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Titolo:
Suppression of resistance to drugs targeted to human immunodeficiency virus reverse transcriptase by combination therapy
Autore:
Balzarini, J;
Indirizzi:
Catholic Univ Louvain, Rega Inst Med Res, B-3000 Louvain, Belgium CatholicUniv Louvain Louvain Belgium B-3000 es, B-3000 Louvain, Belgium
Titolo Testata:
BIOCHEMICAL PHARMACOLOGY
fascicolo: 1, volume: 58, anno: 1999,
pagine: 1 - 27
SICI:
0006-2952(19990701)58:1<1:SORTDT>2.0.ZU;2-W
Fonte:
ISI
Lingua:
ENG
Soggetto:
HIGH-LEVEL RESISTANCE; POTENT NONNUCLEOSIDE INHIBITORS; IMP DEHYDROGENASE STIMULATE; AMINO-ACID SUBSTITUTIONS; ENCODES CROSS-RESISTANCE; TYPE-1 MUTANTS RESISTANT; DNA-POLYMERASE-ACTIVITY; POL GENE-MUTATIONS; IN-VITRO SELECTION; HIV-1 INFECTION;
Keywords:
HIV resistance; combination therapy; reverse transcriptase (RT); AIDS; nucleoside RT inhibitors (NRTIs); non-nucleoside RT inhibitors (NNRTIs);
Tipo documento:
Review
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
215
Recensione:
Indirizzi per estratti:
Indirizzo: Balzarini, J Catholicain,v Louvain, Rega Inst Med Res, Minderbroedersstr 10, B-3000 Louv Catholic Univ Louvain Minderbroedersstr 10 Louvain Belgium B-3000
Citazione:
J. Balzarini, "Suppression of resistance to drugs targeted to human immunodeficiency virus reverse transcriptase by combination therapy", BIOCH PHARM, 58(1), 1999, pp. 1-27

Abstract

There are currently thirteen drugs approved for the treatment of human immunodeficiency virus (HIV)-infected individuals. Seven of them are targeted against the virus-encoded reverse transcriptase (RT). Appearance of drug-resistant virus strains under the selective pressure of anti HIV chemotherapyrapidly occurs as a consequence of the low fidelity of the RT-catalyzed DNA polymerisation reaction and the massive viral turnover. Resistance-associated mutations appear in the RT of virus strains that are under selective pressure of both nucleoside RT inhibitors (NRTIs) and non-nucleoside RT inhibitors (NNRTIs). A variety of these mutations cause cross-resistance to several other NRTIs or NNRTIs and consequently may hamper the effectiveness ofthe other drugs. Other RT mutations are quite specific and selective in their drug-resistance spectrum and do not influence the potency of the majority of other available drugs. Moreover, drug-specific mutations are identified that are able to restore drug sensitivity again when concomitantly present with other drug-specific mutations. Combination therapy has proven to beable to markedly suppress virus replication (and subsequent appearance of drug resistance) for a relatively long time period. However, in a number ofcases, multiple drug combination therapy results in the appearance of a different mutation spectrum than is expected to emerge under monotherapy. Also, it has been shown that drugs that alter cellular deoxynucleotide pools not only are able to potentiate the antiviral efficacy of some RT inhibitors, but also may influence the resistance spectrum of certain anti HIV drugs. All available information argues fur the use of a rational combination of different anti-HIV inhibitors with different resistance spectra to suppressvirus replication efficiently and to delay the emergence of drug-resistantvirus as long as possible, but it also indicates that there is a strong need for additional drugs to further optimize and improve the efficacy of long-term HIV treatment. BIOCHEM PHARMACOL 58;1:1-27, 1999. (C) 1999 Elsevier Science Inc.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 28/09/20 alle ore 14:06:27