Chronic Inflammation with Increased Human Immunodeficiency Virus (HIV) RNA Expression in the Vaginal Epithelium of HIV-Infected Thai Women

Heterosexual transmission accounts for most new HIV infections worldwide. Of the 39 million or more HIV-positive people, most are in sub-Saharan Africa, India and Asia where heterosexual transmission is the most common route of infection. In the United States, however, with less than 1 million cases of HIV infection, injection drug use and homosexual contact account for most infections. Although the overall rate of AIDS diagnoses in the United States is decreasing, the percentage accounted for by heterosexual spread continues to increase, from 8.5 percent in 1991 to 16.8 percent in 1998.

Both host cell and viral factors have been cited for the disparity in heterosexual transmission between sub-Saharan Africa, Asia and India, compared with the United States and Europe. Mathematical studies have shown that the rate of female-to-male heterosexual transmission of subtype B HIV in the United States occurs at a probability of .01 per act. This is in sharp contrast to the probability of female-to-male transmission in Thailand (.056 per heterosexual contact). In addition, among Thai men who gave a history of STDs, there was a 5.1-fold increase in transmission. A separate study in Thailand reported that in male-to-female transmission with men infected with subtype E (where the initial infection was attributed to heterosexual transmission) compared with subtype B (where the initial infection was attributed to injection drug use) the percentage of female partners infected by their male partner was significantly higher in the subtype E group. This suggests an increased propensity for heterosexual transmission of subtype E.

Because it is known that subtype E has an increased ability to replicate in epithelial Langerhans cells (LC) and that these cells may be the first to encounter the virus after mucosal transmission, it is thought that virus replication in LC might explain the epidemiologic findings of increased heterosexual transmission in Southeast Asia. To analyze the host factors involved in heterosexual transmission, vaginal epithelial biopsies from HIV-seropositive women from Thailand and the United States were evaluated for tissue virus load and histologic makeup.

Blood samples were obtained from 45 Thai and 25 US HIV-infected women, and eight Thai uninfected women. Virus serotyping demonstrated that 43 of the 45 Thai women were infected with HIV serotype E, one with serotype B, and one with untypeable virus. All 25 US women were infected with serotype B. No Thai subjects were receiving antiretroviral therapy; 12 of 25 US women were receiving antiretroviral medication. No Thai or US subject had virus loads below the level of detection of the assay (40 copies/mL). US subjects gave a history of being infected by a male partner; only one reported a history of injection drug use. Thai subjects were housewives who reported being infected by their husbands. The primary risk factor reported by the Thai husbands was contact with a commercial sex worker.

According to the authors, "In all, 84 percent of Thai and 14 percent of US women exhibited a chronic inflammatory T cell infiltrate in the vaginal epithelium. In Thai tissue, the infiltrate was associated with elevated levels of HIV RNA in the epidermis. Uninfected Thai women also had vaginal epithelial inflammation. Inflammation did not correlate with sexually transmitted diseases or HIV disease stage. The higher rates and increased risk of heterosexual transmission in Thailand may be due to chronic inflammation at the site where the virus is transmitted, which leads to the accumulation of activated T cells." The presence of a local infiltrate in this study -- an infiltrate of CD4 T cells into the dermis and epidermis of vaginal tissue, according to the investigators, "might act as targets for initial viral infection and subsequently as reservoirs that support efficient transmission."

The authors found significant implications from the present study for the development of future therapies. They reported that "the identification of the mechanism and etiologic agent responsible for the chronic lymphocytic inflammation of genital tract tissue demonstrated in this study could lead to the use of therapies, likely an inexpensive antibiotic, directed at the etiological agent, likely a vaginal pathogen, to decrease heterosexual transmission of HIV and thus contribute significantly to the ultimate goal of reducing HIV transmission."

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