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Women's "Weaker Response" to HIV Could Be Key to More Effective Treatment

By Olivia Ford

August 11, 2009

Although women may show up more often for health care, some experts consider women the "weaker sex" when it comes to how well their bodies respond to HIV in the long term. The fact is that women control HIV better early on in their infection, but then progress to AIDS more quickly, compared to men who have similar levels of the virus in their blood. Although this fact is well known, it's still little understood among HIV specialists. However, the results of a study published on July 13 in the online edition of Nature Medicine may help researchers get to the bottom of this enigma.

The team of U.S. researchers set out to explore known gender differences in the immune system. They focused on particular immune cells called plasmacytoid dendritic cells, or pDCs, which are some of the first cells to recognize and fight HIV when it enters the body.

It turned out that, when exposed to HIV, a higher percentage of pDCs from HIV-negative women became activated than pDCs from HIV-negative men. However, this difference vanished when post-menopausal women's pDCs were compared to men's pDCs.

This discovery led researchers to look into the role of hormones. They discovered that higher levels of the hormone progesterone were tied to greater activation of pDCs in the presence of HIV.

Once they discovered this, the researchers wanted to see if the increased activation of pDCs led to increased immune activation. Indeed, when they tested HIV-positive women and men with identical viral loads who weren't yet on treatment, they found that the women had higher levels of activated CD8+ T cells, which help fight HIV.

This increased immune activation can sometimes be good news, sometimes bad news. A stronger response from the immune system is desirable when someone is first infected with HIV, since it tends to lower levels of HIV viral replication. Immune activation bodes well for women at this stage. However, as the study's lead researcher, Marcus Altfeld, M.D., Ph.D., sums it up: "Persistent viral replication and stronger chronic immune activation can lead to the faster progression to AIDS that has been seen in women."

These results open a rich cache of future exploration for researchers. This includes continued study of immune activation as a separate issue from viral replication, as well as the role of sex hormones in determining immune cell response to HIV. According to Agence France-Presse, further study could even lead to new drugs that hinder this chronic immune response and slow, or even stop, progression to AIDS.

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