Trial reportPLoS pathogens2014
HIV acquisition is associated with increased antimicrobial peptides and reduced HIV neutralizing IgA in the foreskin prepuce of uncircumcised men.
Trial report in PLoS pathogens, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 33 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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
33 citing papers in PubMed.
- HIV-1-Neutralizing IgA Detected in Genital Secretions of Highly HIV-1-Exposed Seronegative Women on Oral Preexposure Prophylaxis.Journal of virology · 2016Trial
- HIV Transmission and Immunology of the Male Reproductive Tract.American journal of reproductive immunology (New York, N.Y. : 1989) · 2026Review
- Douching Is Associated With Dysregulated Rectal Mucosal Immunity in Sexual Minority Men.The Journal of infectious diseases · 2026Article
- Immunoinformatics approach to engineer a multi-epitope vaccine against SdrG in skin commensal Staphylococcus epidermidis.PloS one · 2026Article
- Article
- Review
- Defensins: defenders of human reproductive health.Human reproduction update · 2023Review
- How Does Voluntary Medical Male Circumcision Reduce HIV Risk?Current HIV/AIDS reports · 2022Review
- Infant Circumcision for Sexually Transmitted Infection Risk Reduction Globally.Global health, science and practice · 2022Article
- Review
- Condomless receptive anal intercourse is associated with markers of mucosal inflammation in a cohort of men who have sex with men in Atlanta, Georgia.Journal of the International AIDS Society · 2021Article
- Environmental Pollutants, Mucosal Barriers, and Pathogen Susceptibility; The Case for Aflatoxin BPathogens (Basel, Switzerland) · 2021Review
- Penile bacteria associated with HIV seroconversion, inflammation, and immune cells.JCI insight · 2021Article
- Antiviral Activities of Human Host Defense Peptides.Current medicinal chemistry · 2020Review
- Intimate Relations: Molecular and Immunologic Interactions BetweenFrontiers in microbiology · 2020Review
- Review
- Mucosal Vaccine Approaches for Prevention of HIV and SIV Transmission.Current immunology reviews · 2019Article
- Generation of a Dual-Target, Safe, Inexpensive Microbicide that Protects Against HIV-1 and HSV-2 Disease.Scientific reports · 2018Article
- The biology of how circumcision reduces HIV susceptibility: broader implications for the prevention field.AIDS research and therapy · 2017Review
- The rectal mucosa and condomless receptive anal intercourse in HIV-negative MSM: implications for HIV transmission and prevention.Mucosal immunology · 2017Article
Corrections and comments
- Erratum issued
Authors and funding
15 authors.
Funding
Abstract
backgroundThe foreskin is the site of most HIV acquisition in uncircumcised heterosexual men. Although HIV-exposed, seronegative (HESN) uncircumcised men demonstrate HIV-neutralizing IgA and increased antimicrobial peptides (AMPs) in the foreskin prepuce, no prospective studies have examined the mucosal immune correlates of HIV acquisition.
methodsTo assess the association of foreskin immune parameters with HIV acquisition, antimicrobial peptides and IgA with the capacity to neutralize a primary clade C HIV strain were quantified by blinded investigators, using sub-preputial swabs collected longitudinally during a randomized trial of male circumcision for HIV prevention in Rakai, Uganda.
resultsParticipants were 99 men who acquired HIV (cases) and 109 randomly selected controls who remained HIV seronegative. At enrollment, 44.4% of cases vs. 69.7% of controls demonstrated IgA neutralization (adjusted OR = 0.31; 95% CI, 0.16-0.61). IgA neutralization was detected in 38.7% of cases and 70.7% of controls at the last seronegative case visit prior to HIV acquisition and the comparable control visit (adjusted OR 0.21; 95% CI, 0.11-0.39). Levels of the α-defensins and secretory leukocyte protease inhibitor (SLPI) were over ten-fold higher in the foreskin prepuce of cases who acquired HIV, both at enrollment (mean 4.43 vs. 3.03 and 5.98 vs. 4.61 log(n) pg/mL, P = 0.005 and 0.009, respectively), and at the last seronegative visit (mean 4.81 vs. 3.15 and 6.46 vs. 5.20 log(n) pg/mL, P = 0.0002 and 0.013).
conclusionsThis prospective, blinded analysis is the first to assess the immune correlates of HIV acquisition in the foreskin. HIV-neutralizing IgA, previously associated with the HESN phenotype, was a biomarker of HIV protection, but other HESN associations correlated with increased HIV acquisition. This emphasizes the importance of prospective epidemiological studies or in vitro tissue studies to define the impact of mucosal parameters on HIV risk.
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