3rd Conference on Retroviruses and Opportunistic Infections Washington, DC - January 28-February 1, 1996

Conf Retroviruses Opportunistic Infect 1996 Jan 28-Feb 1; 3rd:54 (abstract no. 8)

Zhang H, Dornadula G, Wu Y, Havlir D, Richman DD, Pomerantz RJ
The Dorrance H. Hamilton Laboratories, Section of Molecular Retrovirology, Thomas Jefferson University, 1020 Locust Street Philadelphia, PA.

Intravirion reverse transcripts have been identified in the blood plasma of human immunodeficiency virus type 1 (HIV-l)-infected-individuals. In the present studies, the kinetic processes of intravirion HIV-1 reverse transcription, in the blood plasma of HIV-1-infected persons treated with nevirapine, were investigated. Nevirapine is a non-nucleoside inhibitor of reverse transcriptase (RT) which decreases the level of HIV-1 viral particles in the blood plasma of infected-individuals. By analyzing HIV-1 virions at different time points prior to and after initiation of nevirapine therapy in vivo, the levels of intravirion reverse transcripts have been demonstrated to be dramatically susceptible to this anti-RT agent out of proportion to effects on plasma virion load. The intravirion reverse transcripts were also documented to rebound to the pre-treatment levels, concomitant with the development of resistant viral mutants. In addition, the infectivity of HIV-1 virions dramatically decreased after nevirapine treatment, further indicating that the effects of this anti-RT agent begin within the cell-free virions. As the levels of intravirion reverse transcripts were altered according to the susceptibility or resistance of the HIV-1 RT enzyme to this inhibitor, these data demonstrate that the formation of intravirion reverse transcripts is a dynamic process in vivo. Moreover, because the alteration in ratios between intravirion HIV-1 reverse transcripts and viral genomic RNA directly reflects the efficiency of reverse transcription, we propose that the determination of these ratios in the blood plasma of HIV-l-positive patients maybe a useful and, most importantly, a direct assay to monitor the efficacy of anti-RT agents in vivo.

960128
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