Atherosclerosis and Cardiovascular Complications in People Living with HIV: A Focused Review
, Andrea Marino 2,*, Benedetto Maurizio Celesia 2, Serena Spampinato 1, Carmen Giarratana 1, Emmanuele Venanzi Rullo 1, Bruno Cacopardo 2 and Giuseppe Nunnari 2Round 1
Reviewer 1 Report (New Reviewer)
Comments and Suggestions for AuthorsThe comprehensive manuscript by Raddusa et al. focuses on the atherosclerosis and cardiovascular complications among people living with HIV.
Living with HIV significantly impacts patients' lives, notably accelerating cardiovascular diseases such as atherosclerosis and related complications. The use of antiretroviral therapy, along with other medications and infections, further complicates matters, contributing to increased morbidity and mortality. Despite advancements, the field remains in its infancy, with ample opportunities for further exploration of these intricate connections.
The authors have meticulously covered essential aspects including pathology, the role of chronic inflammation, infection, and treatment strategies in a well-structured manner, with the support of recent literature. Figure 2 and Table 1 are in particularly summarizes the paper. This manuscript can be accepted in the current form (if the content in the “track changes version” remains unchanged).
Author Response
The comprehensive manuscript by Raddusa et al. focuses on the atherosclerosis and cardiovascular complications among people living with HIV.
Living with HIV significantly impacts patients' lives, notably accelerating cardiovascular diseases such as atherosclerosis and related complications. The use of antiretroviral therapy, along with other medications and infections, further complicates matters, contributing to increased morbidity and mortality. Despite advancements, the field remains in its infancy, with ample opportunities for further exploration of these intricate connections.
The authors have meticulously covered essential aspects including pathology, the role of chronic inflammation, infection, and treatment strategies in a well-structured manner, with the support of recent literature. Figure 2 and Table 1 are in particularly summarizes the paper. This manuscript can be accepted in the current form (if the content in the “track changes version” remains unchanged).
Reply: Thank you, we hope our work will add something useful to this field.
Reviewer 2 Report (New Reviewer)
Comments and Suggestions for AuthorsIn this study, the authors summarized how HIV infection is associated with cardiovascular diseases. The authors presented the underlying molecular mechanism, the role of chronic inflammation, metabolic impairment, co-infection, the impact of ART, and potential treatments. The review will serve as an important resource for clinicians and researchers to understand cardiovascular diseases in HIV patients and guide potential management strategies. While the review is generally comprehensive, and the figures and tables are well-made, the writing in each section is not well-organized, with significant repetition and redundant information that should be revised.
My specific comments are as below:
1. In the title, the full name of “PLWH” should be spelled out.
2. The authors should describe how Tat, Nef, and gp120 proteins are related to HIV.
3. The “Role of chronic inflammation and immune activation” section is disorganized and should be reorganized. The first two paragraphs are not related to the topic (line 155-162). Why are they included? Discussions about gut microbe are repeated in lines 187-194 and 209-219, which should be consolidated and simplified. The paragraphs at lines 248-279, 280-281, and 282-286 should be combined.
4. The paragraphs about lipids levels in HIV patients on lines 306-313, 314-317, 318-332 should be combined and redundant information should be removed.
5. The paragraph 370-377 about HIV/HCV co-infection should be merged with the discussion on HIV/HCV in the paragraph on lines 352-361.
6. Full name of INSTI should be mentioned.
7. Subsections should be created within larger sections to make the paper easier to read, especially in the “Role of chronic inflammation and immune activation” and “Role of ART” sections.
8. In the Conclusion section, the authors should mention what is lacking in our understanding of the mechanism of HIV infection and cardiovascular diseases and suggest future research directions to address these gaps.
Comments on the Quality of English LanguageThe quality of English writing is good.
Author Response
In the title, the full name of “PLWH” should be spelled out.
Reply: Done
The authors should describe how Tat, Nef, and gp120 proteins are related to HIV.
