HIV viral set point and host immune control in individuals with HIV-specific CD8+ T-cell responses prior to HIV acquisition

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 log₁₀ 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.