Hiv Reservoirs are supposed to cause persistent low levels of Hiv Rna at a few copies/ml that are detected by study assays in patients on Haart.
One possibility is that this Hiv Rna results from ongoing low levels of viral replication, despite Haart, in particular in tissue reservoirs. The explanation thus would be that Haart is not Hard enough.
Hiv
To tackle this issue, any intensification trials have been conducted over the last 3 years...with diverse results.
All these trials, but one, only addressed Hiv levels in circulating blood and not in tissues.
Most of them used an intensified course of short duration (one to a few months), which is not ideal if Hiv Rna dynamics at these levels are very slow.
Overall, no valuable changes were observed during the intensification duration compared to what was found before and after adding these new drugs. First trials used non nucleoside reverse transcriptase inhibitors or Hiv protease inhibitors; subsequent trials used an integrase inhibitor, raltegravir.
In one study however, 30 percent of patients showed a transient increase in 2-Ltr circles in circulating lymphocytes, when raltegravir was added. This integrase inhibitor blocks reverse transcribed viral Dna to join in Dna cells, thus prominent to the accumulation of un-integrated viral Dna, and the formation of 2-Ltrs. Consequently, this was a proof of persistent low levels Hiv replication in these patients.
Hiv Reservoirs in the gut was only evaluated in one study during Haart intensification. No changes were found in the rectum but a decrease in viral Rna was observed in the terminal ileum. However, due to the sample size which was less than 10 patients, these differences did not reach statistical significance. In an even smaller sub-group of this small group of patients, the nature of Hiv infected cells in blood, rectum and terminal ileum was studied by flow cytometry. The data tended to show that the Hiv stockroom in terminal ileum was not in the same type of cells than in blood or rectum. These results have only been presented orally and not yet published, and need to be confirmed on a larger amount of patients.
In conclusion, the deliberate upon is still open. If ongoing viral replication is not demonstrated in circulating blood, roughly nothing is known of the tissue level where antiretrovirals can be gift at lower concentrations.
Hiv Reservoirs Part 4: Haart Intensification Trials
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