Evidence map›Paper›PMID 31131846›Full record

ArticleClinical infectious diseases : an official publication of the Infectious Diseases Society of America2020

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.

Melanie R Nicol, Prosperity Eneh, Rita Nakalega, Thomas Kaiser, Samuel Kabwigu, Esther Isingel, Mags Beksinska, Craig Sykes, Mary Glenn Fowler, Todd T Brown and 2 more

Registry-linked trialOpen access · bronzeAbstract read
In one paragraph

Article in Clinical infectious diseases : an official publication of the Infectious Diseases Society of America, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT03377608 (Modifiers of Tenofovir Exposure in the Female Genital Tract of African Women on Depo-provera), which is not on this map. Cited by 10 papers.

0numbers the graph read from it
0cells of the map it votes in
10citing papers in PubMed
1.4field-weighted citation impact, top 19% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

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.

2 · The registry

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.

NCT03377608 completednot on this map

Modifiers of Tenofovir Exposure in the Female Genital Tract of African Women on Depo-provera

TypeobservationalSponsorUniversity of MinnesotaRan2017 to 2018Enrolled50ConditionsHIV/AIDS, ContraceptionArmsTenofovir Disoproxil Fumarate, Depo-Provera
3 · Its place in the literature

Who cites it

10 citing papers in PubMed, 16 citations in OpenAlex.

  1. Trial
  2. Article
  3. Article
  4. Review
  5. Article
  6. Article
  7. Article
  8. Article
  9. Review
  10. Understanding and interpreting community sequencing measurements of the vaginal microbiome.BJOG : an international journal of obstetrics and gynaecology · 2020
    Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

12 authors at 5 institutions in 3 countries.

Melanie R NicolDepartment of Experimental and Clinical Pharmacology, University of Minnesota, Minneapolis.
Prosperity EnehDepartment of Experimental and Clinical Pharmacology, University of Minnesota, Minneapolis.
Rita NakalegaMakerere University-John Hopkins University Research Collaboration, Kampala, Uganda.
Thomas KaiserDepartment of Surgery, University of Minnesota, Minneapolis.
Samuel KabwiguMakerere University-John Hopkins University Research Collaboration, Kampala, Uganda.
Esther IsingelMakerere University-John Hopkins University Research Collaboration, Kampala, Uganda.
Mags BeksinskaSchool of Clinical Sciences, University of the Witwatersrand, Durban, South Africa.
Craig SykesDivision of Pharmacotherapy and Experimental Therapeutics, University of North Carolina at Chapel Hill.
Mary Glenn FowlerDepartment of Pathology, John Hopkins University, Baltimore, Maryland.
Todd T BrownDepartment of Medicine, John Hopkins University, Baltimore, Maryland.
Christopher StaleyDepartment of Surgery, University of Minnesota, Minneapolis.
Flavia Kiweewa MatovuMakerere University-John Hopkins University Research Collaboration, Kampala, Uganda.
MUJHU Research Collaboration · UGUniversity of Minnesota · USJohns Hopkins University · USUniversity of North Carolina at Chapel Hill · USUniversity of the Witwatersrand · ZA

Funding

Virology, Immunology, and Microbiology CoreP30AI050410 · NIAID · UNIV OF NORTH CAROLINA CHAPEL HILL · PI DAVID M. MARGOLIS · 2001 to 2026
$76.9M
University of Minnesota Clinical and Translational Science Institute (UMN CTSI)UL1TR002494 · NCATS · UNIVERSITY OF MINNESOTA · PI BLAZAR, BRUCE R, WEISDORF, DANIEL J · 2018 to 2022
$34.9M
The Johns Hopkins University - Uganda Clinical Trials UnitUM1AI069530 · NIAID · JOHNS HOPKINS UNIVERSITY · PI MARY Glenn Fowler, Philippa Musoke · 2012 to 2026
$34.8M
Evaluating Antiretroviral Pharmacology in the Female Genital Tract to Optimize HIV PreventionK08AI134262 · NIAID · UNIVERSITY OF MINNESOTA · PI NICOL, MELANIE RAE · 2018 to 2022
$847k
Bone Mineral Density in a Cohort of Young Women using Depo-provera and TenofovirR01AI118332 · NIAID · MU-JHU CARE · PI MATOVU, FLAVIA KIWEEWA · 2015 to 2019
$687k
NCATS NIH HHS UL1 TR002494NIAID NIH HHS K08 AI134262NIAID NIH HHS P30 AI050410NIAID NIH HHS R01 AI118332NIAID NIH HHS UM1 AI069530
6 · The paper itself

Abstract

backgroundEffective concentrations of antiretrovirals in the female genital tract (FGT) are critical for suppression of viral shedding or effective preexposure prophylaxis. The disposition of tenofovir diphosphate (TFV-DP) and emtricitabine triphosphate (FTC-TP) in the FGT have been previously described. Despite widespread use, however, lamivudine triphosphate (3TC-TP) exposure in the FGT is unknown. Depot medroxyprogesterone acetate (DMPA) and vaginal dysbiosis have been implicated in increased risk of human immunodeficiency virus (HIV) acquisition, but whether they alter TFV-DP or 3TC-TP exposure, and therefore compromise prevention efficacy, is unknown.

methodsFifty premenopausal women living with HIV in Kampala, Uganda, and receiving daily tenofovir disoproxil fumarate/lamivudine were recruited. Ectocervical biopsies were obtained for quantification of TFV-DP and 3TC-TP using liquid chromatography-mass spectrometry. 16S ribosomal RNA gene sequencing was performed on DNA extracted from vaginal swabs. Wilcoxon rank-sum was used to test for differences between contraceptive groups.

results3TC-TP concentrations were on average 17-fold greater than TFV-DP concentrations in cervical tissues. TFV-DP concentrations in cervical biopsies were 76% greater in DMPA users compared with women using nonhormonal contraception (n = 23 per group). Abundance of Lactobacillus in vaginal swabs was correlated with 3TC-TP concentrations in cervical tissues.

conclusionsWe found that TFV-DP concentrations were significantly greater in DMPA users compared with women using nonhormonal contraception, suggesting that prevention efficacy is unlikely to be compromised by DMPA use. Similar to reports of FTC-TP, 3TC-TP exposure was significantly greater than TFV-DP in cervical tissue and was correlated with abundance of Lactobacillus. These data support lamivudine as an option for preexposure prophylaxis. CLINICAL TRIALS REGISTRATION: NCT03377608.

Indexed as

Anti-HIV AgentsHIV InfectionsMicrobiotaPre-Exposure ProphylaxisAdenineCytidine TriphosphateDideoxynucleotidesEmtricitabineFemaleHumansLamivudineMedroxyprogesterone AcetateOrganophosphatesTenofovirUgandaAdenineAnti-HIV AgentsCytidine TriphosphateDideoxynucleotidesEmtricitabineLamivudinelamivudine triphosphateMedroxyprogesterone AcetateOrganophosphatesTenofovirtenofovir diphosphateDMPAHIVlamivudinemicrobiomePrEPtenofovir

Identifiers

PMID31131846
PMCPMC7146007
OpenAlexW2947596755

What OpenQuestion holds

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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.