HTB

Maximum suppression: ART intensification does not reduce residual viral load

Richard Jefferys, TAG

One of the most controversial questions in the field of HIV research is whether current antiretroviral therapy (ART) combinations maximally suppress viral replication. New technologies have allowed researchers to detect down to just 1 copy of HIV RNA per mL of blood and, even when the viral load is undetectable on commercially available tests (which typically can only detect 50 copies or more), most people on ART have a few copies of HIV RNA detectable in their samples. These HIV RNA copies could either be the product of ongoing rounds of viral replication (in which infected cells release new viruses that go on to infect other cells), or alternatively they could be produced by long-lived chronically infected cells. In the latter scenario, ART would prevent the newly-produced virus from being able to infect any other cells, but the drugs would not be able to eliminate the chronically infected cell.

Over the past few years, scientists have debated – often quite heatedly – which of these possibilities is true. Recent evidence has generally favored the view that, in most cases, ART is maximally suppressing HIV replication; for example, a study of viral evolution in people undergoing intermittent ART interruption found no evidence of ongoing viral evolution during the periods when participants were on therapy.

A study just published in PNAS tackles the question another way, by investigating whether intensifying ART by adding new drugs has an effect on residual viral load. [1]

Out of 15 total participants, only 9 consistently showed HIV RNA levels above 1 copy/mL prior to ART intensification (median 3 copies/mL). The highest level detected was around 30 copies/mL. The researchers found that ART intensification had no effect on these residual viral levels, indicating a lack of ongoing HIV replication. The results add to the evidence that low-level HIV RNA detectable in people on ART does not derive from ongoing viral replication, but rather a stable reservoir of infected cells. The major implication is that, in order to cure HIV infection, new strategies are needed to identify and eliminate this reservoir. PNAS has designated the paper “Open Access,” click on the title link for the PDF.

Comment

Preliminary results from this study were first presented at the International Drug Resistance Workshop in 2008, and reported in the August edition of HTB. [2]

References:

  1. Dinoso JB et al. Treatment intensification does not reduce residual HIV-1 viremia in patients on highly active antiretroviral therapy. PNAS. Published online 22 May 2009, doi: 10.1073/pnas.0903107106.
    http://www.pnas.org/content/106/23/9403.full
  2. Lack of virological impact of treatment intensification in suppressed patients supports latent viral reservoir as source of residual viraemia. HTB August 2008.
    http://i-base.info/htb/596

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