Characterization of high-risk HIV-1 seronegative hemophiliacs

Mechanisms that protect most high-risk HIV-1 seronegative (HRSN) persons ar e not well understood. Among hemophiliacs from the Multicenter Hemophilia C ohort Study who remained HIV-1 seronegative despite a high (94%) risk for a cquisition of HIV-1 infection, only 7/43 were homozygous for the protective CCR5 Delta 32 polymorphism. Among the remainder, neither CCR5 density nor beta -chemokine production, nor in vitro susceptibility to infection with t he HIV-1 isolate JR-FL could distinguish HRSN hemophiliacs from healthy con trols. When compared to lymphocytes of healthy controls not at risk for HIV -1 infection, diminished spontaneous lymphocyte proliferation was seen in l ymphocytes of HRSN hemophiliacs as well as in lymphocytes of hemophiliacs n ot at risk for HIV-1 infection. Surprisingly sera/plasmas obtained from hig hrisk HIV-1 seropositive hemophiliacs prior to seroconversion more often co ntained alloreactive antibodies than date-matched sera/plasmas obtained fro m HRSN hemophiliacs. Thus alloreactivity may predispose to acquisition of H IV-1 infection after parenteral exposure. (C) 2000 Academic Press.