Review Reports

Round 1

Reviewer 1 Report

Comments and Suggestions for Authors

Estimated Authors,

I've read with great interest your paper entitled "A Review of Human Immunodeficiency Virus and Hepatitis B Virus Co-infection with a Focus on Research and Management in Botswana".

The present paper provides an informative summary on the scientific research and future options for the study of HBV and HIV infections in Botswana. Although well documented and undoubtfully well written, the present paper would need substantial adjustment of its structure before its potential acceptance for publication, for a series of reasons I'll report in the following lines:

1) the main title suggests that the present paper should focus on HIV/HBV coinfections; Authors should therefore summarise data on HBV epidemiology that are, currently overwhelming over the coinfection data. Table 2 should be redesigned in order to include only data on coinfections, and not consistent data could be moved to appendix material in order to sustain a more concise description of baseline HBV epidemiology; main text should be refined accordingly with section 4.2 simplified by the removal of data on sole HBV infections;

2) introduction provides a significant amount of data on the role of cART, and this content is disproportionately large compared to the section 4.5; as a consequence, Authors should therefore simplify the corresponding section on the introduction;

3) Section "HBV and Non-HIV Disease in Botswana" is not consistent with the aims of the paper and should be removed

4) Section 4.3 is not consistent with the aim of the paper, and should eithe removed or simplified in order to provide only data consistent with description of characteristics of coinfections (e.g. explaining whether certain genotypes are more frequently reported on not during the course of coinfections), currently reported only in rows 385 and following and in a too-concise way to be very informative.

Author Response

Please see the attachment.

Author Response File: Author Response.pdf

Reviewer 2 Report

Comments and Suggestions for Authors

The manuscript “A Review of Human Immunodeficiency Virus and Hepatitis B Virus Co-Infection with a Focus on Research and Management in Botswana”, submitted to the journal Viruses, is devoted to the to summarizing existing research on HBV and HIV-HBV co-infection in Botswana and assess clinical and policy implications.  The work is very important for improvement diseases control and clinical outcomes in Botswana. In addition, identifying mutations of viruses that are resistant to vaccination and treatment is of global importance and requires decisive measures.

I have some comments:

1. The title is too long. Perhaps, it is better to title “Human Immunodeficiency Virus and Hepatitis B Virus Co-Infection in Botswana”.
2. The list of references is compiled carelessly, in particular, in source 10 the title is duplicated, and there are no doi.
3. References to cited literature in the text are not formatted according to the rules.
4. Lines 84-85: nucleoside reverse transcriptase inhibitors (NTRIs),

              Comment: it should be “NRTIs”

5. When analyzing the data in Figure 1, it is not clear why, with the initial number of articles being 68, only 29 remain, while 0 articles were excluded from the study. Although the text states that 39 articles were excluded. Figure 1 should be adjusted.
6. The authors use percentages in their manuscript, including a 54% vaccination of infants. It would be helpful to provide data on Botswana's population size and number of births per year to understand the number of additional vaccine doses needed.

Author Response

Please see the attachment.

Author Response File: Author Response.docx

Reviewer 3 Report

Comments and Suggestions for Authors

Review Report

Thank you for the opportunity to review the manuscript:

“A Review of Human Immunodeficiency Virus and Hepatitis B Virus Co-Infection with a Focus on Research and Management in Botswana”

This manuscript provides a comprehensive review of HIV-HBV co-infection in Botswana, covering epidemiology, molecular findings, clinical management, and future perspectives. The systematic approach and PRISMA diagram strengthen the work.

Major Comments:

1. Population bias: Most studies focus on PLWH, limiting generalizability to the HIV-negative population. Consider emphasizing this limitation and the need for HBV mono-infected cohorts.
2. Occult HBV and prevalence estimates: OBI is undetected using HBsAg testing alone. Highlight the need for HBV DNA testing to capture the true burden.
3. Molecular data interpretation: Vaccine escape mutations, RAMs, and OBI-associated mutations are described, but their clinical impact in Botswana remains largely inferential. Clarify this in the discussion.
4. Variability of HBV prevalence across studies: Prevalence values range widely (2%–46.7%) due to differences in cohort selection, geography, and methodology. A structured discussion of factors influencing this variability is recommended.
5. Response to cART: Suboptimal HBV and HIV control in co-infected participants is noted, but potential confounders such as adherence, duration of infection, and demographic differences are not fully addressed. Discussing these limitations would strengthen the conclusions.
6. Absence of national HBV guidelines: Lack of structured HBV guidelines affects diagnosis, monitoring, and treatment. The manuscript should discuss the practical implications and recommend policy improvements.

Suggestion: Consider including a dedicated paragraph in the Discussion summarizing these limitations to help readers interpret findings appropriately.

Minor Comments:

• Define abbreviations at first mention in each section.
• Consider breaking long paragraphs to improve readability.
• Check citation order and minor typographical issues (“HBV related” → “HBV-related”).

 

Conclusion:  I recommend minor revisions to improve clarity, contextualization, and discussion of limitations.

 

Author Response

Please see the attachment.

Author Response File: Author Response.docx

Round 2

Reviewer 1 Report

Comments and Suggestions for Authors

The paper has been properly upgraded in accord to my previous recommendations.

Only the following issue still remains:

please include in methods section a detailed description on how the recommendations from the final section of the paper have been designed.

After this clarification, the paper could be accepted for publication.

Author Response

Please see the attachment.

Author Response File: Author Response.docx