ACTG A5353: A Pilot Study of Dolutegravir Plus Lamivudine for Initial Treatment of Human Immunodeficiency Virus-1 (HIV-1)-infected Participants With HIV-1 RNA < 500 000 Copies/mL

被引:82
作者
Taiwo, Babafemi O. [1 ,2 ]
Zheng, Lu [3 ]
Stefanescu, Andrei [4 ]
Nyaku, Amesika [5 ]
Bezins, Baiba [1 ,2 ]
Wallis, Carole L. [6 ,7 ]
Godfrey, Catherine [8 ]
Sax, Paul E. [9 ,10 ]
Acosta, Edward [11 ]
Haas, David [12 ]
Smith, Kimberly Y. [13 ]
Sha, Beverly [14 ]
Van Dam, Cornelius [15 ]
Gulic, Roy M. [16 ]
机构
[1] Northwestern Univ, Div Infect Dis, Chicago, IL 60611 USA
[2] Northwestern Univ, Ctr Global Hlth, Chicago, IL 60611 USA
[3] Harvard TH Chan Sch Publ Hlth, Dept Biostat, Boston, MA USA
[4] Harvard TH Chan Sch Publ Hlth, Stat Data Management Ctr, Boston, MA USA
[5] Rutgers State Univ, Div Infect Dis, New Brunswick, NJ USA
[6] BARC South Africa, Johannesburg, South Africa
[7] Lancet Labs, Johannesburg, South Africa
[8] NIAID, Div AIDS, Bethesda, MD 20892 USA
[9] Brigham & Womens Hosp, Div Infect Dis, 75 Francis St, Boston, MA 02115 USA
[10] Harvard Med Sch, Boston, MA USA
[11] Univ Alabama Birmingham, Dept Pharmacol & Toxicol, Birmingham, AL USA
[12] Vanderbilt Univ, Dept Med, Nashville, TN USA
[13] ViiV Healthcare, Res Triangle Pk, NC USA
[14] Rush Univ, Div Infect Dis, Chicago, IL 60612 USA
[15] Cone Hlth, Reg Ctr Infect Dis, Greensboro, NC USA
[16] Weill Cornell Med, Div Infect Dis, New York, NY USA
基金
美国国家卫生研究院;
关键词
dolutegravir; lamivudine; 2-drug therapy; mutation; naive; ANTIRETROVIRAL-NAIVE ADULTS; ONCE-DAILY DOLUTEGRAVIR; DOUBLE-BLIND; OPEN-LABEL; INFECTION; RALTEGRAVIR; RESISTANCE; INTEGRASE; RITONAVIR; REGIMENS;
D O I
10.1093/cid/cix1083
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Background. Limited data exist on initial human immunodeficiency virus type 1 (HIV-1) treatment with dolutegravir plus lamivudine. Methods. A5353 is a phase 2, single-arm, pilot study of once-daily dolutegravir (50 mg) plus lamivudine (300 mg) in treatment-naive participants with HIV-1 RNA >= 1000 and < 500 000 copies/mL. Exclusion criteria included active hepatitis B or major protease, reverse transcriptase, or integrase resistance. The primary efficacy measure was the proportion with HIV-1 RNA < 50 copies/mL (FDA [US Food and Drug Administration] Snapshot) at week 24. Virologic failure (VF) was confirmed HIV-1 RNA > 400 copies/mL at week 16/20 or > 200 copies/mL at or after week 24. Dolutegravir levels and drug resistance testing were performed at VF. Results. One hundred and twenty participants (87% male, median age 30 years, 37 (31%) HIV-1 RNA > 100 000 copies/mL) initiated study treatment. Median entry HIV-1 RNA and CD4 count were 4.61 log(10) copies/mL and 387 cells/mm(3). Virologic efficacy at week 24 was 108/120 (90%, confidence interval [83%, 95%]), with comparable results in the > 100 000 copies/mL and <= 100 000 copies/mL strata, that is, 89% (75%, 97%) and 90% (82%, 96%), respectively. Three participants with VF, had undetected plasma dolutegravir at >= 1 time points; the M184V and R263R/K mutations developed in 1 participant. Two participants experienced grade 3 possible/probable treatment-related adverse events; none discontinued treatment due to adverse events. Conclusions. Dolutegravir plus lamivudine demonstrated efficacy in individuals with pretreatment HIV-1 RNA up to 500 000 copies/mL in this pilot trial, but a participant developed resistance mutations.
引用
收藏
页码:1689 / 1697
页数:9
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