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M94A0717.TXT
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1994-10-21
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Document 0717
DOCN M94A0717
TI Drug resistance and Sl phenotype; implications for chemotherapy.
DT 9412
AU Richman DD; University of California San Diego 92093-0679.
SO Annu Conf Australas Soc HIV Med. 1993 Oct 28-30;5:22 (abstract no.
FPI-2). Unique Identifier : AIDSLINE ASHM5/94348938
AB The clinical and therapeutic significance of the emergence of diminished
drug susceptibility has been difficult to elucidate. Two recent studies,
one with nucleosides and one with a non-nucleoside reverse transcriptase
inhibitor (NNRTI) address this issue. A multicenter virologic analysis
of ACTG 116B/117 documented that the acquisition of AZT resistance was a
highly negative prognostic marker although the implications for
therapeutic decisions between AZT and ddl are unclear. A study of the
NNRTI, nevirapine, more clearly provides compelling evidence that loss
of drug activity can be attributed to the acquisition of drug
resistance. In addition when drug doses were increased to generate
plasma levels that exceeded the susceptibility of the resistant virus,
sustained antiviral activity was observed. This may have important
implications for the development of many antiretroviral drugs, including
protease inhibitors. Moreover, the combination of nevirapine with AZT
resulted in a dramatic shift in the patterns of drug resistance
mutations utilised by the virus. The syncytium-inducing (S.I.) phenotype
of HIV evolves in just over one-half of patients during their course of
HIV infection, with the proportion progressively increasing as CD4 cells
decline. The acquisition of the SI phenotype accelerates the rate of CD4
cell decline 3 fold, thus shortening the natural history of HIV
infection in those patients. Of note however, the SI phenotype does not
increase the relative risk of mortality per se independent of its effort
on CD4 cell decline. The relative risk of the SI phenotype exceeds the
relative benefits of any antiretroviral drugs identified to date. It is
thus essential that this viral phenotype be considered in the assessment
of chemotherapeutic or immunologic interventions.
DE Antiviral Agents/ADVERSE EFFECTS/*THERAPEUTIC USE Clinical Trials
Didanosine/ADVERSE EFFECTS/THERAPEUTIC USE Drug Therapy, Combination
Human HIV Infections/*DRUG THERAPY/IMMUNOLOGY/MICROBIOLOGY Leukocyte
Count/DRUG EFFECTS Prognosis Pyridines/ADVERSE EFFECTS/THERAPEUTIC USE
Reverse Transcriptase/*ANTAGONISTS & INHIB T4 Lymphocytes/IMMUNOLOGY
Zidovudine/ADVERSE EFFECTS/THERAPEUTIC USE MEETING ABSTRACT
SOURCE: National Library of Medicine. NOTICE: This material may be
protected by Copyright Law (Title 17, U.S.Code).