Early HIV infection in vivo: branching-process model for studying timing of immune responses and drug therapy

被引:26
作者
Wick, D [1 ]
Self, SG [1 ]
机构
[1] Fred Hutchinson Canc Res Ctr, Seattle, WA 98109 USA
关键词
primary HIV infection; primary SIV infection; early intervention; antiretroviral treatment; in vivo kinetics; PMPA; pathogen eradication; HAART; branching-process models; extinction;
D O I
10.1016/S0025-5564(00)00013-4
中图分类号
Q [生物科学];
学科分类号
07 ; 0710 ; 09 ;
摘要
We propose a stochastic, branching-process model of early events in vivo in human or simian immunodeficiency virus (HIV or SIV) infection and study the influence that the time of appearance of virus-specific antibodies or cytotoxic cells, or of administration of antiretroviral drugs, has on the probability of progression to a chronic infection. III some biological scenarios, our model pr-edicts that a few days' delay in response or intervention would make little difference, while in others it would be highly deleterious. We show that prophylactic efficacy does not require perfect efficiency at neutralizing infectious virus. Data from a trial of PMPA, a potent antiretroviral drug, as post-exposure therapy for SIV infection in macaques, reported by C.-C, Tsai, P. Emau, K.E. Follis, T.W. Beck, R.E, Beneveniste, N. Bischofberger, J.D. Lifson, W.R. Morton (J. Virol. 72 (1998) 4265), provides a test of the model. We show that their observations are consistent with a branching-process without invoking supplementary viral- or host-variability. Finally, most animal trials of antiviral drugs or vaccines use very high viral inoculums; our model demonstrates that in such experiments we risk greatly underestimating the efficacy of these agents. (C) 2000 Elsevier Science Inc. All lights reserved.
引用
收藏
页码:115 / 134
页数:20
相关论文
共 55 条
[1]   NEF INDUCES CD4 ENDOCYTOSIS - REQUIREMENT FOR A CRITICAL DILEUCINE MOTIF IN THE MEMBRANE-PROXIMAL CD4 CYTOPLASMIC DOMAIN [J].
AIKEN, C ;
KONNER, J ;
LANDAU, NR ;
LENBURG, ME ;
TRONO, D .
CELL, 1994, 76 (05) :853-864
[2]  
ASCHER MS, 1988, CLIN EXP IMMUNOL, V73, P165
[3]   Immunologic crosstalk [J].
Atzpodien, J ;
Dittmar, KEJ .
NEW ENGLAND JOURNAL OF MEDICINE, 1999, 340 (22) :1732-1732
[4]  
Blauvelt Andrew, 1997, American Journal of Medicine, V102, P16, DOI 10.1016/S0002-9343(97)00055-7
[5]  
Busch Michael P., 1997, American Journal of Medicine, V102, P117, DOI 10.1016/S0002-9343(97)00077-6
[6]   Early establishment of a pool of latently infected, resting CD4+ T cells during primary HIV-1 infection [J].
Chun, TW ;
Engel, D ;
Berrey, MM ;
Shea, T ;
Corey, L ;
Fauci, AS .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1998, 95 (15) :8869-8873
[7]   Target cell limited and immune control models of HIV infection: A comparison [J].
De Boer, RJ ;
Perelson, AS .
JOURNAL OF THEORETICAL BIOLOGY, 1998, 190 (03) :201-214
[8]   INFECTIOUSNESS OF HIV BETWEEN MALE-HOMOSEXUAL PARTNERS [J].
DEGRUTTOLA, V ;
SEAGE, GR ;
MAYER, KH ;
HORSBURGH, CR .
JOURNAL OF CLINICAL EPIDEMIOLOGY, 1989, 42 (09) :849-856
[9]   QUANTITATION OF HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 INFECTION KINETICS [J].
DIMITROV, DS ;
WILLEY, RL ;
SATO, H ;
CHANG, LJ ;
BLUMENTHAL, R ;
MARTIN, MA .
JOURNAL OF VIROLOGY, 1993, 67 (04) :2182-2190
[10]   Latent infection of CD4+ T cells provides a mechanism for lifelong persistence of HIV-1, even in patients on effective combination therapy [J].
Finzi, D ;
Blankson, J ;
Siliciano, JD ;
Margolick, JB ;
Chadwick, K ;
Pierson, T ;
Smith, K ;
Lisziewicz, J ;
Lori, F ;
Flexner, C ;
Quinn, TC ;
Chaisson, RE ;
Rosenberg, E ;
Walker, B ;
Gange, S ;
Gallant, J ;
Siliciano, RF .
NATURE MEDICINE, 1999, 5 (05) :512-517