CGIDR Stories

Publication Q&A: Cells Producing Residual Viremia During Antiretroviral Treatment Appear to Contribute to Rebound Viremia Following Interruption of Treatment

August 2020 – Hadega Aamer shares insights from a recent publication in Plos Pathogens, with contributing authors from the Frenkel Lab at the Center for Global Infectious Disease Research (CGIDR).

Cells Producing Residual Viremia During Antiretroviral Treatment Appear to Contribute to Rebound Viremia Following Interruption of Treatment

Hadega A. Aamer, Jan McClure, Daisy Ko, Janine Maenza, Ann C. Collier, Robert W. Coombs, James I. Mullins, Lisa M. Frenkel

Published in Plos Pathogens, August 2020

Read article in Plos Pathogens

What is your lab's current research focus?

The global burden of HIV is immense, with a total of 36 million adults and 2 million children infected in 2019. While treatment has changed, the course of infection and HIV-associated co-morbidities are increasing, lifespans are shortened and there is still no practical cure.

Our group works to understand why HIV infection persists despite years of effective treatment.

What is the significance of the findings of this publication?

We found that during successful therapy, low levels of virus are produced by infected cell clones. Our recent study sought to determine the (1) timespan that specific clones produced viruses as an indicator of whether immunity could eliminate these infected clones, and (2) when antiretroviral therapy (ART) was stopped, if viruses from these clones contributed to infection of new cells to gauge the relevance of these clones in sustaining HIV infection.

We found that clones of infected cells producing the low level viruses can survive for at least 8 years. In addition, we found that low levels of viruses from clones are infectious, and when treatment is stopped appear to renew infection.

HIV-infected cell clones producing the low levels of virus are either not detected and/or eliminated by the immune system and are able to rekindle infection when the person stops their therapy. These viruses may be escaping immune surveillance due to “gaps” in inherited human immune function or the immune response to these viruses may be “exhausted” due to prolonged infection. This subpopulation of infected cellular clones would need to be eliminated to cure HIV infection.

What are the next steps for this research?

Given this work shows that the HIV-infected cells contributing to the low levels of virus persist for years, we are working to determine the role of “escape” from the killer T cells and/or “exhaustion” of the immune response, so that interventions that specifically work to overcome one or both mechanisms can be added to strategies to cure HIV infection. 

Seattle Children’s CGIDR contributing authors:

  • Hadega A. Aamer, Postdoctoral Researcher
  • Lisa M. Frenkel, Co-Director / Professor of Pediatrics and Laboratory Medicine
  • Daisy Ko, Research Technician III