Molecular and spatial epidemiology of HCV among people who inject drugs in Boston, Massachusetts

Thomas J. Stopka; Omar Yaghi; Min Li; Elijah Paintsil; Kenneth Chui; David Landy; Robert Heimer

doi:10.1371/journal.pone.0266216

Peer Review History

Original SubmissionMarch 15, 2022
22 Apr 2022 Decision Letter - Joël Mossong, Editor PONE-D-22-07761Molecular and spatial epidemiology of HCV among people who inject drugs in Boston, MassachusettsPLOS ONE Dear Dr. Heimer, 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. ==============================The two reviewers made many constructive comments by which your manuscript could be improved. Please address all of them before resubmitting, in particular by also making sequence data available on public repositories. ============================== Please submit your revised manuscript by Jun 06 2022 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. 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Support for Dr. Heimer was provided through Grant Number R01DA030420 from the National Institute on Drug Abuse. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institute of Allergy and Infectious Diseases or the National Institute of Health." We note that you have provided funding information. However, funding information should not appear in the Funding section or other areas of your manuscript. We will only publish funding information present in the Funding Statement section of the online submission form. Please remove any funding-related text from the manuscript and let us know how you would like to update your Funding Statement. Currently, your Funding Statement reads as follows: "The research was funded by an internal grant from Tufts University (no number assigned) with additional funding from the Providence-Boston Center for AIDS Research (PI: Stopka), through Grant Number P30AI042853 from the National Institute of Allergy and Infectious Diseases. Support for Dr. Heimer was provided through Grant Number R01DA030420 from the National Institute on Drug Abuse. Initials of the authors who received each award TJS for Tufts Institute for Innovation (TII), which is now defunct The TII award did not have a grant number; internal mechanism The full name of each funder See above and below URL of each funder website TII no longer exists; no website Additional support from the Providence-Boston CFAR: https://cfar.med.brown.edu/ P30AI042853 from NIAiD; https://www.niaid.nih.gov/ RH received support through R01DA030420 from NIDA. NIDA: https://nida.nih.gov/ Did the sponsors or funders play any role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript? No The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript." Please include your amended statements within your cover letter; we will change the online submission form on your behalf. 4. We note that you have stated that you will provide repository information for your data at acceptance. Should your manuscript be accepted for publication, we will hold it until you provide the relevant accession numbers or DOIs necessary to access your data. If you wish to make changes to your Data Availability statement, please describe these changes in your cover letter and we will update your Data Availability statement to reflect the information you provide. [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: Yes ****** 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: In their manuscript, “Molecular and special epidemiology of HCV among who inject drugs in Boston, Massachusetts”, the authors use survey data from 61 individuals and sequence data from 63 individuals in attempt to find evidence of viral clustering and factors associated with that clustering for potential targets for intervention. Unfortunately, their survey size was entirely too small for the goals of the research presented, namely “We aimed to find evidence of disease clusters or transmission patterns outside of known outbreaks” lines 66-67. Otherwise this is a very good study and the paper is well written. The limitations section was particularly well written and enlightening. There are a couple issues to address to clarify the study. 1) The conclusion in the abstract, “Social and special networks, while interesting, may be too ephemeral to inform transmission dynamics when the date and location of infection are indeterminant”, is not supported by the data presented. The data presented simply does not have the depth of sampling to explore transmission dynamics of HCV in Boston. The authors estimate 14,000 new HCV infections over the last seven years (line 60) and the average duration of infection of the 102 individuals recruited was 12 years. The authors, were able to survey about <1% of HCV infected individuals in their population. It would seem incredibly unlikely that any clusters or evidence of transmission patterns would be identified in such a small survey size. 2) The authors spent 9 months (February to October 2016, line 82) recruiting subjects. Why was there such a low yield in study subjects? 3) How many individuals were surveyed to identify the 102 HCV antibody positive subjects? How many individuals were approached? How many individuals had their blood tested? 