Tenofovir Alafenamide Versus Tenofovir Disoproxil Fumarate in the First Protease Inhibitor-Based Single-Tablet Regimen for Initial HIV-1 Therapy: A Randomized Phase 2 Study

被引：131

作者：

Mills, Anthony ^{[1
,2
]}

Crofoot, Gordon, Jr.

McDonald, Cheryl ^{[3
]}

Shalit, Peter ^{[4
]}

Flamm, Jason A. ^{[5
]}

Gathe, Joseph, Jr. ^{[6
]}

Scribner, Anita ^{[7
]}

Shamblaw, David ^{[8
]}

Saag, Michael ^{[9
]}

Cao, Huyen ^{[10
]}

Martin, Hal ^{[10
]}

Das, Moupali ^{[10
]}

Thomas, Anne ^{[10
]}

Liu, Hui C. ^{[10
]}

Yan, Mingjin ^{[10
]}

Callebaut, Christian ^{[10
]}

Custodio, Joseph ^{[10
]}

Cheng, Andrew ^{[10
]}

McCallister, Scott ^{[10
]}

机构：

[1] Mens Hlth Fdn, Southern Calif Mens Med Grp, Gordon Crofoot Res, Los Angeles, CA USA

[2] Univ Calif Los Angeles, Med Clin, Los Angeles, CA USA

[3] Tarrant Cty Infect Dis Associates, Ft Worth, TX USA

[4] Univ Washington, Sch Med, Div Allergy & Infect Dis, Seattle, WA USA

[5] Kaiser Permanente, Sacramento, CA USA

[6] Therapeut Concepts, Houston, TX USA

[7] DCOL Ctr Clin Res, Longview, TX USA

[8] La Playa Med Grp & Clin Res, San Diego, CA USA

[9] Univ Alabama Birmingham, Ctr AIDS Res, Birmingham, AL USA

[10] Gilead Sci Inc, 333 Lakeside Dr, Foster City, CA 94404 USA

来源：

JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES | 2015年 / 69卷 / 04期

关键词：

tenofovir alafenamide; GS-7340; darunavir; cobicistat; single-tablet regimen; AGE-RELATED COMORBIDITIES; FIXED-DOSE COMBINATION; BONE-MINERAL DENSITY; PHOSPHONOAMIDATE PRODRUGS; HIV-1-INFECTED PATIENTS; ABACAVIR-LAMIVUDINE; INFECTED ADULTS; EFFICACY; SAFETY; TENOFOVIR/EMTRICITABINE;

D O I：

10.1097/QAI.0000000000000618

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

Objectives: To evaluate the safety and efficacy of the novel tenofovir prodrug, tenofovir alafenamide (TAF), as part of the first protease inhibitor-based single-tablet regimen (STR) for initial treatment of HIV-1 infection. Methods: Antiretroviral therapy (ART)-naive adults with estimated glomerular filtration rate >= 70 mL/min were randomized 2:1 to receive the darunavir/cobicistat/emtricitabine/tenofovir alafenamide (D/C/F/TAF) STR (TAF: N = 103) or darunavir + cobicistat + emtricitabine/tenofovir disoproxil fumarate (TDF:N = 50) once daily with matched placebos for 48 weeks. Results: At week 24, viral suppression (HIV-1 RNA <50 copies/mL) rates were similar (TAF 74.8% vs. TDF 74.0%). At week 48, rates were TAF 76.7% vs. TDF 84.0%; the difference was driven by higher rate of discontinuations in TAF (6.8%) vs. TDF (2%). Among those with virologic failure, none developed resistance. Most adverse events were of mild/moderate severity. The mean change in serum creatinine from baseline at week 48 was 0.06 mg/dL (95% confidence interval: 0.04 to 0.08) for TAF vs. 0.09 mg/dL (95% confidence interval: 0.05 to 0.14) for TDF (P = 0.053). The % change in retinol binding protein/Cr ratio was +9 (TAF) vs. +54 (TDF), P = 0.003; the % change in urine beta-2 microglobulin/Cr ratio was -42.0 (TAF) vs. +2.3 (TDF), P = 0.002. The % change in hip bone mineral density (BMD) was -0.84 (TAF) vs. -3.82 (TDF), P < 0.001 and in spine BMD was -1.57 (TAF) vs. -3.62 (TDF), P = 0.003. There were no fractures in either group. Conclusions: The TAF arm had significantly improved renal and bone safety parameters: less proteinuria and less change in hip and spine BMD, consistent with results from a similarly designed study of the elvitegravir/C/F/TAF STR. This D/C/F/TAF STR offers a promising option for initial HIV treatment, with the high barrier to resistance of darunavir, and the potential for improved long-term renal and bone safety with TAF.

引用

页码：439 / 445

页数：7

共 45 条

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