Dear Dr. Mwakasungura,

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Additional Editor Comments:

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Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. Is the manuscript technically sound, and do the data support the conclusions?

Reviewer #1: Yes

Reviewer #2: Yes

**********

2. Has the statistical analysis been performed appropriately and rigorously? -->?>

Reviewer #1: No

Reviewer #2: Yes

**********

3. Have the authors made all data underlying the findings in their manuscript fully available??>

The PLOS Data policy

Reviewer #1: Yes

Reviewer #2: No

**********

4. Is the manuscript presented in an intelligible fashion and written in standard English??>

Reviewer #1: No

Reviewer #2: Yes

**********

Reviewer #1: General comments:

• In this paper, authors analyzed factors associated with HIV and HBV coinfection in Tanzania using available data from a nationally representative survey conducted in 2022-2023. The survey methods were robust and ensure that findings are representative of the general population in Tanzania.

• The manuscript overall addresses an important topic. In order to strengthen the analysis and generate findings that can be used by policy makers, I would suggest that the authors incorporate in their analysis, factors associated with HBV infection among persons with HIV rather than only looking at factors associated with overall prevalence of HIV/HBV coinfection in the population. This would follow the usual trend in analyzing such data and can be compared to existing global and regional studies. Policy makers need more clarity on how to integrate HBV testing and treatment among persons with HIV. Therefore, analyzing the data to look at factors associated with HBV infection among persons with HIV would help present clear recommendations to policy makers in Tanzania.

• The discussion specifically needs to be significantly revised to avoid repetitions, compare similar populations and present comprehensive suggestions to diagnose, manage and prevent HIV/HBV coinfections in Tanzania. It is also important that the authors incorporate the role of hepatitis B vaccination in newborns and children to prevent HBV infection. The risk of progression to chronic HBV infection is highest among newborns and children aged <5 years. Only 5% of adults exposed to HBV progress to chronic HBV infection while up to 90% of newborns exposed to HBV progress to chronic HBV infection. Tanzania only provides hepatitis B vaccine for free for children at the age of 6, 10 and 14 weeks (https://immunizationdata.who.int/dashboard/regions/african-region/TZA). Hepatitis B birth dose which prevents vertical transmission has not been introduced. Vertical transmission is the main reason for HBV infections in Tanzania and most of Sub-Saharan Africa. While this survey could not assess MTCT as a risk factor due to the cross-sectional nature, it is expected that many of the persons with HBV were infected at birth or in early childhood (https://www.thelancet.com/journals/langas/article/PIIS2468-1253(25)00375-9/fulltext).

Specific comments:

• For the results, suggest first starting by describing the participant characteristics before presenting the HIV/HBV infection prevalence. Usually, results start with a general description of the study population before presenting the main outcomes.

• Lines 182-184: the sentence is unclear and there is no mention of the age groups with highest HIV/HBV co-infection. It is unclear which age groups refer to the adult population, and which age groups refer to the younger population. In addition, adults are usually defined as people aged 18 and older which does not seem to be the definition that the authors are using. Recommend clearly including the age groups (25-64 years, 15-24 years, 65-80 years) that are being referred to in all sentences of this manuscript instead of mentioning adults, young and elderly. The use of the word “elderly” is not recommended, a better term is older adults.

• Tables 2 and 3: For the analysis of healthcare risk factors, it is recommended to create separate variables because risks are different: receipt of blood transfusion; history of dialysis; receipt of transplant; exposure to surgical procedures. By lumping all those exposures together, authors might miss an important risk factor such as dialysis and blood transfusions.

