Cabotegravir for HIV Prevention in Cisgender Men and Transgender Women
2021 · paper · Clinical trials
A randomized trial of 4566 men who have sex with men and transgender women comparing injectable cabotegravir every 8 weeks with daily oral tenofovir–emtricitabine for HIV prevention. Cabotegravir was superior (hazard ratio 0.34), though some infections showed integrase inhibitor resistance.
8 findings
Reference or label Methods, Analysis of Drug Concentrations: "...at the first visit at which the participant was determined to be HIV positive and at selected previous visits.17" cites reference 17 (HPTN 077 tail-phase cabotegravir paper) for tenofovir testing in HPTN 083 TDF–FTC seroconverters; reference 18 appears to be intended.
- p. 4 Methods, Analysis of Drug Concentrations, last sentence
HIV positive and at selected previous visits.17
- p. 16 Reference 17
a secondary analysis of the HPTN 077 trial
Only the authors can say what is right here.
Judge's note: Page 4 image shows superscript 17 on this sentence and 18 on the two preceding sentences of the same paragraph. Page 16 image: ref 17 is Landovitz et al., tail-phase safety/PK of cabotegravir in HIV-uninfected adults, secondary analysis of HPTN 077; ref 18 is Marzinke et al., characterization of HIV infection in HPTN 083. The titles make 18 the plausible source, but only the authors can say which was meant, so author_query.
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Reference or label Results, HIV Infection: "Using a prespecified testing algorithm,17 we identified HIV infection in 57 participants" cites reference 17 (HPTN 077 tail-phase pharmacokinetics paper), whereas the Methods cite reference 18 for HIV status determination and adjudication in HPTN 083.
- p. 5 Results, HIV Infection, first sentence
Using a prespecified testing algorithm,17 we identified HIV infection in 57 participants
- p. 16 Reference 17
Tail-phase safety, tolerability, and pharmacokinetics of long-acting injectable cabotegravir in HIV-uninfected adults
- p. 5 Results, HIV Infection, first sentence
Using a prespecified testing algorithm,17
- p. 5 HIV infection
Using a prespecified testing algorithm,17 we identified HIV infection
Only the authors can say what is right here.
Judge's note: Page 5 image shows superscript 17. Page 4 image: the Methods cite 18 for retrospective HIV testing, HIV status determination and end-point adjudication. Page 16: ref 17 is a secondary analysis of a different trial (HPTN 077); ref 18 is the HPTN 083 infection-characterization report. Probably a mis-numbered citation; the authors must confirm. The page-4 'selected previous visits.17' part of this cluster is handled in C001.
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Reference or label Results, HIV Infection: "Detailed descriptions of each case, including virologic and pharmacologic assessments, are presented in a separate report.17" cites reference 17 (HPTN 077 tail-phase paper); the separate report on HPTN 083 infections is reference 18, cited as "a separate report.18" in the Methods.
- p. 6 Results, HIV Infection, 2nd paragraph
are presented in a separate report.17
- p. 16 Reference 17
a secondary analysis of the HPTN 077 trial
- p. 4 Methods, Primary End Points
additional information is provided in a separate report.18
- p. 16 Reference 18
Characterization of HIV infection in cisgender men and transgender women who have sex with men receiving injectable cabotegravir for HIV prevention: HPTN 083
Judge's note: Page 6 image shows superscript 17. Page 4 image: 'additional information is provided in a separate report.18'. Page 16: ref 17 is a 2020 secondary analysis of HPTN 077 in HIV-uninfected adults and cannot hold HPTN 083 case descriptions; ref 18 (Marzinke et al., 'Characterization of HIV infection ... HPTN 083') matches the sentence. Evident fix: 18.
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Reference or label Author affiliations give the country as Brazil for US institutions: "Fred Hutchinson Cancer Research Center, Seattle, Brazil" (Donnell, Hanscom, Cottle, Li, Wang) and "Louisiana State University Health Sciences Center, New Orleans, Brazil" (Clement).
- p. 9 Authors list (D. Donnell, B. Hanscom, L. Cottle; repeated on pp 11, 13, 14)
Fred Hutchinson Cancer Research Center, Seattle, Brazil
- p. 9 Authors list, M.E. Clement
Louisiana State University Health Sciences Center, New Orleans, Brazil
Only the authors can say what is right here.
Judge's note: Rests on outside knowledge: Seattle and New Orleans are in the United States, not Brazil. The page 9 image shows both strings as quoted. The text layer repeats them on PDF page 11 (Li, Wang) and in the Affiliations list on pages 13–14. This looks like an author-manuscript conversion error, but it is printed in this version.
