Abacavir-lamivudine versus tenofovir-emtricitabine for initial HIV-1 therapy.
BACKGROUND
The use of fixed-dose combination nucleoside reverse-transcriptase inhibitors (NRTIs) with a nonnucleoside reverse-transcriptase inhibitor or a ritonavir-boosted protease inhibitor is recommended as initial therapy in patients with human immunodeficiency virus type 1 (HIV-1) infection, but which NRTI combination has greater efficacy and safety is not known.


METHODS
In a randomized, blinded equivalence study involving 1858 eligible patients, we compared four once-daily antiretroviral regimens as initial therapy for HIV-1 infection: abacavir-lamivudine or tenofovir disoproxil fumarate (DF)-emtricitabine plus efavirenz or ritonavir-boosted atazanavir. The primary efficacy end point was the time from randomization to virologic failure (defined as a confirmed HIV-1 RNA level > or = 1000 copies per milliliter at or after 16 weeks and before 24 weeks, or > or = 200 copies per milliliter at or after 24 weeks).


RESULTS
A scheduled interim review by an independent data and safety monitoring board showed significant differences in virologic efficacy, according to the NRTI combination, among patients with screening HIV-1 RNA levels of 100,000 copies per milliliter or more. At a median follow-up of 60 weeks, among the 797 patients with screening HIV-1 RNA levels of 100,000 copies per milliliter or more, the time to virologic failure was significantly shorter in the abacavir-lamivudine group than in the tenofovir DF-emtricitabine group (hazard ratio, 2.33; 95% confidence interval, 1.46 to 3.72; P<0.001), with 57 virologic failures (14%) in the abacavir-lamivudine group versus 26 (7%) in the tenofovir DF-emtricitabine group. The time to the first adverse event was also shorter in the abacavir-lamivudine group (P<0.001). There was no significant difference between the study groups in the change from the baseline CD4 cell count at week 48.


CONCLUSIONS
In patients with screening HIV-1 RNA levels of 100,000 copies per milliliter or more, the times to virologic failure and the first adverse event were both significantly shorter in patients randomly assigned to abacavir-lamivudine than in those assigned to tenofovir DF-emtricitabine. (ClinicalTrials.gov number, NCT00118898.)
Sax
Paul E
PE
Division of Infectious Diseases and the Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA. psax@partners.org
Tierney
Camlin
C
Collier
Ann C
AC
Fischl
Margaret A
MA
Mollan
Katie
K
Peeples
Lynne
L
Godfrey
Catherine
C
Jahed
Nasreen C
NC
Myers
Laurie
L
Katzenstein
David
D
Farajallah
Awny
A
Rooney
James F
JF
Ha
Belinda
B
Woodward
William C
WC
Koletar
Susan L
SL
Johnson
Victoria A
VA
Geiseler
P Jan
PJ
Daar
Eric S
ES
D000225:Adenine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000293:Adolescent; D000328:Adult; D000704:Analysis of Variance; D019380:Anti-HIV Agents / Q000009:adverse effects / Q000627:therapeutic use*; D018791:CD4 Lymphocyte Count; D003841:Deoxycytidine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D015224:Dideoxynucleosides; D004311:Double-Blind Method; D004338:Drug Combinations; D024882:Drug Resistance, Viral; D000068679:Emtricitabine; D005260:Female; D050723:Fractures, Bone / Q000139:chemically induced; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology; D015497:HIV-1 / Q000235:genetics / Q000302:isolation & purification; D006801:Humans; D019259:Lamivudine / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D063065:Organophosphonates / Q000009:adverse effects / Q000627:therapeutic use*; D012367:RNA, Viral / Q000097:blood; D000068698:Tenofovir; D013810:Therapeutic Equivalency; D013997:Time Factors; D017211:Treatment Failure; D019562:Viral Load; D055815:Young Adult; D000099227:Abacavir
D000225:Adenine; D019380:Anti-HIV Agents; D003841:Deoxycytidine; D015224:Dideoxynucleosides; D004338:Drug Combinations; D000068679:Emtricitabine; D019259:Lamivudine; D063065:Organophosphonates; D012367:RNA, Viral; D000068698:Tenofovir; C492871:abacavir, lamivudine drug combination; D000099227:Abacavir