• Table 3: recommend keeping age as categorical variable (15-24; 25-64; 65-80) to be consistent with the presentation in Table 2. In addition, revise the text that reports on age in multivariate analysis accordingly. I suspect that the main age group impacted by coinfection would be 15-64 years as shown in table 2. This is important especially to highlight in the discussion as they are the economically productive age groups and early deaths due to coinfection would impact economic productivity in Tanzania. Of note the lower prevalence in persons aged 65-80 is expected as most of the persons coinfected would have died earlier due to complications of their infections especially liver cirrhosis and cancer which tends to present earlier among people in Africa. https://pmc.ncbi.nlm.nih.gov/articles/PMC10204139/. https://www.sciencedirect.com/science/article/pii/S2949916X24000112

• In the discussion, the authors mention that the overall prevalence of HIV/HBV co-infection is low, but they also point out that HBV co-infection among persons living with HIV is almost 7% which is high. Given this finding, it would be more useful if the authors analyzed factors associated with HBV co-infection among persons with HIV compared to persons who do not have HIV rather than looking at factors associated with overall prevalence of coinfection in the population. Therefore, I would recommend that the authors incorporate in their bivariate and multivariate analysis, factors associated with being co-infected with HBV among people living with HIV. For programmatic planning and to inform policy makers, it would be more useful to approach it from that perspective rather than looking at overall prevalence of HIV/HBV co-infection in the population. Policy makers need more clarity on how to integrate HBV testing and treatment among persons with HIV and the analysis using HBV infection among persons with HIV would help present clear recommendations to policy makers in Tanzania.

• Discussion lines 215-216: while hepatitis B vaccine was introduced in children as part of the pentavalent vaccine in Tanzania in 2002, the hepatitis B birth dose is not available for free and is not part of the routine immunization program in Tanzania. As for adult hepatitis B vaccination, while it might be available and mainly targets healthcare workers, there is no recommendation for universal adult vaccination against hepatitis B in Tanzania and the vaccine is not free. Reference 21 that the authors cite is focused on healthcare workers and not the general population or persons with HIV. Authors need to revise this sentence to reflect the current availability of hepatitis B vaccine in Tanzania in newborns, children and adults. The lack of hepatitis B birth dose vaccine to prevent vertical transmission of HBV is not mentioned anywhere by the authors. Vertical transmission is a key risk factor for progression to chronic HBV infection. While some persons coinfected with HIV and HBV could have acquired HBV infection at birth, this cross-sectional survey cannot identify this risk.

• Lines 219-221: data from this manuscript do not support those assumptions. The only risk factor in this study were age and number of sex partners. Medical procedures and cosmetic practices were not significant. In addition, for hepatitis B, the main risk factor for chronic HBV infection is vertical transmission. The risk of progression to chronic HBV infection after exposure is up to 90% in newborns and drops to 5% in persons older than 5 years. The authors never address this risk factor in their discussion which would miss a key intervention that would further prevent HBV infections including coinfections in the future.

• Lines 225-227: the prevalence of hepatitis B along persons with HIV was almost 7% in this survey, so it does match what has been reported previously in Tanzania and is not lower than previous estimates. I think authors are confusing overall prevalence of coinfection in the general population with HBV coinfection among persons with HIV. Usually, all studies assess HBV coinfection among persons with HIV as it would be most relevant for policy decisions. Hence, my previous recommendation to the analysis to assess factors associated with HBV coinfection among persons with HIV rather than the general population.

• Revise lines 222-227 to incorporate some of the information with the next paragraph starting at line 228as they are related. All literature looked at HBV infection among persons with HIV.

• Line 233: need to add the importance of introducing hepatitis B birth dose to prevent vertical transmission of HBV.

• Lines 237-239: Ref 28 refers to people who inject drugs and should not be cited to compare to general population without context. The 7.4% (ref 27) refers to prevalence of hepatitis B among persons with HIV globally and is not much different than what the authors found in Tanzania. The discussion needs revision and several sections can be combined to summarize the prevalence of HBV infection among persons with HIV and link to suggested recommendations like screening all persons with HIV for hepatitis B and incorporating hepatitis B testing in HIV clinics as well as during antenatal care, providing hepatitis B vaccination to persons with HIV wo have not been exposed (total anti-HBc negative) and to newborns to prevent vertical transmission.

