Evaluation of the presence of 2-LTR HIV-1 unintegrated DNA as a simple molecular predictor of disease progression.
In a preliminary cross-sectional analysis of 109 human immunodeficiency virus type 1 (HIV-1)-infected subjects the presence of 2-long terminal repeat (LTR) unintegrated circular HIV-1 DNA in peripheral blood mononuclear cells (PBMC) was found to be associated with both symptomatic infection (P = 0.0037) and low CD4 counts (P = 0.0004). To investigate the prognostic significance of the presence of 2-LTR HIV-1 DNA, a subset of 23 2-LTR-negative and 25 2-LTR-positive asymptomatic individuals were followed up for 12-24 months. The two groups did not differ in terms of baseline CD4 counts, zidovudine (ZDV) therapy, and duration of HIV-1 infection. Longitudinal analysis of CD4 values did not indicate a significantly different CD4 outcome between the two groups. However, 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 development of CDC stage B or C symptoms were considered as indicators of disease progression, there was a significantly higher number of events in the 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 investigation as a simple, qualitative, molecular predictor of disease progression and decreased response to antiretroviral therapy.
Zazzi
M
M
Dipartimento di Biologia Molecolare, Università di Siena, Italy.
Romano
L
L
Catucci
M
M
Venturi
G
G
De Milito
A
A
Almi
P
P
Gonnelli
A
A
Rubino
M
M
Occhini
U
U
Valensin
P E
PE
D003430:Cross-Sectional Studies; D004270:DNA, Circular / Q000737:chemistry* / Q000235:genetics; D004279:DNA, Viral / Q000737:chemistry*; D018450:Disease Progression; D015658:HIV Infections / Q000097:blood / Q000175:diagnosis* / Q000235:genetics* / Q000821:virology; D016325:HIV Long Terminal Repeat / Q000235:genetics*; D015497:HIV-1 / Q000737:chemistry* / Q000235:genetics*; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000821:virology; D008137:Longitudinal Studies; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D012307:Risk Factors; D016662:Virus Integration; D015215:Zidovudine / Q000627:therapeutic use
D004270:DNA, Circular; D004279:DNA, Viral; D015215:Zidovudine