Impact of analytical treatment interruption on the central nervous system in a simian-HIV model

• Published in: AIDS (London) Vol. 33 Suppl 2; no. Supplement 2; pp. S189 - S196
• Main Authors: Hsu, Denise C, Silsorn, Decha, Inthawong, Dutsadee, Kuncharin, Yanin, Sopanaporn, Jumpol, Im-Erbsin, Rawiwan, Chumpolkulwong, Kesara, O’connell, Robert J, Michael, Nelson L, Ege, Christine A, Vasan, Sandhya
• Format: Journal Article
• Language: English
• Published: England Copyright Wolters Kluwer Health, Inc 01.12.2019
• Subjects: AIDS/HIV
• ISSN: 0269-9370; 1473-5571
• DOI: 10.1097/QAD.0000000000002270

OBJECTIVE(S):Analytical treatment interruption (ATI) studies are often used to evaluate potential HIV cure strategies. This study was conducted to determine the impact of ATI on simian-HIV (SHIV) infection in the central nervous system. DESIGN:Animal study. METHODS:Nine rhesus macaques were inoculated with SHIV-1157ipd3N4. Antiretroviral therapy (ART) was administered from week 2 to 18. At week 18, four animals were euthanized (no-ATI-group) and five underwent ATI (ATI-group) and were euthanized at 12 weeks post viral rebound. Plasma and cerebrospinal fluid (CSF) SHIV-RNA, markers of inflammation and brain CD3+, CD68+/CD163+ and RNA+ cells were measured. RESULTS:All nine animals were SHIV-infected, with median pre-ART plasma and CSF SHIV-RNA of 6.2 and 3.6 log10copies/ml. Plasma and CSF IL-15, monocyte chemoattractant protein-1, IFN-γ-induced protein-10 and neopterin increased postinfection. ART initiation was associated with rapid and complete suppression of plasma viremia and reductions in plasma and CSF IL-15, IFN-γ-induced protein-10, neopterin and CSF monocyte chemoattractant protein-1. Median time to plasma viral rebound was 21 days post-ATI. At 12 weeks postrebound, CSF SHIV-RNA was undetectable and no increases in plasma and CSF markers of inflammation were found. Higher numbers of CD3+ and CD68+/CD163+ cells were seen in the brains of 3/5 and 1/5 animals, respectively, in the ATI-group when compared with no-ATI-group. SHIV-RNA+ cells were not identified in the brain in either group post-ATI. CONCLUSION:ATI in macaques that initiated ART during early SHIV-1157ipd3N4 infection was associated with mild, localized T-cell infiltrate in the brain without detectable SHIV-RNA in the brain or CSF, or elevation in CSF soluble markers of inflammation.