The role of premorbid cognitive performance in the neuropsychological assessment of people with HIV in South Africa

Anna J. Dreyer; John A. Joska; Kevin G. F. Thomas; Caroline Sabin; Alan Winston; Saye Khoo; Sam Nightingale

doi:10.1371/journal.pone.0349942

Peer Review History

Original SubmissionDecember 28, 2025
1 Feb 2026 Decision Letter - Ioannis Liampas, Editor -->PONE-D-25-56373-->-->The role of premorbid cognitive performance in the neuropsychological assessment of people with HIV in South Africa-->-->PLOS One Dear Dr. Dreyer, Thank you for submitting your manuscript to PLOS ONE. After careful consideration, we feel that it has merit but does not fully meet PLOS ONE’s publication criteria as it currently stands. Therefore, we invite you to submit a revised version of the manuscript that addresses the points raised during the review process. Please submit your revised manuscript by Mar 18 2026 11:59PM. If you will need more time than this to complete your revisions, please reply to this message or contact the journal office at plosone@plos.org. When you're ready to submit your revision, log on to https://www.editorialmanager.com/pone/ and select the 'Submissions Needing Revision' folder to locate your manuscript file. 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If you are reporting a retrospective study of medical records or archived samples, please ensure that you have discussed whether all data were fully anonymized before you accessed them and/or whether the IRB or ethics committee waived the requirement for informed consent. If patients provided informed written consent to have data from their medical records used in research, please include this information. 3. Thank you for stating in your Funding Statement: “Research reported in this publication was supported by the South African Medical Research Council, with funds received from the South African National Department of Health and the UK Medical Research Council, with funds received from the UK Government’s Newton Fund, awarded to Sam Nightingale.” Please provide an amended statement that declares all the funding or sources of support (whether external or internal to your organization) received during this study, as detailed online in our guide for authors at http://journals.plos.org/plosone/s/submit-now. Please also include the statement “There was no additional external funding received for this study.” in your updated Funding Statement. Please include your amended Funding Statement within your cover letter. We will change the online submission form on your behalf. 4. 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Data are available on request from the authors for researchers who meet the criteria for access to confidential data. All PLOS journals now require all data underlying the findings described in their manuscript to be freely available to other researchers, either 1. In a public repository, 2. Within the manuscript itself, or 3. Uploaded as supplementary information. This policy applies to all data except where public deposition would breach compliance with the protocol approved by your research ethics board. If your data cannot be made publicly available for ethical or legal reasons (e.g., public availability would compromise patient privacy), please explain your reasons on resubmission and your exemption request will be escalated for approval. 6. Please include captions for your Supporting Information files at the end of your manuscript, and update any in-text citations to match accordingly. 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[Note: HTML markup is below. Please do not edit.] Reviewers' comments: Reviewer's Responses to Questions -->Comments to the Author 1. Is the manuscript technically sound, and do the data support the conclusions? The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented. --> Reviewer #1: Partly Reviewer #2: Yes ******** -->2. Has the statistical analysis been performed appropriately and rigorously? --> Reviewer #1: Yes Reviewer #2: Yes ****** -->3. Have the authors made all data underlying the findings in their manuscript fully available? The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.--> Reviewer #1: Yes Reviewer #2: No ****** -->4. Is the manuscript presented in an intelligible fashion and written in standard English? PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.--> Reviewer #1: Yes Reviewer #2: Yes ****** -->5. Review Comments to the Author Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)--> Reviewer #1: 1) Initial assessment: The manuscript presents a technically coherent body of work grounded in established methodologies and internally consistent analytical procedures. The data, as presented, support the primary empirical observations and intermediate inferences. However, several higher-order conclusions would benefit from clearer delimitation between empirically supported findings and theoretical or interpretive extensions. With minor revisions clarifying the scope and status of such claims, the conclusions would be appropriately supported by the data. 2) Secondary assessment: This manuscript presents an ambitious and interdisciplinary contribution that integrates empirical analysis with a broader theoretical framework. The work is technically sound, and the analyses are competently executed. To strengthen suitability for publication in a general scientific journal, I recommend minor revisions that more explicitly distinguish between empirically supported results and higher-order theoretical interpretation. In particular, clarifying which claims are directly supported by data versus those offered as conceptual models or hypotheses would improve falsifiability and interpretive precision. Additional minor refinements to statistical reporting transparency and the Data Availability Statement would further enhance reproducibility and clarity. These suggested revisions do not require additional experimentation, but rather improved framing and delineation of scope. With these adjustments, the manuscript would meet the journal’s criteria for technical soundness and clarity. Reviewer #2: The paper is well-written and advances our understanding of the influence of psychosocial factors, premorbid cognitive performance and cognitive performance in people with HIV. However, a few minor corrections could enhance the quality of the paper. 