{"id":9249,"date":"2019-06-09T18:53:39","date_gmt":"2019-06-09T22:53:39","guid":{"rendered":"https:\/\/blogs.nejm.org\/hiv-id-observations\/?p=9249"},"modified":"2019-06-12T12:04:43","modified_gmt":"2019-06-12T16:04:43","slug":"is-it-safe-to-alter-the-ccr5-receptor-and-how-will-this-influence-hiv-cure-studies","status":"publish","type":"post","link":"https:\/\/blogs.nejm.org\/hiv-id-observations\/index.php\/is-it-safe-to-alter-the-ccr5-receptor-and-how-will-this-influence-hiv-cure-studies\/2019\/06\/09\/","title":{"rendered":"Is It Safe to Alter the CCR5 Receptor? And How Will This Influence HIV Cure Studies?"},"content":{"rendered":"

\"\"<\/a>The HIV cure effort suffered a potential setback this week, as researchers reported an association between having two copies of the CCR5-\u220632 mutation and shorter survival<\/a>.<\/p>\n

(Quick reminder — the CCR5 receptor is required for most HIV strains to enter target cells. People homozygous for the CCR5-\u220632 mutation are almost completely protected from contracting HIV.)<\/p>\n

By evaluating over 400,000 individuals in a British registry that included genetic information including CCR5 status, the investigators compared the prevalence of CCR5-\u220632 homozygosity among people between the ages of 41 and 76. Over time, the prevalence substantially declined, consistent with a 21% increase in all-cause mortality compared to those with either no \u220632 mutation, or heterozygotes.<\/p>\n

The authors postulate that this excess mortality may be driven by the reported worse outcomes among those with \u220632 homozygosity who develop influenza<\/a> or other infectious diseases. Since most influenza deaths occur in older people, this could explain why earlier studies of populations with \u220632 reported them to be healthy.<\/p>\n

(By contrast, it might be that historical epidemic infections of childhood and young adults<\/a> — smallpox, plague, dysentery among them — could have selected for \u220632 many centuries ago, with the result that approximately 10% of people of European heritage carry at least one mutation.)<\/p>\n

As noted in the excellent editorial accompanying the new study<\/a>, the findings should give researchers pause before making permanent changes to the host genome:<\/p>\n

The most important point raised by the current publication is that considerable risk comes with generating mutations in the genome of human beings, no matter how obvious the benefit that those mutations offer.<\/p><\/blockquote>\n

I’d amplify this concern by noting that individuals born with two CCR5-\u220632 mutations — who grow up with it — may differ from those in whom CCR5 is altered during adulthood. We simply don’t know whether people who acquire it late in life will be better or worse off than those born with the mutation.<\/p>\n

So why is this recent study relevant to curing HIV? Considerable research has already been done on this receptor related to HIV cure:<\/p>\n