Effective Treatment of SIVcpz-Induced Immunodeficiency in a Captive Western Chimpanzee

Hannah J Barbian, Raven Jackson-Jewett, Corrine S. Brown, Frederic Bibollet-Ruche, Gerald H Learn, Timothy Decker, Edward F. Kreider, Yingying Li, Thomas Denny, Paul M. Sharp, George M Shaw, Jeffrey Lifson, Edward P. Acosta, Michael S. Saag, Katharine J. Bar, Beatrice H Hahn

Research output: Contribution to journalArticlepeer-review

Abstract

Background: Simian immunodefciency virus of chimpanzees (SIVcpz), the progenitor of human immunodefciency virus type 1 (HIV-1), is associated with increased mortality and AIDS-like immunopathology in wild-living chimpan‑ zees (Pan troglodytes). Surprisingly, however, similar fndings have not been reported for chimpanzees experimentally infected with SIVcpz in captivity, raising questions about the intrinsic pathogenicity of this lentivirus. 
Findings: Here, we report progressive immunodefciency and clinical disease in a captive western chimpanzee (P. t. verus) infected twenty years ago by intrarectal inoculation with an SIVcpz strain (ANT) from a wild-caught eastern chimpanzee (P. t. schweinfurthii). With sustained plasma viral loads of 105 to 106 RNA copies/ml for the past 15 years, this chimpanzee developed CD4+ T cell depletion (220 cells/μl), thrombocytopenia (90,000 platelets/μl), and persis‑ tent soft tissue infections refractory to antibacterial therapy. Combination antiretroviral therapy consisting of emtric‑ itabine (FTC), tenofovir disoproxil fumarate (TDF), and dolutegravir (DTG) decreased plasma viremia to undetectable levels (<200 copies/ml), improved CD4+ T cell counts (509 cell/μl), and resulted in the rapid resolution of all soft tissue infections. However, initial lack of adherence and/or diferences in pharmacokinetics led to low plasma drug con‑ centrations, which resulted in transient rebound viremia and the emergence of FTC resistance mutations (M184V/I) identical to those observed in HIV-1 infected humans. 
Conclusions: These data demonstrate that SIVcpz can cause immunodefciency and other hallmarks of AIDS in cap‑ tive chimpanzees, including P. t. verus apes that are not naturally infected with this virus. Moreover, SIVcpz-associated immunodefciency can be efectively treated with antiretroviral therapy, although sufciently high plasma concentra‑ tions must be maintained to prevent the emergence of drug resistance. These fndings extend a growing body of evidence documenting the immunopathogenicity of SIVcpz and suggest that experimentally infected chimpanzees may beneft from clinical monitoring and therapeutic intervention. Keywords: SIVcpz, Chimpanzees, Antiretroviral therapy, AIDS, Drug resistance
Original languageEnglish
Pages (from-to)35-43
Number of pages9
JournalRetrovirology
Volume14
Issue number1
DOIs
Publication statusPublished - 2 Jun 2017

Keywords

  • SIVcpz
  • chimpanzees
  • antiretroviral therapy
  • AIDS
  • drug resistance

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