1. Please ensure all abbreviations are written out the first time they appear, in the abstract and main text. 2. Line 54: For readers unfamiliar with the field, “neuroHIV” may be a new term and could benefit from a brief explanation. 3. Line 61-62: Suggestion to rephrase as “…, clustered into 3 components by PCA”, as the current phrasing suggests you perform the PCA in the current study. 4. Line 70: Typo? “ps” should likely be “p” 5. Introduction: To improve readability you could consider linking the aim of the present study to your previous work and clarifying what it adds. Suggestion: "Building on our previous findings that childhood psychosocial adversity contributes to observed cognitive differences between people with and without HIV, the present study introduces an estimate of premorbid cognitive performance to further clarify these associations.” 6. Line 124: Suggest rephrasing “the associations” to “its association” to clearly indicate you are referring to premorbid cognitive performance. 7. Line 125: Original sentence: “We hypothesized that premorbid cognitive performance would relate to more adverse psychosocial in people with HIV, …” Suggestion: “… worse premorbid cognitive performance…” To clarify the direction of association. In addition, this sentence reads like you expect stronger associations specifically among people with HIV compared to people without HIV. This requires further clarification. Otherwise, I suggest rephrasing the hypothesis without implying differential effects by HIV status. 8. Line 160: Was a formal translation method used for the measures? If not, could this introduce potential psychometric issues? 9. Line 149: Suggestion to shortly explain the rationale for these exclusion criteria. Is it due to their expected associations with the cognition outcome measures? 10. Line 321: Appears to be an extra closing parenthesis “)”. 11. Page 20: Table 3 layout differs from the previous tables. 12. Page 21 (line numbers are missing): The last sentence of the first paragraph contains a misplaced “)”. 13. Page 29: Reference 23 contains an extra or misplaced “[”. ****** -->6. PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files. If you choose “no”, your identity will remain anonymous but your review may still be made public. Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy.--> Reviewer #1: Yes: Jacob A. Eder, PhD Reviewer #2: No ******** [NOTE: If reviewer comments were submitted as an attachment file, they will be attached to this email and accessible via the submission site. Please log into your account, locate the manuscript record, and check for the action link "View Attachments". If this link does not appear, there are no attachment files.] To ensure your figures meet our technical requirements, please review our figure guidelines: https://journals.plos.org/plosone/s/figures You may also use PLOS’s free figure tool, NAAS, to help you prepare publication quality figures: https://journals.plos.org/plosone/s/figures#loc-tools-for-figure-preparation. NAAS will assess whether your figures meet our technical requirements by comparing each figure against our figure specifications. --> Attachments Attachment Submitted filename: Reviewer Annotations.pdf https://doi.org/10.1371/journal.pone.0349942.r001
Revision 1
24 Apr 2026 Author Response Academic Editors’ comments: 1. Please ensure that your manuscript meets PLOS ONE's style requirements, including those for file naming. The PLOS ONE style templates can be found athttps://url.za.m.mimecastprotect.com/s/YSWDCBgX56fVXx4K5h1uKI2Lgif and https://url.za.m.mimecastprotect.com/s/sRoACDRZ58iBL7VAlhRC8IjjY4. Response: Thank you for the links to the PLOS ONE style templates. We have revised our manuscript accordingly and it now meets the style requirements. 2. Please provide additional details regarding participant consent. In the ethics statement in the Methods and online submission information, please ensure that you have specified (1) whether consent was informed and (2) what type you obtained (for instance, written or verbal, and if verbal, how it was documented and witnessed). If your study included minors, state whether you obtained consent from parents or guardians. If the need for consent was waived by the ethics committee, please include this information. If you are reporting a retrospective study of medical records or archived samples, please ensure that you have discussed whether all data were fully anonymized before you accessed them and/or whether the IRB or ethics committee waived the requirement for informed consent. If patients provided informed written consent to have data from their medical records used in research, please include this information. Response: We have amended the manuscript to provide all relevant additional details regarding participant consent. Please refer to the ethics statement on page 9, lines 178-180 of the ‘Revised Manuscript with Track Changes’. 