HIV‐specific CD8 + T‐cell proliferation is prospectively associated with delayed disease progression

Human immunodeficiency virus (HIV)‐specific CD8 + T‐cell proliferation is consistently correlated with enhanced host HIV immune control, but whether proliferative responses are a cause or consequence of immune protection is unclear. We measured Env‐specific CD8 + T‐cell proliferation and interferon (IFN)‐γ secretion in HIV‐infected participants with CD4 counts >200, who then completed 121 person‐years of prospective follow‐up to monitor HIV disease progression. In all, 13 of 31 participants (42%) reached end point during longitudinal follow‐up. Strong Env‐specific CD8 + T‐cell proliferation (>10% of CD8 + T cells) was observed in 14/31 participants at baseline, and this was associated with a longer time to HIV disease progression end point, stratified baseline CD4 count ( P =0.016). No associations were observed for IFN‐γ ELISPOT responses and progression ( P >0.2). Strong proliferation remained significant in multivariate Cox regression analyses ( P =0.044) as an independent predictor of delayed HIV disease progression, along with baseline CD4 count ( P =0.04). Duration of HIV infection was associated with more rapid progression in univariate, but not multivariate, analysis ( P =0.112). Age and baseline viral load were not predictive of progression. HIV‐specific CD8 + T‐cell proliferation was a correlate of protective immunity in this prospective study; such responses may be important for HIV vaccine protection.