STRONG CYTOTOXIC T-CELL AND WEAK NEUTRALIZING ANTIBODY-RESPONSES IN ASUBSET OF PERSONS WITH STABLE NONPROGRESSING HIV TYPE-1 INFECTION

Some individuals in well-defined cohorts have now been infected with H IV-1 for well over a decade and yet remain clinically asymptomatic wit h normal CD4 counts, To determine immunologic and virologic parameters in these individuals, we examined 10 persons from the San Francisco C ity Clinic with firmly documented infection of 11-15 years duration wh o had maintained stable CD4 counts above 500 cells/mu l. Our results i ndicate that long-term nonprogressors are a heterogeneous group with r espect to viral load and HIV-l-specific immune responses, and that pro gression can occur even after 15 years of stable infection, However, i n a subset of persons with the lowest viral loads and persistent nonpr ogressive infection, we detected strong CTL responses, whereas neutral izing antibody studies revealed weak to undetectable titers against a panel of 10 primary isolates, This study demonstrates that a vigorous irt vivo activated HIV-1-specific CTL response can be part of the host immune response in stable nonprogressive HIV-1 infection, and that ci rculating activated CTL can be detected in the setting of an extremely low viral load, These results also indicate that long-term nonprogres sing HIV-1 infection does not require the presence of broadly cross-re active neutralizing antibodies.