lopinavir-ritonavir group (P=0.006) but was not significantly different in the NRTI-sparing group from the time in either of the other two groups. At week 96, the proportion of patients with fewer than 50 copies of plasma HIV-1 RNA per milliliter was 89% in the efavirenz group, 77% in the lopinavir-ritonavir group, and 83% in the NRTI-sparing group (P=0.003 for the comparison between the efavirenz group and the lopinavir-ritonavir group). The groups did not differ significantly in the time to discontinuation because of toxic effects. At virologic failure, antiretroviral resistance mutations were more frequent in the NRTI-sparing group than in the other two groups.


CONCLUSIONS
Virologic failure was less likely in the efavirenz group than in the lopinavir-ritonavir group. The virologic efficacy of the NRTI-sparing regimen was similar to that of the efavirenz regimen but was more likely to be associated with drug resistance. (ClinicalTrials.gov number, NCT00050895 [ClinicalTrials.gov].).
Riddler
Sharon A
SA
University of Pittsburgh, Pittsburgh, USA. riddler@dom.pitt.edu
Haubrich
Richard
R
DiRienzo
A Gregory
AG
Peeples
Lynne
L
Powderly
William G
WG
Klingman
Karin L
KL
Garren
Kevin W
KW
George
Tania
T
Rooney
James F
JF
Brizz
Barbara
B
Lalloo
Umesh G
UG
Murphy
Robert L
RL
Swindells
Susan
S
Havlir
Diane
D
Mellors
John W
JW
D000293:Adolescent; D000328:Adult; D000480:Alkynes; D048588:Benzoxazines / Q000009:adverse effects / Q000627:therapeutic use*; D003521:Cyclopropanes; D024882:Drug Resistance, Viral / Q000235:genetics; D004359:Drug Therapy, Combination; D005260:Female; D015658:HIV Infections / Q000188:drug therapy*; D017320:HIV Protease Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D015497:HIV-1 / Q000235:genetics / Q000302:isolation & purification; D006801:Humans; D053208:Kaplan-Meier Estimate; D061466:Lopinavir; D008297:Male; D008875:Middle Aged; D009154:Mutation; D011446:Prospective Studies; D011744:Pyrimidinones / Q000009:adverse effects / Q000627:therapeutic use*; D012367:RNA, Viral / Q000097:blood; D018894:Reverse Transcriptase Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D019438:Ritonavir / Q000009:adverse effects / Q000627:therapeutic use*; D017211:Treatment Failure
D000480:Alkynes; D048588:Benzoxazines; D003521:Cyclopropanes; D017320:HIV Protease Inhibitors; D011744:Pyrimidinones; D012367:RNA, Viral; D018894:Reverse Transcriptase Inhibitors; D061466:Lopinavir; C098320:efavirenz; D019438:Ritonavir