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  • Title: Determinants of progression of HIV infection in a Greek hemophilia cohort followed for up to 16 years after seroconversion.
    Author: Touloumi G, Karafoulidou A, Gialeraki A, Katsarou O, Milona I, Kapsimali V, Mandalaki T, Hatzakis A.
    Journal: J Acquir Immune Defic Syndr Hum Retrovirol; 1998 Sep 01; 19(1):89-97. PubMed ID: 9732075.
    Abstract:
    Our objectives are to describe the progression of HIV disease and to assess the influence of hemophilia-related variables, age at infection, and antibodies to cytomegalovirus infection (anti-CMV) in a Greek cohort of 158 HIV-1-positive hemophilic men, who received prospective follow-up for up to 16 years after infection. A total of 79 patients had died, representing a cumulative progression rate of 72.4% (95% confidence interval [CI], 56.6-83.3). A significant proportion of the mortality (30%) resulted from conditions not formally related to AIDS, with liver failure and cerebral hemorrhage predominant. At 16 years after seroconversion, 66 patients had developed clinical AIDS, a cumulative progression rate of 58.2% (95% CI, 47.1%-86.3%) whereas 15 years after infection 81.5% (95% CI, 74.2%-87.9%) of the patients had AIDS or a CD4 cell count <200 cells/mm3. Hemophilia-related variables or presence of anti-CMV were not significantly associated with disease progression. Age at infection was a strong prognostic factor for all three endpoints. Appropriate modeling showed a nonlinear age effect, with a steeper increase of relative hazard for patients >40 years of age at seroconversion. The age effect remained significant even after controlling for current CD4 cell count. Further investigation is required to elucidate the mechanisms of the age effect and the contribution of HCV coinfection on the disease progression. The Greek Hemophilia Cohort Study encompasses 158 HIV-positive men with documented seroconversion dates. The present study estimated the rate of progression to all-cause mortality, clinical AIDS, or advanced immunodeficiency 16 years after seroconversion and evaluated the independent effects of hemophilia-related factors, age at seroconversion, and cytomegalovirus status early in the course of infection. Seroconversion dates extended from September 1980 to December 1985. By 1996, after a median follow-up of 11.6 years, 117 of the 158 men had developed AIDS or had a CD4 cell count of 20 cells/cu. mm, and 79 had died. The estimated cumulative incidence rates of clinical AIDS and death over 16 years since infection were 58.1% and 72%, respectively. 30% of the mortality was due to diseases not formally associated with AIDS (e.g., liver failure and cerebral hemorrhage). A significant association existed between older age at seroconversion and more rapid progression to both AIDS and death, with a particularly steep gradient for patients over 40 years old at seroconversion. The age effect remained significant even after controlling for current CD4 cell count. Increases of 1.32-fold and 1.33-fold in the risks of dying and developing AIDS, respectively, were obtained with every one unit decrease in CD4 cell count on the square root scale. Severity of hemophilia, dosage of clotting factor concentrates, and antibodies to cytomegalovirus were not associated with either AIDS risk or mortality. Further investigations are urged to clarify the mechanisms underlying the age effect observed in this study.
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