4) The authors state in their method that a phylogenetic tree was generated (lines 105 to 110) and provide a figure of the tree (Figure 1B), however, there is no presentation of the results It is unclear if there was any viral clustering. Were there any viral clusters? The figure legend needs more information. It is not clear what the values of on the phylogenetic tree mean. Reviewer #2: In this study, the authors aim to see if phylogenetic analysis, when combined with behavioural, network and spatial data, can add to the understanding of transmission patterns among PWID outside of outbreak settings. I think the topic is interesting, and the manuscript is well written but having said that, I do think the sample size used for the study was small. I wonder if re-framing the study slightly, to be clearer that the authors were trying to see if this recruitment and analysis approach can be informative at uncovering disease clusters and transmission patterns might help a bit more – currently this is only mentioned at the end of the article in the conclusions. Minor comments • Line 103/4 – it would be helpful if the authors referenced where they got the sequencing protocol they used here. More detail on genotyping methods would be useful – I note the authors mention mixed genotype infections in the discussion but didn’t say if they found any themselves. Did the genotyping method mean they were unable to identify these? • Is there a particular reason the core region was chosen for this analysis – is it the best region for this type of analysis? • HCV sequencing results and comparison – is gt1a vs non gt1a a reasonable comparison? From my understanding, the spread of gt3a among PWID has been more recent than gt1a and seems consistent with the observation that older individuals in the cohort were infected with gt1b/2b. Whilst numbers are low, I wonder if the authors would see more trends associated with age/location/IDU duration if they further split the non-1a group? • Perhaps consider adding a table with some of the data from lines 133-164 comparing people with different HCV genotypes (1a, 3a, other genotypes?) – might make all the information easier to digest for readers • Line 200 - given the authors were aiming to look at transmission clusters between PWID outside of known outbreaks, I agree the sample size is small particularly outside of an outbreak context. The authors say it needs to be expanded – I would be interested to know what they think a reasonable size would be? • I think some discussion around the issue that phylogenetic linkage will only be possible for samples with the same genotype is missing. Did the authors consider if there was a better way to sample the population to get a larger cohort? • Table 1, is the age mean or median? • Could the authors please confirm they will upload the HCV sequences into a sequence repository and cite these in the manuscript if accepted. Typos Line 64/5; analysis of HCV has identified [a range of] HCV subtypes among Line 126; Forty [participants] (66%) described themselves as ****** 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: No 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.] While revising your submission, please upload your figure files to the Preflight Analysis and Conversion Engine (PACE) digital diagnostic tool, https://pacev2.apexcovantage.com/. PACE helps ensure that figures meet PLOS requirements. To use PACE, you must first register as a user. Registration is free. Then, login and navigate to the UPLOAD tab, where you will find detailed instructions on how to use the tool. 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Revision 1
20 Jun 2022 Author Response Reviewer 1 Comments: Reviewer #1: In their manuscript, “Molecular and special epidemiology of HCV among who inject drugs in Boston, Massachusetts”, the authors use survey data from 61 individuals and sequence data from 63 individuals in attempt to find evidence of viral clustering and factors associated with that clustering for potential targets for intervention. Unfortunately, their survey size was entirely too small for the goals of the research presented, namely “We aimed to find evidence of disease clusters or transmission patterns outside of known outbreaks” lines 66-67. Otherwise this is a very good study and the paper is well written. The limitations section was particularly well written and enlightening. Response: Thank you for the positive feedback on the writing and enlightening limitations sections of our manuscript. While a typical survey with a sample size such as ours (n=61) would be considered small for typical analyses, phylogenetic analyses introduce an additional level of complexity, and there are few studies in the US that have large samples sizes that facilitate assessment of phylogenetic clusters. Admittedly, future studies, with larger funding levels should aim to recruit, enroll, and analyze larger samples, but our study is one of only a few in the Northeastern US that have begun to employ combined spatial and phylogenetic analyses. Please also see our related response to the first comment from Reviewer #2 below. There are a couple issues to address to clarify the study. 