[26] PARTIAL VIRAL SUPPRESSION WITH COMBINATION THERAPY IS ASSOCIATED WITH ENHANCED HIV-SPECIFIC CD4 AND CD8 T CELL RESPONSES

5th International Workshop on HIV Drug Resistance & Treatment Strategies

4-8 June 2001, Scottsdale, Arizona

[TITLE:] PARTIAL VIRAL SUPPRESSION WITH COMBINATION THERAPY IS ASSOCIATED WITH ENHANCED HIV-SPECIFIC CD4 AND CD8 T CELL RESPONSES

[AUTHOR(S):] SG Deeks¹, E Sinclair², J Harris², E Hagos¹, L Epling², R Ronquillo², B Bredt², JN Martin¹ and JM McCune²
¹ University of California, San Francisco, Calif., USA; and ² Gladstone Institute of Virology and Immunology, San Francisco, Calif., USA
Antivir Ther. 2001;6 Suppl 1:21

BACKGROUND: We investigated the role of HIV-specific T cell responses in maintaining partial suppression of viral replication in the setting of virologic failure of HAART.

METHODS: This is a cross-sectional study of three groups of HIV infected adults: (1) complete viral responders (n=42): viral load <50 copies/ml on HAART; (2) partial virological responders (n=24): viral load >50 copies/ml on HAART for >6 months; and (3) untreated (n=12): treatment-naïve patients or patients off HAART for >6 months. The proportion of CD4 and CD8 cells expressing gamma-interferon after exposure to a pool of overlapping peptides spanning the p55 protein sequence was measured (cytokine flow cytometry).

RESULTS: There was a positive correlation between viral load and the percent of HIV-specific CD8 cells (ρ=0.60, P<0.001); this association persisted when the analysis was limited to patients with detectable viraemia (ρ=0.42, P=0.01). The median percentage of HIV-specific CD8 cells was 0.37 in complete virological responders, 0.97 in partial virological responders, and 1.96 in untreated patients (P<0.05 for each pairwise comparison). In contrast, there was no association between viral load and the percentage of HIV-specific CD4 cells. The percentage of HIV-specific CD4 cell counts was 0.08 in complete virological responders, 0.25 in partial responders and 0.07 in untreated patients (P<0.05 for the comparison between the partial virological responders and each of the other two groups). The proportion of patients with a positive HIV-specific CD4 cell response (>0.1% above background) was higher in the partial virological responders (20/24 patients, 83%) than in the complete virological responders (17/42, 40%) or in the untreated patients (4/12, 33%).

CONCLUSION: Partial suppression of viral replication with HAART was associated with the presence of both a CD4 and CD8 HIV-specific T cell response. In contrast, untreated HIV infection was associated with a detectable CD8 cell response but a significantly reduced CD4 cell response. The presence of a robust CD4 and CD8 response in patients with partial viral suppression suggests that these cells may contribute to a lower viral set-point in treated patients with drug-resistant viraemia.

PRESENTING AUTHOR: SG Deeks

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