March 7, 2012
As has been reported for a few years, people with a delta 32/delta 32 mutation of the gene that governs the CCR5 receptor are resistant to HIV infection -- at least from viruses using the CCR5 receptor. A group of researchers from the Autonomous University of Barcelona has been able to identify one of these individuals who has actually been infected with CXCR4-tropic virus. We all suspected this could happen, but this is the first case report of such a person.
It is believed that people infected with X4-tropic HIV do not fare as well as those infected with R5-tropic virus. However, this individual is doing well despite having been infected in 1996.
The research team believes that the individual's good viral control on HAART has to do with the presence of HLA-B*5701. HLA-B (major histocompatibility complex, class I, B) is a human gene that provides instructions for making a protein that plays a critical role in the immune system. It is part of a family of genes called the human leukocyte antigen (HLA) complex. The HLA complex helps the immune system distinguish the body's own proteins from proteins made by foreign invaders such as viruses and bacteria.
The HLA-B gene has many different normal variations, allowing each person's immune system to react to a wide range of foreign invaders. Hundreds of versions (alleles) of HLA-B are known, each of which is given a particular number.
A version of HLA-B designated HLA-B*5701 is associated with slower HIV disease progression and extreme sensitivity to abacavir (ABC, Ziagen). People with abacavir hypersensitivity often develop a fever, chills, rash, upset stomach, and other symptoms when treated with this drug.
This poster reinforces what we have been telling Timothy Brown (the Berlin patient): Even if you are "immune" to CCR5-tropic HIV, you still need to protect yourself against X4-tropic virus infection. X4-tropic virus infection in patients with the double delta 32 mutation in their CCR5 gene does not seem very common but, as described in this case report, it is possible. And patients like Brown are vulnerable to it.
For more information, read CROI poster 292, "HIV-1 Infection in a CCR5-D32/D32, HLA-B*5701, and HLA-A*2402 Subject: A Case Report," presented by Ester Ballana.
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