• Line 275: Older adults (aged 65 and older) do not have higher prevalence than adults aged 15-64 years. The authors need to use age groups to describe their data rather than saying older adults.

• Ref 29 is missing authors. If it is referring to the WHO guidelines, the reference needs to be updated to the more recent guidelines published in 2024. https://www.who.int/publications/i/item/9789240090903

• Discussion and associated references could also be strengthened by including the guidance of incorporating HBV screening and treatment in HIV services. https://www.who.int/publications/i/item/9789240119529

Reviewer #2: This a well written manuscripts on HIV/HBV coinfection. The authors should consider the following:

1. Describe the laboratory testing methods: for screening and confirmation of HIV and HBV infection

2. Provide any details on prevalence among pregnant women if that data was collected...if not provide this in the limitations because elimination of mother to child HBV infection is top priority.

3. Discuss infant immunization program in Tanzania to help explain the low number of vaccinated individuals in the study 200 vs 32,688. They could account for the proportion of participants who should have benefited from the global immunization program initiative from the time it was rolled out in Tanzania. How is the coverage so far?

4. In the discussion, include comparison with close neighbors such as Kenya and Uganda as part of regional data. for example, Kenya: https://pubmed.ncbi.nlm.nih.gov/39541401/

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Reviewer #1: No

Reviewer #2: No

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Dear Dr. Mwakasungura,

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 Jul 10 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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We look forward to receiving your revised manuscript.

Kind regards,

Hans L. Tillmann

Academic Editor

PLOS One

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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.

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.

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Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

Reviewer #1: (No Response)

Reviewer #2: All comments have been addressed

**********

2. Is the manuscript technically sound, and do the data support the conclusions??>

Reviewer #1: Partly

Reviewer #2: Yes

**********

3. Has the statistical analysis been performed appropriately and rigorously? -->?>

Reviewer #1: Yes

Reviewer #2: Yes

**********

4. Have the authors made all data underlying the findings in their manuscript fully available??>

The PLOS Data policy

Reviewer #1: Yes

Reviewer #2: No

**********

5. Is the manuscript presented in an intelligible fashion and written in standard English??>

Reviewer #1: No

Reviewer #2: Yes

**********

Reviewer #1: Appreciate that the authors addressed most of my comments and revised the manuscript. However, there are still key areas that need to be addressed to ensure adequate presentation and interpretation of results.

1- Table 2: weighted percentages for the negative and no category should also be presented rather than only showing % among positive and yes.

2- Table 3: while the confidence intervals might be large if age is presented as a categorical variable or exposure to certain medical procedures, this should not restrict the presentation of those data as it is important to analyze data by age group and to differentiate medical exposures. Based on Table 1, the sample size in each age category is more than enough to present data by age groups in Table 3. It is also inadequate to lump blood transfusion with transplant and dialysis and surgical procedures. Those categories should be separated into blood transfusion (findings inform safety of blood in the country), dialysis (high risk medical intervention for acquiring HBV and HCV), and then other medical procedures (including transplant).

3- While authors are interested in overall population level prevalence of HIV/HBV co-infection, the results would not be useful from a programmatic and public health perspective as their data cannot be used to come up with key recommendations to improve HBV screening and treatment based on HIV status. Is coinfection driven by acquiring HIV in adulthood or acquiring HBV in adulthood? It seems that the coinfection is driven by the HIV infection in adults. HBV infection probably occurred in infancy and childhood. However, authors did not look at that to present key drivers of coinfection. Analyzing data looking at HBV coinfection among persons with HIV compared to those who do not have HIV has not been done at the population level in Tanzania and none of the papers cited used large scale nationally representative surveys like THIS. I would highly recommend the authors to reconsider that comment as it would not preclude them from presenting overall prevalence in the population as well. Hence, adding this analysis would help guide national viral hepatitis and HIV policies in Tanzania.

