Genital shedding of HIV fluctuates with a woman's menstrual cycle

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The shedding of HIV in vaginal and cervical secretions fluctuates with a woman’s menstrual cycle, according to a study published in the June 15th edition of Clinical Infectious Diseases, which is now available online. The findings also suggest that the risk of HIV transmission may be higher at certain points in the menstrual cycle.

Investigators from Kenya and the US wished to establish the relationship between hormonal fluctuations during the menstrual cycle and HIV RNA shedding in cervical and vaginal secretions. During the course of a complete menstrual cycle, 17 women with HIV had daily swabs to determine the level of HIV shedding in the cervix and vagina. Blood tests were performed three times a week to establish serum HIV viral load and serum levels of the hormones estradiol and progesterone. In particular, the investigators wished to establish if there was any relationship between the luteinizing hormone surge and cervical and vaginal secretion of HIV.

The 17 women attended 98% of their required study visits. Individuals had a median serum viral load of 26,690 copies/ml, a median cervical viral load of 3578 copies per swab, and a median vaginal viral load of 386 copies per swab. The investigators found that there was a marginally significant correlation between serum levels of progesterone and serum HIV viral load (p = 0.04).

Glossary

cervix

The cervix is the neck of the womb, a tight ‘collar’ of tissue that closes off the womb except during childbirth. Cancerous changes are most likely in the transformation zone where the vaginal epithelium (lining) and the lining of the womb meet.

serum

Clear, non-cellular portion of the blood, containing antibodies and other proteins and chemicals.

 

hormone

A chemical messenger which stimulates or suppresses cell and tissue activity. Hormones control most bodily functions, from simple basic needs like hunger to complex systems like reproduction, and even the emotions and mood.

shedding

Viral shedding refers to the expulsion and release of virus progeny (offspring such as competent particles, virions, etc.) following replication. In HIV this process occurs in the semen, the vaginal secretions and other bodily fluids, making those fluids more infectious.

replication

The process of viral multiplication or reproduction. Viruses cannot replicate without the machinery and metabolism of cells (human cells, in the case of HIV), which is why viruses infect cells.

Vaginal secretion of HIV was significantly associated with serum HIV viral load (p < 0.001), menstruation, and the presence of HIV-infected cells in the vagina (p = 0.006). Douching was associated with reduced odds of detection of vaginal HIV secretions (p = 0.02).

Serum viral load was strongly predictive of cervical HIV levels (p < 0.001), and the investigators also found that there was a statistically significant relationship between the amount of HIV secreted in the cervix and the number of days from the luteinizing hormone surge (p = 0.02).

In further analysis, which adjusted for serum HIV viral load, unprotected sex, douching, and menstruation, the investigators confirmed a statistically significant association between the amount of HIV detected in cervical swabs and the number of days from the luteinizing hormone surge (p = 0.008). The lowest levels of cervical HIV shedding were observed at the luteinizing hormone surge and then increased steadily before the start of menstruation.

The investigators comment, “this is the first study to describe the daily changes in HIV… RNA levels in cervical and vaginal compartments in association with the menstrual cycle. We show that cervical virus levels were lowest at the [luteinizing hormone] surge and then increased before the onset of the next menses.”

These data suggest to the investigators that fluctuating hormone levels during the menstrual cycle can affect the level of HIV production in the genital mucosa. They believe that these changes may be due to the direct effect of the hormones on HIV replication, or could be because changing hormone levels affect either the availability, or susceptibility, of HIV’s target cells to infection. They cite evidence from other studies showing that reproductive hormones have the potential to upregulate both HIV replication and the susceptibility of cells to infection.

The investigators conclude that their study “implies that there may be more risk of the transmission of HIV… at certain times during the menstrual cycle.”

References

Benki S et al. Cyclic shedding of HIV-1 RNA in cervical secretions during the menstrual cycle. Clinical Infectious Diseases: 189 (on-line edition), 2004.