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 tr eated 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 wi th zidovudine (mean of 34 months) were studied to determine the relati onship of SI phenotype and the codon 215 pol gene mutation (a marker o f zidovudine resistance) to virus burden and CD4 cell decline. Patient s 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) strain s 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. Amon g patients with NSI strains, changes in CD4 cells depended on the pres ence of the codon 215 mutation (-160 CD4 cells/mu l), compared with th ose wild-type at codon 215 (+ 28 CD4 cells/mu l) (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 re gression, SI phenotype and the codon 215 mutation were found to indepe ndently predict CD4 cell decline and increased virus burden in zidovud ine-treated patients.