Document 0836
 DOCN  M9480836
 TI    Polymerase chain reaction detection of HIV-1 2-LTR circular DNA may
       predict CD4 decline.
 DT    9410
 AU    Byrne BC; Parisi JM; Baxter JD; UMDNJ/RWJ Medical School, Camden 08103.
 SO    Abstr Gen Meet Am Soc Microbiol. 1994;94:555 (abstract no. C-368).
       Unique Identifier : AIDSLINE ASM94/94313109
 AB    CD4(+)-T cell counts reflect a consequence of HIV infection but are not
       markers of viral activity. We seek ways to monitor aspects of HIV
       infection as potential tools in clinical trials of antiretroviral agents
       or clinical management of infected patients. HIV RNA genomes are reverse
       transcribed into double stranded linear DNA molecules following cellular
       infection. The linear molecule may integrate into the host chromosome
       initiating a new focus of infection or, linking the 5' and 3' LTR
       regions, circularize. Proviral 2-LTR circles are apparent dead ends in
       the retroviral life cycle, but provide unique targets for polymerase
       chain reaction (PCR). Appropriately designed primers within the LTR will
       fail to produce product from linear proviral DNA because (1) they are
       directed outward from one another or (2) they span too large a sequence
       (ca. 9KB) to form PCR product. Circles, by their topography, yield PCR
       products and may be used generically for the low molecular weight
       proviral DNA indicative of recent retroviral activity. We designed
       nested primers within the LTR of HIV-1 to amplify closed circular DNA
       and retrospectively selected 12 samples of peripheral blood mononuclear
       cells from 12 patients having CD4 counts of approximately 500,
       approximately 200 or approximately 20 cells/mm3 at the time of sampling.
       These patients thereafter either exhibited stable or declining counts.
       Quantitative PCR for HIV circles was most intense for two patients in
       the approximately 500 CD4 class; these two patients also showed the most
       profound rate of CD4 decline. Abundant closed circular DNA detected by
       PCR may be a marker of retroviral activity that heralds imminent CD4
       decline and might have implications for antiretroviral therapy.
 DE    Acquired Immunodeficiency Syndrome/CLASSIFICATION/*IMMUNOLOGY  DNA,
       Circular/*ANALYSIS  DNA, Viral/*ANALYSIS  Human  *HIV Long Terminal
       Repeat  HIV-1/GENETICS/*ISOLATION & PURIF  HIV-2/GENETICS/*ISOLATION &
       PURIF  Polymerase Chain Reaction/*METHODS  Predictive Value of Tests  T4
       Lymphocytes/*IMMUNOLOGY/MICROBIOLOGY  MEETING ABSTRACT

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