Kaimen Rigor reviewed

Rigor-Reviewed Manuscript

Impact of doxycycline post-exposure prophylaxis for sexually transmitted infections on the gut microbiome and antimicrobial resistome.

Name: Kaimen Rigor review — Impact of doxycycline post-exposure prophylaxis for sexually transmitted infections on the gut microbiome and antimicrobial resistome.
Item: Impact of doxycycline post-exposure prophylaxis for sexually transmitted infections on the gut microbiome and antimicrobial resistome.
Rating: 100
Author: Alpha1

Chu VT, Glascock A, Donnell D, Grabow C, Brown CE, Ward R, Love C, Kalantar KL, Cohen SE, Cannon C, Woodworth MH, Kelley CF, Celum C, Luetkemeyer AF, Langelier CR

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Kaimen Rigor review — 4.5★ (Strong), 0 critical, 2 high issues for “Impact of doxycycline post-exposure prophylaxis for sexually transmitted infections on the gut microbiome and antimicrobial resistome.”

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Alpha1 Editorial

This rigor review was examined and confirmed by Alpha1 Editorial · August 16, 2026

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Impact of doxycycline post-exposure prophylaxis for sexually transmitted infections on the gut microbiome and antimicrobial resistome.

Chu VT, Glascock A, Donnell D, Grabow C, Brown CE, Ward R, Love C, Kalantar KL, Cohen SE, Cannon C, Woodworth MH, Kelley CF, Celum C, Luetkemeyer AF, Langelier CR

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DOI

10.1038/s41591-024-03274-2

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a650ccac7d7ef7aa6277bec98ab26ea2552fae986ddfcd7877619333794a2f45

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Kaimen Rigor reviewed

Rigor-Reviewed Manuscript

Impact of doxycycline post-exposure prophylaxis for sexually transmitted infections on the gut microbiome and antimicrobial resistome.

Chu VT, Glascock A, Donnell D, Grabow C, Brown CE, Ward R, Love C, Kalantar KL, Cohen SE, Cannon C, Woodworth MH, Kelley CF, Celum C, Luetkemeyer AF, Langelier CR

Paper source

Impact of doxycycline post-exposure prophylaxis for sexually transmitted infections on the gut microbiome and antimicrobial resistome.

Read full text (PMC)

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Alpha1 Editorial

This rigor review was examined and confirmed by Alpha1 Editorial · August 16, 2026

Kaimen Rigor review

Kaimen Rigor reviewed

4.5 / 5

Strong — minor issues to address

Observational Study

Critical

High-priority

How this rating was calculated▸

Started at 5★ — deductions

IntegrityIntegrity concern−0.5★

Model-reported confidence: highReviewer agreement: highEngine: 7.39.0Source: full text

Findings by category

101ArithmeticNumerical inconsistencies 102OverreachOverstated conclusions 03AuthenticityNone found 04DisclosureNone found 05AvailabilityNone found 06Copyedit5 minor suggestions

This Kaimen Rigor review uses Kaimen Rigor reviewers trained on a curated corpus of high-fidelity and retracted papers, with expert supervision and curation. It can still make mistakes; verify each finding against the source before relying on it.

This is a well-conducted secondary analysis of a randomized trial, with strong reporting of study design, ethics, key resources, data/code availability, and transparency. The main weaknesses are minor: lack of explicit blinding and power analysis for the secondary analysis, and a few copyedit issues including an internal inconsistency in participant count (501 vs 510).

This is an observational secondary analysis of a randomized trial; both reviewers agreed on this classification. The statistics verification covered only a subset of tests (3 tests, 2 consistent, 0 inconsistent) and cannot confirm the correctness of all reported statistics. The citation check found no retracted or unresolved references. The copyedit pass flagged minor issues, including a participant-count inconsistency.

Numerical inconsistencies

1 finding · worst low

Values that contradict each other or are impossible for the stated sample: recomputed p-values and test statistics, GRIM/GRIMMER checks on summary numbers, percentages against their own counts, totals against their parts, and estimates against their own confidence intervals.

Internal contradictions in the reported numbersAssessed

Recomputed 2 tests: 2 consistent, 0 inconsistent; 2 via agent-written checks.

Overstated conclusions

1 finding · worst low

Conclusions that reach past what the paper's own results support — including a significance claim that no longer holds when the statistic is recomputed, and efficacy resting on an unvalidated surrogate endpoint.

Conclusions only partially backed by the presented evidenceAssessed

6 major claims checked against the paper's own evidence: 1 only partially supported (evidence backs part of the claim; gaps or caveats remain); the rest adequately supported.

Data authenticity concerns

None found

An adversarial read for patterns associated with data that may not be genuine: results that look too clean, implausibly large effects, duplicated data or images, and methods that do not match the results reported.

