AVANTI 2. Randomized, double-blind trial to evaluate the efficacy and safety of zidovudine plus lamivudine versus zidovudine plus lamivudine plus indinavir in HIV-infected antiretroviral-naive patients

被引：0

作者：

Gartland, M ^{[1
]}

Gerstoft, J ^{[1
]}

Goebel, F ^{[1
]}

Clumeck, N ^{[1
]}

Cooper, DA ^{[1
]}

Gatell, J ^{[1
]}

Gazzard, B ^{[1
]}

Gerstoft, J ^{[1
]}

Goebel, F ^{[1
]}

Lange, J ^{[1
]}

Montaner, J ^{[1
]}

Reiss, P ^{[1
]}

Rozenbaum, W ^{[1
]}

Vella, S ^{[1
]}

Beveridge, A ^{[1
]}

Cooper, DA ^{[1
]}

Duncombe, C ^{[1
]}

Gold, J ^{[1
]}

Haberl, M ^{[1
]}

Clumeck, N ^{[1
]}

Luyts, D ^{[1
]}

Montaner, J ^{[1
]}

Rachlis, A ^{[1
]}

Marina, R ^{[1
]}

Gerstoft, J ^{[1
]}

Wandall, JH ^{[1
]}

Elbrond, B ^{[1
]}

Molina, JM ^{[1
]}

Pialloux, G ^{[1
]}

Rozenbaum, W ^{[1
]}

Beauvais, L ^{[1
]}

Goebel, FD ^{[1
]}

Staszewski, S ^{[1
]}

Bruns, I ^{[1
]}

Hug, M ^{[1
]}

Reiss, P ^{[1
]}

Lange, J ^{[1
]}

Frissen, PHJ ^{[1
]}

van der Ende, ME ^{[1
]}

Bosboom, M ^{[1
]}

Baas, C ^{[1
]}

Milazzo, F ^{[1
]}

Moroni, M ^{[1
]}

Panebianco, R ^{[1
]}

Clotet, B ^{[1
]}

Artigas, JMG ^{[1
]}

Gonzalez-Lahoz, J ^{[1
]}

Leal, M ^{[1
]}

Rodriguez-Lopo, C ^{[1
]}

Gandarias, B ^{[1
]}

机构：

[1] Glaxo Wellcome Res & Dev Ltd, Greenford UB6 0HE, Middx, England

来源：

AIDS | 2000年 / 14卷 / 04期

关键词：

antiretroviral therapy; clinical trials; combination therapy; protease inhibitors; reverse transcriptase inhibitors;

D O I：

暂无

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 investigate the effect of combination antiretroviral therapy on plasma HIV-1 RNA as measured by HIV RNA PCR and to assess their safety and tolerability. Design: A randomized, multicentre, double-blind, placebo-controlled trial. Setting: Multicentre study in eight European countries, Australia and Canada. Patients: Antiretroviral naive patients (n = 103) with CD4 cell counts between 150 and 500 x 10(6)/I. Intervention: Patients were randomly assigned to zidovudine (ZDV; 200 mg three times per day) plus lamivudine (3TC; 150mg twice per day) or to ZDV + 3TC + indinavir (IND; 800 mg q8h) for 52 weeks. Main outcome measures: Degree and duration of reduction of plasma HIV-1 RNA as measured by RNA PCR; Development of drug-related toxicities sufficiently severe to warrant dose modification, interruption or permanent discontinuation. Results: ZDV + 3TC + IND reduced plasma HIV-1 RNA (P < 0.001) and increased CD4 cell count significantly (P = 0101) more than ZDV + 3TC. The addition of IND to ZDV + 3TC as initial therapy markedly increased the proportion of patients with plasma HIV-1 RNA values 500 copies/ml (31/52, 60%) or 20 copies/ml (24/52, 46%) as compared with ZDV + 3TC (9/50, 18% or 2/50, 4% respectively) at week 52 in an intention-to-treat, missing = failure analysis. Assessment of time to virological rebound (> 0.5 log(10) copies/ml above nadir) showed that patients who attained a minimum plasma HIV-1 RNA of less than or equal to 20 copies/ml were less likely to rebound than those who did not reach this threshold. The addition of IND to ZDV + 3TC did not result in any significant increase in adverse experiences. Conclusion: ZDV + 3TC + IND resulted in a considerable improvement compared with the double combination, in reduction in plasma HIV-1 RNA, increase in CD4 cell count and proportion of patients with HIV RNA below the limit of detection. Despite an average 3 log(10) decrease in plasma HIV-1 RNA on triple therapy, however, maximal suppression (less than or equal to 20 copies/ml) was only attained in about one-half of the patients in an intent-to-treat analysis. (C) 2000 Lippincott Williams & Wilkins

引用

页码：367 / 374

页数：8

共 16 条

[11] A controlled trial of two nucleoside analogues plus indinavir in persons with human immunodeficiency virus infection and CD4 cell counts of 200 per cubic millimeter or less [J].

Hammer, SM ;

Squires, KE ;

Hughes, MD ;

Grimes, JM ;

Demeter, LM ;

Currier, JS ;

Eron, JJ ;

Feinberg, JE ;

Balfour, HH ;

Dayton, LR ;

Chodakewitz, JA ;

Fischl, MA .

NEW ENGLAND JOURNAL OF MEDICINE, 1997, 337 (11) :725-733

[12] A trial comparing nucleoside monotherapy with combination therapy in HIV-infected adults with CD4 cell counts from 200 to 500 per cubic millimeter [J].

Hammer, SM ;

Katzenstein, DA ;

Hughes, MD ;

Gundacker, H ;

Schooley, RT ;

Haubrich, RH ;

Henry, WK ;

Lederman, MM ;

Phair, JP ;

Niu, M ;

Hirsch, MS ;

Merigan, TC ;

Blaschke, TF ;

Simpson, D ;

McLaren, C ;

Rooney, J ;

Salgo, M .

NEW ENGLAND JOURNAL OF MEDICINE, 1996, 335 (15) :1081-1090

[13] Safety and efficacy of lamivudine-zidovudine combination therapy in antiretroviral-naive patients - A randomized controlled comparison with zidovudine monotherapy [J].

Katlama, C ;

Ingrand, D ;

Loveday, C ;

Clumeck, N ;

Mallolas, J ;

Staszewski, S ;

Johnson, M ;

Hill, AM ;

Pearce, G ;

McDade, H .

JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION, 1996, 276 (02) :118-125

[14]

MONTANER J, 1997, 6 EUR C CLIN ASP TRE

[15] Decrease of HIV-1 RNA levels in lymphoid tissue and peripheral blood during treatment with ritonavir, lamivudine and zidovudine [J].

Notermans, DW ;

Jurriaans, S ;

de Wolf, F ;

Foudraine, NA ;

de Jong, JJ ;

Cavert, W ;

Schuwirth, CM ;

Kauffmann, RH ;

Meenhorst, PL ;

McDade, H ;

Goodwin, C ;

Leonard, JM ;

Goudsmit, J ;

Danner, SA .

AIDS, 1998, 12 (02) :167-173

[16] Safety and efficacy of lamivudine-zidovudine combination therapy in zidovudine-experienced patients - A randomized controlled comparison with zidovudine monotherapy [J].

Staszewski, S ;

Loveday, C ;

Picazo, JJ ;

Dellamonica, P ;

Skinhoj, P ;

Johnson, MA ;

Danner, SA ;

Harrigan, PR ;

Hill, AM ;

Verity, L ;

McDade, H .

JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION, 1996, 276 (02) :111-117

← 1 2 →