Wednesday, January 5, 2011

Asymptomatic HIV Positive Individuals – How are they different?

AIDS is a horrific disease characterized by a severely compromised immune system. Without a competent immune system, the body is unable to combat infectious diseases and non-infectious ailments such as cancer. It has, of course, been well established that AIDS is a result of an infection caused by HIV-1, a retrovirus that preferentially attacks Helper T cells (CD4+) – cells that are primary players in a functioning immune system. The symptoms characteristic of AIDS ordinarily show themselves once the number of circulating CD4+ cells reaches a dangerously low level. There is a direct correlation between the number of viral particles circulating in the blood – the so-called “viral load” – and the onset of symptoms. Most infected individuals demonstrate a viral load exceeding 10,000 viral copies/ml of blood. The new life-saving therapeutic drugs are able to decrease this viral load substantially.

There are a small number of HIV-1+ individuals, however, who have depressed viral loads without the use of drugs. These individuals are collectively referred to as HIV Controllers. They show stable and normal levels of CD4+ cells, do not show signs of disease and are less likely to be infectious.

It would, therefore, invaluable to understand what makes HIV Controllers different. There is for this reason a large study underway to unravel this mystery. This study is referred to as The International HIV Controllers Study with literally hundreds of contributing scientists from around the world. One of the goals of this study is to discover the genetic basis for this apparent advantage shared by HIV Controllers. To do this, genomic DNA – the full complement of DNA within an individual – was sampled from Controllers and Progressors – those HIV-1 -infected individuals who progress to full blown disease - and subsequently compared between these two groups. The results reported in the December 10, 2010 edition of the renowned scientific journal Science showed that there were over 300 single nucleotide polymorphisms (SNPs) within the major histocompatibility complex (MHC). The MHC region in the human genome has been shown to have strong genetic associations with infection and inflammatory diseases.

To quote the authors, “Altogether, these results link the major genetic impact of host control of HIV-1 to specific amino acids – the chemical building blocks of protein - involved in the presentation of viral peptides – small protein molecules - on infected cells. This represents a significant finding that helps elucidate the nature of the protection that Controllers naturally possess and may eventually prove useful in devising therapies against AIDS.