Shorter Survival in Advanced Human Immunodeficiency Virus Type 1 Infection Is More Closely Associated with T Lymphocyte Activation than with Plasma Virus Burden or Virus Chemokine Coreceptor Usage

TLDR

Immune activation, rather than virus burden, is a major determinant of survival in advanced HIV‑1 disease. The study aimed to identify predictors of survival time in late HIV‑1 disease by comparing long‑ and short‑duration survivors after CD4+ T cells fell to ≤50/mm³. They assessed CD4+ and CD8+ T‑cell activation, virus burden, and coreceptor usage in patients whose CD4+ counts had fallen to ≤50/mm³. Elevated CD38 expression on CD4+ and CD8+ T cells strongly predicted shorter survival, whereas low naive T‑cell reserve, higher virus burden, and coreceptor usage did not.

Abstract

To define predictors of survival time in late human immunodeficiency virus type 1 (HIV-1) disease, long- and short-duration survivors were studied after their CD4+ T cells fell to ⩽50/mm3. Immune activation of CD4+ and CD8+ T cells, as measured by elevated cell surface expression of CD38 antigen, was strongly associated with shorter subsequent survival (P ⩾ .002). The naive CD45RA+CD62L+ T cell reserve was low in all subjects and did not predict survival (P = .34 for .34+ and .08 for CD8+ cells). Higher virus burden correlated with CD8+ but not CD4+ cell activation and, after correcting for multiple comparisons, was not associated with shorter survival (P = .02). All of the patients' viruses used CCR5, CXCR4, or both, and coreceptor usage did not predict survival (P = .27). Through mechanisms apparently unrelated to higher virus burden, immune activation is a major determinant of survival in advanced HIV-1 disease.