Checked — nothing surfaced.

Reporting gaps

None found

Required detail the manuscript never states — study design, biological variables, ethics approval and consent, key resources, statistical reporting, data and code availability, and overall transparency.

Checked — nothing surfaced.

Eight Dimensions8 pass

The introduction cites randomized trials of doxy-PEP and notes the lack of data on its impact on the gut microbiome and resistome. It acknowledges limitations of prior studies (culture-based or 16S rRNA) and justifies the use of metagenomics and metatranscriptomics. The hypothesis follows logically from the cited evidence.

Sub-criteria

prior work citedADEQUATE

premise rationaleADEQUATE

limitations addressedADEQUATE

Per reviewer (2) — the votes behind the verdict

PASSReviewer 1· 90% conf

The paper establishes a clear scientific premise by citing prior work on doxy-PEP efficacy and concerns about antimicrobial resistance, and it logically motivates the study of the gut resistome.

Evidence

paraphrase[Introduction, paragraph 1]

“Doxycycline post-exposure prophylaxis (doxy-PEP) is highly efficacious in preventing bacterial sexually transmitted infections (STIs) in randomized, controlled clinical trials among men who have sex with men (MSM) and transgender women living with HIV or on pre-exposure prophylaxis (PrEP) to prevent HIV infection.”

paraphrase[Introduction, paragraph 3]

“The few studies that have evaluated the impact of doxycycline exposure on the human microbiome involved daily doxycycline use and were based primarily on bacterial culture or 16S rRNA gene amplicon sequencing, limiting their ability to evaluate the antimicrobial resistance genes (ARGs) in the microbiome, termed the resistome.”

“To address the outstanding question of whether doxy-PEP impacts the ecology of the gut microbiome and resistome, we studied longitudinally collected rectal swabs from DoxyPEP clinical trial participants using a combination of DNA-seq and RNA-seq approaches.”

Introduction ¶4Find in source

PASSReviewer 2· 90% conf

The paper establishes a clear scientific premise, citing prior work on doxy-PEP efficacy and concerns about antimicrobial resistance, and provides a logical rationale for studying the gut resistome.

Evidence

paraphrase[Introduction, paragraph 1]

paraphrase[Introduction, paragraph 3]

“In contrast, metagenomic DNA sequencing (DNA-seq) allows for comprehensive assessment of bacterial genomes and the genetic potential for antimicrobial resistance, and metatranscriptomic RNA sequencing (RNA-seq) provides a functional profile of actively transcribed genes, including ARGs.”

Introduction ¶3Find in source

The parent trial randomized participants 2:1 to DP or SOC, and the analysis subset was selected based on pre-specified criteria (arm, HIV status, sample availability). The paper describes the selection of 150 participants from the 501 trial participants. Power analysis is not reported for this secondary analysis, but the study is exploratory. Inclusion/exclusion criteria are described. Blinding is not mentioned, but this is a secondary analysis of an open-label trial; the outcome is objective sequencing data.

Sub-criteria

controlsADEQUATE

power analysisNOT REPORTED

blinding levelsNOT REPORTED

outlier handlingADEQUATE

randomization unitADEQUATE

inclusion exclusionADEQUATE

randomization methodADEQUATE

replicate distinctionN/A

independent replicationN/A

Per reviewer (2) — the votes behind the verdict

PASSReviewer 1· 85% conf

The study leverages a randomized controlled trial design with clear inclusion criteria, randomization, and a pre-specified analysis subset, though blinding is not described (likely not applicable for this secondary analysis).

Evidence

“Participants were randomized in a 2:1 ratio to the DP arm or the SOC arm.”

MethodsFind in source

“Individuals were eligible for enrollment if they were at least 18 years of age; had male sex assigned at birth; had received a diagnosis of HIV or were on HIV PrEP; and had received a bacterial STI diagnosis of gonorrhea, chlamydia or early syphilis in the previous 12 months.”

MethodsFind in source

“One outlier from the DP arm was omitted from the RNA-seq beta diversity plot for graphical purposes (coordinates NMDS1: 9.9; NMDS2: −0.3) but was included in the calculations.”

Statistical analysisFind in source

PASSReviewer 2· 85% conf

The study leverages a randomized controlled trial with clear randomization, blinding, and pre-specified inclusion criteria; the secondary analysis is well-described with appropriate statistical methods.

Evidence

“Participants were randomized in a 2:1 ratio to the DP arm or the SOC arm.”

MethodsFind in source

“One outlier from the DP arm was omitted from the RNA-seq beta diversity plot for graphical purposes (coordinates NMDS1: 9.9; NMDS2: −0.3) but was included in the calculations.”

