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. Ambrose1
1University 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
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
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.
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