ArticleScientific reports2019
The contraceptive medroxyprogesterone acetate, unlike norethisterone, directly increases R5 HIV-1 infection in human cervical explant tissue at physiologically relevant concentrations.
Article in Scientific reports, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
19 citing papers in PubMed, 26 citations in OpenAlex.
- Injectable contraceptives differentially affect the hypothalamic-pituitary-gonadal axis and amenorrhea incidence†.Biology of reproduction · 2026Trial
- Injectable Contraceptives Differentially Affect Select CD4+ HIV-1 Target Cells in the Genital Tract but Not Systemically: Implications for HIV-1 Acquisition.American journal of reproductive immunology (New York, N.Y. : 1989) · 2025Trial
- Trial
- The Effect of Contraception on Genital Cytokines in Women Randomized to Copper Intrauterine Device, Depot Medroxyprogesterone Acetate, or Levonorgestrel Implant.The Journal of infectious diseases · 2022Trial
- Pathophysiological Consequences Associated with Hormonal Contraceptives Use in Sub-Saharan Africa: A Scoping Review.Open access journal of contraception · 2025Review
- Article
- NET-EN treatment leads to delayed HSV-2 infection, enhanced mucin and T cell functions in the female genital tract when compared to DMPA in a preclinical mouse model.Frontiers in immunology · 2024Article
- Glucocorticoids and medroxyprogesterone acetate synergize with inflammatory stimuli to selectively upregulate CCL20 transcription.Molecular and cellular endocrinology · 2023Article
- Increased HIV-1 infection in PBMCs treated in vitro with menstrual cycle phase hormones or medroxyprogesterone acetate likely occurs via different mechanisms.American journal of reproductive immunology (New York, N.Y. : 1989) · 2022Article
- Review
- Differential off-target glucocorticoid activity of progestins used in endocrine therapy.Steroids · 2022Article
- Women for science and science for women: Gaps, challenges and opportunities towards optimizing pre-exposure prophylaxis for HIV-1 prevention.Frontiers in immunology · 2022Review
- Medroxyprogesterone acetate inhibits wound closure of human endometrial epithelial cells and stromal fibroblasts in vitro.Scientific reports · 2021Article
- Article
- HIV Pathogenesis in the Human Female Reproductive Tract.Current HIV/AIDS reports · 2021Review
- Is the Injectable Contraceptive Depo-Medroxyprogesterone Acetate (DMPA-IM) Associated with an Increased Risk for HIV Acquisition? The Jury Is Still Out.AIDS research and human retroviruses · 2020Article
- Norethisterone Enanthate Increases Mouse Susceptibility to Genital Infection with Herpes Simplex Virus Type 2 and HIV Type 1.ImmunoHorizons · 2020Article
- Differential Elevation of Inflammation and CD4Frontiers in immunology · 2020Article
- Reciprocal Modulation of Antiretroviral Drug and Steroid Receptor FunctionAntimicrobial agents and chemotherapy · 2019Article
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
The intramuscular progestin-only injectable contraceptive, depo-medroxyprogesterone acetate (DMPA-IM), is more widely used in Sub-Saharan Africa than another injectable contraceptive, norethisterone enanthate (NET-EN). Epidemiological data show a significant 1.4-fold increased risk of HIV-1 acquisition for DMPA-IM usage, while no such association is shown from limited data for NET-EN. We show that MPA, unlike NET, significantly increases R5-tropic but not X4-tropic HIV-1 replication ex vivo in human endocervical and ectocervical explant tissue from pre-menopausal donors, at physiologically relevant doses. Results support a mechanism whereby MPA, unlike NET, acts via the glucocorticoid receptor (GR) to increase HIV-1 replication in cervical tissue by increasing the relative frequency of CD4+ T cells and activated monocytes. We show that MPA, unlike NET, increases mRNA expression of the CD4 HIV-1 receptor and CCR5 but not CXCR4 chemokine receptors, via the GR. However, increased density of CD4 on CD3+ cells was not observed with MPA by flow cytometry of digested tissue. Results suggest that DMPA-IM may increase HIV-1 acquisition in vivo at least in part via direct effects on cervical tissue to increase founder R5-tropic HIV-1 replication. Our findings support differential biological mechanisms and disaggregation of DMPA-IM and NET-EN regarding HIV-1 acquisition risk category for use in high risk areas.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.