Compartmentalization of Resistance-Associated Substitutions in HIV/HCV-Infected Patients: Possible Correlation with Infecting HCV Genotype

Round 1

Reviewer 1 Report

Thanks for the opportunity to review the manuscript "Compartmentalization of Resistance-Associated Substitutions in Hiv/Hcv Infected Patients: Possible Correlation with Infecting Hcv Genotype" proposed by Morsica et al.

The topic is important, and addresses a current medical problem. However, one of the major problems of this manuscript is the very low level of English. In addition, some sections are incomplete or confusing, with suboptimal flow.

 

Abstract:

1. The study design and setting are missing.
2. The background may be expanded.
3. The methods should be included.
4. The section lacks clarity, and requires through polishing.
5. "who performed liver biopsy" is not right. the patients underwent...

 

Introduction

1. The section does not provide enough background for an average reader.
2. Epidemiology, morbidity, and mortality data should be provided to stress the clinical significance of this work.
3. The flow is suboptimal, with a lack of transition between the main ideas.
4. The authors should include some description of Refs 8-10 to indicate the current knowledge ("Few data are available ..." is a bit vague).
5. Again, the whole section requires polishing by a native English-speaking scientist.

 

Methods:

1. The section is a bit confusing, with the information scattered all over the place.
2. It would help to structure the Methods section, with appropriate subtitles.
3. The design is confusing. Although it is retrospective, the authors claimed they "we decided to include HIV-1 positive patients".
4. The statistical part is very abbreviated.
5. A lot of unclear passages and grammar issues. The whole section requires polishing by a native English-speaking scientist.

 

Results

1. This section should be fully structured as well. There are some subtitles, but the beginning of the section needs to be structured as well.
2. Also, the existing subtitles are not appropriate for the Results section. They sound like Methods' subtitles instead.

 

Discussion

1. The section is poorly written, difficult to read and full of language issues.
2. The authors should present their results in the context of previous findings.
3. The conclusion seems to be placed in the middle of the discussion.
4. The authors should evoke the limitations of their study.

 

 

 

 

 

Author Response

Manuscript ID: viruses-1213185 Type of manuscript: Article Title:

>> COΜPARTMENTALIZATION OF RESISTANCE-ASSOCIATED SUBSTITUTIONS IN

>> HIV/HCV INFECTED PATIENTS: POSSIBLE CORRELATION WITH INFECTING HCV

>> GENOTYPE Authors: Giulia Morsica *, Riccardo Vercesi, Hamid

>> Hasson, Emanuela Messina, Caterina Uberti-Foppa, Sabrina Bagaglio

 

 

We submit the manuscript revised in accordance with Reviewer’s comments. A native English- speaking Scientist carefully edited the whole manuscript.

Therefore, a number of changes were added along the manuscript.

Since we made a number of grammatical and verbal changes throughout the paper in an attempt to increase readability and/or correctness, only major changes are included in the comments.

The Journal requests no headings in the abstract. It should be a single paragraph. Therefore, headings were deleted. According with the suggestions by the Reviewers the words count for this section is now 216 instead of 200.

On the basis of requests from the Reviewers, references were added and the reference number was changed.

Finally, we thank the Reviewers for the comments that have improved the quality of the manuscript in line with the aim of the study.

 

 

 

 

Reviewer 1

 

Abstract

-1. Background was expanded: see page 2, lines 22-24.

-2 and 3. Study design and setting was added and Methods were better-detailed page 2 lines 24-28.

-4. The full section was polished.

-5. “Who performed liver biopsy” was changed in “who underwent diagnostic liver biopsy”.

 

Introduction

1and 2. Background was changed and information concerning epidemiology morbidity and mortality in the special population of HIV positive patients was added: see page 4, lines 64-70. With regard to biological characteristics of HCV information was added at page 4, lines 78-79.

3 . The flow of the text was corrected along the Introduction section.

4. The description of ref 8-10 (now ref 14-16) was added to indicate the current knowledge on the issue of RAS compartmentalization. However, data concerning these studies were better detailed in the Discussion section.
5. This section was carefully edited by a native English- speaking Scientist.

