Seroprevalence of Human Cytomegalovirus Infection among HIV Patients in Edo State, Southern Nigeria

Round 1

Reviewer 1 Report

The work conducted by Moses-Otutu and colleagues is interesting and raises relevant questions about HCMV and HIV co-infection that can have an impact on the health of this low-resource population. However, some questions deserve further clarification:

The observations in the conclusion of the abstract are not included in the main findings of the abstract, like “religion” and “location” as risk factos for HCMV

Please indicate HIV data and demographic data obtained for ths study in methods section

What would be the positive patients in table 2? IgG or IgM or both?

The Co-existence of HCMV IgG and IgM antibodies among HIV the patients is not clear in Table 3. Maybe Table 3 and 4 should merge

HCMV IgM and IgG antibodies is not exaclty in the “co-infection” category because its antibodies. A term like “co-detection” sounds better.

How many patients among IgM or IgG pos. were engaged in HAART therapy?

To what do the authors attribute the higher frequency of HCMV IgM among the Christian population and lower frequency among the Muslim population?

As a policy recommendation, I would add CMV viral load testing to better monitor the infection and treatment in HIV-positive patients.

Author Response

Reviewer’s Comments 1

1) The work conducted by Moses-Otutu and colleagues is interesting and raises relevant questions about HCMV and HIV co-infection that can have an impact on the health of this low-resource population. However, some questions deserve further clarification:

Response: Thank you for the kind comment.

2) The observations in the conclusion of the abstract are not included in the main findings of the abstract, like “religion” and “location” as risk factors for HCMV.

Response: Thank you for your comment. The conclusion of the abstract is derived from the observations in the results and discussions of the findings of the work. The result is found in Table 2 and discussed in 4^th paragraph of the discussion section.

3) Please indicate HIV data and demographic data obtained for this study in methods section.

Response: Thank you for the insightful comment. The data of the HIV patients obtained and used for this study is now provided under the “The Study area and Population” sub-section of the Materials and Methods.

4) What would be the positive patients in table 2? IgG or IgM or both?

Response: The positive patients in table 2 is IgM only.

5) The Co-existence of HCMV IgG and IgM antibodies among HIV the patients is not clear in Table 3. Maybe Table 3 and 4 should merge.

Response: The two tables 3 and 4 have been merged to become table 3.

6) HCMV IgM and IgG antibodies is not exactly in the “co-infection” category because its antibodies. A term like “co-detection” sounds better.

Response: Thank you for your comment. We have changed “co-infection” to “co-detection”.

7) How many patients among IgM or IgG pos. were engaged in HAART therapy?

Response: All the recruited patients were engaged in HAART therapy, as all the participants were recruited from a government designated state HIV clinic. So, all the participants were already receiving antiretroviral therapy.

8) To what do the authors attribute the higher frequency of HCMV IgM among the Christian population and lower frequency among the Muslim population?

Response: The authors noted in the 4^th paragraph of the discussion section that religion is not a known predisposing factor to the acquisition of HCMV infection among HIV patients. Therefore, we attributed the higher prevalence observed among the Christian population compared to their Muslim counterparts, may be to population difference. It is observed that study participants who identified as Christians were much more than those who identified as Muslims.

9) As a policy recommendation, I would add CMV viral load testing to better monitor the infection and treatment in HIV-positive patients.

Response: Thank you for your insightful comments and suggestions. This have been considered and updated in the policy recommendation section

Reviewer 2 Report

In this manuscript, the authors collected HIV patients' sera and detected HCMV IgG and IgM to analyze the prevalence of HCMV in HIV individuals. The co-infection relationship between the two types of viruses was discussed, as well as the socio-demographic characteristics, which will be greatly helpful in recording the significance of the location of African populations. 

The data was well organized, and the aims were clear. The samples were significant for the local population. The discussion section was well written, addressing the sections and Table with comparisons. The authors also discussed the hypothesis of the infectious cause for the infection rate in each age group. 

 However, some weaknesses need to be improved. 

The structures of HCMV and HIV were shown in Figures 1 and 2, which were more like textbooks and had less information than the rest of the paper. The review doesn't talk about the structure of the two viral particles, but the rigid engraftment does.

Absence of a control group of HIV-negative persons infected with HCMV. It might be more helpful to know the HCMV without HIV co-infection.

The interpretation of Figure 2 is inconsistent with the conclusion. 

Most of the introductions in the review are on HIV or HCMV, respectively, and the last paragraph links the two somewhat inadvertently and not very well. 

The pregnant women's data in the first part of the discussion is somewhat fuzzy, as if they were not mentioned in the preceding article.

