HIV-1 RNA response to antiretroviral treatment in 1280 participants in the Delta Trial:: an extended virology study

被引：25

作者：

Aboulker, JP ^{[1
]}

Babiker, AG ^{[1
]}

Brun-Vézinet, F ^{[1
]}

Darbyshire, JH ^{[1
]}

Flandre, P ^{[1
]}

Gazzard, B ^{[1
]}

Nunn, AJ ^{[1
]}

Goodall, R ^{[1
]}

Aber, V ^{[1
]}

Bragman, K ^{[1
]}

Breckenridge, AM ^{[1
]}

Carbon, C ^{[1
]}

Charreau, I ^{[1
]}

Chene, G ^{[1
]}

Collis, P ^{[1
]}

Cooper, D ^{[1
]}

Dormont, J ^{[1
]}

Fiddian, P ^{[1
]}

Flepp, M ^{[1
]}

Goebel, FD ^{[1
]}

Hooker, M ^{[1
]}

Lange, J ^{[1
]}

Lüthy, R ^{[1
]}

Peto, TEA ^{[1
]}

Reiss, P ^{[1
]}

Seligmann, M ^{[1
]}

Stone, AB ^{[1
]}

Thomis, J ^{[1
]}

Vella, S ^{[1
]}

Walckenaer, G ^{[1
]}

Warrell, D ^{[1
]}

Weller, IVD ^{[1
]}

Wilber, R ^{[1
]}

Yeni, P ^{[1
]}

Yeo, J ^{[1
]}

Withnall, R ^{[1
]}

Goudsmit, J ^{[1
]}

Huraux, JM ^{[1
]}

van der Noorda, J ^{[1
]}

Weiss, R ^{[1
]}

Boucher, C ^{[1
]}

Schuurman, R ^{[1
]}

Descamps, D ^{[1
]}

Jeffries, D ^{[1
]}

Tedder, R ^{[1
]}

Weber, J ^{[1
]}

Krzyanowski, C ^{[1
]}

Weverling, G ^{[1
]}

机构：

[1] UCL, Sch Med, Mortimer Market Ctr, MRC,Clin Trials Unit, London WC1E 6AU, England

来源：

AIDS | 1999年 / 13卷 / 01期

关键词：

antiviral therapy; progression; HIV-1; RNA; viral load;

D O I：

10.1097/00002030-199901140-00008

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 assess changes in HIV RNA and their relationship to disease progression. Design and setting: Delta was a randomized double-blind trial comparing zidovudine (ZDV) monotherapy with ZDV plus didanosine (ddl) or ZDV plus zalcitabine (ddC). Participants had AIDS (with CD4 cell counts above 50 x 10(6)/l), AIDS-related complex, or were asymptomatic with CD4 cell counts below 350 x 10(6)/l. The trial included both ZDV-naive and ZDV-experienced participants. Participants: A total of 1280 participants in the Delta trial whose serum samples had been stored at -70 degrees C and who had a minimum of one sample taken before the start of treatment and at least one later sample. Methods: HIV-1 RNA quantification was performed using the nucleic acid sequence-based amplification HIV-1 RNA quantitative assay with a cut-off of 800 copies/ml. Results: Reductions in HIV RNA by treatment group were consistent with the clinical results; in ZDV-naive participants the maximum median fall occurred at 4 weeks for all three groups (ZDV, 0.54 log(10) copies/ml; ZDV-ddl, 1.38 log(10) copies/ml; ZDV-ddC, 1.31 log(10), copies/ml). On average the reductions were smaller in ZDV-experienced participants but the difference between the monotherapy and combination arms was very similar in ZDV-naive and experienced participants. Baseline HIV RNA levels, adjusted for CD4 cell counts were highly predictive of time to virological response (HIV RNA < 800 copies/ml); HIV RNA nadirs achieved were predictive of survival. Viral load rebound following response was independent of treatment group and previous ZDV therapy. Conclusions: Virological changes in response to treatment are of Value in assessing prognosis and the activity of new therapies; in particular, there is a strong association between the minimum HIV RNA achieved in the first 16 weeks and subsequent clinical response. CD4 cell counts are independently predictive of response. (C) 1999 Lippincott Williams & Wilkins.

引用

页码：57 / 65

页数：9

共 14 条

[1]

Aber V, 1996, LANCET, V348, P283, DOI 10.1016/S0140-6736(96)05387-1

[2] HIV-1 viral load, phenotype, and resistance in a subset of drug-naive participants from the Delta trial [J].

