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Titolo:
SELECTIVE-INHIBITION OF SYNCYTIUM-INDUCING AND NONSYNCYTIUM-INDUCING HIV-1 VARIANTS IN INDIVIDUALS RECEIVING DIDANOSINE OR ZIDOVUDINE, RESPECTIVELY
Autore:
VANTWOUT AB; RAN LJ; DEJONG MD; BAKKER M; VANLEEUWEN R; NOTERMANS DW; LOELIGER AE; DEWOLF F; DANNER SA; REISS P; BOUCHER CAB; LANGE JMA; SCHUITEMAKER H;
Indirizzi:
NETHERLANDS RED CROSS,BLOOD TRANSFUS SERV,CENT LAB,DEPT CLIN VIROIMMUNOL,PLESMANLAAN 125 NL-1066 CX AMSTERDAM NETHERLANDS NETHERLANDS RED CROSS,BLOOD TRANSFUS SERV,CENT LAB,DEPT CLIN VIROIMMUNOL NL-1066 CX AMSTERDAM NETHERLANDS UNIV AMSTERDAM,EXPT & CLIN IMMUNOL LAB NL-1066 CX AMSTERDAM NETHERLANDS UNIV AMSTERDAM,ACAD MED CTR,NATL AIDS THERAPY EVALUAT CTR NL-1105 AZ AMSTERDAM NETHERLANDS UNIV AMSTERDAM,ACAD MED CTR,DEPT INTERNAL MED,DIV INFECT DIS TROP MED& AIDS NL-1105 AZ AMSTERDAM NETHERLANDS UNIV AMSTERDAM,ACAD MED CTR,DEPT HUMAN RETROVIROL NL-1105 AZ AMSTERDAM NETHERLANDS UNIV AMSTERDAM,ACAD MED CTR,DEPT VIROL,ANTIVIRAL THERAPY LAB NL-1105 AZ AMSTERDAM NETHERLANDS
Titolo Testata:
The Journal of clinical investigation
fascicolo: 9, volume: 100, anno: 1997,
pagine: 2325 - 2332
SICI:
0021-9738(1997)100:9<2325:SOSANH>2.0.ZU;2-Z
Fonte:
ISI
Lingua:
ENG
Soggetto:
HUMAN-IMMUNODEFICIENCY-VIRUS; BLOOD MONONUCLEAR-CELLS; AIDS DEMENTIA COMPLEX; DISEASE PROGRESSION; BIOLOGICAL PHENOTYPE; TYPE-1 INFECTION; CUBIC MILLIMETER; COMBINATION THERAPY; VIRAL PHENOTYPE; CD4 CELLS;
Keywords:
HIV-1 BIOLOGICAL PHENOTYPE; ANTIRETROVIRAL THERAPY; AIDS; CELL CYCLE DEPENDENCY; RITONAVIR;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Citazioni:
55
Recensione:
Indirizzi per estratti:
Citazione:
A.B. Vantwout et al., "SELECTIVE-INHIBITION OF SYNCYTIUM-INDUCING AND NONSYNCYTIUM-INDUCING HIV-1 VARIANTS IN INDIVIDUALS RECEIVING DIDANOSINE OR ZIDOVUDINE, RESPECTIVELY", The Journal of clinical investigation, 100(9), 1997, pp. 2325-2332

Abstract

By studying changes in the clonal composition of HIV-1 populations during the first weeks of zidovudine (ZDV) treatment before the development of ZDV resistance-conferring mutations, we demonstrated previouslya selective inhibition of nonsyncytium-inducing (NSI) HIV-1, even when present as coexisting population in individuals also harboring syncytium-inducing (SI) HIV-1. In this study, we observed the opposite in individuals receiving didanosine (ddI) treatment. In these individuals (n = 7) a median -0.98 log change (range -1.55-0.08) in infectious cellular SI load was observed, whereas the coexisting NSI load was only minimally affected (median -0.15 log, range -1.27-0.50; P = 0.03). The virus phenotype-dependent treatment responses were independent of the clonal composition of HIV-1 populations at baseline. Individuals treated with a combination of ZDV and ddI revealed an equal decline of bothNSI and SI infectious cellular load (n = 4; NSI: median -1.55 log, range -2.19 to -1.45; SI: median -1.47 log, range -1.81 to -0.86; P = 0.56). To test the hypothesis that the previously reported optimal activation of ZDV and ddI in activated and resting T cells, respectively, in combination with the differential T cell tropism of NSI and SI HIV-1is the basis for the observed virus phenotype specific efficacy of nucleoside analogs, we studied the effect of treatment with a protease inhibitor that does not require intracellular activation. Individuals receiving ritonavir (n = 4) indeed showed equal declines in NSI and SI infectious cellular load (NSI: median -2.37 log, range -2.59 to -2.16;SI: median -2.82 log, range -3.14 to -2.50; P = 0.25). Our data suggest HIV-1 phenotype as an additional parameter in the design of optimaltreatment regimens.

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Documento generato il 04/12/20 alle ore 06:52:47