ArticlePloS one2014
Sex hormones regulate tenofovir-diphosphate in female reproductive tract cells in culture.
Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 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
24 citing papers in PubMed, 26 citations in OpenAlex.
- Single-dose pharmacokinetics of tenofovir alafenamide and its active metabolite in the mucosal tissues.The Journal of antimicrobial chemotherapy · 2017Trial
- PrEP at the site of action in cisgender and transgender women: A pharmacology study of blood and rectal CD4British journal of clinical pharmacology · 2026Article
- Tenofovir, Interferon Pathways, and Mucosal Immunity: Implications for People Living With HIV.American journal of reproductive immunology (New York, N.Y. : 1989) · 2026Review
- Pharmacokinetics of Emtricitabine/Tenofovir Disoproxil Fumarate Among Transgender Adolescents and Young Adults Without HIV Receiving Gender Affirming Hormones.AIDS research and human retroviruses · 2022Observational
- Expression, Activity, and Regulation of Phosphorylating Enzymes in Tissues and Cells Relevant to HIV-1 Sexual Transmission.AIDS research and human retroviruses · 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
- HIV Pathogenesis in the Human Female Reproductive Tract.Current HIV/AIDS reports · 2021Review
- Depot Medroxyprogesterone Acetate and the Vaginal Microbiome as Modifiers of Tenofovir Diphosphate and Lamivudine Triphosphate Concentrations in the Female Genital Tract of Ugandan Women: Implications for Tenofovir Disoproxil Fumarate/Lamivudine in Preexposure Prophylaxis.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2020Article
- Decreased Tenofovir Diphosphate Concentrations in a Transgender Female Cohort: Implications for Human Immunodeficiency Virus Preexposure Prophylaxis.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2019Article
- Transgender women on oral HIV pre-exposure prophylaxis have significantly lower tenofovir and emtricitabine concentrations when also taking oestrogen when compared to cisgender men.Journal of the International AIDS Society · 2019Article
- Epithelial Cells and Fibroblasts from the Human Female Reproductive Tract Accumulate and Release TFV and TAF to Sustain Inhibition of HIV Infection of CD4+ T cells.Scientific reports · 2019Article
- Pharmacology of Antiretrovirals in the Female Genital Tract for HIV Prevention.Journal of clinical pharmacology · 2018Review
- Differences in Local and Systemic TFV PK Among Premenopausal Versus Postmenopausal Women Exposed to TFV 1% Vaginal Gel.Journal of acquired immune deficiency syndromes (1999) · 2018Article
- The role of menopause in tenofovir diphosphate and emtricitabine triphosphate concentrations in cervical tissue.AIDS (London, England) · 2018Article
- Hormonal Contraceptives Differentially Suppress TFV and TAF Inhibition of HIV Infection and TFV-DP in Blood and Genital Tract CD4+ T cells.Scientific reports · 2017Article
- Recent advances in pre-exposure prophylaxis for HIV.BMJ (Clinical research ed.) · 2017Review
- HIV Prevention Among Transgender Populations: Knowledge Gaps and Evidence for Action.Current HIV/AIDS reports · 2017Review
- Tenofovir Inhibits Wound Healing of Epithelial Cells and Fibroblasts from the Upper and Lower Human Female Reproductive Tract.Scientific reports · 2017Article
- Pre-exposure prophylaxis for HIV prevention in women: current perspectives.International journal of women's health · 2017Review
- Pharmacologic Considerations for Preexposure Prophylaxis in Transgender Women.Journal of acquired immune deficiency syndromes (1999) · 2016Review
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
The conflicting results of recent pre-exposure prophylaxis (PrEP) trials utilizing tenofovir (TFV) to prevent HIV infection in women led us to evaluate the accumulation of intracellular TFV-diphosphate (TFV-DP) in cells from the female reproductive tract (FRT) and whether sex hormones influence the presence of TFV-DP in these cells. Following incubation with TFV, isolated epithelial cells, fibroblasts, CD4+ T cells and CD14+ cells from the FRT as well as blood CD4+ T cells and monocyte-derived macrophages convert TFV to TFV-DP. Unexpectedly, we found that TFV-DP concentrations (fmol/million cells) vary significantly with the cell type analyzed and the site within the FRT. Epithelial cells had 5-fold higher TFV-DP concentrations than fibroblasts; endometrial epithelial cells had higher TFV-DP concentrations than cells from the ectocervix. Epithelial cells had 125-fold higher TFV-DP concentrations than FRT CD4+ T cells, which were comparable to that measured in peripheral blood CD4+ T cells. These findings suggest the existence of a TFV-DP gradient in the FRT where epithelial cells > fibroblasts > CD4+ T cells and macrophages. In other studies, estradiol increased TFV-DP concentrations in endometrial and endocervical/ectocervical epithelial cells, but had no effect on fibroblasts or CD4+ T cells from FRT tissues. In contrast, progesterone alone and in combination with estradiol decreased TFV-DP concentrations in FRT CD4+ T cells. Our results suggest that epithelial cells and fibroblasts are a repository of TFV-DP that is under hormonal control. These cells might act either as a sink to decrease TFV availability to CD4+ T cells and macrophages in the FRT, or upon conversion of TFV-DP to TFV increase TFV availability to HIV-target cells. In summary, these results indicate that intracellular TFV-DP varies with cell type and location in the FRT and demonstrate that estradiol and/or progesterone regulate the intracellular concentrations of TFV-DP in FRT epithelial cells and CD4+ T cells.
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