1) The conclusion in the abstract, “Social and special networks, while interesting, may be too ephemeral to inform transmission dynamics when the date and location of infection are indeterminant”, is not supported by the data presented. The data presented simply does not have the depth of sampling to explore transmission dynamics of HCV in Boston. The authors estimate 14,000 new HCV infections over the last seven years (line 60) and the average duration of infection of the 102 individuals recruited was 12 years. The authors, were able to survey about <1% of HCV infected individuals in their population. It would seem incredibly unlikely that any clusters or evidence of transmission patterns would be identified in such a small survey size. Response: Our study was relatively small, by design, as an exploratory mixed methods study, and we met our recruitment goals. The comments from Reviewer 1 regarding the external validity of our study may have some merit. It is also important to bear in mind that we don’t have a definition for a cluster. We were looking for relative sequence similarity, acknowledging that people in a linked social network would have more similarity in their sequences than people in a chain who were not connected through a social network. We have removed the term “cluster” from our manuscript and replaced it with “sequence alignment” throughout the manuscript. We have also defined the genetic distance terminology. There is no concordance between the network structure of recruitment and the genetic distance. 2) The authors spent 9 months (February to October 2016, line 82) recruiting subjects. Why was there such a low yield in study subjects? Response: Our overall study incorporated a mixed methods approach, including qualitative in-depth interviews, development and fielding of an Audio Computer Assisted Self Interview (ACASI), piloting of a text messaging (chatbot) system, HCV rapid testing, phlebotomy, specimen preparation, PCR testing, phylogenetic and bioinformatics analyses and additional study components. Thus, as part of a mixed methods exploratory study, we completed all of our target recruitment goals for our qualitative (n=24) [https://pubmed.ncbi.nlm.nih.gov/30071457/], ACASI survey (n=252) [https://pubmed.ncbi.nlm.nih.gov/29482054/], HCV testing (n=102), and phylogenetic analyses (n=62). This was the first such mixed methods study conducted with PWID in the Boston Area, and as an exploratory study, we were interested in assessing the relationship between social network structure and phylogenetic similarity, and we achieved this goal. 3) How many individuals were surveyed to identify the 102 HCV antibody positive subjects? How many individuals were approached? How many individuals had their blood tested? Response: We aimed to conduct HCV rapid testing until we achieved identification of 100 study participants who tested HCV antibody positive. While we surveyed 252 individuals using our ACASI instrument, we limited the number of participants who would undergo confirmatory blood draws and phylogenetic analyses given the costs and the limited budget of our pilot project. We ultimately obtained blood specimens from 102 participants. Among these 102 participants, 40% had cleared the virus or did not have sufficient virus to be sequenced. We could only confirm chronic infection in 63 participants and 61 yielded readable sequences. We don’t know how many individuals were approached as the protocol did not require that we keep information on potential recruits who were not ultimately consented. 4) The authors state in their method that a phylogenetic tree was generated (lines 105 to 110) and provide a figure of the tree (Figure 1B), however, there is no presentation of the results. It is unclear if there was any viral clustering. Were there any viral clusters? The figure legend needs more information. It is not clear what the values of on the phylogenetic tree mean. Response: Given word count limitations, we were succinct in our results section, but we acknowledge that additional details are merited. We have now added additional text in our results section and in the legend for Figure 1B to denote that genetic distances are reported. Reviewer #2: In this study, the authors aim to see if phylogenetic analysis, when combined with behavioural, network and spatial data, can add to the understanding of transmission patterns among PWID outside of outbreak settings. I think the topic is interesting, and the manuscript is well written but having said that, I do think the sample size used for the study was small. I wonder if re-framing the study slightly, to be clearer that the authors were trying to see if this recruitment and analysis approach can be informative at uncovering disease clusters and transmission patterns might help a bit more – currently this is only mentioned at the end of the article in the conclusions. Response: Thank you for the positive feedback. Considering the first comments from both Reviewers 1 and 2, we have reframed the manuscript slightly, per recommendations, clarifying that our study aimed to determine whether recruitment and analysis approaches can be informative at uncovering disease sequences and transmission patterns, better aligning our intro, methods, results and discussion. We were looking to determine if there was an alignment of sequences among individuals who appeared to be linked to each other/know each other based on recruitment patterns compared to others for whom we did not have linkage data. Although we were mildly disappointed to discover that this was not the case, our discussion helps to contextualize our findings in the larger literature and how our approach can help to inform