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The image of HIV spreading throughout the body rarely conjures up thoughts of a person’s gut. Yet the gut is one of HIV’s primary target sites, perhaps especially when a person is infected with HIV through rectal intercourse, oral sex, or ingestion of infected breast milk. "People need to know that this underscores the need for preventive efforts and prophylactic measures," says Peter Anton, MD, principal investigator and associate professor of medicine in the division of digestive diseases at the UCLA AIDS Institute, a part of the University of California at Los Angeles.
UCLA researchers have found that HIV may replicate more easily within the gut than through the circulatory system. This would suggest that HIV transmission through oral sex and anal sex is even riskier than previously thought.
The study compared the expression of chemokine receptor CCR5, which is the co-receptor most associated with HIV-1 in early infection, on mucosal mononuclear cells (MMCs) to that of peripheral blood mononuclear cells (PBMCs), and found an enhanced expression on MMCs. The proportions of mucosal CD4 cells expressing CCR5 and the amount of CCR5 expressed per cell were increased, Anton says.
Investigators further showed that these enhanced levels were functionally correlated with a greater level of productive infection of MMCs than of PBMCs, suggesting that HIV can do more damage more quickly in the gastrointestinal tract. "The gut is the largest immune organ of the body, with more lymph cells than all the other organs combined," Anton says. "It has to have a lot of protective immunity lining it to determine what’s nutritious and safe to absorb and what’s pathogenic." For this reason, a large proportion of the gut’s T-cells are activated, and HIV targets activated T-cells more than resting naive T-cells, Anton adds.
The investigators also are studying how HIV disease causes diarrhea, malabsorption, and wasting, much like what occurs in an inflammatory disease. They plan to present future research on whether anti-inflammatory medications will help slow down the pace of the disease, Anton says. "Anti-inflammatories could be an adjunct to antiretroviral medications," he adds.
Another research area that might benefit from studies about how HIV affects the gut is the development of microbicides to target mucosal cells, whether these are the cervical vaginal mucosa or rectal mucosa.