The increase in viraemia in AHI was associated with rapid activation of a striking systemic cytokine cascade, including rapid and transient elevations in IFNalpha and IL-15, rapid and more sustained increases in TNFalpha, IP-10 and MCP-1, more slowly-initiated elevations in additional pro-inflammatory factors including IL-6, IL-8, IL-18 and IFNgamma and a late-peaking increase in IL-10. Most analytes returned to baseline as viraemia declined, but low-level elevations in some factors were sustained into early infection. Multiple cytokines/chemokines were transiently elevated in CVL during AHI. Some, e.g. TNFalpha, IL-1beta and IL-8, were typically already highly elevated in CVL at the earliest timepoint studied (even prior to peak viraemia), suggestive of a local pro-inflammatory response preceding systemic immune activation. Others, e.g. IFNgamma, MIP-1beta and IL-10 were only elevated in CVL around peak viraemia. Modest elevations in seminal plasma cytokine/chemokine levels occurred in AHI in parallel with systemic analyte increases.