[LbOr12] Strong CD4+ T cell responses to HIV antigens in treated patients is not predictive of restriction of viral replication

14th International AIDS Conference

Barcelona, Spain — July 7-12, 2002

[TITLE:] Strong CD4+ T cell responses to HIV antigens in treated patients is not predictive of restriction of viral replication

[AUTHOR(S):] John Tilton, Christiana Iyasere, Stephen Migueles, Alisha Laborico, Mark Connors¹

Int Conf AIDS. 2002 Jul 7-12;14:Abstract No. LbOr12

BACKGROUND: Proliferative responses to HIV antigens are absent in most untreated patients despite persistence of significant frequencies of HIV-specific CD4+ T cells. Strong HIV-specific CD4+ T cell responses to viral antigens are thought to contribute to restriction of virus replication. The HIV-specific CD4+ T cell responses and ability to restrict virus replication was studied in a cohort of patients with strong HIV-specific CD4+ T cell responses during serial interruptions of therapy.

METHODS: Thirteen patients with progressive disease with proliferative responses while on therapy (cpm 1671-19674) were recruited. Patients were leukopheresed prior to, during and after therapy interruption. T cell frequencies and proliferation to gag, pol and nef peptide pools, p24, CMV and tetanus antigens were determined.

RESULTS: Although proliferative responses to HIV antigens before therapy interruption were equivalent to those of nonprogressors, responses were rapidly and completely abrogated during viremia following interruption. Proliferation returned with viral suppression upon therapy resumption. High frequencies of total HIV-specific CD4+ T cells were present in all subjects (mean 0.59%; range 0.17-1.52%). These frequencies persisted during viremia for all antigens (p>0.05); gag (mean 0.29% on therapy vs 0.43% off therapy), pol (.09 vs .09) and nef (.11 vs .09). The frequency of IL-2 producing HIV-gag or CMV-specific cells was not significantly diminished (p>0.5). Proliferation to HIV antigens prior to treatment interruption was not predictive of viral restriction off therapy (1-5 interruptions; viral loads: mean 31,651; 74-113,269).

CONCLUSIONS: Proliferative responses to HIV antigens were not predictive of control of viremia. During viremia, proliferation of HIV-specific CD4+ T cells was rapidly and completely abrogated. These data strongly suggest that HIV-specific CD4+ proliferation appears to be a result, rather than a cause, of effective viral restriction.

Presenting author: John Tilton

1Laboratory of Immunoregulation/NIAID/NIH, Bethesda, MD, United States.

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