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. 1)

Kuritzkes DR, Welles S, Johnson VA, D'Aquila RT, Richman DD, Crumpacker CS, Reichlederfer P, Degruttola V, Japour AJ
University of Colorado, Denver, CO

Codons 41 and 215 of HIV-1 reverse transcriptase (RT) were examined by a selective PCR technique in 147 study subjects from whom baseline viral isolates were available. Of these, codon 215 was wild-type (WT) in 37 (25%), mutant (MUT) in 71 (48%), and mixed in 9(6%). No signal was obtained from 30 isolates (20%). Among the 80 isolates in which codon 41 was also examined, this codon was wild-type in 34 (43%), mutant in 26 (33%), and mixed in 10 (13%). The median ZDV IC₅₀ of MUT isolates was significantly greater than WT isolates (0.227 µM vs. 0.020 µM, p<0.0015). In a univariate Cox proportionate hazards model, the presence of the T215Y mutation was associated with an increased risk of clinical progression (RR=2.2;p=0.02). The magnitude of this increased risk was similar to that reported for patients from the same cohort with high-level ZDV resistant isolates (IC₅₀ ≥1 µM) by D'Aquila et al Int Conf AIDS 1993 Jun 6-11; 9:476 (Abstract Po-B26-2046). However, in a multiple regression model that included CD4 count, virus phenotype (SI/NSI), and diagnosis of AIDS at baseline, the presence of the 215 mutation was not an independent risk factor for clinical progression. Additional analyses are being performed to determine whether the combined presence of mutations at codon 41 and 215 improves the prognostic power of this test.

Keywords: Acquired Immunodeficiency Syndrome, BaseLine, CD4 Lymphocyte Count, Codon, Disease Progression, Glass Ionomer Cements, HIV-1, HIV-1 Reverse Transcriptase, Health Personnel, Humans, Mutation, Prevalence, Risk Factors, Zidovudine, epidemiology, genetics

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1993-12-12
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