future studies. Minor comments • Line 103/4 – it would be helpful if the authors referenced where they got the sequencing protocol they used here. More detail on genotyping methods would be useful. Response: We have added references for sequencing of HCV core region and sequence alignment as suggested by the reviewer. – I note the authors mention mixed genotype infections in the discussion but didn’t say if they found any themselves. Did the genotyping method mean they were unable to identify these? Response: We don’t think so, but we only performed consensus and not deep sequencing. • Is there a particular reason the core region was chosen for this analysis – is it the best region for this type of analysis? Response: The core region is a very conservative region and quite popular in these types of analyses. Like others, we used this approach in a previous study in St. Petersburg, Russia (citation #8). • HCV sequencing results and comparison – is gt1a vs non gt1a a reasonable comparison? From my understanding, the spread of gt3a among PWID has been more recent than gt1a and seems consistent with the observation that older individuals in the cohort were infected with gt1b/2b. Whilst numbers are low, I wonder if the authors would see more trends associated with age/location/IDU duration if they further split the non-1a group? Response: We conducted these analyses employing a number of approaches. We re-ran the analyses of the 3a genotypes, but we found no differences. We have edited a sentence to the manuscript to clarify that we looked but did not find any network characteristics associated with genotypes. (p. 7, lines: 216-217). • Perhaps consider adding a table with some of the data from lines 133-164 comparing people with different HCV genotypes (1a, 3a, other genotypes?) – might make all the information easier to digest for readers Response: Since brief reports only allow 2 tables and figures, we refrained from creating additional tables and figures. However, we now include a supplemental table, per the reviewer’s recommendation, while retaining the existing table and figure. • Line 200 - given the authors were aiming to look at transmission clusters between PWID outside of known outbreaks, I agree the sample size is small particularly outside of an outbreak context. The authors say it needs to be expanded – I would be interested to know what they think a reasonable size would be? Response: We have removed mentions of clusters throughout the manuscript. We do not have an explicit definition of the closeness of a sequence to be considered a cluster, so we can’t really answer this question. As the reviewer noted, we obtained sequences from a very small subset of people in Boston infected with HCV, so we have no information on how the 61 sequences we have align with we vast array of virus in circulation among PWID in the Boston area. Thus, we do not have the necessary data to make such an estimate. • I think some discussion around the issue that phylogenetic linkage will only be possible for samples with the same genotype is missing. Did the authors consider if there was a better way to sample the population to get a larger cohort? Response: The purpose of this exploratory study was to determine what resources would be necessary to obtain a fuller picture of HCV transmission dynamics. Unless we have a way to link rapid deep sequencing to recruitment patterns, the effort is unlikely to identify recent outbreaks in a timely fashion and to an extent that is superior to simply enhancing widespread HCV testing in the focal/key populations who inject drugs. This would require collaboration with other sites and pooling data. • Table 1, is the age mean or median? Response: Mean age and standard deviation. We have updated wording in the table to make this clear. • Could the authors please confirm they will upload the HCV sequences into a sequence repository and cite these in the manuscript if accepted. Response: Yes, we have submitted the sequences to GenBank and they are under review. We will provide the accession number can confirm that Dr. Paintsil has the sequences and will upload them if the manuscript is accepted for publication. Typos Line 64/5; analysis of HCV has identified [a range of] HCV subtypes among Line 126; Forty [participants] (66%) described themselves as Response: Thank you for catching these. We have corrected the typos. Attachments Attachment Submitted filename: ResponseToReviewers_FINAL copy.docx https://doi.org/10.1371/journal.pone.0266216.r002
4 Jul 2022 Decision Letter - Joël Mossong, Editor PONE-D-22-07761R1Molecular and spatial epidemiology of HCV among people who inject drugs in Boston, MassachusettsPLOS ONE Dear Dr. Heimer, 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. ============================== ACADEMIC EDITOR:One reviewer still has some minor comments. Please address all of these. ============================== Please submit your revised manuscript by Aug 18 2022 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. 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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. [Note: HTML markup is below. Please do not edit.] Reviewers' comments: Reviewer's Responses to Questions Comments to the Author 1. 