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Reference or label Affiliation for A.H. Gaur reads "St. Jude Children's Research Hospital, Memphis, TN, North Carolina", giving two different states.
- p. 10 Authors list, A.H. Gaur (repeated on p 13)
St. Jude Children's Research Hospital, Memphis, TN, North Carolina
Judge's note: The page 10 image shows the string as quoted. It is internally contradictory (TN and North Carolina in the same line); the trailing 'North Carolina' is evidently spurious. The text layer repeats the string in the Affiliations list on PDF page 13.
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Reference or label Reference 19 prints "National Institutes of Health, 72017 (https://rsc.niaid.nih.gv/sites/default/files/daidsgradingcorrectedv21.pdf)": the domain reads "nih.gv" and the date is garbled as "72017".
- p. 16 Reference 19
National Institutes of Health, 72017 (https://rsc.niaid.nih.gv/sites/default/files/daidsgradingcorrectedv21.pdf)
- p. 16 Reference 19
https://rsc.niaid.nih.gv/sites/default/files/daidsgradingcorrectedv21.pdf
- p. 16 Reference 19
National Institutes of Health, 72017
Judge's note: Viewed page 16. Both defects are on the page image. "72017" is not a valid year (probably a month fused to 2017) and "nih.gv" is not a valid domain, so the URL does not resolve as printed. That ".gov" is the intended domain is evident.
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Reference or label Reference 14 prints an implausible page range, "Lancet HIV2017;4(8):e31–e340"; reference 15 prints "PLoS Med2018;1(11):e002690", which also looks to have lost digits.
- p. 16 Reference 14
Lancet HIV2017;4(8):e31–e340
- p. 16 Ref 14
4(8):e31–e340
- p. 16 Ref 15
PLoS Med2018;1(11):e002690
- p. 16 Ref 16
Nephron1976;1:3–41
Only the authors can say what is right here.
Judge's note: Rests on outside knowledge: the correct first page of reference 14 (reviewers suggest e331) and the correct volume and article number of reference 15 (reviewers suggest 15(11):e1002690) are not in the files. Page 16 prints both strings as quoted. A range of e31–e340 would be about 310 pages for one trial report, so a dropped digit is very likely. Reference 16 (Nephron) is judged separately under C021.
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Reference or label Reference 16 (Cockcroft and Gault) is printed as "Nephron1976;1:3–41.", with volume and first page apparently truncated.
- p. 16 Reference 16
Nephron1976;1:3–41.
- p. 16 Reference 16
Nephron1976;1:3–41
Only the authors can say what is right here.
Judge's note: Rests on outside knowledge: the standard citation is Nephron 1976;16:31–41, which cannot be checked from the files. Page 16 prints "Nephron1976;1:3–41." as quoted. The same reference list shows dropped characters elsewhere (refs 2, 14, 15, 19), which supports truncation. This is a different reference from C020's primary item, so it is not treated as a duplicate.
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10 minor (typos and the like; most checked by the judge only)
Wording Figure 2A numbers at risk start at 2281 (TDF–FTC) and 2280 (cabotegravir), while Figure 1B gives "2247 Were included in the primary efficacy analysis" and 2243, and the text says "71 participants who had no follow-up HIV testing after enrollment were excluded from the primary efficacy analysis".
- p. 19 Figure 2A, No. at Risk, week 0
2281 2132 2081
- p. 18 Figure 1B, bottom boxes
2247 Were included in the primary efficacy analysis
- p. 5 Results, Trial Participants
71 participants who had no follow-up HIV testing after enrollment were excluded from the primary efficacy analysis
Judge's note: Viewed Figure 1B (p18) and Figure 2A (p19). The week-0 at-risk counts equal the intention-to-treat population minus baseline infections only; Figure 1B and the Results text on page 5 subtract a further 34 and 37 with no follow-up testing. The Methods (page 4) define the modified intention-to-treat analysis as excluding only participants with HIV infection at enrollment, which matches Figure 2A. Participants with no follow-up testing contribute no person-time, so the estimates are unaffected. The paper nevertheless gives two sizes for the same analysis population without saying how the 71 are handled in the at-risk row. Either form could be legitimate.
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Wording "No resistance was detected when viral escape or HIV acquisition occurred during the period of cabotegravir decay after the last injection (tail phase; cases A3, B1, B3, and B4)" is unqualified, but Figure 3 shows NNRTI mutations "Y181C, H221Y" for case B1 and "NA" (no genotyping result) for case B4.
