A study published in the August 14 issue of the American Journal of Human Genetics reports discovery of a new genetic marker associated with slow progression of HIV infection in some women.

HIV infection is known to progress differently in men and women; however, the causes of these differences have remained elusive. A recent article in the journal Nature Medicine (abstract) reported that women with HIV may progress faster to AIDS than men because their immune systems respond more strongly to the infection, which paradoxically allows the virus to replicate faster.

The new study in the American Journal of Human Genetics is the first to definitively show a genetic link to sex differences in HIV-induced disease progression between men and women.

The scientists first studied simian immunodeficiency virus (SIV)-infected rhesus monkeys and found a previously unknown genetic variation that was associated with slower SIV disease progression. Surprisingly, this variation was located on the X chromosome.

Women have two X chromosomes, while men have only one (plus one Y chromosome), so genes located on the X chromosome can lead to medical differences between men and women.

“The X chromosomes of monkeys and humans are very, very similar,” said Dr. Roman Siddiqui, a molecular geneticist at the Leibniz Institute for Age Research – Fritz Lipmann Institute and a lead author of the study. “So, that told us the position of the variant in the human genome.” The researchers then looked for and pin-pointed a single nucleotide variation in HIV-infected women.

Researchers found that the alteration correlated to lower viral loads in women. “This variation was associated with slower progression to AIDS and slower CD4 decline (on white blood cells) in 17 percent of the women in the study,” said Dr. Siddiqui. Men with the genetic variant, in contrast, showed no difference in disease progression.

Scientists are not certain why women with the variation have slower disease progression than men with the genetic difference, but speculate it might be due to other differences in genetics or aspects of being female, such as biochemistry. The researchers also found that the genetic variation was more common in Asian women than in women of European or African descent.

Dr. Siddiqui hopes the discovery of this special genetic link in HIV disease progression will lead to more careful study of gender differences in AIDS in the future. “It was really not well established that there is a genetic male- or female-specific difference between HIV patients,” said Dr. Siddiqui. “I think this data will help encourage more studies to detect genetic sex differences that impact disease progression.”

Dr. Siddiqui’s research team will next focus on trying to determine the function of the genes surrounding the variation and their role in HIV disease progression. Doing so may lead to a better understanding of the disease and possibly new antiretroviral treatments, for both genders, in the future.

For more information, please see the press release from the Fritz Lipmann Institute or the study in the American Journal of Human Genetics (abstract).