BrunVezinet, F ;

Boucher, C ;

Loveday, C ;

Descamps, D ;

Fauveau, V ;

Izopet, J ;

Jeffries, D ;

Kaye, S ;

Krzyanowski, C ;

Nunn, A ;

Schuurman, R ;

Seigneurin, JM ;

Tamalet, C ;

Tedder, R ;

Weber, J ;

Weverling, GJ ;

Aber, V ;

Aboulker, JP ;

Babiker, AG ;

Bragman, K ;

Breckenridge, AM ;

Carbon, C ;

Charreau, I ;

Chene, G ;

Collis, P ;

Cooper, D ;

Darbyshire, JH ;

Dormont, J ;

Fiddian, P ;

Flepp, M ;

Gazzard, B ;

Goebel, FD ;

Hooker, M ;

Lange, J ;

Luthy, R ;

Peto, TEA ;

Reiss, P ;

Seligmann, M ;

Stone, AB ;

Thomis, J ;

Vella, S ;

Walckenaer, G ;

Warrell, D ;

Weller, IVD ;

Wilber, R ;

Yeni, P ;

Yeo, J ;

Withnall, R ;

Babiker, A ;

Bloch, J .

LANCET, 1997, 350 (9083) :983-990

[3] The relation of virologic and immunologic markers to clinical outcomes after nucleoside therapy in HIV-infected adults with 200 to 500 CD4 cells per cubic millimeter [J].

Katzenstein, DA ;

Hammer, SM ;

Hughes, MD ;

Gundacker, H ;

Jackson, JB ;

Fiscus, S ;

Rasheed, S ;

Elbeik, T ;

Reichman, R ;

Japour, A ;

Merigan, TC ;

Hirsch, MS .

NEW ENGLAND JOURNAL OF MEDICINE, 1996, 335 (15) :1091-1098

[4] Plasma viral load and CD4(+) lymphocytes as prognostic markers of HIV-1 infection [J].

Mellors, JW ;

Munoz, A ;

Giorgi, JV ;

Margolick, JB ;

Tassoni, CJ ;

Gupta, P ;

Kingsley, LA ;

Todd, JA ;

Saah, AJ ;

Detels, R ;

Phair, JP ;

Rinaldo, CR .

ANNALS OF INTERNAL MEDICINE, 1997, 126 (12) :946-954

[5] Serum HIV-1 RNA levels and time to development of AIDS in the multicenter hemophilia cohort study [J].

OBrien, TR ;

Blattner, WA ;

Waters, D ;

Eyster, ME ;

Hilgartner, MW ;

Cohen, AR ;

Luban, N ;

Hatzakis, A ;

Aledort, LM ;

Rosenberg, PS ;

Miley, WJ ;

Kroner, BL ;

Goedert, JJ .

JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION, 1996, 276 (02) :105-110

[6] Changes in plasma HIV RNA levels and CD4(+) lymphocyte counts predict both response to antiretroviral therapy and therapeutic failure [J].

OBrien, WA ;

Hartigan, PM ;

Daar, ES ;

Simberkoff, MS ;

Hamilton, JD .

ANNALS OF INTERNAL MEDICINE, 1997, 126 (12) :939-945

[7]

OPRAVIL M, 1997, INT WORKSH HIV DRUG

[8]

PERDERSEN C, 1997, J ACQ IMMUN DEF SYND, V16, P93

[9] HIV-1 RNA levels and the development of clinical disease [J].

Phillips, AN ;

Eron, JJ ;

Bartlett, JA ;

Rubin, M ;

Johnson, J ;

Price, S ;

Self, P ;

Hill, AM ;

Akil, B ;

Beall, G ;

Bellos, N ;

Berry, P ;

Brummit, C ;

Cameron, B ;

Cohen, C ;

Donabedian, H ;

Mayar, K ;

McKinley, G ;

Sepulveda, G ;

Thompson, M ;

Tsoukas, C ;

Walmsley, S ;

Horton, J ;

Kerkering, T ;

Matthew, E ;

Pearce, D ;

Peterson, D ;

Pottage, J ;

Sampson, J ;

Smith, W ;

Yangco, B ;

Cowan, J ;

Kaczka, C ;

Zameck, R ;

Dawson, D ;

Pobiner, B ;

Gilbert, C ;

ScottLennox, J ;

DeMasi, R ;

Jarrett, P ;

Yuen, G ;

Esinhart, J ;

Quinn, J ;

Fallon, MA ;

Benoit, S .

AIDS, 1996, 10 (08) :859-865

[10] Multicenter comparison of three commercial methods for quantification of human immunodeficiency virus type 1 RNA in plasma [J].

Schuurman, R ;

Descamps, D ;

Weverling, GJ ;

Kaye, S ;

Tijnagel, J ;

Williams, I ;

vanLeeuwen, R ;

Tedder, R ;

Boucher, CAB ;

BrunVezinet, F ;

Loveday, C .

JOURNAL OF CLINICAL MICROBIOLOGY, 1996, 34 (12) :3016-3022

← 1 2 →