UNINTEGRATED CIRCULAR HIV-1 DNA IN THE PERIPHERAL MONONUCLEAR-CELLS OF HIV-1-INFECTED SUBJECTS - ASSOCIATION WITH HIGH-LEVELS OF PLASMA HIV-1 RNA, RAPID DECLINE IN CD4 COUNT, AND CLINICAL PROGRESSION TO AIDS

We observed 36 HIV-infected patients to evaluate whether the presence of tandem 2-long terminal repeat circular unintegrated HIV-1 DNA (2-LT R) in peripheral blood mononuclear cells (PBMC) at baseline was associ ated with acceleration of HIV disease, Detection of 2-LTR at baseline correlated with high plasma HIV-1 RNA levels (p < .01), recovery of cu lturable HIV-1 from plasma (p = .02), and progression to AIDS during f ollow-up (p = .01). More patients with 2-LTR (68%) than without 2-LTR (31%) had a decline in CD4 levels of >50 cells/mm(3) over the first 18 months of follow-up (p = .04), and the average annual CD4 decline was 35% in patients with 2-LTR compared with 16% in those without 2-LTR ( p = 0.06). Detection of 2-LTR in PBMC at baseline was an independent p redictor of high plasma HIV-1 RNA levels and subsequent CD4 cell decli ne in this cohort of patients with predominantly non-syncytium-inducin g (NSI) isolates at baseline. The presence of 2-LTR in PBMC appears to be reflective of ongoing HIV-1 replication, as measured by plasma HIV -1 RNA levels, and identifies persons at risk for immunologic and clin ical decline.