Abstract

THAA0102 - Oral Abstract Session

Viral tissue reservoirs are determined early and little viral RNA is detected during suppression by three or four drug regimens in the macaque model

Presented by Zandrea Ambrose (United States).

C. Kline¹, J. Ndjomou¹, T. Franks¹, R. Kiser², V. Coalter², M. Piatak, Jr.², J. Estes², J. Mellors¹, J. Lifson², Z. Ambrose<sup>1

1</sup>University of Pittsburgh School of Medicine, Medicine, Pittsburgh, United States, ²SAIC-Frederick, Inc., NCI Frederick, AIDS and Cancer Virus Program, Frederick, United States

Background: Although HIV-infected individuals can suppress plasma viremia to undetectable levels with antiretroviral therapy, infected cells remain in the body and can contribute to viremia when therapy is discontinued. Macaque models allow investigators to more easily characterize viral reservoirs.
Methods: Twelve male macaques were infected with RT-SHIV, an SIV virus containing HIV-1 reverse transcriptase, and monitored for plasma viremia and CD4 counts. After 10-14 weeks post-infection, 6 animals were not treated and 6 animals were treated for 17-20 weeks with 3 drugs (tenofovir, lamivudine, and efavirenz) or 4 drugs (tenofovir, lamivudine, efavirenz, and an integrase inhibitor). Viral RNA and viral DNA were measured longitudinally in the blood and at necropsy in over 20 different tissues by quantitative PCR and normalized for cellular RNA and DNA.
Results: In untreated and treated animals, RT-SHIV DNA was highest in lymphoid and gastrointestinal tissues and very low to absent in the brain, genital tract, and kidney. The amount of viral DNA detected in multiple lymphoid tissues correlated with the level of plasma viremia 1 week post-infection. RT-SHIV RNA was abundant in the lymphoid tissues of untreated macaques with detectable viremia, but was detected variably in different regions of the gastrointestinal tract. Little or no viral RNA was detected in the tissues from animals after 17-20 weeks of therapy. There was no obvious difference in RT-SHIV RNA levels between animals treated with 3 or 4 drugs.
Conclusions: Our results suggest that the majority of virally-infected cells are located in lymphoid tissues with variable levels in the gastrointestinal tract. The number of infected cells in these reservoirs correlates with viremia one week after infection, suggesting that viral reservoirs are seeded within days of infection. Little viral RNA is evident in tissue after suppressive therapy with either 3 or 4 antiretroviral drugs.