4- I would recommend revising the discussion to compile common information together and avoid redundancy. For example, lines 241-250 discuss HIV/HBV coinfection prevalence and similarly lines 259-269 discuss that same point. The ideas in those paragraphs can be combined and summarized in one paragraph. Lines 251-258 mix different ideas (hepB birth dose with integration of HBV in HIV services) and the data presented in this manuscript do not show how incorporating HBV screening and treatment in HIV clinics is useful without showing the difference in prevalence at the population level of HBV infection among persons with HIV compared to HBV infection among persons who do not have HIV.

5- The authors did not highlight that the main risk of HBV infection in high prevalence settings is perinatal and early childhood transmission. This is important to bring up as most people most likely acquired HBV infection in childhood due to MTCT and later acquired HIV infection through sexual transmission. The risk of progression to chronic HBV infection is highest among newborns and children aged <5 years. Only 5% of adults exposed to HBV progress to chronic HBV infection while up to 90% of newborns exposed to HBV progress to chronic HBV infection.

6- Reference list could be improved by removing ref 32 and 34 which are redundant and are an old guidance. This is the updated WHO guidance: https://www.who.int/publications/i/item/9789240090903

Ref 35 needs an author.

7- Recommend authors proofread their manuscript for grammatical errors before submitting. Example lines 50-52 are incoherent. Data is usually a plural term as it contains more than one piece of information (line 142: data were cleaned rather than data was cleaned). Lines 183-185: do not need to say age groups of the population (revise to among persons aged 25-64 or among persons 25-64 years of age etc.). lines 265-269.

Reviewer #2: (No Response)

**********

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Reviewer #1: No

Reviewer #2: No

**********

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Dear Dr. Mwakasungura,

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 Sep 12 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.

• A letter that responds to each point raised by the academic editor and reviewer(s). You should upload this letter as a separate file labeled 'Response to Reviewers'.
• A marked-up copy of your manuscript that highlights changes made to the original version. You should upload this as a separate file labeled 'Revised Manuscript with Track Changes'.
• An unmarked version of your revised paper without tracked changes. You should upload this as a separate file labeled 'Manuscript'.

If you would like to make changes to your financial disclosure, please include your updated statement in your cover letter. Guidelines for resubmitting your figure files are available below the reviewer comments at the end of this letter.

If applicable, we recommend that you deposit your laboratory protocols in protocols.io to enhance the reproducibility of your results. Protocols.io assigns your protocol its own identifier (DOI) so that it can be cited independently in the future. For instructions see: https://journals.plos.org/plosone/s/submission-guidelines#loc-laboratory-protocols. Additionally, PLOS ONE offers an option for publishing peer-reviewed Lab Protocol articles, which describe protocols hosted on protocols.io. Read more information on sharing protocols at https://plos.org/protocols?utm_medium=editorial-email&utm_source=authorletters&utm_campaign=protocols.

As the corresponding author, your ORCID iD is verified in the submission system and will appear in the published article. PLOS supports the use of ORCID, and we encourage all coauthors to register for an ORCID iD and use it as well. Please encourage your coauthors to verify their ORCID iD within the submission system before final acceptance, as unverified ORCID iDs will not appear in the published article. Only  the individual author can complete the verification step; PLOS staff cannot  verify ORCID iDs on behalf of authors.

We look forward to receiving your revised manuscript.

Kind regards,

Hans L. Tillmann

Academic Editor

PLOS One

Journal Requirements:

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.

[Note: HTML markup is below. Please do not edit.]

Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

Reviewer #1: All comments have been addressed

**********

2. Is the manuscript technically sound, and do the data support the conclusions??>

Reviewer #1: Partly

**********

3. Has the statistical analysis been performed appropriately and rigorously? -->?>

Reviewer #1: I Don't Know

**********

4. Have the authors made all data underlying the findings in their manuscript fully available??>

The PLOS Data policy

Reviewer #1: Yes

**********

5. Is the manuscript presented in an intelligible fashion and written in standard English??>

Reviewer #1: No

**********

Reviewer #1: Thank you for addressing and responding to my comments. Some suggestions to improve the manuscript.