Reply: We added few lines for each protein
The “Role of chronic inflammation and immune activation” section is disorganized and should be reorganized. The first two paragraphs are not related to the topic (line 155-162). Why are they included?
Reply: We removed them, as you suggested.
Discussions about gut microbe are repeated in lines 187-194 and 209-219, which should be consolidated and simplified. The paragraphs at lines 248-279, 280-281, and 282-286 should be combined.
Reply: We tried to change what you suggested to improve readability.
The paragraphs about lipids levels in HIV patients on lines 306-313, 314-317, 318-332 should be combined and redundant information should be removed.
Reply: We rephrased the lines you suggested, thank you.
The paragraph 370-377 about HIV/HCV co-infection should be merged with the discussion on HIV/HCV in the paragraph on lines 352-361.
Reply: We merged the two paragraphs you pointed out.
Full name of INSTI should be mentioned.
Reply: Done
Subsections should be created within larger sections to make the paper easier to read, especially in the “Role of chronic inflammation and immune activation” and “Role of ART” sections.
Reply: We changed the text as you suggested
In the Conclusion section, the authors should mention what is lacking in our understanding of the mechanism of HIV infection and cardiovascular diseases and suggest future research directions to address these gaps.
Reply: We added what you suggested in the conclusion section
This manuscript is a resubmission of an earlier submission. The following is a list of the peer review reports and author responses from that submission.
Round 1
Reviewer 1 Report
Comments and Suggestions for AuthorsThe manuscript by Paternò Raddusa and colleagues provides a thorough examination of the causes, mechanisms, and current treatments of atherosclerosis in people living with HIV (PLWH). The treatment-related section is notably comprehensive, offering insights into the beneficial and adverse effects of various medications. Particularly commendable is the coverage of antiretroviral therapy (ART) components, which are described in detail.
However, the review's main focus on HIV-related causative factors and mechanisms appears weak and lacks persuasiveness. The discussion of pathogenic effects of HIV proteins contributing to atherosclerosis is limited to listing final pathogenic products without elucidating how these products are stimulated by HIV proteins. Additionally, there is a noticeable absence of consideration for influential factors such as age, gender, race, and other pertinent variables.
Enhancing the clarity and depth of explanation regarding the interplay between HIV proteins and atherosclerosis pathogenesis, along with incorporating a broader analysis of demographic and contextual factors, would significantly strengthen the manuscript's overall impact and contribution to the field.
Comments on the Quality of English LanguageThe quality of English and style is fine.
Author Response
Please find the attachment for detail.
Author Response File: 
Author Response.pdf
Reviewer 2 Report
Comments and Suggestions for AuthorsFirst of all I would like to congratulate the authors for the preparations of the manuscript. My concerns are regarding the following issues:
1 The article is very general, only 1-2 studies with mentioned results are found within the manuscript. The rest of the text is a general overview on the subjects relating HIV infection, treatment, atherosclerosis, chronic inflammation and so on. I would recommend less volume of text and increased specificity.
2. There is very little data and description of the types of cardiovascular diseases (CVDs), I would recommend adding some more information about what means CVD, which diseases does it include, and what is the difference (in numbers) between HIV-negative people and PLWH regarding incidence, prevalence of atherosclerosis, age of starting the symptoms and so on. What are the risk factors for CVD? Why did you choose to talk only about Atherosclerosis? if you have explanations for these questions please include the answers in the manuscript.
3.In chapter 4 you talk about Metabolic impairment in PLWH. (pages 193-202) Could you please use the universal Staging of HIV in order to find it clear which population are more exposed to risk factor. Maybe you could add some statistical analysis, comparisons between centres (studies), from own hospital or from literature.
4. The conclusions are very general. In my opinion 4-5 ideas should be stated in conclusions. In conclusion section we don't use references or what other studies say.
Author Response
Please find the attachment for detail.
Author Response File: Author Response.pdf
