Zinc Fingers and Gene Therapies for HIV: Mimicking the Cured Berlin Patient?

One of the themes coming out of CROI this year has been different from that in the past. In the past the main themes have been on new medications and treating HIV with antiretrovirals. This year however themes have been on exploring possibilities of curing HIV? Very Very exciting research, to say the least.

Here is an excerpt from an article written by Nelson Vergel on “Zinc Fingers and Gene Therapies for HIV: Mimicking the Cured Berlin Patient?”

Some HIV-infected patients who have an undetectable viral load while taking HIV medications continue to have low CD4+ cell counts. Lalezari et al decided to perform their proof-of-concept study on six of these patients: Each was on HIV antiretrovirals, had an undetectable HIV viral load, had a CD4+ cell count between 200 and 500, and had been HIV infected for more than 20 years. The patients were enrolled in one of two cohorts: in one, 10 billion total cells were modified; in the other, 20 billion. Autologous (i.e., derived from the patient) R5-disrupted T cells were then expanded and modified with ZFNs outside the patients’ bodies and re-infused. Subjects were followed weekly for one month and then monthly for 11 months post-infusion; blood and rectal mucosa samples were taken.

This novel study construction is the result of a history of groundbreaking findings. CCR5 has long been of interest to HIV researchers because many people who are resistant to HIV infection have a mutation in their CCR5 gene: the delta32 mutation. A minority of people of northern European descent (1% to 2.5%) have this mutation in the CCR5 receptor. After studying these patients, the oral CCR5 inhibitor drug maraviroc (MVC, Selzentry) was developed and ultimately approved in 2007. Fears that blocking the CCR5 receptor would lead to more rapid HIV disease progression or the emergence of other health problems have slowly dissipated since the drug was first given to humans in studies. (That said, there are some known adverse effects of CCR5 receptor blocking, including increased susceptibility to West Nile virus.)

To see the full article, go to www.michrx.com

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