It is now apparent that a proportion of individuals (5-8 %) remains cl
inically free of HIV-1 disease with normal levels of CD4(+) lymphocyte
s (greater than or equal to 500/mu l) for more than 8 years following
infection, However, the proportion of these individuals who ultimately
progress to AIDS remains to be established, We determined the virolog
ical and immunological characteristics of a cohort of long-term nonpro
gressors in Australia and examined the role of these factors in predic
ting disease progression, Individuals with documented asymptomatic HIV
-1 infection for at least 8 years with CD4(+) lymphocyte counts >500 c
ells/mu l were recruited from hospital clinics and general practices s
erving the eastern area of Australia, CD4(+) lymphocyte count, rate of
CD4(+) lymphocyte change, CD8(+) lymphocyte count, beta(2)-microglobu
lin, immune complex dissociated (TCD) HIV-1 p24 antigen, and plasma HI
V-1 RNA were measured at baseline and multiple visits at B-month inter
vals over an average period of 2 years, Up to November 1996, 67 study
participants were recruited, of whom 72% had been infected with HIV-1
for at least 10 years, HIV-1 RNA correlated with beta 2-microglobulin,
ICD p24 antigen, and the ability to isolate virus in culture but not
with levels of CD4(+) or CD8(+) lymphocytes. Serum beta(2)-microglobul
in was a stronger predictor of CD4(+) lymphocyte decline than HIV-1 RN
A and the only factor significantly associated with CD4(+) lymphocyte
decline, These findings show that the serum concentration of beta(2)-m
icroglobulin is a strong predictor of immunological progression in peo
ple with long-term asymptomatic HIV-1 infection and provides additiona
l prognostic information to HIV-1 RNA in determining the risk of disea
se progression.