Longitudinal patterns of HIV type 1 RNA among individuals with late disease progression

Longitudinal measurements of plasma HIV RNA were analyzed using novel segmented regression models for 62 men in the Multicenter AIDS Cohort Study who at enrollment in 1985 were HIV seropositive and who had stable CD4(+) lymphocyte counts and no clinical disease progression for a 6-year period between 1985 and 1991. Through 1996, 20 of the men developed clinical AIDS or died (late progressors) and 42 remained asymptomatic (nonprogressors). Using segmented regression model methods, we estimated, for each individual, the time when a change in HIV RNA trajectory was most likely to have occurred. Prior to this time, late progressors and nonprogressors had stable plasma HIV RNA levels, although the mean level in late progressors was 0.42 log(10) copies/ml higher than in nonprogressors (p = 0.018). Furthermore, late progressors showed significant increases in HIV RNA levels of 0.23 log(10) copies/ml/year (1.7-fold increase/year). This increase in HIV RNA in the late progressors began approximately 1.1 years prior to the onset of their decline in CD4(+) lymphocytes, and 4.8 years prior to the onset of AIDS. These results provide evidence that an increase in the slope of plasma levels of HIV RNA is a sign of incipient progression of HIV disease.