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
[11]   Identification of a reservoir for HIV-1 in patients on highly active antiretroviral therapy [J].
Finzi, D ;
Hermankova, M ;
Pierson, T ;
Carruth, LM ;
Buck, C ;
Chaisson, RE ;
Quinn, TC ;
Chadwick, K ;
Margolick, J ;
Brookmeyer, R ;
Gallant, J ;
Markowitz, M ;
Ho, DD ;
Richman, DD ;
Siliciano, RF .
SCIENCE, 1997, 278 (5341) :1295-1300
[12]   HIV infection: how effective is drug combination treatment? [J].
Grossman, Z ;
Feinberg, M ;
Kuznetsov, V ;
Dimitrov, D ;
Paul, W .
IMMUNOLOGY TODAY, 1998, 19 (11) :528-532
[13]  
HRABA T, 1989, FOLIA BIOL-PRAGUE, V35, P156
[14]   Human immunodeficiency virus type 1 neutralizing antibodies accelerate clearance of cell-free virions from blood plasma [J].
Igarashi, T ;
Brown, C ;
Azadegan, A ;
Haigwood, N ;
Dimitrov, D ;
Martin, MA ;
Shibata, R .
NATURE MEDICINE, 1999, 5 (02) :211-216
[15]   STATISTICAL-ANALYSIS OF HIV INFECTIVITY BASED ON PARTNER STUDIES [J].
JEWELL, NP ;
SHIBOSKI, SC .
BIOMETRICS, 1990, 46 (04) :1133-1150
[16]   Dramatic rise in plasma viremia after CD8+ T cell depletion in simian immunodeficiency virus-infected macaques [J].
Jin, X ;
Bauer, DE ;
Tuttleton, SE ;
Lewin, S ;
Gettie, A ;
Blanchard, J ;
Irwin, CE ;
Safrit, JT ;
Mittler, J ;
Weinberger, L ;
Kostrikis, LG ;
Zhang, LQ ;
Perelson, AS ;
Ho, DD .
JOURNAL OF EXPERIMENTAL MEDICINE, 1999, 189 (06) :991-998
[17]   Acute human immunodeficiency virus type 1 infection [J].
Kahn, JO ;
Walker, BD .
NEW ENGLAND JOURNAL OF MEDICINE, 1998, 339 (01) :33-39
[18]   TEMPORAL ASPECTS OF DNA AND RNA-SYNTHESIS DURING HUMAN IMMUNODEFICIENCY VIRUS-INFECTION - EVIDENCE FOR DIFFERENTIAL GENE-EXPRESSION [J].
KIM, SY ;
BYRN, R ;
GROOPMAN, J ;
BALTIMORE, D .
JOURNAL OF VIROLOGY, 1989, 63 (09) :3708-3713
[19]   THEORY FOR AGE AND GENERATION TIME DISTRIBUTION OF A MICROBIAL-POPULATION [J].
LEBOWITZ, JL ;
RUBINOW, SI .
JOURNAL OF MATHEMATICAL BIOLOGY, 1974, 1 (01) :17-36
[20]   MONONUCLEAR PHAGOCYTES OF BLOOD AND BONE-MARROW - COMPARATIVE ROLES AS VIRAL RESERVOIRS IN HUMAN IMMUNODEFICIENCY VIRUS TYPE-1 INFECTIONS [J].
MCELRATH, MJ ;
PRUETT, JE ;
COHN, ZA .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1989, 86 (02) :675-679