 

Methods

1-2 The methods section was structured with appropriate subtitles as following: Study group; Sequence analysis of the NS3 protease and NS5A domain; Statistical analysis.

3. The design of the study was better described. Concerning the comment on the retrospective design of the study, we decided in 2019 to analyse previously stored coupled specimens (plasma and paraffin-embedded liver tissues). Plasma samples were stored during years 2000-2006 for other immunological and virological studies, while on the basis of available plasma samples and infecting genotypes, were also chosen liver tissues.
4. The statistical part was changed, better explained and we added the significance of comparative data in Table 1 . Additionally, we evaluated the association between mutations and the infecting HCV genotype. This data was added in the Results section.

 

 

 

Results

1. The section was structured according to Methods section.

 

Discussion

1- The Discussion was re-edited according to suggestion by the Reviewer.

2- The limitations of the study were added as suggested: see page 19, lines 374-397.

 

 

Author Response File: Author Response.docx

Reviewer 2 Report

It is a very interesting article including 34 HIV/HCV coinfected patients who per formed a liver biopsy    aimed to investigate the possible compartmentalisation of naturally occurring NS3 and NS5A RASs in the liver tissue and plasma of HIV/HCV coinfected pa-45 tients according to different HCV genotypes.

 

Major points to address:

1. Clinical data: Some clinical data could be interesting to detail. Was HVB coinfection present in some patient?. Alcohol consumption ? Explain the presence of cirrhosis in two patients wih only moderat degree of fibrosis.
2. Limitations of the study should be acknowledged. a) the limited number of patients analysed. b) none of the 13 patients treated with DAAs in the years 2015-2018 had available a subsequent plasma sample for virological investigation; c) The sequences obtained represent specific snapshots of the evolution of the viral quasispecies. It is not possible to exclude further diversity of quasispecies in liver regions that were not tested

Author Response

Manuscript ID: viruses-1213185 Type of manuscript: Article Title:

>> COΜPARTMENTALIZATION OF RESISTANCE-ASSOCIATED SUBSTITUTIONS IN

>> HIV/HCV INFECTED PATIENTS: POSSIBLE CORRELATION WITH INFECTING HCV

>> GENOTYPE Authors: Giulia Morsica *, Riccardo Vercesi, Hamid

>> Hasson, Emanuela Messina, Caterina Uberti-Foppa, Sabrina Bagaglio

 

 

We submit the manuscript revised in accordance with Reviewer’s comments. A native English- speaking Scientist carefully edited the whole manuscript.

Therefore, a number of changes were added along the manuscript.

Since we made a number of grammatical and verbal changes throughout the paper in an attempt to increase readability and/or correctness, only major changes are included in the comments.

The Journal requests no headings in the abstract. It should be a single paragraph. Therefore, headings were deleted. According with the suggestions by the Reviewers the words count for this section is now 216 instead of 200.

On the basis of requests from the Reviewers, references were added and the reference number was changed.

Finally, we thank the Reviewers for the comments that have improved the quality of the manuscript in line with the aim of the study.

 

 

 

Reviewer 2

 

Information on HBV coinfection was added in the Results section see page 10, lines 203-207 and Table 1.

With regard to alcohol intake , unfortunately we did not collect in years 2000-2006 this important information in the majority of patients. Therefore, it was not possible to obtain this data from the recorded files within the data base.

It is unclear the comment concerning the presence of cirrhosis in two patients with only moderate degree of fibrosis. In detail, in the result section we indicated that seven patients had advanced liver disease (fibrosis degree >F3) and 2 of these 7 had cirrhosis. In Table 1, 7 patients had fibrosis F3/F4 and 2 of them had cirrhosis. Therefore, we did not find along the manuscript the data concerning the presence of cirrhosis in two patients with only moderate degree of fibrosis.

 

We added limitations of the study as suggested: see page 19, lines 374-397.

With regard to the limited number of patients included in the study: this is the first study that analysed RASs in paired liver and plasma samples of 34 patients. Previous studies analysed paired specimens from 18 or less patients. Therefore, on the basis of these previous studies the sample size is not too small.

 

Round 2

Reviewer 1 Report

The authors have addressed most of my comments. I recommend the manuscript for publication after its proofreading by a native English speaking scientist.