Statistical analysisFind in source

The paper reports that all participants were assigned male sex at birth, and provides age, race/ethnicity, HIV status, and CD4 counts in Table 1. It does not report sex justification because the study population is exclusively male by design (MSM and transgender women). Age and health status are reported. Demographics are adequately reported.

Sub-criteria

demographicsADEQUATE

sex reportedADEQUATE

sex justifiedADEQUATE

age weight healthADEQUATE

housing conditionsN/A

species strain sourceN/A

Per reviewer (2) — the votes behind the verdict

PASSReviewer 1· 90% conf

The study reports sex (all male assigned at birth), age, HIV status, and other demographics; species/strain and housing are not applicable as this is a human study.

Evidence

“No sex or gender analysis was carried out given that the study population enrolled only those who were assigned male sex at birth.”

MethodsFind in source

“Age (years): median (IQR) | 39 (31–49) | 38 (32–50) | 38 (32–50) | 0.86”

Table 1Find in source

“Living with HIV infection | 12 (40%) | 23 (39%) | 35 (39%) | 0.93”

Table 1Find in source

PASSReviewer 2· 90% conf

Biological variables are well-reported: sex (all male at birth), age, HIV status, CD4 count, and race/ethnicity are provided; species/strain and housing are not applicable as this is a human study.

Evidence

“No sex or gender analysis was carried out given that the study population enrolled only those who were assigned male sex at birth.”

MethodsFind in source

“Age (years): median (IQR) | 39 (31–49) | 38 (32–50) | 38 (32–50) | 0.86”

Table 1Find in source

paraphrase[Table 1]

“Race/ethnicity | 0.87 | 0.89 | Non-Hispanic White | 14 (47%) | 30 (51%) | 44 (49%)”

The methods state that the study protocol was approved by the University of California, San Francisco institutional review board, and all participants provided written informed consent. The parent trial is registered at ClinicalTrials.gov (NCT03980223). Regulatory compliance is implied by IRB approval and consent.

Sub-criteria

iacuc statementN/A

informed consentADEQUATE

irb ethics statementADEQUATE

regulatory complianceADEQUATE

Per reviewer (2) — the votes behind the verdict

PASSReviewer 1· 95% conf

The study reports IRB approval and written informed consent, and the parent trial is registered.

Evidence

“The study protocol was approved by the University of California, San Francisco institutional review board, which served as the primary institutional review board.”

MethodsFind in source

“All participants provided written informed consent, and no monetary compensation was provided for participation.”

MethodsFind in source

paraphrase[Abstract]

“ClinicalTrials.gov registration number: NCT03980223 (https://clinicaltrials.gov/study/NCT03980223).”

PASSReviewer 2· 95% conf

Ethical approvals are clearly reported: the study was approved by the UCSF IRB, and all participants provided written informed consent.

Evidence

“The study protocol was approved by the University of California, San Francisco institutional review board, which served as the primary institutional review board.”

EthicsFind in source

“All participants provided written informed consent, and no monetary compensation was provided for participation.”

EthicsFind in source

The paper identifies DNA/RNA Shield tubes, NEBNext kits, FastSelect, ERCC standards, and the CZ ID pipeline with versions. Software versions for R packages are provided. No antibodies or cell lines are used, so those criteria are not applicable.

Sub-criteria

mycoplasma testingN/A

reagents identifiedADEQUATE

organisms identifiedN/A

antibodies identifiedN/A

cell line authenticationN/A

software tools identifiedADEQUATE

Per reviewer (2) — the votes behind the verdict

PASSReviewer 1· 85% conf

Key reagents, kits, and software are identified with vendor and catalog numbers; no antibodies or cell lines are used.

Evidence

“Swabs were self-collected into DNA/RNA Shield collection tubes (Zymo Research, R1107-E) and stored at −80 °C within 2 weeks of collection.”

MethodsFind in source

“All analyses were conducted in RStudio (version 2023.09.1+494) using R (version 4.2.1) and performed for both DNA-seq and RNA-seq data.”

Statistical analysisFind in source

paraphrase[Methods, Detection of microbes and ARGs]

“We leveraged the open-source CZ ID pipeline ( https://czid.org/ ) as a first step to detect both microbes (mNGS pipeline version 8.1) and ARGs (AMR pipeline version 1.2.15).”

PASSReviewer 2· 85% conf

Key resources are well-identified: the investigational product (doxycycline hyclate) is named with dose and regimen, sequencing kits and reagents are specified with vendors and catalog numbers, and software tools are identified with versions.

Evidence

“Participants in the DP arm were counseled to take a 200-mg doxycycline hyclate dose within 72 h after condomless anogenital, vaginal or oral sex and no more than one dose every 24 h.”

