1. Integrase inhibitors and cellular immunity suppress retroviral replication in rhesus macaques
- Author
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Hazuda, Daria J., Young, Steven D., Guare, James P., Anthony, Neville J., Gomez, Robert P., Wai, John S., Vacca, Joseph P., Handt, Larry, Motzel, Sherri L., Klein, Hilton J., Dornadula, Geethanjali, Danovich, Robert M., Witmer, Marc V., Wilson, Keith A.A., Tussey, Lynda, Schleif, William A., Gabryelski, Lori S., Jin, Lixia, Miller, Michael D., Casimiro, Danilo R., Emini, Emilio A., and Shiver, John W.
- Subjects
Drug therapy ,Physiological aspects ,Research ,HIV -- Research -- Physiological aspects -- Drug therapy ,HIV (Viruses) -- Research -- Physiological aspects -- Drug therapy - Abstract
The substantial incidence of resistance observed in therapy-experienced patients and newly acquired HIV-1 infections (1-5) traderscores the need for new antiretroviral agents, as well as the importance of maximizing the [...], We describe the efficacy of L-870812, an inhibitor of HIV-1 and SIV integrase, in rhesus macaques infected with the simian-human immunodeficiency virus (SHIV) 89.6P. When initiated before CD4 cell depletion, L-870812 therapy mediated a sustained suppression of viremia, preserving CD4 levels and permitting the induction of virus-specific cellular immunity. L-870812 was also active in chronic infection; however, the magnitude and durability of the effect varied in conjunction with the pretreatment immune response and viral load. These studies demonstrate integrase inhibitor activity in vivo and suggest that cellular immunity facilitates chemotherapeutic efficacy in retroviral infections.
- Published
- 2004