Polymerase chain reaction detection of HIV-1 2-LTR circular DNA may predict CD4 decline.

Important note: Information in this article was accurate in 1994. The state of the art may have changed since the publication date.

Polymerase chain reaction detection of HIV-1 2-LTR circular DNA may predict CD4 decline.

Abstr Gen Meet Am Soc Microbiol. 1994;94:555 (abstract no. C-368). Unique Identifier : AIDSLINE ASM94/94313109
Byrne BC; Parisi JM; Baxter JD; UMDNJ/RWJ Medical School, Camden 08103.

Abstract: 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.

Keywords: Acquired Immunodeficiency Syndrome/CLASSIFICATION/*IMMUNOLOGY CD4-Positive T-Lymphocytes/*IMMUNOLOGY/MICROBIOLOGY 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 ABSTRACT
941030
M94A0845

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