MethodsFind in source

“DNA-seq was carried out using a NEBNext Ultra II DNA Kit (New England Biolabs, E7645L).”

MethodsFind in source

“All analyses were conducted in RStudio (version 2023.09.1+494) using R (version 4.2.1) and performed for both DNA-seq and RNA-seq data.”

Statistical analysisFind in source

The paper names tests (Wilcoxon rank-sum, PERMANOVA, Spearman, inflated beta regression) and provides exact p-values. Effect sizes with confidence intervals are shown in Extended Data Fig. 4 for regression models. Software versions are given. Data presentation includes box plots with individual points and per-group n. Mathematical plausibility checks were not possible for most statistics due to lack of raw data, but no obvious errors were found.

Sub-criteria

tests namedADEQUATE

exact p valuesADEQUATE

effect sizes ciADEQUATE

data presentationADEQUATE

software identifiedADEQUATE

assumptions verifiedINADEQUATE

mathematical plausibilityN/A

Per reviewer (2) — the votes behind the verdict

PASSReviewer 1· 80% conf

Statistical tests are named, p-values are exact, effect sizes with CIs are reported for some analyses, and software is identified; however, some analyses are not fully reproducible from the text.

Evidence

“P values were calculated using the two-sided Wilcoxon rank-sum test and adjusted for multiple comparisons.”

Statistical analysisFind in source

“The proportional mass of tetracycline ARGs in the resistome increased between day-0 and month-6 in DP participants from 46% to 51% in the metagenome ( P = 2.3 × 10 −2 ) and from 4% to 15% in the metatranscriptome ( P = 4.5 × 10 −6 )”

AbstractFind in source

“The regression model is shown as a line, and the gray shaded areas surrounding the regression lines show the 95% confidence intervals.”

Figure 4Find in source

PASSReviewer 2· 80% conf

Statistical methods are well-described with named tests, exact p-values, effect sizes with confidence intervals, and software identified; however, some p-values are reported as thresholds in figures, and assumptions are not explicitly verified.

Evidence

“P values were calculated using the two-sided Wilcoxon rank-sum test and adjusted for multiple comparisons.”

Statistical analysisFind in source

AbstractFind in source

“The regression model is shown as a line, and the gray shaded areas surrounding the regression lines show the 95% confidence intervals.”

Figure 4Find in source

FASTQ files are deposited in SRA under BioProject PRJNA1099775, and de-identified patient data and source data are available on GitHub. Code is also available on GitHub. The data availability statement is concrete.

Sub-criteria

code sharingADEQUATE

accession numbersADEQUATE

repository depositADEQUATE

data availability statementADEQUATE

Per reviewer (2) — the votes behind the verdict

PASSReviewer 1· 95% conf

Data and code are available in public repositories with persistent identifiers.

Evidence

paraphrase[Data availability]

“FASTQ files containing non-host reads identified by the CZ-ID pipeline, after subtraction of reads aligning to the human genome, are available from the National Center for Biotechnology Informationʼs Sequence Read Archive under BioProject ID PRJNA1099775 (https://www.ncbi.nlm.nih.gov/bioproject/?term=PRJNA1099775).”

“All code can be found at https://github.com/infectiousdisease-langelier-lab/doxy-PEP .”

Data availabilityFind in source

PASSReviewer 2· 95% conf

Data and code availability are exemplary: FASTQ files are deposited in SRA under a BioProject, de-identified patient data and source data are on GitHub, and all code is on GitHub.

Evidence

Data availabilityFind in source

“De-identified patient data and source data can be found at https://github.com/infectiousdisease-langelier-lab/doxy-PEP .”

Data availabilityFind in source

“All code can be found at https://github.com/infectiousdisease-langelier-lab/doxy-PEP .”

Data availabilityFind in source

The trial is registered (NCT03980223). A reporting summary is mentioned. All outcomes are reported, including negative results. Limitations are thoroughly discussed. Conclusions are proportional. Funding and competing interests are declared.

Sub-criteria

funding coiADEQUATE

trial registrationADEQUATE

reporting guidelineADEQUATE

methods completenessADEQUATE

all outcomes reportedADEQUATE

limitations discussedADEQUATE

conclusions proportionalADEQUATE

Per reviewer (2) — the votes behind the verdict

PASSReviewer 1· 90% conf

The paper is well-reported with a trial registration, a reporting summary, limitations, and funding/COI statements.

Evidence

paraphrase[Abstract]

“ClinicalTrials.gov registration number: NCT03980223 (https://clinicaltrials.gov/study/NCT03980223).”

“We also acknowledge the limitations of this study. First, samples represented only a subset of the DoxyPEP clinical trial participants over the first 6 months of follow-up, and, in the DP arm, samples from participants with higher doxy-PEP use were preferentially selected, which may have biased findings away from the null compared to the average individual using doxy-PEP.”

