HIV Risk Greatest During Follicular Phase of Menstrual Cycle

The follicular phase of the menstrual cycle may be the most vulnerable time for HIV-1 acquisition in women—not the luteal phase, as previously thought—according to the results of a new study published online October 31 in The Journal of Infectious Diseases.

“Our study showed that levels of the chemokine CCL2 were higher in the follicular phase and represented an accurate marker of that phase when controlled for multiple factors,” Keith Fowke, PhD, from the University of Manitoba, Winnipeg, Canada, the study’s principal investigator, shared in an interview with Contagion®.

HIV-1 infection is a public health issue that disproportionally affects women of reproductive age, wrote Genevieve Boily-Larouche, PhD, also from the University of Manitoba, and colleagues. They note that genital immune parameters are key factors that drive the sexual transmission of HIV in women.

Dr. Fowke explained that inflammation in the female reproductive tract is a known risk factor for HIV because it brings HIV target cells (CD4+ T cells) into the area. It is also known that the immune system varies throughout the menstrual cycle, he added. However, how this variation affects HIV susceptibility is not known.

With this in mind, the investigators conducted a longitudinal study to measure markers of inflammation and HIV target cells from the blood and genital tract of 37 women during the follicular and luteal phases of the menstrual cycle.

They found significant differences in the cervical concentrations of certain factors between the 2 phases of the cycle. In particular, the follicular phase was characterized by increased CCL2 levels, decreased interleukin 1α and interleukin 1β concentrations, and a significant rise in the proportion of CD4+ T cells that expressed CD69.

“The genital concentration of CCL2 was the best marker to distinguish the follicular from the luteal phase in univariate and multivariate analyses, and remained independent of elevated genital inflammation and bacterial vaginosis,” the authors wrote.

According to Dr. Fowke, the role of CCL2 is to attract immune cells to the genital tract, and so, it makes sense that the follicular phase also showed higher levels of CD4+ T cells with the activation/tissue retention marker CD69 on them.

“Because activated CD4+ T cells are highly susceptible to HIV infection, this study suggests that the follicular phase of the menstrual cycle, and not the luteal phase as previously thought, may be the phase of the menstrual cycle where HIV risk is greatest,” he noted.

Understanding how the menstrual cycle affects HIV risk is important when designing HIV prevention strategies, Dr. Fowke said. As well as helping to map out the cause and effect of how chemokine fluctuations affect HIV target cells during the menstrual cycle, this study could also help future studies by narrowing down all of the potential immune parameters that can be measured, to just a few key factors that help define menstrual cycle stage and assess HIV risk—namely CCL2, and CD69 on CD4+ T cells.

“Tracking these key factors will help other researchers determine the impact of their intervention on HIV risk,” Dr. Fowke said.

However, he also emphasized the need for follow-up studies to test the findings of this current study in different cohorts. “Studies testing the susceptibility of cells taken from different phases of the menstrual cycle to HIV infection in vitro, will help determine if cells from one phase are more likely to be infected by HIV,” Dr. Fowke concluded.

Dr. Parry, a board-certified veterinary pathologist, graduated from the University of Liverpool in 1997. After 13 years in academia, she founded Midwest Veterinary Pathology, LLC, where she now works as a private consultant. Dr. Parry writes regularly for veterinary organizations and publications.