Longitudinal analysis of serum chemokine levels in the course of HIV-1 infection

Objectives: To investigate the correlation between the serum levels of the CC-chemokines RANTES, macrophage inflammatory protein (MIP)-1 alpha and MIP -1 beta, and the progression of HIV-1 disease. Design: Retrospective analysis of serial serum samples from HIV-1 seroconve rters selected according to clinical outcome. Methods: Twenty-one patients, derived from a cohort recruited between 1985 and 1996 for a prospective study of the natural history of HIV infection, w ere analysed. All patients had at least one HIV-1-seronegative sample withi n 1 year prior to the first seropositive test acid were followed longitudin ally throughout the course of HIV-1 infection (mean follow-up, 73.5 months) . Nine were rapid progressors (RP; patients who developed AIDS within 60 mo nths of antibody seroconversion), seven were slow progressors (SP; patients who developed AIDS after GO months), and five were long-term asymptomatic (LTA; patients with circulating CD4+ cells higher than 400 x 10(6)/l, no si gns of HIV disease, no antiretroviral therapy for more than 96 months). A t otal of 339 serum samples was studied (mean, 16.1 per patient). The levels of RANTES, MIP-1 alpha and MIP-1 beta were measured by enzyme-linked immuno sorbent assay and correlated with different immunological and clinical para meters. Results: Over the entire follow-up period, the geometric mean of serum RANT ES was significantly higher in RP [68.6 ng/ml; 95% confidence interval (CI) , 56.9-82.7] than in SP (23.7 ng/ml; 95% CI, 20.0-28.2; P < 0.001) and LTA (19.5 ng/ml; 95% CI, 15.5-24.5; P < 0.001). This difference was already sig nificant during the early clinical stages, when patients had peripheral blo od CD4+ cell counts still greater than 400 x 10(6)/l (P < 0.001). By contra st, the mean serum levels of MIP-1 alpha and MIP-1 beta did not differ sign ificantly between the three study groups. Multivariate analysis using the C ox proportional hazard model demonstrated that the mean serum concentration of RANTES before the development of AIDS was independently associated with the time to AIDS (relative risk, 4.5; 95% CI, 1.1-18.2; P = 0.035). in pat ients with low versus high mean serum RANTES before the fall of CD4+ cells below 400 x 10(6)/l, the median AIDS-free time was 117.5 and 42.7 months, r espectively (P = 0.037). Conclusion: These data suggest that an elevation of serum RANTES predicts a rapid progression of the disease since the early stages of HIV-1 infection . (C) 1999 Lippincott Williams & Wilkins.