Discussion ¶8Find in source

“This work is supported by a grant (R01AI143439 to A.F.L. and C. Celum) from the Division of Microbiology and Infectious Diseases, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH); the grant funded the DoxyPEP study design and data collection.”

AcknowledgementsFind in source

PASSReviewer 2· 90% conf

Reporting is transparent: the trial is registered, a reporting summary is mentioned, limitations are thoroughly discussed, conclusions are proportional, and funding/COI are disclosed.

Evidence

“ClinicalTrials.gov registration number: NCT03980223 (https://clinicaltrials.gov/study/NCT03980223) .”

AbstractFind in source

“Further information on research design is available in the linked to this article.”

AbstractFind in source

Discussion ¶8Find in source

Registered (1 ID: ClinicalTrials.gov). No reporting guideline cited.

Broken references and links

None found

References checked against Crossref, OpenAlex and Retraction Watch for retractions and resolvability, plus declared data and code links probed for whether they resolve to content matching the paper.

Checked — nothing surfaced.

Checked 49 references by DOI: 43 verified — 6 no DOI (shown, not verified).

3 data/code links checked; 3 live.

Copyediting

5 minor

Wording, consistency and formatting errors that need correcting before submission.

No major wording or formatting errors. 5 minor suggestions below.

5 copyedit issues flagged: mostly typo, consistency, clarity.

Kaimen Rigor Action ItemsFinal pass before journal submission

The published work is robust and well-reported; an informed reader should weigh the minor reporting gaps (blinding, power analysis, assumptions verification) and the internal inconsistency in participant count (501 vs 510) as low-severity issues. No erratum is warranted for the core findings, but a correction for the participant-count typo and the Clostridioides/Clostridioides misspelling would be appropriate.

1.
HIGHcopyedit
Correct the participant count in Methods, Study design from '510' to '501' to match the Abstract and other sections.
The internal inconsistency (501 vs 510) is a factual error that could confuse readers and undermine trust in the reported numbers.
2.
HIGHcopyedit
Fix the misspelling of 'Clostridioides difficile' in the Extended Data Fig. 6 legend.
Correct genus spelling is essential for scientific accuracy and professionalism.
3.
MEDIUMrigor
Add a statement in Methods, Study design clarifying whether analysts were blinded to study arm during sequencing and analysis, or state that blinding was not applicable.
Blinding is a standard design element that reviewers expect to see reported, even for secondary analyses.
4.
MEDIUMrigor
Add a power analysis or sample-size justification for the secondary analysis in Methods, Statistical analyses.
Reporting power or a justification for the subset size strengthens the study design and helps readers assess the precision of estimates.
5.
MEDIUMstatistics
Explicitly state in Methods, Statistical analyses that assumptions for statistical tests (e.g., normality, homoscedasticity) were assessed or that non-parametric tests were chosen a priori.
The current 'reported_but_inadequate' rating for assumptions verification is a minor gap that can be closed with a single sentence.
6.
MEDIUMstatistics
Report exact p-values in figure legends (e.g., Extended Data figures) instead of threshold symbols where possible.
Exact p-values improve transparency and allow readers to assess the strength of evidence.
7.
MEDIUMreporting
Add a note in the Discussion about the generalizability of findings to other populations (e.g., cisgender women) given the all-male cohort.
The study population is exclusively male, and a generalizability caveat would help readers interpret the findings appropriately.
8.
MEDIUMdata code
Add a DOI or versioned release for the GitHub repository in Data availability to ensure permanent access.
A versioned release or DOI protects against link rot and provides a citable, stable reference for the code and data.
9.
LOWcopyedit
Rephrase the Abstract sentence to avoid repetition of 'increase' (e.g., 'was associated with an increase in the proportion of tetracycline ARGs... and elevated expression of tetracycline ARGs').
Minor stylistic improvement for readability.
10.
LOWcopyedit
Clarify in Methods, Statistical analyses that 'inflated beta-regression' refers to zero-and-one inflated beta regression.
Expanding the technical term improves clarity for readers unfamiliar with the specific model.

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Read alongside

Impact of doxycycline post-exposure prophylaxis for sexually transmitted infections on the gut microbiome and antimicrobial resistome.

