HIV-1 GENETIC VARIATION IN INFECTED HEMOPHILIACS OVER TIME

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Following infection by HIV-1, there is considerable variation in duration of the latency period, host immunological response, and the rate of CD4 T-cell decline. Three possible causes of the variability observed in outcome to HIV-1 infection may be cofactors such as other viruses, host genetic differences, and variants within the HIV-1 swarm. The goal of this project is to analyze the extent and pattern of HIV-1 sequence divergence over the course of infection in four stable, non-progressors and four rapid progressors whose CD4 T-cell count declined more than 75% in the first 24 months following enrollment into the Hemophilia Growth and Development Study. The study is comparing the quantitative and qualitative differences over time in viral sequences between these two dichotomous groups by using nested polymerase chain reaction (PCR) to amplify selected regions of env, gag, pol, and nef from cDNA obtained by reverse transcriptase PCR of plasma virion RNA, DNA from integrated provirus, and virus isolates. The PCR products of viral sequences (obtained from peripheral mononuclear blood cells, plasma, and isolates) are cloned and the nucleotide sequences from each patient from baseline through visit seven are compared. Progress to date includes the successful sequencing and preliminary phylogenetic analysis of clones from two fast and two slow progressors at seven time points for the V3 loop of the env.