Evidence map›Paper›PMID 36101483›Full record

ArticleThe Journal of antimicrobial chemotherapy2022

A post-mortem analysis of tenofovir, lamivudine, efavirenz and fluconazole penetration in female genital tissues.

Fan Wang, Olivie C Namuju, Katelyn A Pastick, Kizito Abdusalaamu, Usha Mishra, Lindsey Collins, David R Boulware, Robert Lukande, David B Meya, Melanie R Nicol

Open access · greenAbstract read
In one paragraph

Article in The Journal of antimicrobial chemotherapy, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
0.2field-weighted citation impact, top 49% 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.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

2 citing papers in PubMed, 3 citations in OpenAlex.

  1. Article
  2. Article
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

10 authors at 3 institutions in 2 countries.

Fan WangDepartment of Experimental and Clinical Pharmacology, University of Minnesota, Minneapolis, MN, USA.
Olivie C NamujuInfectious Disease Institute, Kampala, Uganda.
Katelyn A PastickDepartment of Medicine, University of Minnesota, Minneapolis, MN, USA.ORCID 0000-0002-1306-1713
Kizito AbdusalaamuInfectious Disease Institute, Kampala, Uganda.
Usha MishraDepartment of Experimental and Clinical Pharmacology, University of Minnesota, Minneapolis, MN, USA.
Lindsey CollinsDepartment of Experimental and Clinical Pharmacology, University of Minnesota, Minneapolis, MN, USA.
David R BoulwareDepartment of Medicine, University of Minnesota, Minneapolis, MN, USA.ORCID 0000-0002-4715-0060
Robert LukandeMakerere University, Kampala, Uganda.
David B MeyaDepartment of Medicine, University of Minnesota, Minneapolis, MN, USA.
Melanie R NicolDepartment of Experimental and Clinical Pharmacology, University of Minnesota, Minneapolis, MN, USA.ORCID 0000-0001-5513-5509
University of Minnesota · USInfectious Diseases Institute · UGMakerere University · UG

Funding

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
Improving Diagnostics and Neurocognitive Outcomes in HIV/AIDS-related MeningitisR01NS086312 · NINDS · UNIVERSITY OF MINNESOTA · PI David R Boulware, David Bisagaya Meya · 2013 to 2026
$8.3M
Operational Research for Cryptococcal Antigen Screening (ORCAS) of HIV PatientsU01AI125003 · NIAID · UNIVERSITY OF MINNESOTA · PI BOULWARE, DAVID R, MEYA, DAVID BISAGAYA · 2016 to 2020
$3.4M
Evaluating Antiretroviral Pharmacology in the Female Genital Tract to Optimize HIV PreventionK08AI134262 · NIAID · UNIVERSITY OF MINNESOTA · PI NICOL, MELANIE RAE · 2018 to 2022
$847k
Medical Student Summer Research Program in Infection and ImmunityT35AI118620 · NIAID · UNIVERSITY OF MINNESOTA · PI MUELLER, DANIEL L · 2015 to 2025
$351k
Pharmacology of Antiretrovirals in Anatomical Brain Tissue among persons with chronic HIV infectionR21NS108344 · NINDS · UNIVERSITY OF MINNESOTA · PI LUKANDE, ROBERT, NICOL, MELANIE RAE · 2018 to 2019
$341k
NCATS NIH HHS UL1 TR002494NIAID NIH HHS K08 AI134262NIAID NIH HHS T35 AI118620NIAID NIH HHS U01 AI125003NINDS NIH HHS R01 NS086312NINDS NIH HHS R21 NS108344
6 · The paper itself

Abstract

backgroundOptimal penetration of anti-infectives in the female genital tract (FGT) is paramount in the treatment and prevention of infectious diseases. While exposure of anti-infectives in lower FGT tissues (e.g. cervix, vagina) has been described, little data exist on upper genital tissues (e.g. ovary, uterus).

methodsAutopsies were performed and post-mortem tissues were collected within 24 h of death for female participants with advanced HIV in Uganda (n = 27). Tenofovir, lamivudine, efavirenz and fluconazole concentrations were measured using LC-MS/MS in plasma, ovarian, uterine, cervical and vaginal tissues. Tissue penetration was calculated as tissue-to-plasma concentration ratios (TPRs).

resultsTPRs of tenofovir, lamivudine and fluconazole were highest in vaginal tissue (medians 1.86, 1.83 and 0.94, respectively), while the TPR of efavirenz was highest in ovarian tissue (median 0.65). With cervix as a reference compartment, vaginal TPRs were significantly higher than cervical for all four drugs; TPRs of efavirenz in uterine and ovarian compartments were also significantly higher than cervical. Most of the post-mortem FGT samples had a TPR of greater than 1 for tenofovir and lamivudine, while less than 50% had a TPR of greater than 1 for both efavirenz and fluconazole.

conclusionsPenetration of anti-infectives was not homogeneous among the FGT compartments. Approximately 70% of FGT tissues had a TPR of greater than 1 for tenofovir and lamivudine, favouring the prevention of local HIV replication and transmission in the FGT.

Indexed as

Anti-HIV AgentsHIV InfectionsAlkynesAutopsyBenzoxazinesChromatography, LiquidCyclopropanesFemaleFluconazoleGenitalia, FemaleHumansLamivudineTandem Mass SpectrometryTenofovirAlkynesAnti-HIV AgentsBenzoxazinesCyclopropanesefavirenzFluconazoleLamivudineTenofovir

Identifiers

PMID36101483
PMCPMC10205621
OpenAlexW4295761139

What Socratic holds

Textmetadata
Read underepoch 390

Registered trials

None linked

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 Socratic graph.