Scant embers of infection can reignite viralreplication

1 December 2010. Related: Basic science and immunology.

Richard Jefferys, TAG

Whittling down reservoirs of HIV-infected cells in the body is thought to be an important first step in the pursuit of a cure.

Whether there might be a threshold HIV reservoir size below which the body could contain the virus without additional intervention has been unclear; there have been some reports of individuals who have interrupted antiretroviral therapy (ART) and controlled viral load to undetectable levels for extended periods, most recently from a group of French researchers who described five people (out of a total of 32) maintaining levels below 50 copies/mL for a median of around 6 years of follow up. [1] However, the magnitude of the infectious HIV reservoir in these individuals prior to ART interruption was not reported.

In a study just published online in the journal AIDS, Tae-Wook Chun and colleagues describe the case of an individual treated early in the course of HIV infection who maintained viral suppression for over a decade on ART. [2]

Detailed evaluation of the size of the replication-competent HIV reservoir revealed an average of one infected CD4 T cell out of every 1.7 billion CD4 T cells, which the authors describe as “the lowest infectious HIV burden recorded to date in our laboratory.” With the individual’s consent, an exploratory interruption of ART was conducted. Viral load remained below 50 copies/mL for 50 days—longer than the previously described average of nine—but then rebounded to 1,593 copies/mL before falling back below the detection threshold again for around 70 more days. At day 143 after the interruption, viral load climbed to 8,684 copies/mL and at that point ART was restarted.

The researchers conclude that even a tiny number of infected cells can spark viral load rebound upon ART interruption. They go on to state:

“In order to achieve a condition under which HIV does not rebound for extended periods of time in the absence of ART, novel therapeutic strategies aimed at more specifically targeting these extremely rare infected cells maybe necessary with or without the use of therapeutic vaccination to boost immune system control of viral rebound.”

Source: TAG basic science blog. (21 October 2010). http://tagbasicscienceproject.typepad.com/tags_basic_science_vaccin/2010/10/scant-embers-f-infection-can-reignite-viral-replication.html

References:

1. Hocqueloux L et al. Long-term immunovirologic control following antiretroviral therapy interruption in patients treated at the time of primary HIV-1 infection. AIDS. 2010 Jun 19;24(10):1598-601. http://www.ncbi.nlm.nih.gov/pubmed/20549847
2. Chun T-W et al. Rebound of plasma viremia
   following cessation of antiretroviral therapy despite profoundly low levels of HIV reservoir: implications for eradication. AIDS 19 October 2010. doi:
   10.1097/QAD.0b013e328340a239. http://journals.lww.com/aidsonline/Abstract/2010/11270/Rebound_of_plasma_viremia_following_cessation_of.6.aspx?AuthenticationFailureReason=LoginFailed