Viral phenotype and genotype as markers in clinical trials.

Treatment of AIDS and HIV infection is increasingly dependent on the use of surrogate markers to assess the efficacy of drug and biologic therapies in individual patients and in the clinical trials. Recent developments in laboratory techniques have resulted in new assays to measure circulating viral RNA in HIV-infected individuals, standardized methods to assess genotypic changes in virus associated with drug resistance and biologic assays for syncytia-inducing phenotype, a viral characteristic associated with rapid clinical progression. Studies from our laboratory have examined the relationship between surrogate markers of drug efficacy, CD4 cell changes, quantitative HIV plasma RNA and cell dilution cultures, genotypic changes associated with drug resistance and the syncytia-inducing phenotype. The results of these studies suggest that drug-resistance genotype and syncytia-inducing phenotype are independent factors that contribute to disease progression in patients receiving zidovudine. The design of studies of drugs and biologics for the treatment of HIV should include assessment of genotypic and phenotypic characteristics of HIV in addition to CD4 cell numbers and virus load.