In the first paper, researchers from the Fred Hutchinson Cancer Research Institute in Seattle took haematopoeic stem cells (HSCs), bone-marrow cells that are the progenitors of all blood cells, from two pigtail macaque monkeys and transformed them genetically by splicing an inserted gene sequence for mC46 into their CCR5 receptor gene.

They then injected the cells back into the monkeys. One monkey had 20%of its HSCs replaced by the C34-producing cells and the second had over 50% replaced.

A week later, they infected them and two control monkeys with a particularly lethal strain of genetically engineered human/monkey SHIV, which destroys CD4 cells fast and usually develops a steady-state viral load in the order of several million copies/ml.

In the control animals, their CD4 counts declined from around 600 cells/mm3 before infection to between 10 and 50 cells/mm3 within two to three weeks. In the monkeys with mC46, the CD4 cell count dipped to about 100 cells/mm3 within two weeks of infection, but then rose slowly back to pre-infection levels over the next six months.

At the time of highest SHIV viral load and fewest CD4 cells, 90% of the CD4 cells in the mC46 monkeys had the fusion-inhibitor-generating insert in them, which is what one would expect, given that SHIV so decimates non-mutated CD4 cells.

What was unexpected to the scientists, though, was that after the period of peak viral load, the non-mutated CD4 cells made a partial recovery in one monkey to about 60% of all CD4 cells and in the other about 20%. This is promising, as it shows that one would not need to replace all or even most of the CD4 cells in the body with HIV-resistant ones in order to contain an HIV infection, and that increasing numbers of non-resistant cells does not lead to a new burst of virus.

This may also mean that it would not be necessary to take the dangerous step of having to destroy a persons immune system with whole-body radiation, as happened to the 'Berlin patient' Timothy Ray Brown, in order for the new cells to repopulate the immune system.

As we said, SHIV reproduces furiously and peak viral load in all monkeys ten days after infection was one billion copies/ml. After that, viral load in the control monkeys declined to about half a million in one and about ten million in the other. In the mC46 monkeys, it fell to about 100,000 in the monkey with 20% of its cells replaced by mC46 cells and down to a few hundred in the one with more than 50% of its cells replaced.

Viral load was about 320-fold lower (2.5 logs) in the first monkey and about 1400-fold (3.15 logs) lower in the second. This would transform a typical HIV viral load in an untreated human of 70,000 copies/ml to 50 copies/ml before any ARVs were taken.

Although there was a partial recovery of unmutated CD4 cells in the blood, memory cells in the lymph nodes that form the reservoir of proviral HIV DNA remained predominantly the HIV-resistant mC46 cells, which is exactly where one would want them to be.

Original post:
Gene therapy studies show potential for HIV control without drugs

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