AEGiS-15IAC: [LbOrA06] HIV-SPECIFIC CYTOLYTIC RESPONSE AS MEASURED BY FLOW CYTOMETRY CORRELATES WITH VIRAL LOAD IN A UGANDAN COHORT

15th International AIDS Conference

Bangkok, Thailand — July 11-July 16, 2004

[LbOrA06] HIV-SPECIFIC CYTOLYTIC RESPONSE AS MEASURED BY FLOW CYTOMETRY CORRELATES WITH VIRAL LOAD IN A UGANDAN COHORT

Int Conf AIDS. 2004 Jul 11-16;15:Abstract No. LbOrA06

N Jones¹, B Barugahare², M Eggena³, M McElroy¹, K Carlson¹, S Mutalya², M Okello², C Kityo², P Mugyenyi², H Cao¹
¹California Department of Health Services, Richmond, United States; ²Joint Clinical Research Centre, Kampala, Uganda; ³University of California, San Francisco, United States

BACKGROUND: HIV-specific CD8+ T cell responses play an important role in the control of HIV replication. However, previous evaluation of T cell responses by IFN-γ release assay failed to correlate the presence of antiviral response to viral load. Measurement of surface expression of CD107 is shown to correlate with degranulation allation and loss of intracellular perforin and represents a better functional assessment of antigen-specific CD8+ T cells in HIV infection.

METHOD: HIV seropositive adult Ugandan volunteers were recruited to participate in a cross- sectional T cell study at the Joint Clinical Research Centre in Kampala, Uganda. Measurement of CD107a/b expression following Gag and Nef peptides stimulation was performed on cryopreserved PBMC using anthe the Becton-Dickinson LSRII flow cytometer. Results are considered positive if twice above background and greater than 0.1%. Linear regression models were used for analysis and statistical significance was defined as p>0.05.

RESULTS: 33 out of 40 volunteers demonstrated HIV-specific CD8+ cytolytic activity, as measured by upregulation of CD107, in responses to Gag or Nef antigens. High concordance of responses between the CD107 and ELISPOT assays was observed (Rsquare= 0.49, p=0.05). However, only HIV-specific responses, as measured by the CD107 upregulation, positively correlated with HIV viral load with and without controlling for CD4 cell count (p=0.018 and 0.021, respectively).

CONCLUSION: HIV-specific cytolytic activity, as measured by CD107 expression, correlates with HIV viral load and represents an alternative, functional surrogate to measure antiviral effector responses in HIV disease progression.

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LbOrA06