Incidence of sexually transmitted infections among HIV-infected women using depot medroxyprogesterone acetate contraception

Overton, Edgar Turner; Shacham, Enbal; Singhatiraj, Ekachai; Nurutdinova, Diana

doi:10.1016/j.contraception.2008.03.015

Cited by 20 publications

(15 citation statements)

References 27 publications

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“…DMPA also inhibits the effector function of CD8 T cells, including IFN-␥ production, and induces reactivation of HSV-1 in mice (32,33). A significant association was also found between the use of DMPA and the acquisition of sexually transmitted diseases other than HIV (7). Whether DMPA use increases the risk of acquiring HIV has been a matter of dispute, but recent reports by Morrison et al and Heffron et al supported this concept (2, 3).…”

Section: Discussionmentioning

confidence: 67%

“…Some recent publications suggest that DMPA use is associated with a significantly higher risk of acquiring HIV (2)(3)(4), although other studies did not find this association (5,6). Use of DMPA has previously also been linked to increased risk of acquisition of other sexually transmitted diseases, such as Trichomonas vaginalis, Neisseria gonorrhoeae, and Chlamydia trachomatis (7). DMPA is a contraceptive administered to women as an intramuscular injection once every 3 months.…”

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confidence: 99%

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The Contraceptive Depot Medroxyprogesterone Acetate Impairs Mycobacterial Control and Inhibits Cytokine Secretion in Mice Infected with Mycobacterium tuberculosis

et al. 2013

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dThe contraceptive depot medroxyprogesterone acetate (DMPA), with progestin as the single active compound, possesses selective glucocorticoid activity and can alter the expression of glucocorticoid receptor-regulated genes. We therefore propose that pharmacological doses of DMPA used for endocrine therapy could have significant immune modulatory effects and impact on susceptibility to, as well as clinical manifestation and outcome of, infectious diseases. We investigated the effect of contraceptive doses of DMPA in two different murine Mycobacterium tuberculosis models. Multiplex bead array analysis revealed that DMPA altered serum cytokine levels of tumor necrosis factor alpha (TNF-␣), granulocyte colony-stimulating factor (G-CSF), and interleukin 10 (IL-10) in C57BL/6 mice and gamma interferon (IFN-␥) in BALB/c mice. DMPA also suppressed antigen-specific production of TNF-␣, G-CSF, IL-10, and IL-6 and induced the production of IP-10 in C57BL/6 mice. In BALB/c mice, DMPA altered the antigen-specific secretion of IFN-␥, IL-17, granulocyte-macrophage colony-stimulating factor (GM-CSF), IL-6, and monocyte chemotactic protein 1 (MCP-1). Furthermore, we show that C57BL/6 mice treated with doses of DMPA, which result in serum concentrations similar to those observed in contraceptive users, have a significantly higher bacterial load in their lungs. Our data show for the first time that DMPA impacts tuberculosis (TB) disease severity in a mouse model and that the effects of this contraceptive are not confined to infections of the genital tract. This could have major implications for the contraceptive policies not only in developing countries like South Africa but also worldwide.

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Section: Discussionmentioning

confidence: 67%

mentioning

confidence: 99%

The Contraceptive Depot Medroxyprogesterone Acetate Impairs Mycobacterial Control and Inhibits Cytokine Secretion in Mice Infected with Mycobacterium tuberculosis

et al. 2013

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“…This increased our ability to detect changes and generate hypotheses, but might have also allowed the introduction of spurious associations. Although the number of participants in this study was limited, their ages, which varied from 15 to 47 years, overlap with the age range of 15 to 44 years considered by the CDC as representative for the use of contraceptive methods in the U.S. and with previously published demographics of DMPA in HIV-infected users [70, 71]. The limited number of participants in this analysis was counterbalanced by the longitudinal design using intra-subject comparison approaches, which minimized the introduction of DMPA-unrelated variables.…”

Section: Discussionmentioning

confidence: 99%

Effect of Depot Medoxyprogesterone Acetate on Immune Functions and Inflammatory Markers of HIV-Infected Women

