141. SIV persistence in ART-treated infant rhesus macaques
Session: Poster Abstract Session: Big Viruses in Little People (Pediatric Viral Diseases)
Thursday, October 27, 2016
Room: Poster Hall
Background: Of the estimated 37 million people worldwide infected by HIV, 2.6 million are children. While antiretroviral therapy (ART) greatly reduces the mortality and morbidity of HIV infection, this treatment is not a cure due to the persistence of the virus in reservoirs. A fundamental barrier to an HIV cure is our incomplete understanding of anatomic reservoirs that are difficult to study in humans. Given the specific characteristics of the infant immune system, pediatric studies of the HIV reservoir are of critical importance.

Methods: Infant rhesus macaques (RM) were orally infected with SIVmac251 and treated with a potent 3-drug ART regimen (PMPA+FTC+DTG) initiated 35 days post-infection. Elective necropsy was performed after 6-9 months of ART and tissue levels of SIV, ART drugs, and immune activation in ART-suppressed infant RM were compared to those of viremic infants and ART-treated adult macaques.

Results: For the first time, we demonstrate persistent suppression of viremia below the limit of detection of our standard viral load assay in SIV-infected infant RM treated with ART. In keeping with results from HIV-infected infants, plasma viral loads declined to <60 copies/ml over a range of 4-22 weeks after ART initiation. State-of-the-art detection of SIV-RNA in tissues at necropsy using SIV RNAscope revealed reduced SIV-RNA in the spleen, lymph nodes, and lymphoid aggregates of the gut but similar levels in the brain and gut lamina propria of ART-treated infant RM compared to viremic infant RM. ART drug levels were readily detected in plasma, but were undetectable in the brain and heterogeneous in the lymph nodes and colon of infant RM as measured by infrared matrix-assisted laser desorption-electrospray ionization (IR-MALDESI). Compared to viremic infant RM, TNF-a and Mx-1 in lymph nodes, spleen, ileum and brain and soluble CD14 in plasma were decreased in ART-suppressed infants.

Conclusion: Using our model of pediatric SIV infection and ART, we provide the first description of virus and drug levels in infant tissues. This experimental in vivo platform can be applied to further study SIV reservoirs and test cure strategies in the period of infancy.

Maud Mavigner, PhD1, Claire Deleage, Ph.D.2, Jakob Habib, BA1, Elias Rosen, PhD3, Angela Kashuba, BScPhm, PharmD, DABCP3, Franck Amblard, PhD1, Raymond Schinazi, PhD, DSc1, Romas Geleziunas, PhD4, Joseph Hesselgesser, PhD4, Bei Li, PhD4, Jillian Hattersley, PhD4, Colleen Mcgary, BA1, Mirko Paiardini, PhD1, Matthew Wood, PhD5, Donald Sodora, PhD5, Guido Silvestri, MD1, Jacob Estes, Ph.D.2 and Ann Chahroudi, MD, PhD1, (1)Emory University, Atlanta, GA, (2)Frederick National Laboratory for Cancer Research, Frederick, MD, (3)University of North Carolina, Chapel Hill, NC, (4)Gilead Sciences, Inc., Foster City, CA, (5)Center for Infectious Disease Research, Seattle, WA

Disclosures:

M. Mavigner, None

C. Deleage, None

J. Habib, None

E. Rosen, None

A. Kashuba, None

F. Amblard, None

R. Schinazi, None

R. Geleziunas, None

J. Hesselgesser, None

B. Li, None

J. Hattersley, None

C. Mcgary, None

M. Paiardini, None

M. Wood, None

D. Sodora, None

G. Silvestri, None

J. Estes, None

A. Chahroudi, None

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