HIV-1 GENETIC VARIATION IN INFECTED HEMOPHILIACS OVER TIME

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This is a project to examine the extent and pattern of HIV-1 sequence divergence within selected HIV-1-infected patients from the Hemophilia Growth and Development Study, a multi-center collaboration to define the effects of HIV-1 infection on the social, neuropsychological, and physical growth of male children and adolescents with hemophilia. Initially the study will focus on quantitative and qualitative differences in virus load and sequence variation at selected HIV-1 regions of rapid progressors defined as participants whose CD4 counts per mm3 decline by 75% between baseline (study entry) and second annual exam, and slow progressors defined as participants whose CD4 counts remain stable or increase over the 2-year period between baseline and annual visit two. Nested primer polymerase chain reaction will be used to amplify variable regions of env, gag, and nef in both proviral DNA and cDNA of free virions found in plasma. This will be followed by cloning and sequence analysis to detect and catalog the accumulation of mutations during the evolution of the HIV- 1 "quasispecies" under the selective constraints of the host immune system. At least 20 clones will be sequenced from each individual from several sequential time points.