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-LTR) in peripheral blood mononuclear cells (PBMC) at baseline was associated with acceleration of HIV disease. Detection of 2-LTR at baseline correlated with high plasma HIV-1 RNA levels (p < .01), recovery of culturable HIV-1 from plasma (p = .02), and progression to AIDS during follow-up (p = .01). More patients with 2-LTR (68%) than without 2-LTR (31%) had a decline in CD4 levels of >50 cells/mm3 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 predictor of high plasma HIV-1 RNA levels and subsequent CD4 cell decline in this cohort of patients with predominantly nonsyncytium-inducing (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 clinical decline.
Panther
L A
LA
Department of Medicine, University of Washington, Seattle, USA.
Coombs
R W
RW
Zeh
J E
JE
Collier
A C
AC
Corey
L
L
D000328:Adult; D019380:Anti-HIV Agents / Q000627:therapeutic use; D018791:CD4 Lymphocyte Count; D015331:Cohort Studies; D004270:DNA, Circular / Q000097:blood*; D004279:DNA, Viral / Q000097:blood*; D018450:Disease Progression; D005500:Follow-Up Studies; D015658:HIV Infections / Q000188:drug therapy / Q000276:immunology*; D015497:HIV-1 / Q000235:genetics / Q000302:isolation & purification / Q000502:physiology*; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000821:virology*; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D016133:Polymerase Chain Reaction; D012367:RNA, Viral / Q000097:blood*; D012091:Repetitive Sequences, Nucleic Acid; D014766:Viremia / Q000188:drug therapy / Q000276:immunology; D015215:Zidovudine / Q000627:therapeutic use
D019380:Anti-HIV Agents; D004270:DNA, Circular; D004279:DNA, Viral; D012367:RNA, Viral; D015215:Zidovudine