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

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