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. J. Med. Virol. 52:20–25, 1997. © 1997 Wiley‐Liss, Inc.