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

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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.

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