Antiretroviral Drug Activity in Macaques Infected during Pre-Exposure Prophylaxis Has a Transient Effect on Cell-Associated SHIV DNA Reservoirs

Details

• Alternative Title:
  PLoS One
• Personal Author:
  Cong, Mian-er ; Pau, Chou-Pong ; Heneine, Walid ; García-Lerma, J. Gerardo
• Description:
  Background
  
  Pre-exposure prophylaxis (PrEP) with emtricitabine and tenofovir disoproxil fumarate (FTC/TDF) is a novel HIV prevention strategy. Suboptimal PrEP adherence and HIV infection creates an opportunity for continued antiretroviral drug activity during undiagnosed infection. We previously showed that macaques infected with SHIV during PrEP with FTC/TDF display reduced acute plasma viremias and limited virus diversity. We investigated the effect of PrEP on acute SHIV DNA dynamics and on the size of the persistent virus reservoir in lymphoid tissues.
  
  Design
  
  Cell-associated SHIV DNA levels in PBMCs were measured in 8 macaques infected during PrEP with FTC/TDF or single-agent TAF and was compared to those seen in untreated infections (n = 10). PrEP breakthrough infections continued treatment with 1–2 weekly drug doses to model suboptimal drug exposure during undiagnosed HIV infection in humans. SHIV DNA was also measured in lymphoid tissues collected from FTC/TDF PrEP breakthroughs after 1 year of infection.
  
  Results
  
  Compared to untreated controls, PrEP infections had reduced plasma RNA viremias both at peak and throughout weeks 1–12 (p<0.005). SHIV DNA levels were also reduced at peak and during the first 12 weeks of infection (p<0.043) but not throughout weeks 12–20. At 1 year, SHIV DNA reservoirs in lymphoid tissues were similar in size among macaques that received PrEP or placebo.
  
  Conclusions
  
  Antiviral drug activity due to PrEP limits acute SHIV replication but has only a transient effect on cell-associated SHIV DNA levels. Our model suggests that suboptimal drug exposure in persons that are taking PrEP and become infected with HIV may not be sufficient to reduce the pool of HIV-infected cells, and that treatment intensification may be needed to sustain potential virological benefits from the PrEP regimen.
  
  
• Subjects:
  Animals Anti-HIV Agents Case-Control Studies Disease Models, Animal Leukocytes, Mononuclear Lymphoid Tissue Macaca Mulatta Pre-Exposure Prophylaxis Proviruses Simian Acquired Immunodeficiency Syndrome Simian Immunodeficiency Virus Time Factors Viral Load

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• Source:
  PLoS One. 11(11).
• Pubmed ID:
  27806064
• Pubmed Central ID:
  PMC5091888
• Document Type:
  Journal Article
• Volume:
  11
• Issue:
  11
• Collection(s):
  CDC Public Access
• Main Document Checksum:
  urn:sha256:eacbc1201d86c9901d89f5472d80572721695c4e257c97868310fbf251b26739
• Download URL:
  https://stacks.cdc.gov/view/cdc/43041/cdc_43041_DS1.pdf
• File Type:
  [PDF - 1.37 MB ]