CCR5 Expression Levels in HIV-Uninfected Women Receiving Hormonal Contraception

Sciaranghella, Gaia; Wang, Cuiwei; Anastos, Kathryn; Merhi, Zaher; Nowicki, Marek; Stanczyk, Frank Z.; Greenblatt, Ruth M.; Cohen, Mardge H.; Golub, Elizabeth T.; Watts, D. Heather; Alter, Galit; Young, Mary; Tsibris, Athe

doi:10.1093/infdis/jiv233

Cited by 24 publications

(25 citation statements)

References 15 publications

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“…However, a cross sectional study performed by Sciaranghella detected significantly higher CCR5 MFI on CD4 + T cells from Depo-Provera users compared to a control group without hormonal contraception (28). We found a significant increase in integrin α4β7 + CD4 + T cells, and an increasing trend in CCR5 + CD4 + T cells 1 month after Depo-Provera injection compared to baseline or 3 months after Depo-Provera injection.…”

Section: Discussionmentioning

confidence: 98%

“…One cross-sectional study showed no significant difference in the percentage of CCR5 + CD8 + or CCR5 + CD4 + T cells, but found a significant increase in expression (mean fluorescent intensity, MFI) of CCR5 on CD4 + T cells of Depo-Provera users compared to women not using hormonal contraception (28). TLR-9 stimulation of pDCs resulted in reduced production of TNFα and IFNα in Depo-Provera users compared to women not using hormonal contraception (29).…”

Section: Introductionmentioning

confidence: 99%

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Depot Medroxyprogesterone Acetate Administration Alters Immune Markers for HIV Preference and Increases Susceptibility of Peripheral CD4+ T Cells to HIV Infection

et al. 2017

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Depot medroxyprogesterone acetate (Depo-Provera) has been associated with an increased risk of HIV acquisition. In a longitudinal study, we investigated the impact of Depo-Provera use by healthy women on expression of immune markers for HIV preference and on HIV infection ex vivo at baseline (visit 1), one month (visit 2) and three months (visit 3) after Depo-Provera treatment. We found a significant increase in the frequency and expression of integrin α4β7 on CD4+ T cells at visit 2. Interestingly, Hispanic but not black women exhibited a significant increase in integrin α4β7 cell numbers and expression levels at visit 2, whereas, black but not Hispanic women exhibited a significant change in CCR5 and CD38 expression levels between visit 2 and visit 3. The frequency of terminal effector memory CD4+ T cells decreased significantly in black women from visit 1 to visit 3. Virus production following ex vivo HIV infection of PBMCs was increased at visit 3 compared to visit 1. In black women, the frequency of HIV p24+CD4+ T cells was higher at visit 3 than at visit 1. Expression of integrin α4β7 on HIV p24+CD4+ T cells following ex vivo infection at visit 2 was significantly less than at visit 1. These results demonstrate that Depo-Provera alters the immune profile of peripheral CD4+ T cells and increases susceptibility to HIV infection ex vivo. The observation that these effects differed between women of different ethnicities has implications for developing effective and targeted strategies for HIV prevention.

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Section: Discussionmentioning

confidence: 98%

Section: Introductionmentioning

confidence: 99%

Depot Medroxyprogesterone Acetate Administration Alters Immune Markers for HIV Preference and Increases Susceptibility of Peripheral CD4+ T Cells to HIV Infection

et al. 2017

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“…DMPA-IM has been shown in some clinical studies to increase surface levels of CCR5 on peripheral and female genital tract (FGT) target T cells [55, 56], increase the frequency of CCR5 + T cells in the FGT mucosa [56], decrease the production of several immune modulators by immune cells [57, 58], increase FGT mucosal permeability and expression of barrier function proteins [59] and alter cervicovaginal levels of select secreted immunomodulators [57, 60–66]. Several of these studies are consistent with results from animal studies where MPA serum concentrations are similar to those of human DMPA-IM users [59, 67–71].…”

Section: Dmpa-sc Vs Dmpa-im: Similar or Different Hiv Acquisition Rimentioning

confidence: 99%

Is a lower-dose, subcutaneous contraceptive injectable containing depot medroxyprogesterone acetate likely to impact women's risk of HIV?

et al. 2018

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“…6 Studies of the association between HIV acquisition and injectable progestin-only contraceptives use have not reached consistent conclusions, and although progestins have been shown to have a multitude of effects on immune function in vitro, 7–10 whether these effects are manifest in vivo is unclear. 11,12 …”

Section: Introductionmentioning

confidence: 99%

Association between injectable progestin-only contraceptives and HIV acquisition and HIV target cell frequency in the female genital tract in South African women: a prospective cohort study

Byrne

Anahtar

Cohen

et al. 2016

The Lancet Infectious Diseases

104

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Summary Background The use of injectable progestin-only contraceptives has been associated with increased risk of HIV acquisition in observational studies, but the biological mechanisms of this risk remain poorly understood. We aimed to assess the effects of progestins on HIV acquisition risk and the immune environment in the female genital tract. Methods In this prospective cohort, we enrolled HIV-negative South African women aged 18–23 years who were not pregnant and were living in Umlazi, South Africa from the Females Rising through Education, Support, and Health (FRESH) study. We tested for HIV-1 twice per week to monitor incident infection. Every 3 months, we collected demographic and behavioural data in addition to blood and cervical samples. The study objective was to characterise host immune determinants of HIV acquisition risk, including those associated with injectable progestin-only contraceptive use. Hazard ratios (HRs) were estimated using Cox proportional hazards methods. Findings Between Nov 19, 2012, and May 31, 2015, we characterised 432 HIV-uninfected South African women from the FRESH study. In this cohort, 152 women used injectable progestin-only contraceptives, 43 used other forms of contraception, and 222 women used no method of long-term contraception. Women using injectable progestin-only contraceptives were at substantially higher risk of acquiring HIV (12·06 per 100 person-years, 95% CI 6·41–20·63) than women using no long-term contraception (3·71 per 100 person-years, 1·36–8·07; adjusted hazard ratio [aHR] 2·93, 95% CI 1·09–7·868, p=0·0326). HIV-negative injectable progestin-only contraceptive users had 3·92 times the frequency of cervical HIV target cells (CCR5+ CD4 T cells) compared with women using no long-term contraceptive (p=0·0241). Women using no long-term contraceptive in the luteal phase of the menstrual cycle also had a 3·25 times higher frequency of cervical target cells compared with those in the follicular phase (p=0·0488), suggesting that a naturally high progestin state had similar immunological effects to injectable progestin-only contraceptives. Interpretation Injectable progestin-only contraceptive use and high endogenous progesterone are both associated with increased frequency of activated HIV targets cells at the cervix, the site of initial HIV entry in most women, providing a possible biological mechanism underlying increased HIV acquisition in women with high progestin exposure. Funding The Bill and Melinda Gates Foundation and the National Institute of Allergy and Infectious Diseases.

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CCR5 Expression Levels in HIV-Uninfected Women Receiving Hormonal Contraception

Cited by 24 publications

References 15 publications

Depot Medroxyprogesterone Acetate Administration Alters Immune Markers for HIV Preference and Increases Susceptibility of Peripheral CD4+ T Cells to HIV Infection

Depot Medroxyprogesterone Acetate Administration Alters Immune Markers for HIV Preference and Increases Susceptibility of Peripheral CD4+ T Cells to HIV Infection

Is a lower-dose, subcutaneous contraceptive injectable containing depot medroxyprogesterone acetate likely to impact women's risk of HIV?

Association between injectable progestin-only contraceptives and HIV acquisition and HIV target cell frequency in the female genital tract in South African women: a prospective cohort study

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