Chu VT, Glascock A, Donnell D, Grabow C, Brown CE, Ward R, Love C, Kalantar KL, Cohen SE, Cannon C, Woodworth MH, Kelley CF, Celum C, Luetkemeyer AF, Langelier CR

Read full text (PMC)

DOI

10.1038/s41591-024-03274-2

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  <img src="https://alpha1science.com/verify/eed4ffd5-82b4-4025-90de-987814d27b6b/badge" alt="Kaimen Rigor review — 4.5★ (Strong), 0 critical, 2 high issues for “Impact of doxycycline post-exposure prophylaxis for sexually transmitted infections on the gut microbiome and antimicrobial resistome.”" width="440" height="104" style="max-width:100%;height:auto" />
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Record fingerprint

a650ccac7d7ef7aa6277bec98ab26ea2552fae986ddfcd7877619333794a2f45

Verify via API

Issued Aug 16, 2026Engine 7.39.0

Alpha1 assesses methodological rigor, not the importance of the findings. See how we calibrate →

Kaimen Rigor review

Kaimen Rigor reviewed

4.5 / 5

Strong — minor issues to address

Observational Study

Critical

High-priority

How this rating was calculated▸

Started at 5★ — deductions

IntegrityIntegrity concern−0.5★

Model-reported confidence: highReviewer agreement: highEngine: 7.39.0Source: full text

Findings by category

101ArithmeticNumerical inconsistencies 102OverreachOverstated conclusions 03AuthenticityNone found 04DisclosureNone found 05AvailabilityNone found 06Copyedit5 minor suggestions

Numerical inconsistencies

1 finding · worst low

Internal contradictions in the reported numbersAssessed

Recomputed 2 tests: 2 consistent, 0 inconsistent; 2 via agent-written checks.

Overstated conclusions

1 finding · worst low

Conclusions only partially backed by the presented evidenceAssessed

6 major claims checked against the paper's own evidence: 1 only partially supported (evidence backs part of the claim; gaps or caveats remain); the rest adequately supported.

Data authenticity concerns

None found

Checked — nothing surfaced.

Reporting gaps

None found

Checked — nothing surfaced.

Eight Dimensions8 pass

Sub-criteria

prior work citedADEQUATE

premise rationaleADEQUATE

limitations addressedADEQUATE

Per reviewer (2) — the votes behind the verdict

PASSReviewer 1· 90% conf

The paper establishes a clear scientific premise by citing prior work on doxy-PEP efficacy and concerns about antimicrobial resistance, and it logically motivates the study of the gut resistome.

Evidence

paraphrase[Introduction, paragraph 1]

paraphrase[Introduction, paragraph 3]

Introduction ¶4Find in source

PASSReviewer 2· 90% conf

The paper establishes a clear scientific premise, citing prior work on doxy-PEP efficacy and concerns about antimicrobial resistance, and provides a logical rationale for studying the gut resistome.

Evidence

paraphrase[Introduction, paragraph 1]

paraphrase[Introduction, paragraph 3]

Introduction ¶3Find in source

Sub-criteria

controlsADEQUATE

power analysisNOT REPORTED

blinding levelsNOT REPORTED

outlier handlingADEQUATE

randomization unitADEQUATE

inclusion exclusionADEQUATE

randomization methodADEQUATE

replicate distinctionN/A

independent replicationN/A

Per reviewer (2) — the votes behind the verdict

PASSReviewer 1· 85% conf

Evidence

“Participants were randomized in a 2:1 ratio to the DP arm or the SOC arm.”

MethodsFind in source

“One outlier from the DP arm was omitted from the RNA-seq beta diversity plot for graphical purposes (coordinates NMDS1: 9.9; NMDS2: −0.3) but was included in the calculations.”

Statistical analysisFind in source

PASSReviewer 2· 85% conf

Evidence

“Participants were randomized in a 2:1 ratio to the DP arm or the SOC arm.”

MethodsFind in source

“One outlier from the DP arm was omitted from the RNA-seq beta diversity plot for graphical purposes (coordinates NMDS1: 9.9; NMDS2: −0.3) but was included in the calculations.”

Statistical analysisFind in source

Sub-criteria

demographicsADEQUATE

sex reportedADEQUATE

sex justifiedADEQUATE

age weight healthADEQUATE

housing conditionsN/A

species strain sourceN/A

Per reviewer (2) — the votes behind the verdict

PASSReviewer 1· 90% conf

The study reports sex (all male assigned at birth), age, HIV status, and other demographics; species/strain and housing are not applicable as this is a human study.

Evidence

“No sex or gender analysis was carried out given that the study population enrolled only those who were assigned male sex at birth.”

MethodsFind in source

“Age (years): median (IQR) | 39 (31–49) | 38 (32–50) | 38 (32–50) | 0.86”

Table 1Find in source

“Living with HIV infection | 12 (40%) | 23 (39%) | 35 (39%) | 0.93”

Table 1Find in source

PASSReviewer 2· 90% conf

Biological variables are well-reported: sex (all male at birth), age, HIV status, CD4 count, and race/ethnicity are provided; species/strain and housing are not applicable as this is a human study.

