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Undetectable HIV doesn't preclude transmission.

BOSTON -- Women on highly active antiretroviral therapy for human immunodeficiency virus whose plasma viral load is below detectable levels may continue to shed the virus intermittently in the genital tract, Dr. Susan Cu-Uvin said at the annual meeting of the Infectious Diseases Society for Obstetrics and Gynecology.

"This finding means we cannot rule out the possibility of continued risk of HIV transmission among women in whom the virus appears to be well controlled," said Dr. Cu-Uvin of Brown University, Providence, R.I.

The advent of highly active antiretroviral therapy (HAART) has resulted in significant decreases in the replication of HIV in the blood of infected patients, and in so doing it has substantially reduced the associated morbidity and mortality of the disease, Dr. Cu-Uvin said.

"However, several studies have shown evidence of discordance between the RNA shedding of HIV in the blood and in the female genital tract, and when it comes to sexual transmission of HIV the big player is the amount of genital tract viral load, not the plasma viral load," she said. "Unfortunately, because the only commercially available tools for assessing HIV viral load are those that look at RNA shedding in plasma, we use plasma viral load as a surrogate for how infectious a given patient is, yet this may not always reflect what is happening in the genital tract."

Dr. Cu-Uvin and colleagues sought to assess the pattern of HIV genital tract shedding among women already on HAART with sustained below detectable plasma viral loads. Of 55 women with HIV enrolled in an ongoing study of HAART, 49 with below detectable plasma viral load for at least 6 months were included in the analysis. Each of the women underwent serum plasma and genital tract sampling every 4 weeks for 12 weeks. Genital tract secretions were collected from the endocervix, ectocervix, and vagina in 40 of the women, and from the vagina only in 9 women who had previous hysterectomies. The lower limit of viral detection was 80 copies per milliliter for plasma and 3,300 copies per milliliter for the genital tract, Dr. Cu-Uvin noted.

The immune status of all of the patients was "generally good," with a median CD4 count of 412 cells/mm', said Dr. Cu-Uvin. In terms of demographics, 45% of the patients were African American, 35% were white, and 15% were Hispanic, and the median patient age was 45 years. An assessment for "classic" STDs showed not much gonorrhea, chlamydia, or syphilis, "which was not surprising, because the population was older," Dr. Cu-Uvin said. All of the patients were positive for herpes simplex virus type 2, she noted.

Patients were grouped based on their genital tract HIV RNA patterns, Dr. Cu-Uvin explained. Nonshedders were those women with no evidence of detectable genital tract HIV during study visits. Indeterminate shedders had at least one episode of genital tract shedding with no available measurement prior to or following the episode. Women who had genital tract shedding between negative visits were described as intermittent shedders, and those who had at least two consecutive episodes of genital tract shedding were persistent shedders.

Of the 49 patients enrolled, 46 maintained below detectable plasma viral loads during the course of the study. "What was astonishing to us is that more than half of those women had some degree of detectable genital tract shedding," Dr. Cu-Uvin said. Specifically, 26% of the women with sustained below detectable plasma viral load were indeterminate shedders, 18% were intermittent shedders, and 8% were persistent shedders, "despite being on HAART and having below detectable levels of virus in their plasma," she said. Among the nine women with total hysterectomy, one demonstrated persistent shedding in the vagina, whereas the others were classified as nonshedders, she said.

Although logistic regression analyses showed the probability of detecting HIV RNA in the genital tract subcompartment was low when plasma viral load was below detectable levels, Dr. Cu-Uvin said, "it worries us that there are some women on antiretroviral therapy who have a very good response in the blood, who, if you look hard enough and at multiple time points, will have evidence of genital tract HIV RNA."

What this means clinically, she said, is that the potential for sexual transmission of HIV exists even among women whose virus appears to be well controlled. "So, for example, when a woman on HAART comes to me and says she wants to have a baby, there is no way to assure her, even if she has a below detectable plasma viral load, that it's safe to have unprotected sex."


New England Bureau
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Title Annotation:Infectious Diseases; human immunodefeciency virus
Author:Mahoney, Diana
Publication:Internal Medicine News
Geographic Code:1USA
Date:Oct 1, 2007
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