Objective: To characterize the progression to HIV-1 disease among inje
ction drug users (IDU) according to laboratory markers. D Design: Pros
pective study of cohort of HIV-1-seroprevalent IDU, with case-comparis
on component. Methods: Different laboratory markers were examined as p
redictors of progression to HIV-1-associated diseases including AIDS i
n a cohort of 318 HIV-1-infected IDU. The cohort was enrolled from a m
ethadone treatment program in the Bronx, New York, USA. The independen
t utility of non-CD4 cell markers was evaluated after adjustment for t
he association of low CD4 lymphocyte count with AIDS risk. Clinical ev
ents in the natural history of HIV-1 were related to changes in levels
of two variables related to duration of infection, CD4 lymphocyte cou
nt and serum beta(2)-microglobulin (beta(2)M) concentration. Results:
On univariate analysis, AIDS incidence measured from baseline increase
d with declining CD4 lymphocyte number and percentage, increasing seru
m beta(2)M level, low platelet count, low leukocyte count and p24 anti
genemia. Among HIV-1-related outcomes prior to any AIDS diagnosis, the
relative risk of pyogenic bacterial infections conferred by these mar
kers was similar to the relative risk of AIDs. For all HIV-1 outcomes,
the elevated risk encountered at CD4 lymphocyte number less than or e
qual to 200 x 10(6)/l was entirely due to the high risk at less than o
r equal to 150 x 10(6)/l. On multivariate analysis, control for CD4 ly
mphocyte count eliminated the association of any other marker with inc
reased AIDS hazard. HIV-1-related outcomes tended to occur in this ord
er: multiple constitutional symptoms, oral candidiasis, pyogenic bacte
rial infections of AIDS. Conclusions: In HIV-1-infected IDU, several l
aboratory markers may predict AIDS when analyzed individually. These a
re not, however, independently related to increased AIDS risk after ad
justment for low CD4 lymphocyte count. A CD4 count less than or equal
to 150 x 10(6)/l is more strongly related to immediate risk of adverse
outcome than a count of 200 x 10(6)/l. A progressive series of clinic
al events is associated with markers of duration of HIV-1 infection, p
rior to and including AIDS diagnosis.