Pre-seroconversion immune status predicts the rate of CD4 T cell decline following HIV infection

OBJECTIVE: To study whether immune status prior to HIV seroconversion predicts CD4 T cell decline during HIV infection.

DESIGN: Prospective cohort study including 51 injecting drug users (IDU) who were HIV negative at study entry and seroconverted for HIV during follow-up.

METHODS: Cryopreserved peripheral blood mononuclear cells obtained before HIV seroconversion were used to measure naive (CD45RO-CD27+), memory (CD45RO+CD27+), and total CD4 T cell numbers, the fraction of dividing Ki67+CD4+ T cells, and CD4 T cell receptor excision circles (TREC). The effect of pre-seroconversion immune status, as defined by these markers, on the rate of CD4 T cell decline during HIV infection was assessed using linear regression for repeated measurements.

RESULTS: IDU with low pre-seroconversion CD4 T cell TREC contents lost CD4 T cells at a significantly faster rate during HIV infection than those with a high CD4 T cell TREC content. IDU with higher pre-seroconversion CD4 T cell numbers had a significantly steeper CD4 T cell decline in the first 3 months of HIV infection, but their CD4 T cell counts remained higher throughout HIV infection. Intermediate levels of pre-seroconversion dividing Ki67+CD4+ T cells were associated with a significantly steeper CD4 cell decline than high levels. IDU with the highest pre-seroconversion drug-injecting frequencies showed slower CD4 T cell decline than those who injected less. No correlation was present between pre-seroconversion immune markers and the pre-seroconversion duration or intensity of drug use.

CONCLUSION: Among IDU, immune status prior to HIV infection as measured by TREC content affects the disease course after HIV seroconversion.