Some errors in the References Section: 

Reference 2: Some countries have been mentioned in the literature, but in the reference, only one country has transmitted the virus, and the others have had no problem. 

Reference 14: The main elucidating HIV gene contents do not correspond to the HIV particle contents of this article. 

Reference 15: This article is inconsistent with the reference (2020 is not mentioned, and the number of HIV-infected Africans in Sub-Saharan Africa is suspected). 

Reference 16: The literature reported a cytomegalovirus antibody-positive rate of 92% in 200 donors, which is inconsistent with the 92% reported rate of HCMV infection in the original HIV population. 

Reference 22: page 3, first citation [17,22] in the second paragraph of the inverse of which Ghana's 0% prevalence of HCMV is inconsistent with the literature. 

Both references 31 and 32 are from the same quadruplicated literature. 

Reference 33: No 1999 publication was found; only a 1993 publication was found; the data seem to be inconsistent; and no references are included.

Good.

Author Response

Response to reviewer’s comment 2

1) In this manuscript, the authors collected HIV patients' sera and detected HCMV IgG and IgM to analyze the prevalence of HCMV in HIV individuals. The co-infection relationship between the two types of viruses was discussed, as well as the socio-demographic characteristics, which will be greatly helpful in recording the significance of the location of African populations. 

The data was well organized, and the aims were clear. The samples were significant for the local population. The discussion section was well written, addressing the sections and Table with comparisons. The authors also discussed the hypothesis of the infectious cause for the infection rate in each age group.

Response: Thank you for the encouraging comments.

2) The structures of HCMV and HIV were shown in Figures 1 and 2, which were more like textbooks and had less information than the rest of the paper. The review doesn't talk about the structure of the two viral particles, but the rigid engraftment does.

Response: Thank you for the comment. The two figures were added to provide the reader a quick glance of CMV and HIV.

3) Absence of a control group of HIV-negative persons infected with HCMV. It might be more helpful to know the HCMV without HIV co-infection.

Response: The study was specifically designed to determined the prevalence of HCMV co-infection among HIV patients admitted in the HIV clinic of the State. It was not to compare with non-HIV patients. We may consider to design a study to compare the co-infection of HCMV among HIV patients and non-HIV patients in the future.

4) The interpretation of Figure 2 is inconsistent with the conclusion.

Response: Figure 2 is the structure of HIV particle.

5) Most of the introductions in the review are on HIV or HCMV, respectively, and the last paragraph links the two somewhat inadvertently and not very well.

Response: We hope that this have been corrected.

6) The pregnant women's data in the first part of the discussion is somewhat fuzzy, as if they were not mentioned in the preceding article.

Response: Thank you for your comment. However, we were only comparing our results with those reported from different studies from different location, irrespective of the condition.

7) Reference 2: Some countries have been mentioned in the literature, but in the reference, only one country has transmitted the virus, and the others have had no problem.

Response: Several countries were mentioned in that review, as having co-infection of HCMV.

Reference 14: The main elucidating HIV gene contents do not correspond to the HIV particle contents of this article. 

Response: Thank you for the insight. The correct reference has been added.

Reference 15: This article is inconsistent with the reference (2020 is not mentioned, and the number of HIV-infected Africans in Sub-Saharan Africa is suspected). 

Response: Thank you for your insightful comment. This particular oversight has been corrected.

Reference 16: The literature reported a cytomegalovirus antibody-positive rate of 92% in 200 donors, which is inconsistent with the 92% reported rate of HCMV infection in the original HIV population. 

Response: Thank you for pointing this out. The error has been corrected

Reference 22: page 3, first citation [17,22] in the second paragraph of the inverse of which Ghana's 0% prevalence of HCMV is inconsistent with the literature.

Response: Thank you for the comment. we have corrected the error in page 3.

Both references 31 and 32 are from the same quadruplicated literature.

Response: This has been corrected.

Reference 33: No 1999 publication was found; only a 1993 publication was found; the data seem to be inconsistent; and no references are included

Response: The reference has been removed.

Round 2

Reviewer 2 Report

Advantages: 

1. The text is organized, with a deep-seated, well-aligned plot without monotony. 

2. The number of citations is convincing, and the number of numerical data is straightforward. 

3. The discussion is carefully calibrated, with the sequence of discussion corresponding to one of the variables listed in Table II.

Disadvantages: 

1. Introduction Section. Figure 1.2 is inconsistent. The content below Figure 1 is about HIV, the background and Introduction below Figure 2 are similar, and the HCMV structure is below the Introduction section. 

