The incidence of AIDS-defining illnesses at a current CD4 count ≥ 200 cells/μL in the post-combination antiretroviral therapy era

Abstract

Background: Few studies consider the incidence of individual AIDS-defining illnesses (ADIs) at higher CD4 counts, relevant on a population level for monitoring and resource allocation.

Methods: Individuals from the Collaboration of Observational HIV Epidemiological Research Europe (COHERE) aged ≥14 years with ≥1 CD4 count of ≥200 µL between 1998 and 2010 were included. Incidence rates (per 1000 person-years of follow-up [PYFU]) were calculated for each ADI within different CD4 strata; Poisson regression, using generalized estimating equations and robust standard errors, was used to model rates of ADIs with current CD4 ≥500/µL.

Results: A total of 12 135 ADIs occurred at a CD4 count of ≥200 cells/µL among 207 539 persons with 1 154 803 PYFU. Incidence rates declined from 20.5 per 1000 PYFU (95% confidence interval [CI], 20.0-21.1 per 1000 PYFU) with current CD4 200-349 cells/µL to 4.1 per 1000 PYFU (95% CI, 3.6-4.6 per 1000 PYFU) with current CD4 ≥ 1000 cells/µL. Persons with a current CD4 of 500-749 cells/µL had a significantly higher rate of ADIs (adjusted incidence rate ratio [aIRR], 1.20; 95% CI, 1.10-1.32), whereas those with a current CD4 of ≥1000 cells/µL had a similar rate (aIRR, 0.92; 95% CI, .79-1.07), compared to a current CD4 of 750-999 cells/µL. Results were consistent in persons with high or low viral load. Findings were stronger for malignant ADIs (aIRR, 1.52; 95% CI, 1.25-1.86) than for nonmalignant ADIs (aIRR, 1.12; 95% CI, 1.01-1.25), comparing persons with a current CD4 of 500-749 cells/µL to 750-999 cells/µL.

Discussion: The incidence of ADIs was higher in individuals with a current CD4 count of 500-749 cells/µL compared to those with a CD4 count of 750-999 cells/µL, but did not decrease further at higher CD4 counts. Results were similar in patients virologically suppressed on combination antiretroviral therapy, suggesting that immune reconstitution is not complete until the CD4 increases to >750 cells/µL.

Keywords: AIDS defining illnesses; CD4; cART; immune reconstitution; virologic suppression.