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There are no clear definitions for faster and slower HIV-2 disease progression and for the relationship of the rate of progression with HIV-2 evolution. To address the hypothesis that viral evolution is correlated with disease progression in HIV-2 infection, we determined faster and slower disease progression based on follow-up data from a prospective cohort of police officers in Guinea-Bissau. The analysis showed that although the CD4\n            <jats:sup>+<\/jats:sup>\n            T-cell level and the decline in the level were independently associated with progression to AIDS, only the CD4\n            <jats:sup>+<\/jats:sup>\n            T-cell level or a combined CD4\n            <jats:sup>+<\/jats:sup>\n            T-cell level\/decline stratification was associated with the rate of HIV-2 evolution. The HIV-2 evolutionary rate was almost twice as high among the faster progressors as among the slower progressors. 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