CHANGES IN CELLULAR VIRUS LOAD AND ZIDOVUDINE RESISTANCE OF SYNCYTIUM-INDUCING AND NON-SYNCYTIUM-INDUCING HUMAN-IMMUNODEFICIENCY-VIRUS POPULATIONS UNDER ZIDOVUDINE PRESSURE - A CLONAL ANALYSIS

Zidovudine treatment preferentially benefits persons with only non-syn cytium-inducing (NSI) human immunodeficiency virus type 1 (HIV-1) vari ants. To understand this differential efficacy, changes in cellular vi rus load, clonal composition of HIV-1 populations, and development of resistance-conferring reverse transcriptase mutations were studied in 17 persons initiating zidovudine therapy. Zidovudine treatment resulte d in larger and more sustained decreases in cellular virus load in per sons with NSI variants only compared with persons also carrying syncyt ium-inducing (SI) variants. Although the former group had a delayed em ergence of resistance mutations, differences in initial responses betw een the 2 groups were independent of the emergence of resistance mutat ions. Changes in virus load in subjects also carrying SI variants were due mainly to loss of coexisting NSI virus. Resistance mutations emer ged at similar rates in both coexisting variants. Data suggest that me chanisms other than drug resistance are necessary to completely explai n the phenotype-dependent benefit of zidovudine.