HIV-1 syncytium-inducing phenotype, virus burden, codon 215 reverse transcriptase mutation and CD4 cell decline in zidovudine-treated patients.
The variable rate of disease progression in HIV-1-infected patients treated with zidovudine may be related to certain viral characteristics, such as, antiviral drug resistance, virus burden, and viral syncytium-inducing (SI) capacity. Thirty-two HIV-1-infected patients treated with zidovudine (mean of 34 months) were studied to determine the relationship of SI phenotype and the codon 215 pol gene mutation (a marker of zidovudine resistance) to virus burden and CD4 cell decline. Patients with SI strains and the codon 215 mutation in their proviral DNA had a 54% decline in CD4 cells and a virus burden of 21,480 proviral DNA copies/10(6) CD4 cells. In contrast, patients with non-SI (NSI) strains and wild-type at codon 215 had a 10% increase in CD4 cells and had a viral burden 1/46 that of patients with SI and the 215 mutation. Among patients with NSI strains, changes in CD4 cells depended on the presence of the codon 215 mutation (-160 CD4 cells/microliters), compared with those wild-type at codon 215 (+28 CD4 cells/microliters) (p < 0.01). There was a concordant rise in virus burden between proviral DNA and plasma HIV RNA depending on HIV phenotype and genotype. Using multiple linear regression, SI phenotype and the codon 215 mutation were found to independently predict CD4 cell decline and increased virus burden in zidovudine-treated patients.
Kozal
M J
MJ
Center for AIDS Research, Stanford University Medical Center, California 94305.
Shafer
R W
RW
Winters
M A
MA
Katzenstein
D A
DA
Aguiniga
E
E
Halpern
J
J
Merigan
T C
TC
D015496:CD4-Positive T-Lymphocytes; D003062:Codon / Q000737:chemistry; D004279:DNA, Viral / Q000097:blood; D004352:Drug Resistance, Microbial / Q000235:genetics; D005838:Genotype; D015726:Giant Cells / Q000382:microbiology; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology / Q000382:microbiology*; D054303:HIV Reverse Transcriptase; D015497:HIV-1 / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D006801:Humans; D007958:Leukocyte Count; D007963:Leukocytes, Mononuclear / Q000382:microbiology; D009154:Mutation; D010641:Phenotype; D011533:Proviruses / Q000235:genetics; D012367:RNA, Viral / Q000097:blood / Q000235:genetics; D012194:RNA-Directed DNA Polymerase / Q000235:genetics*; D012044:Regression Analysis; D015215:Zidovudine / Q000494:pharmacology / Q000627:therapeutic use*
D003062:Codon; D004279:DNA, Viral; D012367:RNA, Viral; D015215:Zidovudine; D054303:HIV Reverse Transcriptase; D012194:RNA-Directed DNA Polymerase