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 #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 #2: Yes ****** 3. Has the statistical analysis been performed appropriately and rigorously? Reviewer #2: Yes ****** 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 #2: Yes ****** 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 #2: Yes ****** 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 #2: I am happy with the authors responses to my comments. After reviewing the updates I have a couple more minor queries relating to Figure 1B – I note that genotype 1b sequences cluster with gt2/4 sequences, rather than with gt1a sequences – I assume this is because core is being used rather than NS5B or whole genome? It might be worth commenting on this in the figure legend for those less familiar with HCV phylogenies if so. Could the authors add more information on what exactly the labels on the tree mean into the figure legend? I initially assumed they were labelling HCV subtypes, but I don’t think this is correct. If they are highlighting more closely related sequences, could they please list the criteria (ie distance threshold) for doing this? ****** 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 #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.] While revising your submission, please upload your figure files to the Preflight Analysis and Conversion Engine (PACE) digital diagnostic tool, https://pacev2.apexcovantage.com/. PACE helps ensure that figures meet PLOS requirements. To use PACE, you must first register as a user. Registration is free. Then, login and navigate to the UPLOAD tab, where you will find detailed instructions on how to use the tool. If you encounter any issues or have any questions when using PACE, please email PLOS at figures@plos.org. Please note that Supporting Information files do not need this step. https://doi.org/10.1371/journal.pone.0266216.r003
Revision 2
27 Jul 2022 Author Response Responses to Reviewer #2 Reviewer #2: I am happy with the authors responses to my comments. After reviewing the updates I have a couple more minor queries relating to Figure 1B – I note that genotype 1b sequences cluster with gt2/4 sequences, rather than with gt1a sequences – I assume this is because core is being used rather than NS5B or whole genome? It might be worth commenting on this in the figure legend for those less familiar with HCV phylogenies if so. We have added this point to the figure legend, which now reads: “Genetic distance, reported as the proportion of sequence divergence between connections on the tree. Each sub-genotypes aligns closely, but the relatively short core region of the genome that we chose to sequence and the small number of specimens from people infected with genotype 1b resulted in genotype 1b sequences appearing more closely aligned with genotype 2 and 4 than with genotype 1a sequences.” Could the authors add more information on what exactly the labels on the tree mean into the figure legend? I initially assumed they were labelling HCV subtypes, but I don’t think this is correct. If they are highlighting more closely related sequences, could they please list the criteria (ie distance threshold) for doing this? We address this point in the revision by amending the text to read: “The double-headed arrows indicate connection by referral (n=31). This provides visual evidence that the social network that was accessed to recruit participants contained people infected with different strains of HCV.” Attachments Attachment Submitted filename: Responses to Reviewer_July revision.docx https://doi.org/10.1371/journal.pone.0266216.r004
1 Aug 2022 Decision Letter - Joël Mossong, Editor Molecular and spatial epidemiology of HCV among people who inject drugs in Boston, Massachusetts PONE-D-22-07761R2 Dear Dr. Heimer, 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 for payment will follow shortly after the formal acceptance. To ensure an efficient process, please log into Editorial Manager at http://www.editorialmanager.com/pone/, click the 'Update My Information' link at the top of the page, and double check that your user information is up-to-date. If you have any billing related questions, please contact our Author Billing department directly at authorbilling@plos.org. If your institution or institutions have a press office, please notify them about your upcoming paper to help maximize its impact. If they’ll be preparing press materials, please inform our press team as soon as possible -- no later than 48 hours after receiving the formal acceptance. 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. Kind regards, Joël Mossong, PhD Academic Editor PLOS ONE Additional Editor Comments (optional): Reviewers' comments: https://doi.org/10.1371/journal.pone.0266216.r005
Formally Accepted
9 Aug 2022 Acceptance Letter - Joël Mossong, Editor PONE-D-22-07761R2 Molecular and spatial epidemiology of HCV among people who inject drugs in Boston, Massachusetts Dear Dr. Heimer: I'm pleased to inform you that your manuscript has been deemed suitable for publication in PLOS ONE. Congratulations! Your manuscript is now with our production department. 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. If we can help with anything else, please email us at plosone@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. Joël Mossong Academic Editor PLOS ONE https://doi.org/10.1371/journal.pone.0266216.r006

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