Variations in genital shedding of HIV during menstrual cycle large enough to impact on risk of sexual transmission

Michael Carter
Published: 25 February 2013

Genital shedding of HIV varies considerably during the menstrual cycle, investigators report in the online edition of the Journal of Infectious Diseases. The difference between peak and nadir shedding was approximately 0.74 log10, which the investigators believe would translate into a significant difference in the risk of sexual HIV transmission.

“We found a significant cyclic variation in mucosal HIV-1 shedding,” comment the authors. “The cyclic nature of HIV shedding in the female genital tract must be considered in studies examining HIV transmission and correlates to the risk of HIV transmission during heterosexual contact.”

Factors affecting the detection of HIV in the female genital tract are poorly understood. The impact of the menstrual cycle on viral shedding is especially unclear.

An international team of investigators therefore designed a prospective study examining the effect of the menstrual cycle on HIV shedding in the genital tract.

A total of 67 women co-infected with HIV and herpes simplex virus-2 (HSV-2) were recruited to the study. All were of childbearing age and none were taking antiretroviral therapy. The authors also examined the impact of aciclovir therapy for HSV-2 and hormonal contraception on genital shedding. The research was undertaken in Thailand and was a sub-study of a larger randomised trial examining the impact of aciclovir therapy on HIV shedding.

Participants in the study performed self-collected vaginal swabs over two menstrual cycles. For genital HIV shedding frequency calculations, the menstrual cycle was divided into three phases: around the time of ovulation ( +/- 3 days, periovulatory); the luteal phase (end of periovulatory phases to onset of menses); and the follicular phase (end of menses to beginning of ovulation). Vaginal swabs were not taken during menstruation.

Median CD4 cell count was 366 cells/mm3 and median plasma viral load was approximately 40,000 copies/ml. During the study, 18 women reported the use of hormonal contraception and five women – including four using hormonal contraception – reported no menses.

Overall, shedding occurred in 60%, 48% and 54% of samples collected during the follicular, periovulatory and luteal phases respectively (p = 0.01).

Among women with detectable shedding, levels of HIV were highest immediately following menses and decreased through the remainder of the follicular phase before reaching a nadir at the date of ovulation. These changes were highly significant (p < 0.0001).

Genital HIV levels remained essentially steady during the luteal phase prior to menstruation. However, in women with a CD4 cell count below 350 cells/mm3 the rate of shedding increased during the luteal phase (p = 0.05).

Aciclovir therapy was associated with a fall of 0.5 log10 copy/swab (p < 0.001) and reduced frequency of shedding. However, aciclovir did not have an impact on the pattern of genital shedding during the menstrual cycle.

The overall findings of the study were unaffected when women without menses and those using hormonal contraception were excluded.

The authors believe that variations in HIV shedding during the menstrual cycle could affect the risk of transmission. They explain: “Shedding declined by 0.054 log10 per day. Assuming a 14-day follicular phase, this corresponds to a 0.75 log10 difference between peak and nadir shedding.” They estimate this could represent a 65% difference in the risk of female-to-male transmission.

Reference

Curlin ME et al. Cyclic changes in HIV shedding from the female genital tract during the menstrual cycle. J Infect Dis, online edition, 2013.