Pre-seroconversion Immune Status Predicts the Rate of CD4 T Cell Decline Following HIV Infection

It has been suggested that increased levels of immune activation in healthy individuals prior to infection with HIV may be associated with faster HIV disease progression.

However, because of the paucity of patient material obtained prior to infection with HIV, little is known about the extent to which the immune status before HIV seroconversion determines HIV disease course.

Only one recent study among homosexual men has investigated this issue. The results showed that both low CD4 T cell count and high immune activation (CD4+CD70+ expression) before seroconversion were associated with faster progression to AIDS.

Compared with heterosexual individuals, HIV-negative homosexual men may have increased levels of immune activation owing to increased prevalence of sexually transmitted diseases.

However, the median incubation time to AIDS and death in risk groups with perhaps even higher immune stimulation, such as injecting drug users (IDU) and people living in Sub-Saharan Africa, does not differ from that among homosexual men in industrialized countries in the pre-HAART era.

Nevertheless, pre-seroconversion immune status could be a factor explaining the great inter-individual variation in HIV disease progression within risk groups, as demonstrated by a prior study among homosexual men.

The objective of the current study was to determine whether immune status prior to HIV seroconversion predicts CD4 T cell decline during HIV infection. This prospective cohort study included 51 injecting drug users (IDU) who were HIV negative at study entry and seroconverted for HIV during follow-up.

Cryopreserved peripheral blood mononuclear cells obtained before HIV seroconversion were used to measure naive, memory, 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

In conclusion, the authors write, “Among IDU, immune status prior to HIV infection as measured by TREC content affects the disease course after HIV seroconversion. Since TREC content is a cumulative marker for an individual's immune history, immune status prior to HIV infection thus affects the disease course after HIV seroconversion.”

“Because the number of patients analyzed was small, these results warrant further research in larger groups of patients and other risk groups.”

09/10/04

Reference
L van Asten and others. Pre-seroconversion immune status predicts the rate of CD4 T cell decline following HIV infection. AIDS 18(14): 1885-1893, September 24, 2004.