CONCURRENT EVOLUTION OF REGIONS OF THE ENVELOPE AND POLYMERASE GENES OF HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 OBSERVED DURING ZIDOVUDINE (AZT) THERAPY

Nucleotide sequences of regions of the envelope (env) and polymerase ( pol) genes of human immunodeficiency virus type 1 (HIV-1) proviral DNA were obtained from sequential blood and autopsy samples from an AIDS patient who had been treated with zidovudine for 9 months. Phylogeneti c analyses showed that a reduction in genetic heterogeneity of the env regions of viruses present in the proviral blood population occurred during therapy, and this coincided with an increased pol gene heteroge neity. Differences were observed in different organs obtained post mor tem for both the env and pol coding regions. The cardiac blood provira l population consisted mainly of variants which possessed sequences co ntaining mutations at position 215 of the pol gene, associated with dr ug resistance. By contrast, the brain population consisted entirely of zidovudine sensitive genotypes, and this organ also harboured variant s with genetically distinct env sequences. The lymph tissues obtained after death held more diverse proviral env and pol populations, contai ning both zidovudine sensitive and resistant genotypes.