367   Longitudinal Monitoring of Chronically HIV-1-Infected Individuals for Cell-Associated Virus and Immune Responses.

C. Tremblay*, F. Giguel, D. Merrill, E. Rosenberg, J. Wong, B. Davis, C. Crumpacker, D. Ives, S. Kalams, R. D'Aquila, B. D. Walker, and M. S. Hirsch.
Massachusetts Gen. and Beth Israel Deaconess Hosp., Boston.

Background:Residual lymphocyte viral reservoirs are obstacles in the treatment of HIV-1 infection. Monitoring cell-associated virus in subjects with undetectable plasma HIV-1 RNA as well as characterizing their HIV-1- specific immune responses could help define which individuals are likely to respond to immune-based therapeutic strategies.

Methods:We evaluated cell-associated viremia and HIV-1-specific immune responses in seventeen chronically infected patients with CD4 cells >500/mm³who had undetectable plasma HIV-1 RNA on antiretroviral therapy and were enrolled in the Merck 060 trial.Enhanced culture: Using serial limiting dilutions, PBMC are cultured using IL-2 and a bispecific monoclonal antibody (anti-CD3:8). The results were expressed as infectious units per million PBMC (IUPM).CD4 lymphoproliferative assay: PBMC were incubated in the presence of HIV-1- specific antigens for six days and pulsed with³H-thymidine. Results are expressed as a stimulation index (SI).

Results:There was substantial variation in numbers of IUPM ranging from <0.01 to 8.23 among these subjects. Higher IUPM were associated with higher viral load at entry. In 10 patients for whom longitudinal data are available, five showed either a decline in the frequency of infected cells over time (4) or undetectable virus (1), while 5 others had stable levels of IUPM. The five patients with declining or undetectable IUPM had fewer rebounds of detectable plasma viral RNA over an average of 153 weeks than the others (0.8 episodes vs 9.25). The patient with undetectable cell-associated virus had substantial HIV-1-specific CD4 cell proliferative responses (SI = 46). Four of 6 others tested also showed specific CD4 proliferative responses to HIV p24 antigen as defined by a SI above 10 (range 13.6 to 41.5).

Conclusion:In this population with established HIV-1 infection and high CD4 cell counts, variable patterns of decay were observed among infected PBMC over time. HIV-1-specific CD4 cell proliferative responses were also seen, suggesting that some subjects treated relatively early in infection may behave similarly to those treated during acute HIV syndrome.