Hormonal Contraceptives: Enduring Controversy

The use of hormonal contraceptives in HIV medicine has been clouded with controversy. Do hormonal contraceptives increase HIV risk and influence a woman's susceptibility to HIV infection? From a sexual health point of view, this has been of interest to me.

This themed discussion was led by Betsy Harold from the Albert Einstein College of Medicine at the Bronx, New York and is available now on the CROI webcast. She introduced the session by pointing out that a recent meta-analysis of 18 studies including 37,124 women and 1830 HIV incident infections concluded an adjusted hazard ratio relative to no hormonal contraceptives for DMPA to be 1.50 (1.25-1.83) and for COC to be 1.03 (0.8-1.2). HIV infections appear to be be seen more often in women on DMPA and COC. She mentioned the biological plausibility of these findings including thinning epithelium, increased CCR5 expression, changes in micro biome, increased HSV and other STIs, ulcerative lesions and increased pro-inflammatory or decreased protective mediators.

It is thought that hormonal contraception may increase CCR5 expression favouring HIV infectivity and that oestrogen may modulate CCR5 expression

Four studies were presented that I will try to summarise

Oestrogen Replacement in Healthy Postmenopausal Women Reduces %CCR5+CD4+T Cells

In this study, there is a suggestion that there could be an increased risk of HIV acquisition in older postmenopausal women in that CCR5 is elevated, especially in cervical CD4+cells compared to premenopausal women. Oestrogen replacement was found to reduce %CCR5+CD4+ T cells in these postmenopausal women suggesting it could decrease HIV acquisition in this group. It is noted though that the population studied was healthy.

CCR5 Expression in HIV-Uninfected Women Receiving Hormonal contraception

This study suggested that the use of LNG-IUD and DMPA was associated with increased CCR5 expression on peripheral T cells and that comparative work in the female reproductive tract tissues and blood is needed to evaluate further increases in CCR5 expression associated with hormonal contraception. Again, the study was on uninfected women.

Progesterone Increases are Associated with HIV Susceptibility Factors in Women

Native progesterone and progestin based hormonal contraception are suspected of HIV acquisition risk in women although how these contraceptives affect HIV target cells is uncertain. The results of this study appear to suggest that the endogenous progesterone increase during the menstrual cycle luteal phase is associated with HIV target cells that have increased CCR5 expression, higher levels of activation and response to stimulation. If these progesterone effects exist in genital mucosa, this could be an important measure for identifying progestin based hormonal contraceptive risk factors.

Changes in Vaginal Microbiota and Cytokines in HIV - Seronegative women initiating DMPA

This study looked at the changes in vaginal microbiota and inflammatory milieu after DMPA initiation through which it is thought DMPA may modify HIV susceptibility. The initiation of DMPA was shown to demonstrate sustained shifts in vaginal bacterial concentrations and levels of inflammatory  mediators after adjusting for behavioural and biological confounders possibly impacting on HIV susceptibility. I am reminded of the association between bacterial vaginosis and HIV transmission.

As was pointed out by Betsy Harold, studies in this area have been retrospective studies and there is a need for prospective studies to occur