Evidence map›Paper›PMID 25391483›Full record

ArticleScience translational medicine2014

Semen enhances HIV infectivity and impairs the antiviral efficacy of microbicides.

Onofrio Zirafi, Kyeong-Ae Kim, Nadia R Roan, Silvia F Kluge, Janis A Müller, Shibo Jiang, Benjamin Mayer, Warner C Greene, Frank Kirchhoff, Jan Münch

Open access · greenAbstract read
In one paragraph

Article in Science translational medicine, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers.

0numbers the graph read from it
0cells of the map it votes in
48citing papers in PubMed
5.7field-weighted citation impact, top 4% 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

48 citing papers in PubMed, 71 citations in OpenAlex.

  1. Article
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  7. Utilization of Aminoguanidine Prevents Cytotoxic Effects of Semen.International journal of molecular sciences · 2022
    Article
  8. Review
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  11. Review
  12. Semen: A modulator of female genital tract inflammation and a vector for HIV-1 transmission.American journal of reproductive immunology (New York, N.Y. : 1989) · 2021
    Review
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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 5 institutions in 2 countries.

Onofrio ZirafiInstitute of Molecular Virology, Ulm University Medical Center, 89081 Ulm, Germany.
Kyeong-Ae KimInstitute of Molecular Virology, Ulm University Medical Center, 89081 Ulm, Germany.
Nadia R RoanGladstone Institute of Virology and Immunology, University of California, San Francisco, San Francisco, CA 94158, USA. Department of Urology, University of California, San Francisco, San Francisco, CA 94158, USA.
Silvia F KlugeInstitute of Molecular Virology, Ulm University Medical Center, 89081 Ulm, Germany.
Janis A MüllerInstitute of Molecular Virology, Ulm University Medical Center, 89081 Ulm, Germany.
Shibo JiangLindsley F. Kimball Research Institute, New York Blood Center, New York, NY 10065, USA.
Benjamin MayerInstitute of Epidemiology and Medical Biometry, Ulm University, 89081 Ulm, Germany.
Warner C GreeneGladstone Institute of Virology and Immunology, University of California, San Francisco, San Francisco, CA 94158, USA. Departments of Medicine and Microbiology and Immunology, University of California, San Francisco, San Francisco, CA 94158, USA.
Frank KirchhoffInstitute of Molecular Virology, Ulm University Medical Center, 89081 Ulm, Germany.
Jan MünchInstitute of Molecular Virology, Ulm University Medical Center, 89081 Ulm, Germany. jan.muench@uni-ulm.de.
Universität Ulm · DEGladstone Institutes · USNew York Blood Center · USUniversity of California, San Francisco · USZimmer Biomet (Germany) · DE

Funding

Virology CoreP30AI027763 · NIAID · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI STEVEN Grant DEEKS · 1988 to 2026
$93.6M
Viral and Host Factors Promoting Male-to-Female Transmission of HIVP01AI083050 · NIAID · J. DAVID GLADSTONE INSTITUTES · PI GIUDICE, LINDA C, GREENBLATT, RUTH MARTHA · 2009 to 2013
$10.1M
UCSF KURe Career Development ProgramK12DK083021 · NIDDK · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI BASKIN, LAURENCE, CARROLL, PETER R · 2008 to 2017
$5.9M
In vivo Safety and Efficacy of CAP and Combination FilmsU19AI076964 · NIAID · NEW YORK BLOOD CENTER · PI JIANG, SHIBO · 2007 to 2008
$2.3M
Exploring the Role of Semen Amyloids in Promoting HIV Infection and FertilizationK99AI104262 · NIAID · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI ROAN, NADIA R · 2013 to 2013
$133k
NIAID NIH HHS AO 585882NIAID NIH HHS K99 AI104262NIAID NIH HHS K99AI104262NIAID NIH HHS P01 AI083050NIAID NIH HHS P01 AI083050-01NIAID NIH HHS P30 AI027763NIAID NIH HHS U19 AI076964NIDDK NIH HHS 5K12DK083021-04NIDDK NIH HHS K12 DK083021
6 · The paper itself

Abstract

Topically applied microbicides potently inhibit HIV in vitro but have largely failed to exert protective effects in clinical trials. One possible reason for this discrepancy is that the preclinical testing of microbicides does not faithfully reflect the conditions of HIV sexual transmission. We report that candidate microbicides that target HIV components show greatly reduced antiviral efficacy in the presence of semen, the main vector for HIV transmission. This diminished antiviral activity was dependent on the ability of amyloid fibrils in semen to enhance the infectivity of HIV. Thus, the anti-HIV efficacy of microbicides determined in the absence of semen greatly underestimated the drug concentrations needed to block semen-exposed virus. One notable exception was maraviroc. This HIV entry inhibitor targets the host cell CCR5 co-receptor and was highly active against both untreated and semen-exposed HIV. These data help to explain why microbicides have failed to protect against HIV in clinical trials and suggest that antiviral compounds targeting host factors hold promise for further development. These findings also suggest that the in vitro efficacy of candidate microbicides should be determined in the presence of semen to identify the best candidates for the prevention of HIV sexual transmission.

Indexed as

Anti-HIV AgentsAnti-Infective AgentsCell LineCell Line, TumorCell SurvivalDendrimersFemaleHIV-1HIV InfectionsHumansInhibitory Concentration 50PolylysineSemenAnti-HIV AgentsAnti-Infective AgentsastodrimerDendrimersPolylysine

Identifiers

PMID25391483
PMCPMC4372245
OpenAlexW2171925304

What OpenQuestion holds

Textmetadata
LicenceTDM
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 OpenQuestion graph.