Objectives: It is well established that a low CD4 lymphocyte count is strongly associated with an increased risk of AIDS in HIV infection. We attempted to determine whether the link is sufficiently strong that the wide inter-person variability in times from HIV infection to AIDS can be explained solely by differences in CD4 count experience.
Methods: We followed 1090 HIV-infected individuals for up to 12.8 years from seroconversion (median, 3.5 years; 25% for more than 5.2 years). The median interval between last negative and first positive anti-HIV tests was 9 months. A median of four CD4 counts per subject were measured.
Results: Individuals with CD4 lymphocyte counts above 250 x 10(6)/l cells experienced an AIDS incidence rate of one per 339 years (0.3 per 100 years; 10 cases in 3394 person-years), compared with one per 6 years in those whose count had declined below this level (17.2 per 100 years; 96 cases in 559 person-years) and one per year in those whose count had declined below 50 x 10(6)/l (100.0 per 100 years; 41 cases in 41 person-years). The AIDS rate increased by an average of 33% [relative rate, 1.33; 95% confidence interval (CI), 1.20-1.49; P = 0.0001] with every year from seroconversion; one per 46 years (2.2 per 100 years) for people seropositive for less than 5 years compared with one per 14 years (7.3 per 100 years) for those seropositive for more than 5 years. After adjusting for the tendency for CD4 lymphocyte counts to be higher soon after seroconversion, the relative rate declined to 1.07 (95% CI, 0.94-1.22) per year from seroconversion (P = 0.32). This result was similar when those infected through sharing injecting equipment, homosexual sex, and other routes were considered separately. The relative rate per year from seroconversion for death due to AIDS fell from 1.41 (P = 0.0001) to 1.00 (P = 0.99) after adjusting for CD4 count.
Conclusions: Most of the inter-person variability in time from HIV infection to AIDS appears to result from differences in CD4 lymphocyte counts. HIV infection appears to cause AIDS and death largely by its ability to induce CD4 lymphocytopaenia or some closely correlated abnormality.