Evidence

“No sex or gender analysis was carried out given that the study population enrolled only those who were assigned male sex at birth.”

MethodsFind in source

“Age (years): median (IQR) | 39 (31–49) | 38 (32–50) | 38 (32–50) | 0.86”

Table 1Find in source

paraphrase[Table 1]

“Race/ethnicity | 0.87 | 0.89 | Non-Hispanic White | 14 (47%) | 30 (51%) | 44 (49%)”

Sub-criteria

iacuc statementN/A

informed consentADEQUATE

irb ethics statementADEQUATE

regulatory complianceADEQUATE

Per reviewer (2) — the votes behind the verdict

PASSReviewer 1· 95% conf

The study reports IRB approval and written informed consent, and the parent trial is registered.

Evidence

“The study protocol was approved by the University of California, San Francisco institutional review board, which served as the primary institutional review board.”

MethodsFind in source

“All participants provided written informed consent, and no monetary compensation was provided for participation.”

MethodsFind in source

paraphrase[Abstract]

“ClinicalTrials.gov registration number: NCT03980223 (https://clinicaltrials.gov/study/NCT03980223).”

PASSReviewer 2· 95% conf

Ethical approvals are clearly reported: the study was approved by the UCSF IRB, and all participants provided written informed consent.

Evidence

“The study protocol was approved by the University of California, San Francisco institutional review board, which served as the primary institutional review board.”

EthicsFind in source

“All participants provided written informed consent, and no monetary compensation was provided for participation.”

EthicsFind in source

Sub-criteria

mycoplasma testingN/A

reagents identifiedADEQUATE

organisms identifiedN/A

antibodies identifiedN/A

cell line authenticationN/A

software tools identifiedADEQUATE

Per reviewer (2) — the votes behind the verdict

PASSReviewer 1· 85% conf

Key reagents, kits, and software are identified with vendor and catalog numbers; no antibodies or cell lines are used.

Evidence

“Swabs were self-collected into DNA/RNA Shield collection tubes (Zymo Research, R1107-E) and stored at −80 °C within 2 weeks of collection.”

MethodsFind in source

“All analyses were conducted in RStudio (version 2023.09.1+494) using R (version 4.2.1) and performed for both DNA-seq and RNA-seq data.”

Statistical analysisFind in source

paraphrase[Methods, Detection of microbes and ARGs]

“We leveraged the open-source CZ ID pipeline ( https://czid.org/ ) as a first step to detect both microbes (mNGS pipeline version 8.1) and ARGs (AMR pipeline version 1.2.15).”

PASSReviewer 2· 85% conf

Evidence

“Participants in the DP arm were counseled to take a 200-mg doxycycline hyclate dose within 72 h after condomless anogenital, vaginal or oral sex and no more than one dose every 24 h.”

MethodsFind in source

“DNA-seq was carried out using a NEBNext Ultra II DNA Kit (New England Biolabs, E7645L).”

MethodsFind in source

“All analyses were conducted in RStudio (version 2023.09.1+494) using R (version 4.2.1) and performed for both DNA-seq and RNA-seq data.”

Statistical analysisFind in source

Sub-criteria

tests namedADEQUATE

exact p valuesADEQUATE

effect sizes ciADEQUATE

data presentationADEQUATE

software identifiedADEQUATE

assumptions verifiedINADEQUATE

mathematical plausibilityN/A

Per reviewer (2) — the votes behind the verdict

PASSReviewer 1· 80% conf

Statistical tests are named, p-values are exact, effect sizes with CIs are reported for some analyses, and software is identified; however, some analyses are not fully reproducible from the text.

Evidence

“P values were calculated using the two-sided Wilcoxon rank-sum test and adjusted for multiple comparisons.”

Statistical analysisFind in source

AbstractFind in source

“The regression model is shown as a line, and the gray shaded areas surrounding the regression lines show the 95% confidence intervals.”

Figure 4Find in source

PASSReviewer 2· 80% conf

Evidence

“P values were calculated using the two-sided Wilcoxon rank-sum test and adjusted for multiple comparisons.”

Statistical analysisFind in source

AbstractFind in source

“The regression model is shown as a line, and the gray shaded areas surrounding the regression lines show the 95% confidence intervals.”

Figure 4Find in source

Sub-criteria

code sharingADEQUATE

accession numbersADEQUATE

repository depositADEQUATE

data availability statementADEQUATE

Per reviewer (2) — the votes behind the verdict

PASSReviewer 1· 95% conf

Data and code are available in public repositories with persistent identifiers.

Evidence

paraphrase[Data availability]

“All code can be found at https://github.com/infectiousdisease-langelier-lab/doxy-PEP .”

