NORMAL IMMUNE FUNCTION AND INABILITY TO ISOLATE VIRUS IN CULTURE IN AN INDIVIDUAL WITH LONG-TERM HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 INFECTION

A detailed, longitudinal study was undertaken to investigate the immun ological and virological features of an individual with hemophilia inf ected with human immunodeficiency virus type-1 (HIV-1) for 10 years wi thout disease. Methods applied to serial samples of peripheral blood i ncluded Western blot analysis, neutralizing antibody assays, antibody- dependent cell-mediated cytotoxicity (ADCC) titration, HIV-1 spcific c ytotoxic T lymphocyte (CTL) assays, viral cultures, and PCR with seque nce analysis of viral regulatory genes. Strong antibody responses agai nst HIV-1 antigens as measured by Western blot and ADCC assays have pe rsisted throughout infection. Repeated attempts to isolate HIV-1 using sensitive culture techniques and to demonstrate viremia with standard PCR methods have failed. Using the ''booster'' PCR technique, a perio d of viremia in peripheral blood mononuclear cells was demonstrated. C oncurrent with detection of circulating virus, titers of neutralizing antibodies and circulating HIV-1-specific CTLs became measurable. Sequ encing studies of a portion of the viral genome showed no significant abnormalities of the regulatory genes. In this individual, the combina tion of low viral load in the peripheral blood and a strong, responsiv e immune system is associated with long-term, disease-free coexistence with HIV-1 infection.