More than 30 million people worldwide are living with HIV, and about three million more are infected each year. Although people infected with the virus are living longer and healthier lives thanks to intense research, there is still no cure.

One way to identify new strategies for fighting HIV is to look to those people whose bodies are naturally able to keep the virus as bay, at least for a time.  In 2007 researchers identified a variation near the HLA-C gene that was shown to affect the amount of virus present in the body after acute infection but before onset of AIDS symptoms.  This so-called “viral set point” correlates with rate of disease progression, infectiousness and response to treatment.

Now another set of researchers has yet again shown that this variant affects viral set point.   Their results, published online this week in the journal Nature Genetics, further show that this variant influences the time it takes to progress to AIDS.

Rasmi Thomas and colleagues analyzed the DNA from 828 people infected with HIV, all of European ancestry.  Patients were divided into groups with low, medium and high viral loads (<2,000 copies of viral RNA per milliliter of blood, 2,000-10,000 copies, and >10,000 copies). About 62% of people with two Cs at rs9264942 had a viral load below 2,000, while only about 15% of people with two Ts controlled the HIV virus to this extent.  About 33% of people with CT at rs9264942 fell into the “controller” group.  These results agree with what was found by previous researchers.

(23andMe Complete Edition customers can check their data using the Browse Raw Data feature or the link above.)

In a separate group of 763 people infected with HIV (also all of European descent), the researchers found that the C version of rs9264942 was somewhat protective against progression from HIV infection to extremely low CD4 cell count, a measure of immune system strength.  The C version of this SNP also conferred some protection against progression to an AIDS-defining complications and death.

As noted above, low viral set point is known to correlate with slower progression to AIDS, but the analysis by Thomas et al. indicates that the effects of rs9264942 on viral set point and progression are at least somewhat independent.

The researchers examined blood from 50 health donors to investigate the function of rs9264942.   They found that the C version was associated with increased HLA-C protein on the surface of immune cells.  They conclude that this increased protein expression must be what helps the body fight off HIV, although the details of how increased HLA-C is beneficial are still unknown.  Further research will be needed in order to translate these findings into new strategies for treatment or prevention of HIV infection.

• When rs9264942 was initially identified as a variant that could affect HIV viral set point, researchers suggested that vaccines designed to elicit an immune response mediated by HLA-C might be a good idea.  Perhaps this new research, which further solidifies the importance of HLA-C variation in virus control, will rekindle that idea, especially in light of recent HIV vaccine disappointments (more here and here).

• Several genetic variations to HIV infection and treatment have been identified and are detailed in the following 23andMe reports:
  • HIV Progression
  • Resistance to HIV/AIDS
  • Abacavir Hypersensitivity

• Related Spittoon posts:
  • SNPwatch: Genetic Variation in X Chromosome May Slow Progression of AIDS
  • Very Personalized Medicine: Genetically Customized Bone Marrow Transplant May Have Eradicated Patient’s HIV
  • SNPwatch: Genetic Variant Common in African Americans May Influence Susceptibility to HIV

SNPwatch gives you the latest news about research linking various traits and conditions to individual genetic variations. These studies are exciting because they offer a glimpse into how genetics may affect our bodies and health; but in most cases, more work is needed before this research can provide information of value to individuals. For that reason it is important to remember that like all information we provide, the studies we describe in SNPwatch are for research and educational purposes only. SNPwatch is not intended to be a substitute for professional medical advice; you should always seek the advice of your physician or other appropriate healthcare professional with any questions you may have regarding diagnosis, cure, treatment or prevention of any disease or other medical condition.

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AIDS used to be considered a male-specific health problem — but now, the majority of its victims are female.

Those numbers aside, some studies have shown that certain females take much longer than males to progress to AIDS after being infected with HIV. Now, researchers have now found a mechanism that might explain this difference.

A two-stage study by Siddiqui et al. identified a genetic variant on the X chromosome that may slow progression from HIV-1 to AIDS in women. The study analyzed both primates and humans, demonstrating that genetic association findings can successfully translate across species, even over an evolutionary distance of 25 million years.

The researchers first analyzed 136 rhesus monkeys infected with SIV (simian immunodeficiency virus). They found a common genetic marker on the X chromosome among those monkeys that progressed slowly to AIDS-related disease. Researchers then studied 303 HIV-infected humans and found an analogous marker on the X chromosome —the SNP rs5968255 — that may affect progression to AIDS in human females.

The results, published in the online version of The American Journal of Human Genetics, indicate that in humans, females with one copy of the C version of rs5968255 progressed to AIDS more slowly than either females with TT or males with a C or T. (Note that females have two X chromosomes, while males only have one.)

Females with one copy of the C version of the SNP took an average of eight years to progress from HIV infection to AIDS, nearly four times less than females with no copies or males. Women with two copies of C are so rare that none were found in the study.

Previous research has linked some degree of HIV resistance to a mutation in SNP i3003626, which is in a gene that encodes the CCR5 receptor.

(23andMe customers can check their data for rs5968255 using the Browse Raw Data feature. Information on i3003626 is available in the Resistance to HIV/AIDS Clinical Report.)

The CT genotype of rs5968255 is more frequent among Asians than Europeans or Africans, suggesting that future research may find that HIV-1 positive Asian females have a slower progression to AIDS. Future studies may also be able to use this X chromosomal variant as a clue toward new drug development for both genders.

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