PONE-D-23-20506Predictors of second-line antiretroviral treatment virological failure at Felege hiwot and  University of Gondar comprehensive specialized hospitals Amhara region, Northwest Ethiopia: a case-control studyPLOS ONE

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https://www.researchgate.net/publication/361344207_Referral_challenges_and_outcomes_of_neonates_received_at_Muhimbili_National_Hospital_Dar_es_Salaam_Tanzania

https://bmcinfectdis.biomedcentral.com/articles/10.1186/s12879-019-4148-3

file:///home/nkw-la22-034/Downloads/WHO-CDS-HIV-19.21-eng.pdf

https://www.poz.com/basics/hiv-basics/hiv-drug-resistance?utm_campaign=301_Redirect&utm_source=aidsmeds

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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?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #1: Yes

Reviewer #2: Yes

Reviewer #3: Partly

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

Reviewer #1: Yes

Reviewer #2: Yes

Reviewer #3: Yes

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

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #1: Yes

Reviewer #2: Yes

Reviewer #3: Yes

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

PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #1: No

Reviewer #2: Yes

Reviewer #3: No

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5. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: In the abstract

Objective: To assess the predictors of second line Anti-Retroviral Treatment virological failure among second line ART users

Method and materials: Institutional based unmatched case control study design was conducted.

By case control able to identify associated factors but not identify predictors.

Results: Out of 216 patients recruited, 212 were participated with a response rate of 98.2%. Among the participants, 117 (55.2%) were males and 187 (88.2%) were urban dwellers. 208 (98.1%) of the respondents had age > 24 years, 73 (34.4%) had elementary level of education, 72(34%) had poor ART adherence and 112(52.8) did not disclose their HIV status.

More detail information about socio-demographic characteristics of the study participants – correct this based on your objectives.

Introduction

More than three pages – need to minimize to two pages

Methods and materials

Study settings

Bahir Dar city - Geographical coordinates of Bahir Dar city are 11° 36' 0" North, 37° 23' 0" East and an Elevation of 1,800 m (5,900 ft.) above sea level (52,53).

The city of Gondar - It founds at 12° 36′ 0″ N, latitude 37° 28′ 0″ E longitude coordinates and an elevation of 2133 m above sea level. (54,55).

All the above information - not link with the objectives of this research?

Sample size determination and sampling techniques

Sample size was calculated using EPIINFO version 7.2.4 (a two-population proportion formula). n= sample size (number of participants), 95% confidence level) Z α/2=1.96 (for 0.05 significance level), for 80% power, Z�= 0.84, r = 1/3 (the ratio of cases to controls), p1= 31% (% of cases among exposed), p2= 11.2% (% of cases among non-exposed). From previous study conducted in Wollo, Amhara Regional State, Northeast Ethiopia, the following significant predictors for second-line antiretroviral treatment virological failure were found, Age 15 – 29 years, Poor adherence, Have no disclosure status, BMI < 16 k.g/m2, CD4 count < 100cells/mm3 , CD4 count 100 – 350 cells/mm3, Having opportunistic infections (51). We used this report as a base line data, the minimum sample size including 10% non-respondent rate for this study was 206 participants (52 cases and 154 controls). But we recruited 216 patients (all the cases 60) and 156 controls.

Sampling techniques

Case selection: All HIV patients who had taken a second line ART for at least six months and had developed a virological failure were selected and listed from the patients registration book at FHCSH and UGCSH during the study period. There were 31 patients at FHCSH and 29 patients at UGCSH who were failed for second line ART. Control selection: All HIV patients who had taken…

More detail – focus on main concepts - minimize in order to fit the publication standard

Over all – the method section More detail – focus on main concepts - minimize in order to fit the publication standard

Result

Factors associated to second line ART virological failure

In bi-variable logistic regression from a total of 36 variables the following: Not using condom, Non-disclosure about HIV status, poor Level of Adherence, severely malnutrition nutritional status and Viral load >1000 copes/ml when switched to second line ART were significantly associated with second line virological ART failure (P-value<0.25).

All the above variables are not significantly associated but selected for multivariable binary logistic regression analysis

Reviewer #2: Comments to the authors

1. Abstract section

Conclusion part: You don’t have to repeat what was mentioned in the result section. Explain it in other terms. The statement “…counseling about the importance of disclosure and good adherence for health care providers are crucial” not clear. Would you please re-phrase it in better terms?

2. Introduction

. The detailed description of prior 1st line ART regimen (NNRTI-based regimen) was not required. Focus on magnitude, and details on factors associated with 2nd line ART regimen failure at international, continental, and national level.

. Acronym use like ‘VF’ , I think for virologic failure, should be mentioned after what is.

3. Methods

a. Population subsection

. Describe source and study population separately

b. Definition of terms

Relocate ‘definition of terms’ at the end of methods section.

c. Data processing and analysis

. Line-3: ….was employed to identify determinates of second line ART virological failure’. Do you mean determinants…?

Line-5: ….multivariate logistic regression mode and…. Do you mean model?