- Table 2: the negative category needs to also include weighted 95% confidence intervals. Or a better presentation would be to just present the positive/yes along with total denominator for each variable:

o Example:

Characteristics Number/Total tested Weighted % (95% CI)

HIV positive 1832/ 33263 4.38 (4.07-4.70)

Hepatitis B positive 1187/33263 3.53 (3.26-3.82)

Hepatitis B among PLWHIV 106/1832 6.22 (4.89-7.78)

HIV/HBV coinfection 106/33263 0.27 (0.21-0.34)

- Line 202-209: sentences need to be revised to match the results in Table 3. There is no 1.02 in Table 3. Looks like persons aged 25-64 years had higher odds of HIV/HBV coinfection than those aged 15-24 years. Same for other numbers presented in the text which do not match numbers in Table 3.

- Discussion needs to be improved by focusing on one idea per paragraph. For example, lines 254-261 and 287-298 cover multiple topics which confuses the reader.

- Manuscript needs to be proofread for clarity and English and grammar. All acronyms are defined on first use and lines 183-186 are still unclear.

**********

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Reviewer #1: No

**********

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HIV and Hepatitis B co-infection in Tanzania: analysis of the 2022-2023 Tanzania HIV Impact Survey.

PONE-D-26-12082R3

Dear Dr. Mwakasungura,

Thank you for following through on the requested evisions. 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.

But please correct two minor things when proofreading [or earlier.

1.) in table 4 at section :Received Hepatitis B vaccine where it say 9 (1.00) you likely meant to say 9 (100)

2.) Lines300-302, the reviewer correctly suggests revising for accuracy as these percentages do not reflect hepatitis B chronicity rates but risk of progression to chronic HBV infection based on age of acquisition of HBV infection. “ ….estimated risk of progression to chronic HBV infection are 90% for infections acquired perinatally, 30-60% for early childhood infections and under 10% for HBV infection acquitted in adulthood. “

Thus instead of

"Importantly, in high-endemicity settings like Tanzania, .estimated risk of progression to chronic HBV infection are 90% for infections acquired perinatally, 30-60% for early childhood infections and under 10% for HBV infection acquitted in adulthood falling to under 10% in adulthood [39]"

state

"Importantly, in high-endemicity settings like Tanzania, chronic HBsAg positivity predominantly300

reflects early-life acquisition with estimated chronicity rates of 90% perinatally and 30–60% in301

early childhood, falling to under 10% in adulthood [39}"

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.

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Kind regards,

Hans L. Tillmann

Academic Editor

PLOS One

Additional Editor Comments (optional):

Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

Reviewer #1: All comments have been addressed

**********

2. Is the manuscript technically sound, and do the data support the conclusions??>

Reviewer #1: Yes

**********

3. Has the statistical analysis been performed appropriately and rigorously? -->?>

Reviewer #1: I Don't Know

**********

4. Have the authors made all data underlying the findings in their manuscript fully available??>

The PLOS Data policy

Reviewer #1: Yes

**********

5. Is the manuscript presented in an intelligible fashion and written in standard English??>

Reviewer #1: Yes

**********

Reviewer #1: Thank you for addressing and responding to my comments. Minor suggestions below for consideration.

- Table 4: I think there might be a typo error under received hepatitis B vaccine. The % should be 100% among the 9 who were vaccinated and did not have coinfection.

- Lines300-302: suggest revising for accuracy as these percentages do not reflect hepatitis B chronicity rates but risk of progression to chronic HBV infection based on age of acquisition of HBV infection. “ ….estimated risk of progression to chronic HBV infection are 90% for infections acquired perinatally, 30-60% for early childhood infections and under 10% for HBV infection acquitted in adulthood. “

**********

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

**********