Objectives: Kaposi's sarcoma-associated herpesvirus (KSHV), a newly di
scovered human gammaherpesvirus, is found in the majority of KS lesion
s from patients with and without AIDS. Peripheral blood mononuclear ce
lls (PBMC) were examined for KSHV DNA to determine whether viral infec
tion precedes onset of this neoplasm. Design: Randomized and blinded c
ase-control study of prospectively collected PBMC samples from ongoing
cohort studies. Methods: Paired PBMC drawn before and after KS onset
from 21 AIDS-KS patients were compared to paired PBMC from 23 high-ris
k HIV-infected homo-/bisexual patients who did not develop KS and to a
single PBMC sample from 19 low-risk, HIV-infected hemophiliac patient
s. Extracted DNA samples were amplified by polymerase chain reaction (
PCR) using two non-overlapping nested primer sets to control for poten
tial PCR contamination. Results: In all comparisons, patients who went
on to develop KS were significantly more likely to show evidence of K
SHV infection prior to onset of KS than either control group. Of PBMC
samples from AIDS-KS patients drawn prior to KS, 52% were positive for
KSHV DNA whereas both high- and low-risk control groups had lower rat
es of PBMC infection (9-13%). KSHV infection can precede KS onset by u
p to 21 months among AIDS-KS patients. Conclusions: AIDS-KS patients a
re significantly more likely to show evidence of KSHV infection in PBM
C prior to KS onset than control HIV-infected patients. Because identi
cal PBMC samples from cases and controls were examined blindly, these
results are not caused by a bias in tissue sampling. Homo-/bisexual an
d hemophiliac AIDS patients who do not develop KS appear to have a low
prevalence of infection. These findings indicate that KSHV infection
is specifically associated with the subsequent development of KS in AI
DS patients.