Persistent antibody responses but declining cytotoxic T-lymphocyte responses to multiple human immunodeficiency virus type 1 antigens in a long-term nonprogressing individual with a defective p17 proviral sequence and no detectable viral RNA expression

Abstract

Long-term nonprogressor AD-18 has been infected with human immunodeficiency virus type 1 (HIV-1) for at least 16 years. During the past 5 years, he has had undetectable levels of plasma viremia, and HIV-1 cannot be isolated from him. Sequencing of proviral DNA indicates that the only HIV-1 sequences that can be identified in AD-18 have gross defects in the p17-encoding regions of the gag gene (Y. Huang, L. Zhang, and D. D. Ho, Virology 240:36-49, 1998). However, AD-18 has strong, sustained antibody responses to several HIV-1 antigens, including p17. Cytotoxic T-lymphocyte responses to Env and Gag antigens have gradually diminished over the past 4 years, at a time when the titers of antibodies to the same proteins have remained stable. We discuss what these observations might mean for the generation and maintenance of immunological memory.

FIG. 1

Longitudinal, midpoint titers of antibodies to MN gp120 (•), p24 (▴), and p17 (▪). Day 0 corresponds to the first plasma assayed, beginning on 9 September 1993. Plasma viral load is indicated by the dotted line.

FIG. 2

Longitudinal CTLp responses to IIIBgag (▪), SF2gag (▴), IIIBenv (□), and SF2env (▵), expressed as CTLp per 10⁶ input PBMC. Day 0 corresponds to the first plasma assayed, beginning on 9 September 1993.