Weinberg

Park

Bosch

et al. 2016

JAIDS Journal of Acquired Immune Deficiency Syndromes

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Objectives Depot medroxyprogesterone acetate (DMPA) was associated with increased HIV transmission and accelerated disease progression in untreated women. The potential underlying mechanisms include immune-modulation. We evaluated the effect of a single DMPA injection on cell-mediated immunity (CMI), T cell activation (Tact), regulation (Treg) and inflammation in HIV-infected women on cART. Methods Women with HIV plasma RNA ≤400 c/mL on stable cART received DMPA and had immunologic and MPA measurements at baseline, 4 weeks [peak MPA concentration (Cmax)] and 12 weeks [highest MPA area under the concentration curve (AUC)]. Results At baseline, among 24 women with median 32 years of age and 622 CD4+ cells/μL, ≥68% had HIV, VZV, PHA and CD3/CD28 CMI measured by lymphocyte proliferation and/or IFNγ/IL2 dual-color fluorospot. CMI did not significantly change after DMPA administration except for a 1.4-fold increase in IL2/IFNγ VZV fluorospot at week 12. Tact decreased after DMPA administration, reaching statistical significance at week 12 for CD4+CD25+%. Treg behaved heterogeneously with an increase in CD8+FOXP3+% at week 4 and a decrease in CD4+IL35+% at week 12. There was a decrease in TGFβ at week 12 and no other changes in plasma biomarkers. Correlation analyses showed that high MPA Cmax and/or AUC were significantly associated with increases of IFNγ HIV ELISPOT, CD4+IL35+% and CD4+TGFβ+% Treg and decreases of plasma IL10 from baseline to weeks 4 and/or 12. Conclusions A single dose of DMPA did not have immune-suppressive or pro-inflammatory effects in HIV-infected women on cART. Additional studies need to assess the effect of multiple doses.

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“…Thus, the global impact of the biological effects of hormonal contraceptives needs to be explored in detail to understand how they may affect susceptibility to HIV acquisition and transmission. In nonhuman primate (NHP) studies, progesterone-based hormonal contraceptives were clearly shown to enhance Simian immunodeficiency virus (SIV) vaginal transmission whereas human HIV epidemiological observation studies have proved inconclusive [13][14][15][16][17][18][19][20][21][22]. For instance, World Health Organization guidelines conclude that the most current clinical data neither establish a clear causal association with progesterone-based injectables and HIV acquisition, nor definitively rule out the possibility of an effect [23].…”

Section: Introductionmentioning

confidence: 99%

Progesterone-Based Intrauterine Device Use Is Associated with a Thinner Apical Layer of the Human Ectocervical Epithelium and a Lower ZO-1 mRNA Expression1

Tjernlund

Carias

Andersson

et al. 2015

Biology of Reproduction

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Currently, whether hormonal contraceptives affect male to female human immunodeficiency virus (HIV) transmission is being debated. In this study, we investigated whether the use of progesterone-based intrauterine devices (pIUDs) is associated with a thinning effect on the ectocervical squamous epithelium, down-regulation of epithelial junction proteins, and/or alteration of HIV target cell distribution in the human ectocervix. Ectocervical tissue biopsies from healthy premenopausal volunteers using pIUDs were collected and compared to biopsies obtained from two control groups, namely women using combined oral contraceptives (COCs) or who do not use hormonal contraceptives. In situ staining and image analysis were used to measure epithelial thickness and the presence of HIV receptors in tissue biopsies. Messenger RNA levels of epithelial junction markers were measured by quantitative PCR. The epithelial thickness displayed by women in the pIUD group was similar to those in the COC group, but significantly thinner as compared to women in the no hormonal contraceptive group. The thinner epithelial layer of the pIUD group was specific to the apical layer of the ectocervix. Furthermore, the pIUD group expressed significantly lower levels of the tight junction marker ZO-1 within the epithelium as compared to the COC group. Similar expression levels of HIV receptors and coreceptors CD4, CCR5, DC-SIGN, and Langerin were observed in the three study groups. Thus, women using pIUD displayed a thinner apical layer of the ectocervical epithelium and reduced ZO-1 expression as compared to control groups. These data suggest that pIUD use may weaken the ectocervical epithelial barrier against invading pathogens, including HIV.

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Incidence of sexually transmitted infections among HIV-infected women using depot medroxyprogesterone acetate contraception

Cited by 20 publications

References 27 publications

The Contraceptive Depot Medroxyprogesterone Acetate Impairs Mycobacterial Control and Inhibits Cytokine Secretion in Mice Infected with Mycobacterium tuberculosis

The Contraceptive Depot Medroxyprogesterone Acetate Impairs Mycobacterial Control and Inhibits Cytokine Secretion in Mice Infected with Mycobacterium tuberculosis

Effect of Depot Medoxyprogesterone Acetate on Immune Functions and Inflammatory Markers of HIV-Infected Women

Progesterone-Based Intrauterine Device Use Is Associated with a Thinner Apical Layer of the Human Ectocervical Epithelium and a Lower ZO-1 mRNA Expression1

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