Durable efficacy of tipranavir-ritonavir in combination with an optimised background regimen of antiretroviral drugs for treatment-experienced HIV-1-infected patients at 48 weeks in the Randomized Evaluation of Strategic Intervention in multi-drug resistant patients with Tipranavir (RESIST) studies: an analysis of combined data from two randomised open-label trials

被引:250
作者
Hicks, Charles B. [1 ]
Cahn, Pedro
Cooper, David A.
Walmsley, Sharon L.
Katlama, Christine
Clotet, Bonaventura
Lazzarin, Adriano
Johnson, Margaret A.
Neubacher, Dietmar
Mayers, Douglas
Valdez, Hernan
机构
[1] Duke Univ, Med Ctr, Div Infect Dis & Int Hlth, Durham, NC 27710 USA
[2] Fdn Huesped, Buenos Aires, DF, Argentina
[3] Univ New S Wales, Natl Ctr HIV Epidemiol & Clin Res, Sydney, NSW, Australia
[4] Univ Toronto, Toronto, ON, Canada
[5] Hop La Pitie Salpetriere, Paris, France
[6] Hosp Univ Germans Trias & Pujol, Barcelona, Spain
[7] Vita Salute San Raffaele Univ, Milan, Italy
[8] Royal Free Hosp, London NW3 2QG, England
[9] Boehringer Ingelheim Pharma GmbH & Co KG, Ingelheim, Germany
[10] Boehringer Ingelheim Pharmaceut Inc, Ridgefield, CT 06877 USA
关键词
PROTEASE INHIBITOR TIPRANAVIR; REDUCED SUSCEPTIBILITY; VIROLOGICAL FAILURE; FUSION INHIBITOR; THERAPY; HIV-1; ENFUVIRTIDE; PNU-140690;
D O I
10.1016/S0140-6736(06)69154-X
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Background Treatment options for HIV-1 infected individuals who have received extensive previous antiretroviral therapy are limited. We compared efficacy and safety of the novel non-peptidic protease inhibitor tipranavir co-administered with ritonavir plus an optimised background regimen with that of an investigator-selected ritonavir-boosted comparator protease inhibitor (CPI-ritonavir) in such patients. Methods We did a combined analysis of 48-week data from two ongoing, randomised, open-label, multinational, phase III, RESIST studies. HIV-1-infected adults with 3 months or longer previous triple antiretroviral class experience, two or more previous protease inhibitor regimens, HIV-1 RNA 1000 copies per mL or greater, and genotypically demonstrated primary resistance to protease inhibitor, were eligible. Primary endpoints were proportion of treatment responders (with reduction in viral load of 1 log,, copies per mL or greater below baseline without treatment change) at 48 weeks and time to treatment failure through 48 weeks (intention-to-treat analysis). The RESIST studies are registered with ClinicalTrials.gov, numbers NCT00054717 (RESIST-1) and NCT00144170 (RESIST-2). Findings 3324 patients were screened; 746 received tipranavir-ritonavir and 737 CPI-ritonavir. 486 (65.1%) patients on tipranavir-ritonavir and 192 (26.1%) on CPI-ritonavir remained on assigned treatment until week 48. At week 48, more patients achieved and maintained treatment response in the tipranavir-ritonavir group than in the CPI-ritonavir group (251 [33.6%] vs 113 [15.3%]; p<0.0001). Median time to treatment failure was significantly longer in the tipranavir-ritonavir group than in the CPI-ritonavir group (113 days vs 0 days; p<0.0001). Gastrointestinal system disorders and raised transaminase, cholesterol, and triglycerides were more frequent in the tipranavir-ritonavir group than in the CPI-ritonavir group. Interpretation Compared with CPI-ritonavir, tipranavir-ritonavir with an optimised background regimen provides better virological and immunological responses over 48 weeks in patients who have received extensive previous antiretroviral treatment.
引用
收藏
页码:466 / 475
页数:10
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