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Retrovirology. 2017 Jun 2;14(1):35. doi: 10.1186/s12977-017-0359-0.

Effective treatment of SIVcpz-induced immunodeficiency in a captive western chimpanzee.

Author information

1
Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
2
Department of Medicine, Perelman School of Medicine, University of Pennsylvania, 409 Johnson Pavilion, 3610 Hamilton Walk, Philadelphia, PA, 19104-6076, USA.
3
ChimpHaven, Inc., Keithville, LA, USA.
4
Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC, USA.
5
Institute of Evolutionary Biology, and Centre for Immunity, Infection and Evolution, University of Edinburgh, Edinburgh, UK.
6
AIDS and Cancer Virus Program, Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research, Frederick, MD, USA.
7
Department of Medicine and Center for AIDS Research, University of Alabama at Birmingham, Birmingham, AL, USA.
8
Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA. bhahn@mail.med.upenn.edu.
9
Department of Medicine, Perelman School of Medicine, University of Pennsylvania, 409 Johnson Pavilion, 3610 Hamilton Walk, Philadelphia, PA, 19104-6076, USA. bhahn@mail.med.upenn.edu.

Abstract

BACKGROUND:

Simian immunodeficiency virus of chimpanzees (SIVcpz), the progenitor of human immunodeficiency virus type 1 (HIV-1), is associated with increased mortality and AIDS-like immunopathology in wild-living chimpanzees (Pan troglodytes). Surprisingly, however, similar findings 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 immunodeficiency 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 persistent soft tissue infections refractory to antibacterial therapy. Combination antiretroviral therapy consisting of emtricitabine (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 differences in pharmacokinetics led to low plasma drug concentrations, 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 immunodeficiency and other hallmarks of AIDS in captive chimpanzees, including P. t. verus apes that are not naturally infected with this virus. Moreover, SIVcpz-associated immunodeficiency can be effectively treated with antiretroviral therapy, although sufficiently high plasma concentrations must be maintained to prevent the emergence of drug resistance. These findings extend a growing body of evidence documenting the immunopathogenicity of SIVcpz and suggest that experimentally infected chimpanzees may benefit from clinical monitoring and therapeutic intervention.

KEYWORDS:

AIDS; Antiretroviral therapy; Chimpanzees; Drug resistance; SIVcpz

PMID:
28576126
PMCID:
PMC5457593
DOI:
10.1186/s12977-017-0359-0
[Indexed for MEDLINE]
Free PMC Article

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