Determinants of a Low CD4/CD8 Ratio in HIV-1-Infected Individuals Despite Long-term Viral Suppression

Clin Infect Dis. 2016 May 15;62(10):1297-1303. doi: 10.1093/cid/ciw076. Epub 2016 Feb 14.

Abstract

Background: A low CD4/CD8 ratio in human immunodeficiency virus (HIV)-infected individuals despite effective antiretroviral therapy (ART) reflects ongoing immune activation and has been linked to a higher risk of non-AIDS morbidity and mortality. Our aim was to describe the proportion of individuals with a persistent CD4/CD8 ratio <1 despite long-term viral suppression and to determine associated risk factors.

Methods: This cross-sectional study was conducted in 2012 in a single clinical center. HIV type 1 (HIV-1)-infected individuals were eligible if they had a plasma HIV-1 RNA level <50 copies/mL for at least 2 years on a stable ART regimen. Logistic regression was used to identify risk factors for a persistent CD4/CD8 ratio <1.

Results: We enrolled 719 individuals with a median CD4/CD8 ratio of 0.8 (interquartile range [IQR], 0.6-1.1), CD4 and CD8 T-cell counts of 565 (IQR, 435-742) cells/µL and 727 (IQR, 530-991) cells/µL respectively, and viral suppression for 5.4 (IQR, 3.3-9.1) years. Cytomegalovirus (CMV) serology was positive in 564 of 645 individuals (87%). Persistent CD4/CD8 ratio <1 was observed in 471 patients (66%). The following factors were independently associated with a CD4/CD8 ratio <1: CMV seropositivity (odds ratio [OR], 1.9 [95% confidence interval {CI}, 1.1-3.1]), ART initiation before 1997 (OR, 1.9 [95% CI, 1.2-3.0] compared with 2002 or later), a lower CD4 T-cell nadir (OR, 0.7 [95% CI, .7-.8] per log2 increment), and shorter duration of viral suppression (OR, 0.6 [95% CI, .5-.8] per 5 years).

Conclusions: Most HIV-infected individuals with long-term viral suppression still had a CD4/CD8 ratio <1. Early initiation and long-term effective ART appear to improve this ratio. CMV coinfection, which represents a potential target for therapeutic intervention, was strongly associated with a persistently suboptimal CD4/CD8 ratio.

Keywords: CD4/CD8 ratio; CMV seropositivity; immune restoration; viral suppression.

MeSH terms

  • Adult
  • Anti-HIV Agents / therapeutic use
  • CD4-CD8 Ratio*
  • Cross-Sectional Studies
  • Female
  • HIV Infections / blood
  • HIV Infections / drug therapy
  • HIV Infections / immunology*
  • HIV Infections / virology*
  • HIV-1 / immunology*
  • Humans
  • Male
  • Middle Aged
  • RNA, Viral / blood
  • Risk Factors
  • Viral Load

Substances

  • Anti-HIV Agents
  • RNA, Viral