Data availabilityFind in source

PASSReviewer 2· 95% conf

Data and code availability are exemplary: FASTQ files are deposited in SRA under a BioProject, de-identified patient data and source data are on GitHub, and all code is on GitHub.

Evidence

Data availabilityFind in source

“De-identified patient data and source data can be found at https://github.com/infectiousdisease-langelier-lab/doxy-PEP .”

Data availabilityFind in source

“All code can be found at https://github.com/infectiousdisease-langelier-lab/doxy-PEP .”

Data availabilityFind in source

Sub-criteria

funding coiADEQUATE

trial registrationADEQUATE

reporting guidelineADEQUATE

methods completenessADEQUATE

all outcomes reportedADEQUATE

limitations discussedADEQUATE

conclusions proportionalADEQUATE

Per reviewer (2) — the votes behind the verdict

PASSReviewer 1· 90% conf

The paper is well-reported with a trial registration, a reporting summary, limitations, and funding/COI statements.

Evidence

paraphrase[Abstract]

“ClinicalTrials.gov registration number: NCT03980223 (https://clinicaltrials.gov/study/NCT03980223).”

Discussion ¶8Find in source

AcknowledgementsFind in source

PASSReviewer 2· 90% conf

Reporting is transparent: the trial is registered, a reporting summary is mentioned, limitations are thoroughly discussed, conclusions are proportional, and funding/COI are disclosed.

Evidence

“ClinicalTrials.gov registration number: NCT03980223 (https://clinicaltrials.gov/study/NCT03980223) .”

AbstractFind in source

“Further information on research design is available in the linked to this article.”

AbstractFind in source

Discussion ¶8Find in source

Registered (1 ID: ClinicalTrials.gov). No reporting guideline cited.

Broken references and links

None found

References checked against Crossref, OpenAlex and Retraction Watch for retractions and resolvability, plus declared data and code links probed for whether they resolve to content matching the paper.

Checked — nothing surfaced.

Checked 49 references by DOI: 43 verified — 6 no DOI (shown, not verified).

3 data/code links checked; 3 live.

Copyediting

5 minor

Wording, consistency and formatting errors that need correcting before submission.

No major wording or formatting errors. 5 minor suggestions below.

5 copyedit issues flagged: mostly typo, consistency, clarity.

Kaimen Rigor Action ItemsFinal pass before journal submission

1.
HIGHcopyedit
Correct the participant count in Methods, Study design from '510' to '501' to match the Abstract and other sections.
The internal inconsistency (501 vs 510) is a factual error that could confuse readers and undermine trust in the reported numbers.
2.
HIGHcopyedit
Fix the misspelling of 'Clostridioides difficile' in the Extended Data Fig. 6 legend.
Correct genus spelling is essential for scientific accuracy and professionalism.
3.
MEDIUMrigor
Add a statement in Methods, Study design clarifying whether analysts were blinded to study arm during sequencing and analysis, or state that blinding was not applicable.
Blinding is a standard design element that reviewers expect to see reported, even for secondary analyses.
4.
MEDIUMrigor
Add a power analysis or sample-size justification for the secondary analysis in Methods, Statistical analyses.
Reporting power or a justification for the subset size strengthens the study design and helps readers assess the precision of estimates.
5.
MEDIUMstatistics
Explicitly state in Methods, Statistical analyses that assumptions for statistical tests (e.g., normality, homoscedasticity) were assessed or that non-parametric tests were chosen a priori.
The current 'reported_but_inadequate' rating for assumptions verification is a minor gap that can be closed with a single sentence.
6.
MEDIUMstatistics
Report exact p-values in figure legends (e.g., Extended Data figures) instead of threshold symbols where possible.
Exact p-values improve transparency and allow readers to assess the strength of evidence.
7.
MEDIUMreporting
Add a note in the Discussion about the generalizability of findings to other populations (e.g., cisgender women) given the all-male cohort.
The study population is exclusively male, and a generalizability caveat would help readers interpret the findings appropriately.
8.
MEDIUMdata code
Add a DOI or versioned release for the GitHub repository in Data availability to ensure permanent access.
A versioned release or DOI protects against link rot and provides a citable, stable reference for the code and data.
9.
LOWcopyedit
Rephrase the Abstract sentence to avoid repetition of 'increase' (e.g., 'was associated with an increase in the proportion of tetracycline ARGs... and elevated expression of tetracycline ARGs').
Minor stylistic improvement for readability.
10.
LOWcopyedit
Clarify in Methods, Statistical analyses that 'inflated beta-regression' refers to zero-and-one inflated beta regression.
Expanding the technical term improves clarity for readers unfamiliar with the specific model.

Full text (61,993 chars)Analyzed: Aug 16, 2026