Syphilis serology in human immunodeficiency virus infection: Evidence for false-negative fluorescent treponemal testing

Injection drug users were assessed serologically for human immunodeficiency virus infection and syphilis every 6 months. Treatment histories were reviewed for any high-titer biologic false-positive (BFP) reactors, that is, persons with rapid plasma reagin (RPR) titers ≤1:4 and negative results for fluorescent treponemal antibody absorption (FTA-ABS) tests. Selected sera were analyzed further by immunoblotting for the presence of antibodies reactive with specific Treponema pallidum antigens. Of 112 BFP reactors, 35 (31%) had at least one RPR test reactive at a dilution >1:8 while the FTA-ABS test remained nonreactive. Five reactors (4.5%) converted from nonreactive to reactive by FTA-ABS test; 4 (3.6%) were reactive by FTA- ABS tests but later became nonreactive. Antibodies to T. pallidum membrane antigens were detected in some samples that were persistently nonreactive by FTA-ABS test. Serologic patterns over time, along with very high-titer BFP reactions and reactivity with T. pallidum-specific antigens, suggest that some BFP reactions may represent FTA-negative syphilis.