Long terms trends in CD4(+) cell counts, CD8(+) cell counts, and the CD4(+) : CD8(+) ratio

OBJECTIVE: Model trajectories of CD4(+) and CD8(+) cell counts after starting combination antiretroviral therapy (ART) and use the model to predict trends in these counts and the CD4(+) : CD8(+) ratio. DESIGN: Cohort study of antiretroviral-naïve HIV-positive adults who started ART after 1997 (ART Cohort Collaboration) with more than 6 months of follow-up data. METHODS: We jointly estimated CD4(+) and CD8(+) cell count trends and their correlation using a bivariate random effects model, with linear splines describing their population trends, and predicted the CD4(+) : CD8(+) ratio trend from this model. We assessed whether CD4(+) and CD8(+) cell count trends and the CD4(+) : CD8(+) ratio trend varied according to CD4(+) cell count at start of ART (baseline), and, whether these trends differed in patients with and without virological failure more than 6 months after starting ART. RESULTS: A total of 39 979 patients were included (median follow-up was 53 months). Among patients with baseline CD4(+) cell count at least 50 cells/μl, predicted mean CD8(+) cell counts continued to decrease between 3 and 15 years post-ART, partly driving increases in the predicted mean CD4(+) : CD8(+) ratio. During 15 years of follow-up, normalization of the predicted mean CD4(+) : CD8(+) ratio (to >1) was only observed among patients with baseline CD4(+) cell count at least 200 cells/μl. A higher baseline CD4(+) cell count predicted a shorter time to normalization. CONCLUSION: Declines in CD8(+) cell count and increases in CD4(+) : CD8(+) ratio occurred up to 15 years after starting ART. The likelihood of normalization of the CD4(+) : CD8(+) ratio is strongly related to baseline CD4(+) cell count.