2. In Section 4. In discussion, row 7, the authors state that HIV is a predisposing factor, lacking HIV-negative and HCMV-positive controls. 

3. This study was not conducted exclusively in pregnant women and is, therefore of little significance to other publications on infections in pregnant women. 

4. In the discussion, the influence of religious factors was attributed to the fact that there were more Christians than Islamists in the study population. 1. Expression of Articles and the Contents of the Cited Literature are the following: 

Reference 2 referred to high- and low-income populations, and reference 3 referred to Nigerians, but both were inconsistent with what the authors described as developing and developed countries. 

Reference 13: The content is good, but the publication year is different from the year labeled in the article, and the found publication date is 1987. 

Ref.14: Article Title Missing Word HIV. 3 

Ref.17 and 18: 96% of the data in the literature are for IgG-positive individuals in 96% of regular healthy donors and for non-HIV patients. 

Ref.21: Australia and 40% values are not mentioned. 2. Neither of the coupled images was illustrated, so the comparison fluctuates.

Fine.

Author Response

Please see the attachment in the box.

Manuscript ID: venereology-2606006

Title: “Sero-prevalence of Human Cytomegalovirus Infection among HIV Patients in Edo State, Southern Nigeria”

RE: Revised manuscript submission and response to reviewers’ comments

Dear Editor,

This letter is in reference to your email dated 11^th October, 2023 with Editor’s comments. We are very pleased that the manuscript is potentially acceptable for publication in Venereology once we have carried out the revisions. 

We would like to thank the editor for these insightful and helpful comments and for giving us the chance to revise our manuscript. We believe the revised manuscript has been significantly improved and the editor’s comments have been addressed adequately. We think in its current form it will make a valuable contribution to the literature on this increasingly important topic. 

Please find for your kind consideration the followings:

• A section-by-section response to the comments and suggestions of the reviewer 2 (below). 
• The revised manuscript, provided as a marked-up copy and a clean copy. 

We hope that these changes meet with your favourable consideration. Please do not hesitate to get in touch if you require any further information. 

Chimezie Igwegbe Nzoputam

Corresponding Author 

Response to reviewer’s Comments 2

1. The text is organized, with a deep-seated, well-aligned plot without monotony. 

Response: Thank you for the encouraging comments.

2. The number of citations is convincing, and the number of numerical data is straightforward. 

Response: Thank you for the comment.

3. The discussion is carefully calibrated, with the sequence of discussion corresponding to one of the variables listed in Table II.

Response: Thank you for the encouraging comments.

4. Introduction Section. Figure 1.2 is inconsistent. The content below Figure 1 is about HIV, the background and Introduction below Figure 2 are similar, and the HCMV structure is below the Introduction section. 

Response: Thank you for the comment. The first paragraph of the introduction talks about HCMV in general, globally. We feel that the structure is relevant and its position on the page is in order. We do think that the structure of HCMV should come immediately after HCMV was discussed. However, we have decided to remove the structure of HIV completely from the manuscript.

5. In Section 4. In discussion, row 7, the authors state that HIV is a predisposing factor, lacking HIV-negative and HCMV-positive controls. 

Response: Thank you for the comments. The statement is confusing and therefore have been deleted

6. This study was not conducted exclusively in pregnant women and is, therefore of little significance to other publications on infections in pregnant women.

Response: Thank you for the comments. Yes, the study was not conducted exclusively among pregnant women. However, we did not exclude pregnant women in our participants. We included all the patients attending the HIV clinic, who gave consent to participate in the study, irrespective of sex and status.

7. In the discussion, the influence of religious factors was attributed to the fact that there were more Christians than Islamists in the study population. 1. Expression of Articles and the Contents of the Cited Literature are the following: 

Reference 2 referred to high- and low-income populations, and reference 3 referred to Nigerians, but both were inconsistent with what the authors described as developing and developed countries. 

Response: Thank you for the comments. This has been corrected.

8. Reference 13: The content is good, but the publication year is different from the year labeled in the article, and the found publication date is 1987. 

Response: Thank you for the comments and insight. This also have been corrected.

9. 14: Article Title Missing Word HIV. 3 

Response: Thank you for the comments and insight. The word HIV is now added.

10. 17 and 18: 96% of the data in the literature are for IgG-positive individuals in 96% of regular healthy donors and for non-HIV patients. 

Response: Thank you for the comments and insight. The correction have been made.

11. 21: Australia and 40% values are not mentioned. 2. Neither of the coupled images was illustrated, so the comparison fluctuates.

Response: Thank you for the comments and insight. We have corrected this and added relevant references.

Author Response File: Author Response.docx