Longitudinal measurements of plasma HIV RNA were analyzed using novel segme
nted regression models for 62 men in the Multicenter AIDS Cohort Study who
at enrollment in 1985 were HIV seropositive and who had stable CD4(+) lymph
ocyte counts and no clinical disease progression for a 6-year period betwee
n 1985 and 1991. Through 1996, 20 of the men developed clinical AIDS or die
d (late progressors) and 42 remained asymptomatic (nonprogressors). Using s
egmented regression model methods, we estimated, for each individual, the t
ime when a change in HIV RNA trajectory was most likely to have occurred. P
rior to this time, late progressors and nonprogressors had stable plasma HI
V 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 prog
ressors showed significant increases in HIV RNA levels of 0.23 log(10) copi
es/ml/year (1.7-fold increase/year). This increase in HIV RNA in the late p
rogressors began approximately 1.1 years prior to the onset of their declin
e in CD4(+) lymphocytes, and 4.8 years prior to the onset of AIDS. These re
sults provide evidence that an increase in the slope of plasma levels of HI
V RNA is a sign of incipient progression of HIV disease.