Emerging Trends in HIV-1 Sub-Subtype A6 in Belgium: Transmission Dynamics, Drug Resistance, and Subtyping Tool Evaluation

Round 1

Reviewer 1 Report

Comments and Suggestions for Authors

The study is well designed, and the manuscript is clearly written. The authors characterized the increasing transmission of HIV-1 A6 strains, including their dynamics and associated demographics and drug resistance, among newly diagnosed HIV cases in Belgium. These findings provide useful insights for public health efforts aimed at HIV prevention. In addition, the authors compared different subtyping tools and identified discrepancies among them, which will be helpful for users in selecting appropriate tools for subtyping, especially for the subtype A HIV.

A few minor comments:

1. The title of Table 2 could be reworded to better reflect the nature of comparing subtyping tools.
2. To improve clarity and manuscript quality, consider including a subset tree focused specifically on A6 as a figure in the manuscript, which would help readers better understand the dynamics of A6 transmission, particularly transmission lineages within clusters.
3. The word “one” is missing before “hundred thirty-six” on line 180; please add it.

Author Response

We thank the reviewer for their positive evaluation of our study and for highlighting its relevance to public health and HIV-1 molecular epidemiology.

We appreciate the reviewer’s helpful suggestions to further improve the clarity of the manuscript.

Comments 1: The title of Table 2 could be reworded to better reflect the nature of comparing subtyping tools.

Response 1: In response to the comment on Table 2, we have revised the title to better reflect the comparison of subtyping tools. [updated text in the manuscript]

 

Comments 2: To improve clarity and manuscript quality, consider including a subset tree focused specifically on A6 as a figure in the manuscript, which would help readers better understand the dynamics of A6 transmission, particularly transmission lineages within clusters.

Response 2: Following the reviewer’s suggestion to improve the visualization of A6 transmission dynamics, we have added a new supplementary figure (Figure S2) presenting a phylogenetic tree including only sub-subtype A6 sequences. This figure is annotated with relevant metadata, including risk category, country of birth, year of diagnosis, and identified transmission clusters, to facilitate interpretation. [updated text in the manuscript]

 

Comment 3: The word “one” is missing before “hundred thirty-six” on line 180; please add it.

Response 3: We corrected the minor typographical issue on line 180 by adding the missing word “one” before “hundred thirty-six.” [updated text in the manuscript]

Reviewer 2 Report

Comments and Suggestions for Authors

Thank you for depositing at least a subset of the sequences in GenBank, and providing the accession numbers in the text.  

I used BLAST to identify other HIV-1 sequences related to a few of yours.  The resulting phylogeny is attached.  

I was not aware that some treatments are contraindicated for A6 infections.,  I would like to learn more about that.  Thanks for writing this up and providing the citations to explore this more.

Comments for author File: Comments.pdf

Author Response

We thank the reviewer for their careful evaluation of our manuscript and for their constructive comments.

We appreciate the reviewer’s recognition of our effort to deposit a subset of the sequences in GenBank and to provide the corresponding accession numbers in the manuscript. We agree that public availability of sequence data is important for transparency and reproducibility, and we will continue to expand the dataset in future work.

We are also grateful that the reviewer performed an independent BLAST analysis and generated a phylogeny including related HIV-1 sequences. We find it encouraging that these results are consistent with our interpretations.

Regarding the reviewer’s interest in treatment considerations for subtype A6 infections, we thank the reviewer for their positive feedback on this aspect of the manuscript. We are pleased that this section was found informative and appropriately supported by the cited literature.

We thank the reviewer again for their positive and constructive feedback.