Intensification of a triple-nucleoside regimen with tenofovir or efavirenz in HIV-1-infected patients with virological suppression.
OBJECTIVE
To compare a quadruple-nucleoside with an efavirenz-containing regimen for treatment of HIV-1 infection.


METHODS
A randomized, open-label study of the AIDS Clinical Trials Group (ACTG).


METHODS
Subjects receiving zidovudine/lamivudine/abacavir on ACTG 5095 with HIV-1 RNA less than 200 copies/ml were randomly assigned to intensify either with tenofovir or efavirenz. Subjects were followed for time to treatment failure, defined as either virological failure or treatment discontinuation. Analyses were intent-to-treat.


RESULTS
One hundred and seventy subjects (21% women; 56% non-white) entered the study. At baseline, 95 and 73% had HIV-1-RNA levels less than 200 and 50 copies/ml, respectively; the median CD4 cell count was 453 cells/microl. Over a median 79 weeks follow-up, 165 (97%) completed the study, three (2%) discontinued, and two (1%) died. Treatment failure occurred in 31 subjects: 18 (21%) (quadruple nucleosides) and 13 (15%) (efavirenz-containing regimen); however the failure-time curves crossed and demonstrated a non-constant treatment effect over time, characterized by more early treatment failures on the efavirenz-containing regimen and more late treatment failures on the four-nucleoside regimen. HIV-1 RNA remained suppressed in more than 88% of subjects to less than 200 copies/ml and in more than 78% to less than 50 copies/ml at weeks 24, 48, and 72, without differences by treatment arm. There were no significant differences between the regimens in CD4 cell increases, time to new grade 3/4 adverse events, or adherence.


CONCLUSIONS
The safety, tolerability, and efficacy of the four-nucleoside regimen were not significantly different from the efavirenz-containing regimen. These pilot data support further investigation of the quadruple-nucleoside regimen.
Gulick
Roy M
RM
Weill Medical College of Cornell University, 525 East 68th Street, New York, NY 10021, USA. rgulick@med.cornell.edu
Lalama
Christina M
CM
Ribaudo
Heather J
HJ
Shikuma
Cecilia M
CM
Schackman
Bruce R
BR
Schouten
Jeffrey
J
Squires
Kathleen E
KE
Koletar
Susan L
SL
Pilcher
Christopher D
CD
Reichman
Richard C
RC
Klingman
Karin L
KL
Kuritzkes
Daniel R
DR
D000225:Adenine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000328:Adult; D000368:Aged; D000480:Alkynes; D019380:Anti-HIV Agents / Q000009:adverse effects / Q000627:therapeutic use*; D023241:Antiretroviral Therapy, Highly Active / Q000009:adverse effects / Q000379:methods; D048588:Benzoxazines / Q000009:adverse effects / Q000627:therapeutic use*; D018791:CD4 Lymphocyte Count; D003521:Cyclopropanes; D024882:Drug Resistance, Viral; D005260:Female; D005838:Genotype; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology / Q000821:virology; D015497:HIV-1 / Q000187:drug effects / Q000235:genetics / Q000302:isolation & purification; D006801:Humans; D008297:Male; D008875:Middle Aged; D063065:Organophosphonates / Q000009:adverse effects / Q000627:therapeutic use*; D010349:Patient Compliance; D012367:RNA, Viral / Q000097:blood; D018894:Reverse Transcriptase Inhibitors / Q000009:adverse effects / Q000627:therapeutic use; D000068698:Tenofovir; D016896:Treatment Outcome; D019562:Viral Load
D000480:Alkynes; D019380:Anti-HIV Agents; D048588:Benzoxazines; D003521:Cyclopropanes; D063065:Organophosphonates; D012367:RNA, Viral; D018894:Reverse Transcriptase Inhibitors; D000068698:Tenofovir; D000225:Adenine; C098320:efavirenz