EARLY LEVELS OF CD4, NEOPTERIN, AND BETA(2)-MICROGLOBULIN INDICATE FUTURE DISEASE PROGRESSION

Reduced CD4 T cell level and increased serum neopterin and beta(2)-mic roglobulin levels, which reflect immunological activation and dysregul ation, are three important markers of HIV disease. The aim in this stu dy is to delineate more clearly the relation of activation to future C D4 values and disease progression. By analyzing a cohort of 198 seroco nverters from the Multicenter AIDS Cohort Study with 9 years' follow-u p, the dynamic changes and levels of these three markers and their int errelationships are explored. We observed that the levels of markers i n the first year after seroconversion have a much stronger impact on t he progression of the disease than the preseroconversion marker levels . The actual change during the year after seroconversion is not as imp ortant as the final level reached during that year. The early levels o f markers after seroconversion appear to be good indicators of the sub sequent 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 int o 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 ma intains the highest CD4 level 8 years after seroconversion. The group with the lowest level of neopterin or beta(2)-microglobulin in this pe riod 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 hazar ds of AIDS are found between the groups with the highest and lowest CD 4 count, neopterin, and beta(2)-microglobulin following seroconversion . The three markers are generally correlated throughout the postseroco nversion period but can provide distinct information. High current lev els of neopterin or beta(2)-microglobulin tend to be associated with l ow future CD4 count, while current levels of CD4 count have less assoc iation with future neopterin and beta(2)-microglobulin levels.