Long terms trends in CD4⁺ cell counts, CD8⁺ cell counts, and the CD4⁺:CD8⁺ ratioCD8⁺ 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.