- p. 6 Results, Drug Resistance Mutations
No resistance was detected when viral escape or HIV acquisition occurred during the period of cabotegravir decay after the last injection (tail phase; cases A3, B1, B3, and B4)
- p. 21 Figure 3, Panel B, cases B1 and B4
Y181C, H221Y
Only the authors can say what is right here.
Judge's note: Page 20 image, Figure 3 Panel B: B1 is labelled Y181C, H221Y; B3 is WT; B4 is NA; Panel A: A3 is WT. The page 21 caption classes Y181C and H221Y as major NNRTI resistance mutations and defines NA as no genotyping result available. The paragraph opens with INSTI resistance, so 'No INSTI resistance' is probably meant, but as printed the sentence is unqualified and includes a case with no genotype. Wording ambiguity for the authors to resolve.
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Wording Discussion says the finding held in "participants younger than 30 years of age", but the age subgroup analysed in Figure 2B is "≤30 yr" (versus ">30 yr").
- p. 8 Discussion, 1st paragraph
participants younger than 30 years of age
- p. 19 Figure 2B, Age subgroup
≤30 yr
Judge's note: Page 19 image, Figure 2B: age subgroups are ≤30 yr (HR 0.33) and >30 yr (HR 0.38). Page 8 image: Discussion says 'younger than 30 years of age'. Table 1 uses 18–29 yr. No <30 subgroup analysis appears in the article. A minor threshold wording inconsistency; the substance (similar magnitude) is supported.
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Typo "was readjudicated as a base line infection (case A3)": "baseline" is split by a stray space.
- p. 6 Results, HIV Infection, 2nd paragraph
was readjudicated as a base line infection (case A3)
Judge's note: Visible mid-line on the page 6 image ('a base line infection'); the next sentence and the rest of the article print 'baseline'. Not an extraction artefact.
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Typo "Of 10,666 injection-site reactions in the cabote gravir group": "cabotegravir" is split by a stray space.
- p. 7 Results, Injection-Site Reactions
injection-site reactions in the cabote gravir group
Judge's note: Visible mid-line on the page 7 image ('cabote gravir group'). Not an extraction artefact.
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Typo Reference 2 prints "Lancet2020;396239–54." with the separator between volume 396 and pages 239–54 missing.
- p. 15 Reference 2
Lancet2020;396239–54.
- p. 15 Reference 2
Lancet2020;396239–54
Judge's note: Viewed page 15. Reference 2 reads "Lancet2020;396239–54", while neighbouring entries use volume:pages (e.g. "2015;373:2237–46"). The colon is missing in the printed page, so this is not an extraction artefact.
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Typo Acknowledgments name the funder as "the Eunice Kennedy Shriver Institute for Child Health and Human Development", apparently omitting "National" from the institute's name.
- p. 15 Acknowledgments
Eunice Kennedy Shriver Institute for Child Health and Human Development
Only the authors can say what is right here.
Judge's note: Rests on outside knowledge: the official name of the NIH institute is the Eunice Kennedy Shriver National Institute of Child Health and Human Development. The page image (p15) prints the text as quoted, without "National" and with "for" rather than "of". The files contain nothing to check the official name against.
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Typo Reference 15 prints the first author as "andovitz RJ, Li S, Grinsztejn B, et al." with the initial L of Landovitz missing.
- p. 16 Reference 15
andovitz RJ, Li S, Grinsztejn B, et al.
- p. 16 Reference 15
andovitz RJ, Li S, Grinsztejn B
Judge's note: Viewed page 16. Entry 15 begins "andovitz RJ" on the image itself, whereas entry 17 prints "Landovitz RJ, Li S" and the running head prints "Landovitz et al." This is not an extraction artefact. The malformed volume/article number in the same entry is handled under C020.
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Typo Reference 30 prints the third author as "Dombrowksi JC", apparently a transposition of Dombrowski.
- p. 17 Reference 30
Dombrowksi JC
Only the authors can say what is right here.
Judge's note: Rests on outside knowledge: the cited author's surname is spelled Dombrowski. Page 17 prints "Barbee LA, Khosropour CM, Dombrowksi JC, Golden MR." The "-ksi" ending looks like a transposition, but the files contain no other instance of the name to confirm the spelling.
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Typo Figure 3 legend prints "protein-adjusted 90% cabotegravir inhib itory concentration", with a stray space splitting "inhibitory".
- p. 21 Figure 3 legend, last sentence
protein-adjusted 90% cabotegravir inhib itory concentration
Judge's note: Viewed page 21. The gap in "inhib itory" is visible on the page image, in the last sentence of the legend, and is not an extraction artefact.
Second check: none (judge only)