3. Thank you for stating in your Funding Statement: “Research reported in this publication was supported by the South African Medical Research Council, with funds received from the South African National Department of Health and the UK Medical Research Council, with funds received from the UK Government’s Newton Fund, awarded to Sam Nightingale.” Please provide an amended statement that declares all the funding or sources of support (whether external or internal to your organization) received during this study, as detailed online in our guide for authors at https://url.za.m.mimecastprotect.com/s/dKkGCElX5xiW8wDx5ixFQI7LO7Y. Please also include the statement “There was no additional external funding received for this study.” in your updated Funding Statement. Please include your amended Funding Statement within your cover letter. We will change the online submission form on your behalf. Response: We have amended the funding statement to include all sources of funding. Please refer to the funding statement on the title page. 4. Thank you for stating the following financial disclosure: “Research reported in this publication was supported by the South African Medical Research Council, with funds received from the South African National Department of Health and the UK Medical Research Council, with funds received from the UK Government’s Newton Fund, awarded to Sam Nightingale.” Please state what role the funders took in the study. If the funders had no role, please state: "The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript." If this statement is not correct you must amend it as needed. Please include this amended Role of Funder statement in your cover letter; we will change the online submission form on your behalf. Response: We have amended the funding statement to include the role of the funder. Please refer to the funding statement on the title page. 5. In the online submission form, you indicated that data cannot be shared publicly because it contains personal patient information. Data are available on request from the authors for researchers who meet the criteria for access to confidential data. All PLOS journals now require all data underlying the findings described in their manuscript to be freely available to other researchers, either 1. In a public repository, 2. Within the manuscript itself, or 3. Uploaded as supplementary information. This policy applies to all data except where public deposition would breach compliance with the protocol approved by your research ethics board. If your data cannot be made publicly available for ethical or legal reasons (e.g., public availability would compromise patient privacy), please explain your reasons on resubmission and your exemption request will be escalated for approval. Response: Our dataset contains highly sensitive information, including detailed psychosocial and socioeconomic variables from both childhood and adulthood, as well as HIV status, collected from patients attending a single clinic in Gugulethu, Cape Town. This is a vulnerable population, and due to the granularity and combination of variables, there is a risk of indirect re-identification even after de-identification. Public deposition of these data would therefore compromise participant confidentiality and would not be consistent with the conditions under which ethical approval was obtained or with participants’ informed consent. In line with PLOS policy, we are committed to data transparency while protecting participant privacy. The data are therefore available upon reasonable request from the authors for researchers who meet the criteria for access to confidential data, subject to appropriate data use agreements and, where necessary, institutional ethical approval. 6. Please include captions for your Supporting Information files at the end of your manuscript, and update any in-text citations to match accordingly. Please see our Supporting Information guidelines for more information: https://url.za.m.mimecastprotect.com/s/Ff3oCGZXj8tJNrM45trHJIB_2dq. Response: Our manuscript has no Supporting Information files. 7. If the reviewer comments include a recommendation to cite specific previously published works, please review and evaluate these publications to determine whether they are relevant and should be cited. There is no requirement to cite these works unless the editor has indicated otherwise. Response: The reviewers did not recommend citing any previously published works. 8. Please review your reference list to ensure that it is complete and correct. If you have cited papers that have been retracted, please include the rationale for doing so in the manuscript text, or remove these references and replace them with relevant current references. Any changes to the reference list should be mentioned in the rebuttal letter that accompanies your revised manuscript. If you need to cite a retracted article, indicate the article’s retracted status in the References list and also include a citation and full reference for the retraction notice. Response: We have reviewed our reference list, and it is complete and correct. Reviewers' comments: Reviewer #1: 1) Initial assessment: The manuscript presents a technically coherent body of work grounded in established methodologies and internally consistent analytical procedures. The data, as presented, support the primary empirical observations and intermediate inferences. However, several higher-order conclusions would benefit from clearer delimitation between empirically supported findings and theoretical or interpretive extensions. With minor revisions clarifying the scope and status of such claims, the conclusions would be appropriately supported by the data. 2) Secondary assessment: This manuscript presents an ambitious and interdisciplinary contribution that integrates empirical analysis with a broader theoretical framework. The work is technically sound, and the analyses are competently executed. To strengthen suitability for publication in a general scientific journal, I recommend minor revisions that more explicitly distinguish between empirically supported results and higher-order theoretical interpretation. In particular, clarifying which claims are directly supported by data versus those offered as conceptual