HIV viral set point and host immune control in individuals with HIV-specific CD8+ T-cell responses prior to HIV acquisition.
Kaul R., MacDonald KS., Nagelkerke NJ., Kimani J., Fowke K., Ball TB., Luo M., Kariri A., Jaoko W., Moses S., Rowland-Jones S., Plummer FA.
OBJECTIVE: Vaccine-induced CD8(+) T-cell responses in primates have been associated with a reduced simian immunodeficiency virus plasma viral load and enhanced T-cell responses, but cellular vaccines have shown limited success in human trials. We previously described HIV-specific T-cell responses in two groups of highly exposed, persistently seronegative Kenyan female sex workers, and a subset of these participants have subsequently acquired HIV. We examined the impact of pre-existing CD8(+) T-cell responses on post-acquisition outcomes. DESIGN AND METHODS: HIV-specific CD8(+) T-cell responses had been examined in highly exposed, persistently seronegative participants from the Pumwani and Kibera cohorts, using a combination of virus-specific lysis, proliferation, interferon-gamma production, or all. Plasma viral load set point and HIV-specific T-cell proliferation and cytokine production were now examined post hoc by blinded investigators in the subset of participants who acquired HIV. RESULTS: Pre-acquisition cellular immune assays and post-infection viral load were available for 46 participants, and HIV-specific CD8(+) T-cell responses had been detected in 25 of 46 (54%) participants. Pre-acquisition CD8(+) T-cell responses were associated with a lower post-acquisition HIV viral load set point in both cohorts (pooled analysis, 3.1 vs. 4.1 log(10) RNA copies/ml; P=0.0002) and with enhanced post-acquisition HIV-specific CD8(+) T-cell proliferation (3.8 vs. 1.0%, P=0.03), but with a trend to reduced post-acquisition CD8(+) T-cell interferon-gamma responses. CONCLUSION: HIV-specific CD8(+) T-cell responses prior to HIV acquisition were associated with a lower HIV viral load and an altered functional profile of post-acquisition CD8(+) T-cell responses.