HAART reduces virus in women’s genital tracts

Researchers followed 176 women over four years

Researchers at a Rhode Island hospital have found that women on highly active antire troviral therapy (HAART) have lower levels of HIV in their genital tracts than women who have not received HAART. Study results indicate a close correlation between the level of HIV in the blood plasma and the level of HIV in the genital tract.

The study may be the largest ever undertaken in the United States to measure the effects of HIV treatment on the genital secretions of women. Several previous studies have measured the effects of HIV treatment on men’s semen.

"I think the basic message here is, if you are on good therapy, which we equate with HAART therapy in this day and age, then you have a better chance of having a smaller amount of HIV in your blood and genital tract," says Susan Cu-Uvin, MD, assistant professor of obstetrics and gynecology at Miriam Hospital at Brown University in Providence, RI. (See related story, p. 31.)

The researchers presented the study in November at the 36th Annual Meeting of the Alexandria, VA-based Infectious Diseases Society of America, held in Denver.

Cu-Uvin says HAART also may have an impact on perinatal transmission of HIV, although more research is needed.

Looking beyond the bloodstream

The researchers decided to study HIV levels in women’s vaginal secretions to answer several major questions.

"We are giving the medications, and we know they are affecting the blood, but are they affecting the other areas of the body where the virus might be hiding?" Cu-Uvin says.

"The next question is how much medication reaches the vaginal tract, and that’s a big question," she adds. "We’re encouraging drug companies to take a look at this."

Collecting samples from women presents problems that researchers have not had with men. "The problem with vaginal secretions is there are many diverse ways to get it," she explains. "This is unlike men, where there’s only one way to collect it, by having them masturbate and collecting semen."

Researchers collected vaginal secretions through a cervical vaginal lavage method, which involves putting 10 cc of normal saline in the vaginal area and then collecting the secretions. HIV was detected via cervical vaginal lavage in 40 of the 176 women (23%). This compares to virus being found in plasma in 122 (69%) of the women, with a median of 22,500 copies per milliliter and a range of 420 to 3 million copies. Researchers used an assay that can detect only 400 copies or greater. From 2% to 3% of women who had no detectable HIV in the bloodstream were found to have HIV in the genital fluids.

Sixty-three women (36%) were on HAART; 61 (35%) were on non-HAART treatment; 52 (29%) had no therapy at all at the time researchers collected samples. When the study first began in 1995, protease inhibitors were not available, so early samples included women who had used mono or dual drug therapies. Then, as protease inhibitors became the normal treatment a couple of years into the study, researchers began collecting samples from women who had received HAART, Cu-Uvin says.

The women involved in the study had a median age of 37. They were 52% white, 23% African-American, 23% Latino, and 1% other races, including Native Americans. Forty-six percent of them were injection drug users and probably contracted HIV through dirty needles, and 54% likely contracted HIV through sexual intercourse.

Forty-two (24%) of the women had CD4 counts of less than 200, 88 (51%) had CD4 counts between 200 and 500, and 43 (25%) had CD4 counts greater than 500. The median CD4 count was 343, and the CD4 count range was from four to 1,862. "So it’s a wide range of patients," Cu-Uvin says. "Some were very sick, and some were very healthy."

Duration of medication use remains unknown

Researchers assessed the women’s medication use through a retrospective review of their charts and having them answer a questionnaire. They were asked: Are you currently on therapy? If yes, what medications are you taking? "That’s our gauge of their medication history," Cu-Uvin says. "But we don’t know whether they have been taking this for two months, three months, or one week."

Researchers now are going back to the women’s medical charts to try to determine how long they have been on therapy and when it was prescribed to them, and to compare this information to the time when researchers took samples to determine in more detail how medication use affected the study results.

Among women with a viral load of greater than 10,000 copies of HIV RNA per milliliter of plasma, 47% had detectable HIV in the genital tract. When the plasma viral load was between 400 and 9,999 copies, 8% had HIV in the genital tract. When the women’s plasma viral load was below 400 copies, or undetectable, only 2% had detectable virus in their genital secretions.

About 42% of the women with CD4 cell counts below 200 had detectable virus in their genital tracts, compared with 14% of patients with CD4 counts above 200.

About 15% of the women who reported receiving no therapy had a plasma viral load of less than 400; 21% of those on non-HAART treatment had a plasma viral load of less than 400; and 52% of the women on HAART had a plasma viral load of less than 400. "So it made sense," Cu-Uvin comments. "If you don’t go on therapy, the likelihood of your clearing the virus from your blood is very low."

Cu-Uvin says the research raises more questions that should be studied. For example, if HIV is reduced in women’s genital tracts, will that reduce the likelihood of an HIV-infected mother transmitting the virus to her baby? "We don’t know the answer to that, but in theory we’re hoping that would be the case," she says.

Another big question, Cu-Uvin points out, is whether or not HAART significantly decreases heterosexual transmission of HIV.

The researchers have begun a longitudinal study to determine if HAART benefits hold up over time.