Intensification of a triple-nucleoside regimen with tenofovir or efavirenz in HIV-1-infected patients with virological suppression

被引:16
作者
Gulick, Roy M.
Lalama, Christina M.
Ribaudo, Heather J.
Shikuma, Cecilia M.
Schackman, Bruce R.
Schouten, Jeffrey
Squires, Kathleen E.
Koletar, Susan L.
Pilcher, Christopher D.
Reichman, Richard C.
Klingman, Karin L.
Kuritzkes, Daniel R.
机构
[1] Cornell Univ, Weill Med Coll, New York, NY 10021 USA
[2] Harvard Univ, Sch Publ Hlth, Stat & Data Anal Ctr, Boston, MA 02115 USA
[3] Univ Hawaii, Honolulu, HI 96822 USA
[4] Univ Washington, Seattle, WA 98195 USA
[5] Univ So Calif, Med Ctr, Los Angeles, CA USA
[6] Thomas Jefferson Univ, Jefferson Med Coll, Philadelphia, PA 19107 USA
[7] Ohio State Univ, Columbus, OH 43210 USA
[8] Univ Calif San Francisco, San Francisco, CA 94143 USA
[9] Univ Rochester, Rochester, NY USA
[10] NIAID, Div AIDS, Bethesda, MD 20892 USA
[11] Brigham & Womens Hosp, Boston, MA 02115 USA
[12] Harvard Univ, Sch Med, Boston, MA 02115 USA
关键词
abacavir; antiretroviral therapy; efavirenz; lamivudine; non-nucleoside reverse transcriptase inhibitors; nucleoside reverse transcriptase inhibitors; quadruple nucleosides; tenofovir; zidovudine; ABACAVIR/LAMIVUDINE/ZIDOVUDINE PLUS TENOFOVIR; IMMUNODEFICIENCY-VIRUS-INFECTION; ANTIRETROVIRAL DRUG-RESISTANCE; HIV-1; INFECTION; OPEN-LABEL; PROTEASE INHIBITORS; INITIAL TREATMENT; LAMIVUDINE; THERAPY; ADULTS;
D O I
10.1097/QAD.0b013e32805e8753
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Objective: To compare a quadruple-nucleoside with an efavirenz-containing regimen for treatment of HIV-1 infection. Design: 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/mu l. 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 (151%) (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. Conclusion: 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. (c) 2007 Lippincott Williams & Wilkins.
引用
收藏
页码:813 / 823
页数:11
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