Predictors of immunological failure after initial response to highly active antiretroviral therapy in HIV-1-infected adults: A EuroSIDA study

Abstract

Background. Factors that determine the immunological response to highly active antiretroviral therapy (HAART) are poorly defined. Objective. Our aim was to investigate predictors of immunological failure after initial CD4 + response. Methods. Data were from EuroSIDA, a prospective, international, observational human immunodeficiency virus (HIV) type 1 cohort. Results. Of 2347 patients with an increase in CD4+ cell count ≥100 cells/μL within 6-12 months of the initiation of HAART, 550 (23%) subsequently experienced immunological failure (CD4+ count less than or equal to the pre-HAART value). The incidence of failure was 11.6 incidences/100 person-years of follow-up (95% confidence interval [CI], 10.2-13.4) during the first 12 months and decreased significantly over time (P < .0001). Independent predictors of immunological failure were pre-HAART CD4+ cell count (per 50% higher; relative hazard [RH], 2.05; 95% CI, 1.83-2.31; P < .0001), time-updated virus load (per 1 log10 higher; RH, 1.77; 95% CI, 1.64-1.92; P < .0001), and HIV-1 risk behavior (P = .047 for a global comparison of risk groups). Conclusion. The risk of immunological failure in patients with an immunological response to HAART diminishes with a longer time receiving treatment and is associated with pretreatment CD4+ cell count, ongoing viral replication, and intravenous drug use.