models or hypotheses would improve falsifiability and interpretive precision. Additional minor refinements to statistical reporting transparency and the Data Availability Statement would further enhance reproducibility and clarity. These suggested revisions do not require additional experimentation, but rather improved framing and delineation of scope. With these adjustments, the manuscript would meet the journal’s criteria for technical soundness and clarity. Response: Regarding explicitly distinguishing between empirically supported results and higher-order theoretical interpretations: Thank you for this useful suggestion. The results section only has empirical results. The Discussion section includes speculations about the theoretical implications of these findings. We have amended the Discussion section to more explicitly distinguish between empirically supported results and higher-order theoretical interpretation and revised the manuscript accordingly. See line 387, page 24; line 396, page 25; and line 438, page 26 of the ‘Revised Manuscript with Track Changes’. Regarding the Data Availability Statement: Our dataset contains highly sensitive information, including detailed psychosocial and socioeconomic variables from both childhood and adulthood, as well as HIV status, collected from patients attending a single clinic in Gugulethu, Cape Town. This is a vulnerable population, and due to the granularity and combination of variables, there is a risk of indirect re-identification even after de-identification. Public deposition of these data would therefore compromise participant confidentiality and would not be consistent with the conditions under which ethical approval was obtained or with participants’ informed consent. In line with PLOS policy, we are committed to data transparency while protecting participant privacy. The data are therefore available upon reasonable request from the authors for researchers who meet the criteria for access to confidential data, subject to appropriate data use agreements and, where necessary, institutional ethical approval. Reviewer #2: The paper is well-written and advances our understanding of the influence of psychosocial factors, premorbid cognitive performance and cognitive performance in people with HIV. However, a few minor corrections could enhance the quality of the paper. 1. Please ensure all abbreviations are written out the first time they appear, in the abstract and main text. Response: We have reviewed the manuscript and ensured abbreviations were written in full when they first appear in the abstract and manuscript. For example see amendment to line 67, page 4 of the ‘Revised Manuscript with Track Changes’. 2. Line 54: For readers unfamiliar with the field, “neuroHIV” may be a new term and could benefit from a brief explanation. Response: We have amended the manuscript to include this information. See lines 63, page 4 and lines 458-459, page 27 of the ‘Revised Manuscript with Track Changes’. 3. Line 61-62: Suggestion to rephrase as “…, clustered into 3 components by PCA”, as the current phrasing suggests you perform the PCA in the current study. Response: We have amended the abstract to include this clarification: ‘clustered using principal component analysis in prior analyses’ (see lines 71-72, page 4 of the ‘Revised Manuscript with Track Changes’). 4. Line 70: Typo? “ps” should likely be “p” Response: This is not a typo, ‘ps’ is the plural for ‘p’, there were multiple p-values below .002. We have italicised the ‘s’ to clarify this. See line 80, page 4 of the ‘Revised Manuscript with Track Changes’. 5. Introduction: To improve readability you could consider linking the aim of the present study to your previous work and clarifying what it adds. Suggestion: "Building on our previous findings that childhood psychosocial adversity contributes to observed cognitive differences between people with and without HIV, the present study introduces an estimate of premorbid cognitive performance to further clarify these associations.” Response: Thank you for this suggestion. We have added the suggested sentence to the manuscript. See lines 133-136, page 7 of the ‘Revised Manuscript with Track Changes’. 6. Line 124: Suggest rephrasing “the associations” to “its association” to clearly indicate you are referring to premorbid cognitive performance. Response: We have made this correction in the manuscript. See line 137, page 7 of the ‘Revised Manuscript with Track Changes’. 7. Line 125: Original sentence: “We hypothesized that premorbid cognitive performance would relate to more adverse psychosocial in people with HIV, …” Suggestion: “… worse premorbid cognitive performance…” To clarify the direction of association. In addition, this sentence reads like you expect stronger associations specifically among people with HIV compared to people without HIV. This requires further clarification. Otherwise, I suggest rephrasing the hypothesis without implying differential effects by HIV status. Response: We have amended the sentence to clarify the direction of association. See line 139, page 7 of the ‘Revised Manuscript with Track Changes’. 8. Line 160: Was a formal translation method used for the measures? If not, could this introduce potential psychometric issues? Response: We used a formal translation method. For all measures used in study, we used the standard forward–backward translation procedure to ensure conceptual and linguistic equivalence. We have amended the manuscript to include this information. See lines 174-175, page 9 of the ‘Revised Manuscript with Track Changes’. 9. Line 149: Suggestion to shortly explain the rationale for these exclusion criteria. Is it due to their expected associations with the cognition outcome measures? Response: The Reviewer is correct. We have amended the manuscript to include this information. See lines 162-163, page 9 of the ‘Revised Manuscript with Track Changes’. 