ArticlePloS one2018
Medroxyprogesterone acetate, unlike norethisterone, increases HIV-1 replication in human peripheral blood mononuclear cells and an indicator cell line, via mechanisms involving the glucocorticoid receptor, increased CD4/CD8 ratios and CCR5 levels.
Article in PloS one, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 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
25 citing papers in PubMed, 33 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
- Behavioral effects of different contraceptive methods and HIV acquisition: an ancillary study of the ECHO randomized trial.Reproductive health · 2021Trial
- Gonadocorticoids Have Different Effects on the Expression of Toll-like Receptors When Infected with Various HIV-1 Subtypes.Viruses · 2025Article
- 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
- Female Sex Hormones Upregulate the Replication Activity of HIV-1 Sub-Subtype A6 and CRF02_AG but Not HIV-1 Subtype B.Pathogens (Basel, Switzerland) · 2023Article
- 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
- Medroxyprogesterone acetate inhibits wound closure of human endometrial epithelial cells and stromal fibroblasts in vitro.Scientific reports · 2021Article
- Article
- Hormonally Active Contraceptives Part I: Risks Acknowledged and Unacknowledged.The Linacre quarterly · 2021Article
- HIV-1 Tat promotes age-related cognitive, anxiety-like, and antinociceptive impairments in female mice that are moderated by aging and endocrine status.GeroScience · 2021Article
- 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
- Depot medroxyprogesterone acetate and norethisterone enanthate differentially impact T-cell responses and expression of immunosuppressive markers.American journal of reproductive immunology (New York, N.Y. : 1989) · 2020Article
- Differential Elevation of Inflammation and CD4Frontiers in immunology · 2020Article
- Reciprocal Modulation of Antiretroviral Drug and Steroid Receptor FunctionAntimicrobial agents and chemotherapy · 2019Article
- Article
Corrections and comments
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
High usage of progestin-only injectable contraceptives, which include the intramuscular injectables depo-medroxyprogesterone acetate (DMPA-IM, Depo-Provera) and norethisterone (NET) enanthate (NET-EN or Nur-Isterate), correlates worldwide with areas of high HIV-1 prevalence. Epidemiological data show a significant association between usage of DMPA-IM and increased HIV-1 acquisition but no such association from limited data for NET-EN. Whether MPA and NET have similar effects on HIV-1 acquisition and pathogenesis, and the relationship between these effects and the dose of MPA, are critical issues for women's health and access to suitable and safe contraceptives. We show for the first time that MPA, unlike NET, significantly increases HIV-1 replication in peripheral blood mononuclear cells (PBMCs) and a cervical cell line model. The results provide novel evidence for a biological mechanism whereby MPA, acting via the glucocorticoid receptor (GR), increases HIV-1 replication by at least in part increasing expression of the CCR5 HIV-1 coreceptor on target T-lymphocytes. MPA, unlike NET, also increases activation of T-cells and increases the CD4/CD8 ratio, suggesting that multiple mechanisms are involved in the MPA response. Our data offer strong support for different biological mechanisms for MPA versus NET, due to their differential GR activity. The dose-dependence of the MPA response suggests that significant effects are observed within the range of peak serum levels of progestins in DMPA-IM but not NET-EN users. Dose-response results further suggest that effects of contraceptives containing MPA on HIV-1 acquisition and disease progression may be critically dependent on dose, time after injection and intrinsic factors that affect serum concentrations in women.
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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.