4. Results

a. Table-1

. The variable, Age (in yrs), is not properly grouped. Stratify age interval according to the standard.

b. Table-3

. Foot note for MAM and SAM under the table-3 to explain what it is

. Regarding variables, BMI and Nutritional status: BMI indicate nutritional status. Why a need another variable as ‘nutritional status’. Severity of undernutrition can be verified based on BMI like mild undernutrition as BMI=17.5-18.5kg/m2, Moderate undernutrition as 16-17.5kg/m2, and severe undernutrition as <16kg/m2

. The variable “Viral load when switched to 2nd line ART”

There is no any description in the manuscript regarding switching to 2nd line ART regimen other than virologic failure i.e viral load>1000 copies/ml. Describe reason for switching other than VF for those with VL<1000 copies/ml.

. Clinical and immunological characteristics

Don’t start a sentence with a number. It should be with a text

Eg. “8(13.6%) of the cases and 7(4.6%) of the controls…” It should be “Eight (13.6%) of the cases…”

Table-4

. Insert a column for p-value for COR and AOR

. Your p-value to test significance was at 0.05. Why a need to mention at p-value of 0.01, 0.005, 0.001. Testing at p-value at 0.05 is adequate.

Under the title “Factors associated to second line ART virological failure”, there were 36 variables tested for bivariate analysis. You need to mention those variables tested but not significant in bivariate analysis.

The statement:

“Moreover, the likely hood of developing second line virologic failure among patients with Viral

load >1000 copes/ml when switched to second line ART medication were 3.5 times (AOR=3.56,

95% CI: 1.5 - 8) more likely as compared to those patients who had Viral load result <1000

copes/ml”.

Correction should be made in abstract, results and discussion section.

It should be re-written as “…those with VL>1000 copies/ml had 3.5 times more to develop VF as compared to those with VL<150 copies /ml…”

and ““…those with VL>150-999 copies/ml had 5 times more to develop VF as compared to those with VL<150 copies /ml…”

Discussion

. Citation of reference should be at the end of a sentence, not in the middle of a sentence.

. Acronym ‘…meds…’ do you mean medications. Correct it as required.

. Revise a statement “Double-edged sword of disclosure on ART adherence…”

You mentioned the advantage of disclosure on ART adherence, what was the disadvantage of disclosure on ART adherence.

Reference

It was referenced manually. It should be referenced using Mandalay or EndNote electronically.

Reviewer #3: A language editing service is required for the paper to be published. A lot of findings are there regarding this topic, so the findings may not add new things to the literature communities.

Title modification: Determinants of virological failure among HIV clients on second-line antiretroviral treatment at Felege-hiwot and University of Gondar comprehensive specialized hospitals in the Amhara region, Northwest Ethiopia: a case-control study

Background: It doesn’t show the gap that the research was required to fill. Further justification for the study will be required to be published. A lot of studies were done in Ethiopia for this title. How do new findings come with this study?

Methods: Why are patients on third-line regimens included? Are your findings generalizable to such ART patients?

The study included ART patients on second-line treatment for 6 months, but to detect virological failure, at least two consecutive viral load results are required after 6 months of treatment follow-up. Based on this scenario, could this method follow the correct procedure? Please provide in detail your methodology and the real situation. So, your study should include those ART patients, at least on second-line treatment for 9 months.

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Reviewer #1: Yes: Esubalew Tesfahun (Ph.D)

Reviewer #2: Yes: Abilo Tadesse, MD

Reviewer #3: No

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Attachments

Attachment

Submitted filename: Comments.docx

Title - Determinants of virological failure among HIV clients on second-line antiretroviral treatment at Felege-hiwot and University of Gondar comprehensive specialized hospitals in the Amhara region, Northwest Ethiopia: case-control study.

PONE-D-23-20506R1

Dear Dr. Getie,

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.

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,

Yoon-Seok Chung

Academic Editor

PLOS ONE

Additional Editor Comments (optional):

Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. If the authors have adequately addressed your comments raised in a previous round of review and you feel that this manuscript is now acceptable for publication, you may indicate that here to bypass the “Comments to the Author” section, enter your conflict of interest statement in the “Confidential to Editor” section, and submit your "Accept" recommendation.

Reviewer #1: All comments have been addressed

Reviewer #2: All comments have been addressed

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

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #1: Yes

Reviewer #2: Yes

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

Reviewer #1: Yes

Reviewer #2: Yes

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

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #1: Yes

Reviewer #2: Yes

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

PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #1: Yes

Reviewer #2: Yes

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6. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: All my comments and concerns are adrressed in this version. I checked and revier this version, the authors accept and correct . In this version no addtional comments and concern.

Reviewer #2: Corrections

. Language polishing is required.

Line-92: ...HIV ADIS, is it ...HIV AIDS..?

Line 182: crosschecked .. cross checked...?

Line 280: ..likely hood ... likelihood...

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Reviewer #1: Yes: Esubalew Tesfahun

Reviewer #2: Yes: Abilo Tadesse

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