Oral contraceptive use induces upregulation of the CCR5 chemokine receptor on CD4+ T cells in the cervical epithelium of healthy women

Prakash, Manyu; Kapembwa, Moses; Gotch, Frances; Patterson, Steven

doi:10.1016/s0165-0378(01)00125-5

Cited by 66 publications

(45 citation statements)

References 30 publications

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“…The exact mechanism by which DMPA could increase susceptibility and virus set point is unknown. Potential mechanisms that could increase susceptibility include physiological effects on the integrity of the vaginal epithelium [14], an effect on the cell-surface levels of CCR5 (which is a key molecule for HIV-1 entry) [39,40], or a direct effect on virus expression via hormone response elements within the HIV-1 promoter [41]. In the Mombasa cohort, and oral contraceptive use at the time of HIV-1 infection have both been associated with the acquisition of multiple viral genotypes [42].…”

Section: Discussionmentioning

confidence: 99%

Injectable Contraceptive Use and Genital Ulcer Disease during the Early Phase of HIV‐1 Infection Increase Plasma Virus Load in Women

et al. 2004

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We examined the association between host factors present near the time of human immunodeficiency virus type 1 (HIV-1) acquisition and subsequent virus loads, in a prospective cohort study of women in Mombasa, Kenya. Women were prospectively followed monthly before HIV-1 infection. One hundred sixty-one commercial sex workers who became infected with HIV-1 were followed for a median of 34 months, and 991 plasma samples collected > or =4 months after infection were tested for HIV-1 RNA. The median virus set point at 4 months after infection was 4.46 log10 copies/mL, and the average virus load increase during subsequent follow-up was 0.0094 log10 copies/mL/month. In a multivariate analysis that controlled for sexual behavior, the use of the injectable contraceptive depot medroxyprogesterone acetate (DMPA) at the time of HIV-1 infection was associated with a higher virus set point, and the presence of genital ulcer disease (GUD) during the early phase of HIV-1 infection was associated with greater change in virus load during follow-up. These findings suggest that, in women, the use of DMPA and the presence of GUD during the early phase of HIV-1 infection may influence the natural course of infection.

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Section: Discussionmentioning

confidence: 99%

Injectable Contraceptive Use and Genital Ulcer Disease during the Early Phase of HIV‐1 Infection Increase Plasma Virus Load in Women

et al. 2004

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“…Mechanisms for a hormonal effect on production of virus have been suggested by in vitro studies demonstrating regulation of the HIV-1 long-terminal repeat by steroid hormone receptors [19][20][21] and alterations in expression of chemokine receptors after progesterone treatment [22,23]. In addition, surface expression of the CCR5 chemokine receptor was increased on endocervical CD4 + T lymphocytes in women who were using oral contraceptives [24]. Reproductive hormones may also exert indirect effects on virus replication, as suggested by small clinical studies that report differences in immune function in the genital tract during the menstrual cycle [25][26][27][28][29].…”

Section: Discussionmentioning

confidence: 99%

Cyclic Shedding of HIV‐1 RNA in Cervical Secretions during the Menstrual Cycle

et al. 2004

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The association between hormone fluctuations during the menstrual cycle and human immunodeficiency virus type 1 (HIV-1) RNA shedding in cervical and vaginal secretions was examined daily for 17 HIV-1-seropositive women, for the duration of 1 cycle. Serum levels of RNA were evaluated 3 times/week. A marginally significant positive correlation between serum levels of progesterone and serum levels of HIV-1 RNA (P=.04) was observed. Cervical virus levels were significantly correlated with the number of days from the midcycle surge in luteinizing hormone (LH) (P=.008). The lowest levels of cervical HIV-1 RNA were present at the LH surge, and this nadir was followed by an increase in virus levels that reached a maximum before the start of menses. In contrast, there was no significant association between the number of days from the LH surge and the level of HIV-1 RNA in vaginal secretions (P=.4). These data support the hypothesis that the level of HIV-1 RNA in cervical secretions is influenced by the menstrual cycle, and they suggest that the risk of heterosexual transmission of HIV-1 may increase as menses is approached.

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“…39 Furthermore, women in various progesterone-dominant states have been found to have increased expression of cervical and vaginal lymphocytes expressing CCR5. [39][40][41] Interestingly, they have also been shown to have increased susceptibility to acquire HIV-1. [42][43][44][45] CCR5 is known to be expressed by activated lymphocytes.…”

Section: Figmentioning

confidence: 99%

Depot Medroxyprogesterone Acetate Increases Immune Cell Numbers and Activation Markers in Human Vaginal Mucosal Tissues

Chandra

Thurman

Anderson

et al. 2013

AIDS Research and Human Retroviruses

102

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The relationship between exogenous contraceptive hormones and permissiveness of the female genital tract to human immunodeficiency virus type 1 (HIV-1) is the subject of renewed debate. To better characterize the effect of depot medroxyprogesterone acetate (DMPA) on HIV-1 cellular targets and epithelial integrity in the vagina, we compared leukocyte populations, markers of activation and proliferation, and the density of intercellular junctional proteins in the vaginal epithelium of women during the follicular and luteal phases of the menstrual cycle and approximately 12 weeks after receiving a DMPA injection. This prospective cohort study involved 15 healthy women. Vaginal biopsies were obtained in the follicular and luteal phases of the menstrual cycle, and approximately 12 weeks following a 150-mg intramuscular injection of DMPA. Leukocyte populations, activation phenotype, and epithelial tight junction and adherens proteins were evaluated by immunohistochemistry. After receiving DMPA, the numbers of CD45, CD3, CD8, CD68, HLA-DR, and CCR5 bearing immune cells were significantly ( p < 0.05) increased in vaginal tissues, compared to the follicular and/or luteal phases of untreated cycles. There were no significant differences in immune cell populations between the follicular and luteal phases of the control cycle. There were also no statistically significant differences in epithelial thickness and density of epithelial tight junction and adherens proteins among the follicular, luteal, and post-DMPA treatment sampling points. In this pilot study, vaginal immune cell populations were significantly altered by exogenous progesterone, resulting in increased numbers of T cells, macrophages, and HLA-DR-and CCR5-positive cells.

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Oral contraceptive use induces upregulation of the CCR5 chemokine receptor on CD4+ T cells in the cervical epithelium of healthy women

Cited by 66 publications

References 30 publications

Injectable Contraceptive Use and Genital Ulcer Disease during the Early Phase of HIV‐1 Infection Increase Plasma Virus Load in Women

Injectable Contraceptive Use and Genital Ulcer Disease during the Early Phase of HIV‐1 Infection Increase Plasma Virus Load in Women

Cyclic Shedding of HIV‐1 RNA in Cervical Secretions during the Menstrual Cycle

Depot Medroxyprogesterone Acetate Increases Immune Cell Numbers and Activation Markers in Human Vaginal Mucosal Tissues

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