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  • Title: Evaluation of the presence of 2-LTR HIV-1 unintegrated DNA as a simple molecular predictor of disease progression.
    Author: Zazzi M, Romano L, Catucci M, Venturi G, De Milito A, Almi P, Gonnelli A, Rubino M, Occhini U, Valensin PE.
    Journal: J Med Virol; 1997 May; 52(1):20-5. PubMed ID: 9131453.
    Abstract:
    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.
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