ZIDOVUDINE RESISTANCE, SYNCYTIUM-INDUCING PHENOTYPE, AND HIV DISEASE PROGRESSION IN A CASE-CONTROL STUDY

A case-control study of patients with progressive (cases) or nonprogre ssive (controls) disease was designed to determine the association amo ng disease progression, zidovudine sensitivity, and syncytium-inducing phenotype. Viral isolates were screened for sensitivity to zidovudine using a peripheral blood mononuclear cell-based assay and for syncyti um-inducing (SI) phenotype in MT2 cell culture. Thirty-four patients, whose disease progressed to AIDS or whose CD4 cell numbers fell <200 c ells/mm3, were matched with 34 patients whose conditions had not progr essed or whose CD4 cell numbers remained >200 cells/mm3. Virus was suc cessfully cultured from both the progressor and the nonprogressor in 1 7 of these 34 matched case-control pairs. In six of the 17 pairs, viru s isolated from the progressor had an IC50 (50% inhibitory concentrati on) for zidovudine >1 muM and at least threefold greater than the IC50 of virus isolated from the matched nonprogressor (p = 0.04). In 16 of these 17 pairs the virus isolated from the progressor had the SI phen otype, indicative of high cytopathogenicity, while the virus from the matched nonprogressor had a non-syncytium-inducing phenotype (p < 0.00 01). Zidovudine therapy did not appear to select for the SI phenotype in this patient population. A statistically significant association be tween high-level zidovudine resistance and clinical disease progressio n was demonstrated. A statistically significant association between th e SI phenotype and disease progression was demonstrated. The results s uggest that disease progression while being treated with zidovudine th erapy may be more closely associated with the SI phenotype than with z idovudine resistance.