Early Levels of CD4, Neopterin, and β2-Microglobulin Indicate Future Disease Progression

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Abstract
Reduced CD4 T cell level and increased serum neopterin and β2-microglobulin levels, which reflect immunological activation and dysregulation, are three important markers of HIV disease. The aim in this study is to delineate more clearly the relation of activation to future CD4 values and disease progression. By analyzing a cohort of 198 seroconverters from the Multicenter AIDS Cohort Study with 9 years' follow-up, the dynamic changes and levels of these three markers and their interrelationships are explored. We observed that the levels of markers in the first year after seroconversion have a much stronger impact on the progression of the disease than the preseroconversion marker levels. The actual change during the year after seroconversion is not as important as the final level reached during that year. The early levels of markers after seroconversion appear to be good indicators of the subsequent course of disease as defined by CD4 level and slightly better than the quantitative changes following seroconversion or the changes in the period 1 to 2.5 years after seroconversion. To investigate the variation between subjects, the 198 seroconverters were stratified into three approximately equal-sized groups in 12 ways based on their pre- and postseroconversion levels and changes in the three markers. The group with the highest CD4 level within a year after seroconversion maintains the highest CD4 level 8 years after seroconversion. The group with the lowest level of neopterin or β2-microglobulin in this period has much higher future CD4 counts than the other two groups. The level of markers during the first year after seroconversion has a high predictive power for AIDS onset. Substantial differences in the hazards of AIDS are found between the groups with the highest and lowest CD4 count, neopterin, and β2-microglobulin following seroconversion. The three markers are generally correlated throughout the postseroconversion period but can provide distinct information. High current levels of neopterin or β2-microglobulin tend to be associated with low future CD4 count, while current levels of CD4 count have less association with future neopterin and β2-microglobulin levels.