Background:  Pregnancy and hormonal contraceptive use have been identified as important correlates of virus shedding in the genital tract of HIV-1 infected women. To investigate the relationship between endogenous reproductive hormones and HIV-1, several studies have analyzed cervical and vaginal shedding of virus during the menstrual cycle, but have generated contradictory findings. Here we present a more detailed examination of the relationship between the menstrual cycle and cervical shedding of virus, through quantitative HIV-1 RNA analysis in daily cervical samples provided for 1 month by 17 women.

Methods:  For the duration of 1 menstrual cycle, endocervical swabs and luteinizing hormone (LH) measurements were obtained daily. The Gen-Probe HIV-1 Viral Load Assay was used to quantitate viral RNA levels in cervical swabs. Generalized estimating equations with a Gaussian link and an autoregressive correlation structure were used to evaluate the association between HIV-1 RNA viral load in cervical secretions and potential correlates of viral shedding.

Results:  17 women provided cervical samples at 451 (98%) of 458 expected clinic visits. Viral RNA was detected in 402 (89%) of 451 cervical swabs. The overall median viral load in cervical secretions was 3578 copies/swab (range <18-141,445). In multivariate analysis, there was an increase of 0.05 log₁₀ copies/swab in cervical HIV-1 RNA levels as the number of days from the LH surge increased (p = 0.004). To illustrate this pattern, each observed cervical viral load value at the LH surge (day 0) was subtracted from all other cervical viral load values for that woman. These centered values are summarized as a median (solid line) together with the interquartile range (dotted lines) for all values available on a given day (Figure 1).

 

 

 

 

 

 

 

 

 

 

 

Conclusions:  This analysis suggests that in the cervical mucosa, viral load reaches a nadir during the peri-ovulatory period, and then subsequently increases during the post-ovulatory phase.