Unintegrated HIV-1 circular 2-LTR proviral DNA as a marker of recently infected cells: relative effect of recombinant CD4, zidovudine, and saquinavir in vitro.

Important note: Information in this article was accurate in 1999. The state of the art may have changed since the publication date.

Unintegrated HIV-1 circular 2-LTR proviral DNA as a marker of recently infected cells: relative effect of recombinant CD4, zidovudine, and saquinavir in vitro.

J Med Virol. 1999 Jun;58(2):165-73. Unique Identifier : AIDSLINE MED/99266896
Panther LA; Coombs RW; Aung SA; dela Rosa C; Gretch D; Corey L; Department of Laboratory Medicine, University of Washington,; Seattle 98195, USA.

Abstract: Unintegrated HIV-1 proviral DNA is one of the earliest detectable forms of HIV-1, and the influence of an antiretroviral drug on its appearance may reflect the efficacy of that agent in preventing infection of new cells. We characterized the dynamics of HIV-1 p24 (p24) antigen production, HIV-1 gag DNA, tandem long-terminal-repeat circular unintegrated proviral (2-LTR) HIV-1 DNA, HIV-1 tat mRNA, and cell viability in the presence of three antiretroviral agents: recombinant soluble CD4 (rsCD4), zidovudine, and saquinavir. Interference with HIV-1 entry by rsCD4 decreased p24 antigen levels modestly, decreased HIV-1 gag by twofold, and 2-LTR was detectable at the end of the culture period. Inhibition of reverse transcription by zidovudine decreased p24 antigen levels modestly, decreased HIV-1 gag by 19-fold, and inhibited detection of 2-LTR HIV-1 DNA. The protease inhibitor, saquinavir, had the greatest overall effect, with the lowest levels of p24 antigen and HIV-1 gag, and inhibition of 2-LTR. There was no detection of tat mRNA in the saquinavir-treated cultures. In addition, cell viability was significantly higher in cultures treated with saquinavir. In these experiments, 2-LTR HIV-1 DNA was indicative of the relative inhibitory effects of three antiretroviral agents acting at different steps of the HIV-1 replication cycle. We demonstrated in vitro that 2-LTR HIV-1 DNA was a useful indicator of an antiretroviral drug in preventing new cell infection and could be utilized as a dynamic marker of drug efficacy in HIV-1-infected patients.

Keywords: JOURNAL ARTICLE Anti-HIV Agents/*PHARMACOLOGY Antigens, CD4/PHARMACOLOGY Biological Markers Cell Line DNA, Viral/*DRUG EFFECTS/GENETICS Gene Products, tat/METABOLISM HIV Core Protein p24/METABOLISM HIV Protease Inhibitors/PHARMACOLOGY HIV-1/*DRUG EFFECTS/*PHYSIOLOGY Polymerase Chain Reaction/METHODS Proviruses/*DRUG EFFECTS/GENETICS/PHYSIOLOGY Recombinant Proteins/PHARMACOLOGY Reverse Transcriptase Inhibitors/PHARMACOLOGY RNA, Viral/ISOLATION & PURIF Saquinavir/PHARMACOLOGY Support, U.S. Gov't, P.H.S. Terminal Repeat Sequences/*DRUG EFFECTS/GENETICS Virus Integration Zidovudine/PHARMACOLOGY
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