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

Rachael A Hughes1, Margaret T May1, Kate Tilling1,2

  • 1Population Health Sciences, Bristol Medical School.

AIDS (London, England)
|June 1, 2018
PubMed

Insights

Combination antiretroviral therapy (ART) leads to declining CD8+ cell counts and increasing CD4+/CD8+ ratios for up to 15 years. Achieving a normal CD4+/CD8+ ratio (>1) depends on baseline CD4+ cell count, with higher counts predicting faster normalization.

Area of Science:

  • Immunology
  • Virology
  • Biostatistics

Background:

  • Combination antiretroviral therapy (ART) is crucial for managing HIV.
  • Monitoring CD4+ and CD8+ T-cell dynamics is essential for assessing treatment efficacy.
  • The CD4+/CD8+ ratio is a key indicator of immune reconstitution in HIV-positive individuals.

Purpose of the Study:

  • To model CD4+ and CD8+ T-cell count trajectories after initiating ART.
  • To predict long-term trends in CD4+ and CD8+ cell counts and the CD4+/CD8+ ratio.
  • To evaluate factors influencing immune recovery, including baseline CD4+ count and virological failure.

Main Methods:

  • A cohort study of over 39,000 HIV-positive adults initiating ART after 1997 was analyzed.
  • A bivariate random effects model with linear splines was used to estimate cell count trends.
  • The CD4+/CD8+ ratio trend was predicted, and its association with baseline CD4+ count and virological status was assessed.

Main Results:

  • Predicted mean CD8+ cell counts decreased, and CD4+/CD8+ ratios increased for up to 15 years post-ART.
  • Normalization of the CD4+/CD8+ ratio (>1) was observed only in patients with a baseline CD4+ count of at least 200 cells/microliter.
  • Higher baseline CD4+ cell counts were associated with a shorter time to ratio normalization.

Conclusions:

  • ART initiation leads to sustained declines in CD8+ T-cells and increases in the CD4+/CD8+ ratio over 15 years.
  • The likelihood of achieving a normalized CD4+/CD8+ ratio is strongly dependent on the individual's baseline CD4+ T-cell count.
  • These findings highlight the importance of early ART initiation for optimal immune reconstitution.
Abstract

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