Immunologic and virologic analyses of an acutely HIV type 1-infected patient with extremely rapid disease progression

The immunologic and virologic factors that impact on the rate of disease pr ogression after acute infection with human immunodeficiency virus (HIV) typ e 1 are poorly understood. A patient with an extraordinarily rapid disease course leading to AIDS-associated death within 6 months of infection was st udied intensively for the presence of anti-HIV immune reactivities as well as changes in the genetic and biologic properties of virus isolates. Althou gh altered humoral responses were evident, the most distinctive immunologic feature was a nearly complete absence of detectable HIV-specific CTL respo nses. In addition to a rapid decline in CD3(+)CD4(+) cells, elevated percen tages of CD8(+)CD45RA(+) and CD8(+)CD57(+) cells and diminished CD8(+)CD45R 0(+) and CD8(+)CD28(+) cells were evident. Primary viral isolates recovered throughout the course of infection exhibited limited sequence diversity. C loned viral envelopes were found to have unusually broad patterns of corece ptor usage for cell-cell fusion, although infectivity studies yielded no ev idence of infection via these alternative receptors. The infectivity studie s demonstrated that these isolates and their envelopes maintained an R5 phe notype throughout the course of disease. The absence of demonstrable anti-H IV CTL reactivities, coupled with a protracted course of seroconversion, hi ghlights the importance of robust HIV-specific immune responses in the cont rol of disease progression.