ASSOCIATION OF HLA PROFILES WITH EARLY PLASMA VIRAL LOAD, CD4-1 INFECTION( CELL COUNT AND RATE OF PROGRESSION TO AIDS FOLLOWING ACUTE HIV)

Background: Host genetic factors, such as HLA alleles, play an importa nt role in mediating the course of HIV-1 disease progression through l argely undefined mechanisms. Objectives: To examine the association of HLA markers with HIV-1 RNA plasma viral load and other factors associ ated with course of disease progression in HIV-1 infection. Design and methods: A group of 139 HIV-1 seroconverters from the Multicenter AID S Cohort Study had been typed for a variety of HLA markers. HIV-1 RNA plasma viral load was measured from frozen plasma specimens obtained a pproximately 9 months following seroconversion. CD4+ cell counts were available from the same study visit. Statistical analysis was performe d using survival techniques and linear regression models to quantify t he relative associations of an HLA score profile, HIV-1 RNA plasma vir al load, CD4+ cell count and age with each other and with rate of prog ression to AIDS and death. Results: Cox proportional hazards models sh owed statistically significant differences in time to AIDS by HLA scor e profile category per unit increase [relative hazard (RH), 0.64; P < 0.0001], HIV-1 RNA plasma viral load per 10-fold increase (RH, 2.04; P = 0.0003), and CD4+ cell count per 100 cell (x 10(6)/l) increase (RH, 0.90; P = 0.02). Multivariate linear regression showed that viral loa d was 39% lower (P = 0.0001) for each unit increase in HLA score profi le and 13% lower (P = 0.002) for each 100 cell (x 10(6)/l increase in CD4+ cell count. Conclusions: The means by which the HLA score profile influences the time to AIDS is probably through immunologic responses that affect the rate of HIV-1 replication, as manifested by the HIV-1 RNA plasma viral load during the first 6-12 months following acute in fection. (C) 1998 Lippincott Williams & Wilkins