1st National Conference Human Retroviruses and Related Infections Washington, DC - December 12-16, 1993

Natl Conf Hum Retrovir Relat Infect 1993 Dec 12-16;1: (abstract no. 3)

Mayers DL, Wagner KF, Chung RC, Lane JR, Vahey MT, White FA, Ruiz NM, Hicks CB, Weislow OS, Gardner LI
Military Medical Consortium for Applied Retroviral Research, Rockville, MD

OBJECTIVES: To determine the relationship of the development of AZT resistance to CD4 decline and clinical failure in a cohort of 100 patients (pts) with less than 400 CD4 cells (mean 252±104 CD4 cells pre- rx) on AZT monotherapy.

METHODS: Pts are evaluated every 3 months along with CD4 counts and drug susceptibility of HIV isolates. Primary HIV isolates are expanded and titered on donor PBMC. Drug susceptibility testing is performed using the ACTG/DoD consensus assay. HIV isolates with AZT IC₅₀ ≥1.0 µM are considered AZT resistant (AZT^R). Mutations at RT codon 215 are detected using nested PCR or RT-PCR. Viral burden is assessed using RT-PCR of pt plasma samples.

RESULTS: Several factors predicted early emergence of AZT^R: low CD4 count at initiation of AZT therapy, p24Ag positive status, syncytium inducing (SI) virus phenotype and plasma HIV RNA >10⁵ copies/ml. Pts whose HIV isolates did not develop mutations at codon 215 maintained stable CD4 counts for the 2 years of the study. CD4 counts remained at pre-rx levels when the codon 215 mutation was first detected by PCR at a mean of 73 weeks of AZT therapy. CD4 counts had declined by 40% when phenotypic AZT^R was first detected. Half of the patients whose HIV isolates developed mutations at codon 215 experienced a CD4 decline of greater than 50% during the next 12 months.

CONCLUSIONS: Genotypic evidence of AZT^R virus emerges prior to CD4 decline in patients on AZT monotherapy. 50% of pts who develop codon 215 mutations experience significant CD4 decline in the next 12 months. A model relating host and virus factors to AZT^R and CD4 decline will be presented.

Keywords: Acquired Immunodeficiency Syndrome, Anti-HIV Agents, Antigens, CD4, CD4 Lymphocyte Count, CD4-Positive T-Lymphocytes, Codon, HIV, HIV Infections, HIV Protease Inhibitors, HIV Seropositivity, HIV-1 Reverse Transcriptase, Humans, Viral Load, Zidovudine, genetics, immunology

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1993-12-12
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Copyright © 1993 - The American Society for Microbiology. Reproduction of this abstract (other than one copy for personal reference) must be cleared through the American Society for Microbiology.