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J Acquir Immune Defic Syndr. 2014 Jun 1;66(2):109-17. doi: 10.1097/QAI.0000000000000103.

Cervical inflammation and immunity associated with hormonal contraception, pregnancy, and HIV-1 seroconversion.

Author information

1
*Clinical Sciences, FHI 360, Durham, NC; †Department of Obstetrics, Gynecology and Reproductive Biology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA; ‡CONRAD, Eastern Virginia Medical School, Arlington, VA; §Biostatistics, FHI 360, Durham, NC; ‖Department of Obstetrics and Gynaecology, University of Zimbabwe, Harare, Zimbabwe; ¶Department of Medicine, Case Western Reserve University, Cleveland, OH; and #Department of Obstetrics and Gynecology, CONRAD, Department of Obstetrics and Gynecology, Eastern Virginia Medical School, Norfolk, VA.

Abstract

OBJECTIVE:

Hormonal contraception (HC), younger age, and pregnancy have been associated with increased HIV risk in some studies. We sought to elucidate the biological mechanisms for these associations.

DESIGN:

Case-control selection of specimens from a large, prospective, clinical study.

METHODS:

We enrolled and followed 4531 HIV-negative women from Uganda and Zimbabwe using either the injectable depo-medroxyprogesterone acetate (DMPA), combined oral contraception, or no HC (NH). Innate immunity mediators were measured in cervical samples collected from women at their visit before HIV seroconversion (n = 199) and matched visits from women remaining HIV uninfected (n = 633). Generalized linear models were applied after Box-Cox power transformation.

RESULTS:

Higher RANTES and lower secretory leukocyte protease inhibitor (SLPI) levels were associated with HIV seroconversion. DMPA users had higher RANTES and lower BD-2 levels. Most inflammation-promoting and/or inflammation-inducible mediators were higher [interleukin (IL)-1β, IL-6, IL-8, MIP-3α, vascular endothelial growth factor, and SLPI], and the protective BD-2 and IL-1RA:IL-1β ratio were lower among combined oral contraception users. Pregnant women showed a similar cervical immunity status (higher IL-1β, IL-6, IL-8, vascular endothelial growth factor, SLPI, and IL-1RA; lower IL-1RA:IL-1β). Age <25 years was associated with lower SLPI, IL-8, MIP-3α but higher IL-1RA:IL-1β. Zimbabwean women (with higher HIV seroconversion rates) had overall higher pro-inflammatory and lower anti-inflammatory protein levels than Ugandan women.

CONCLUSIONS:

HC use, pregnancy, and young age alter cervical immunity in different ways known to increase risk of HIV, for example, through increased levels of pro-inflammatory cytokines or decreased levels of SLPI. Higher levels of RANTES may be one factor underlying a possible association between DMPA use and risk of HIV acquisition.

PMID:
24413042
DOI:
10.1097/QAI.0000000000000103
[Indexed for MEDLINE]

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