M. Zazzi et al., EVALUATION OF THE PRESENCE OF 2-LTR HIV-1 UNINTEGRATED DNA AS A SIMPLE MOLECULAR PREDICTOR OF DISEASE PROGRESSION, Journal of medical virology, 52(1), 1997, pp. 20-25
In a preliminary cross-sectional analysis of 109 human immunodeficienc
y virus type 1 (HIV-1)-infected subjects the presence of 2-long termin
al repeat (LTR) unintegrated circular HIV-1 DNA in peripheral blood mo
nonuclear cells (PBMC) was found to be associated with both symptomati
c infection (P = 0.0037) and low CD4 counts (P = 0.0004). To investiga
te the prognostic significance of the presence of 2-LTR HIV-1 DNA, a s
ubset of 23 2-LTR-negative and 25 2-LTR-positive asymptomatic individu
als were followed up for 12-24 months. The two groups did not differ i
n terms of baseline CD4 counts, zidovudine (ZDV) therapy, and duration
of HIV-1 infection. Longitudinal analysis of CD4 values did not indic
ate a significantly different CD4 outcome between the two groups. Howe
ver, when only ZDV-treated subjects were considered, a significant (P
= 0.042) decrease in CD4 counts was found at month 24 with respect to
baseline in 2-LTR-positive (n = 12) but not in 2-LTR-negative (n = 11)
patients. Moreover, when >40% CD4 loss from baseline and/or developme
nt of CDC stage B or C symptoms were considered as indicators of disea
se progression, there was a significantly higher number of events in t
he whole 2-LTR-positive group than in the whole 2-LTR-negative group (
P = 0.0197 at month 12, P = 0.0299 at month 18, P = 0.0373 at month 24
). Thus, the presence of 2-LTR HIV-1 DNA in PBMC merits further invest
igation as a simple, qualitative, molecular predictor of disease progr
ession and decreased response to antiretroviral therapy. (C) 1997 Wile
y-Liss, Inc.