Role of CD4/CD8 ratio on the incidence of tuberculosis in HIV-infected patients on antiretroviral therapy followed up for more than a decade

BACKGROUND: The role of CD4/CD8 ratio on the incidence of tuberculosis (TB) in patients on antiretroviral therapy (ART) is unknown. Thus, we sought to determine whether the CD4/CD8 ratio was associated with development of TB in a cohort of HIV infected individuals on ART followed up for more than a decade in the setting of sub-Saharan Africa (SSA). METHODS: The cohort comprised adult patients who started ART between 2001 and 2007 and followed for up to 15 years. Clinical data were collected in retrospective manner. Patients with an AIDS defining illness or a CD4 count <200 cell/μL were started with a combination of ART. The participants have clinic visits every 6 months and/or as needed. Poisson regression models were used to identify factors associated with development of incident TB. Kaplan-Meier curves were used to estimate the probability of incident TB while on ART. RESULTS: A total of 347 patients with a median duration of follow-up on ART of 11.5 (IQR: 10.0–12.5) years were included. Incident TB developed in 47 patients during the 3259 person-years of follow-up, the majority (76.6%) occurred within five year of ART initiation. On univariate analysis, poor ART adherence (RR:2.57, 95% CI: 1.28–5.17), time-updated CD4 cell count of lower than 200 (RR: 4.86, 95%CI 2.33–10.15), or CD4 cell count between 200 and 500 (RR: 4.68, 95% CI: 2.17–10.09), time-updated CD8 cell count lower than 500 (RR: 2.83 95% CI 1.31–6.10), or CD8 cell count over 1000 (RR: 2.23, 95% CI: 1.12–4.45), time-updated CD4/CD8 ratio of less than 0.30 (RR: 6.00, 95% CI: 2.96–12.14), lack of normalization of CD4 T-cell count (RR: 6.13, 95% CI: 2.20–17.07), and virological failure (RR: 2.35 (95% CI: 1.17–4.71) were all associated with increased risk of incident TB. In multivariate analysis, however, time-updated CD4/CD8 ratio of less than 0.30 (adjusted RR: 4.08, 95% CI: 1.31–12.68) was the only factor associated with increased risk of developing incident TB (p = 0.015). Similar results were obtained in a sensitivity analysis by including only those virally suppressed patients (n = 233, 69% of all patients). In this group, CD4/CD8 ratio of less than 0.30 was associated with development of incident TB (adjusted RR: 4.02, 95% CI: 1.14–14.19, p = 0.031). Overall, the incidence rate of TB in patients with an updated CD4/CD8 ratio of less than 0.30 was more than 5-fold higher when compared with those with a ratio more than 0.45. CONCLUSION: Low CD4/CD8 ratio is independently associated with an increased risk of incident TB despite viral suppression. CD4/CD8 ratio may serve as a biomarker for identifying patients at risk of TB in patients on ART in the setting of SSA.