10. Line 321: Appears to be an extra closing parenthesis “)”. Response: We have removed this additional parenthesis, see line 344, page 21 of the ‘Revised Manuscript with Track Changes’. 11. Page 20: Table 3 layout differs from the previous tables. Response: We have edited table 3 so it has the same formatting as the other tables. See page 22 of the ‘Revised Manuscript with Track Changes’. 12. Page 21 (line numbers are missing): The last sentence of the first paragraph contains a misplaced “)”. Response: We have emended the manuscript to includes line numbers throughout and removed the additional parenthesis on line 359, page 23 of the ‘Revised Manuscript with Track Changes’. 13. Page 29: Reference 23 contains an extra or misplaced “[”. Response: We have removed the misplaced square bracket. See line 525, page 31 of the ‘Revised Manuscript with Track Changes’. Attachments Attachment Submitted filename: Response to the Reviewers.docx https://doi.org/10.1371/journal.pone.0349942.r002
8 May 2026 Decision Letter - Ioannis Liampas, Editor The role of premorbid cognitive performance in the neuropsychological assessment of people with HIV in South Africa PONE-D-25-56373R1 Dear Dr. Dreyer, We’re pleased to inform you that your manuscript has been judged scientifically suitable for publication and will be formally accepted for publication once it meets all outstanding technical requirements. Within one week, you’ll receive an e-mail detailing the required amendments. When these have been addressed, you’ll receive a formal acceptance letter and your manuscript will be scheduled for publication. An invoice will be generated when your article is formally accepted. Please note, if your institution has a publishing partnership with PLOS and your article meets the relevant criteria, all or part of your publication costs will be covered. 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If the authors have adequately addressed your comments raised in a previous round of review and you feel that this manuscript is now acceptable for publication, you may indicate that here to bypass the “Comments to the Author” section, enter your conflict of interest statement in the “Confidential to Editor” section, and submit your "Accept" recommendation.--> Reviewer #1: All comments have been addressed Reviewer #2: All comments have been addressed ******** -->2. Is the manuscript technically sound, and do the data support the conclusions? The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented. --> Reviewer #1: Yes Reviewer #2: (No Response) ****** -->3. Has the statistical analysis been performed appropriately and rigorously? --> Reviewer #1: Yes Reviewer #2: (No Response) ****** -->4. Have the authors made all data underlying the findings in their manuscript fully available? The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.--> Reviewer #1: Yes Reviewer #2: (No Response) ****** -->5. Is the manuscript presented in an intelligible fashion and written in standard English? PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.--> Reviewer #1: Yes Reviewer #2: (No Response) ****** -->6. Review Comments to the Author Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)--> Reviewer #1: Thank you for your revisions; I know the corrections are arduous, wherever they are necessary in our field, especially in a modern age of technological innovation. I appreciate you making the requested corrections, and I wish you the best. Dr. Jacob Eder Reviewer #2: (No Response) ****** -->7. PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files. If you choose “no”, your identity will remain anonymous but your review may still be made public. Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy.--> Reviewer #1: Yes: Jacob Albert Eder Reviewer #2: No ******** https://doi.org/10.1371/journal.pone.0349942.r003
Formally Accepted
Acceptance Letter - Ioannis Liampas, Editor PONE-D-25-56373R1 PLOS One Dear Dr. Dreyer, I'm pleased to inform you that your manuscript has been deemed suitable for publication in PLOS One. Congratulations! Your manuscript is now being handed over to our production team. At this stage, our production department will prepare your paper for publication. This includes ensuring the following: * All references, tables, and figures are properly cited * All relevant supporting information is included in the manuscript submission, * There are no issues that prevent the paper from being properly typeset You will receive further instructions from the production team, including instructions on how to review your proof when it is ready. Please keep in mind that we are working through a large volume of accepted articles, so please give us a few days to review your paper and let you know the next and final steps. Lastly, if your institution or institutions have a press office, please let them know about your upcoming paper now to help maximize its impact. If they'll be preparing press materials, please inform our press team within the next 48 hours. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information, please contact onepress@plos.org. You will receive an invoice from PLOS for your publication fee after your manuscript has reached the completed accept phase. If you receive an email requesting payment before acceptance or for any other service, this may be a phishing scheme. Learn how to identify phishing emails and protect your accounts at https://explore.plos.org/phishing. If we can help with anything else, please email us at customercare@plos.org. Thank you for submitting your work to PLOS ONE and supporting open access. Kind regards, PLOS ONE Editorial Office Staff on behalf of Dr. Ioannis Liampas Academic Editor PLOS One https://doi.org/10.1371/journal.pone.0349942.r004

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