PONE-D-23-25851Effectiveness of a mindfulness and acceptance-based intervention for improving the mental health of adolescents with HIV in Uganda: An open-label trialPLOS ONE

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Reviewer #1: Yes

Reviewer #2: Yes

Reviewer #3: No

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

Reviewer #1: Yes

Reviewer #2: Yes

Reviewer #3: No

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Reviewer #1: Yes

Reviewer #2: Yes

Reviewer #3: Yes

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Reviewer #1: Yes

Reviewer #2: Yes

Reviewer #3: Yes

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5. Review Comments to the Author

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Reviewer #1: dear authors, this is an interesting and innovative study and much needed in the context of support AWH.

My comments are as follows:

A few typos, spaces, please read carefully and fix

Please add a description of the adaptation to Ugandan culture and context. At the moment, I am not clear on that. Did you have a participatory process to adapt it and if yes, how exactly was that done?

Why only 4 sessions: add an explanation to why the local mh experts suggested it and was it based on evidence from other studies?

The sentence around the "14y old clients being young not old" is a bit confusing. Please rephrase, can you add any evidence to your choice of excluding the 14y olds.

Write out abbreviations from time to time (such as DNA-v) for better understanding of the reader

Can you add more information about the trainers. What core competencies did they have?

How do you insure replicability, can the intervention be task-shifted and if yes to whom in the local context?

In standard of care:

How much time on average do/did health care providers spend per adolescent? The program you describe is quite comprehensive and how is fidelity assured?

Tools

Have the BDI ii amd SHAI been validated in your setting? You didnt mention it so I suppose not. You should then discuss this in the limitations.

Discussion

I would appreciate if you had more integration of the program details into the Ugandan culture and context to better understand the applicability of it. It would be good in studies like this to have a qualitative component post intervention to understand the experience of the participants. What barriers did you experience or do you anticipate should such a program be rolled out.

Please also discuss social desirability as a potential bias.

Thank you!

Reviewer #2: PLOS Review

The paper is important and timely. It describes results of a MABI, specifically an ACT-acceptance and commitment therapy model called DNA-v as a way to address mental health distress and life skills of adolescents living with HIV in Uganda. The results are impressive based on four sessions. As authors point out in limitations, an immediate effect is not necessarily sustained. It would be interesting to see if the effects last over time, beyond a four-week period.

Intro: Reads very well, no comments

Methods:

Please clarify the grouping. Were groups mixed gender. How were the sub-groups determined? Did the 3 sub-groups of 4 interact as a bigger group of 11-12? If not, then why did you not randomized into groups of 4 as opposed to 11-12?

Please clarify the DNA-v model v. mindfulness and acceptance. Were both trainers leading different components of the intervention or working together with the three sub-groups during each of the 4 sessions?

What is required to be trained in delivery of the DNA-v model? How is fidelity ensured?

Can you say more as to why in the adaptation phase, 4 sessions were preferred to 6, and what content was cut out to accommodate this change?

For the SHAI. How does the overall reliability have α=.93. When the components are less: The fear of illness sub-scale (items 1-14) has a co-efficient of α=.84 and the negative consequences of an illness sub-scale (items 15-18) has a co-efficient of α=.67?

How were data from youth who were randomized to intervention but never came or missed many sessions handled? Were they still allowed to come for post-intervention visits and where were they grouped? How was missing sessions handled? Were youth allowed to come in any session or was there a criteria for them to attend the first, or a certain number to stay in the group?

Sample size powered for 116, but enrolled 122.

Results:

1. A consort flow diagram might be helpful. More transparency in stating in the text that there was 30% attrition post-assessment? [Doing the math it looks like intervention went from 61 pre to 44 post; control 61 pre to 42 post?]. Were those who did not come for follow up in any way different than those who did? This is somewhat addressed in limitations, but should be addressed in the results section.

2. What was the attendance rate of the intervention group? Did all 44 complete all four sessions?

3. Do you have any HIV RNA viral load data to link the mental health to HIV outcomes?

Discussion:

1. What would need to happen to roll this out in Uganda more broadly? Should it be integrated into clinical care?

2. The discussion statement: line 345 the results can be interpreted that “AWH who received the intervention became open to life experiences non-judgementally, developed self-compassion, and learned how to make choices in ways that bring meaning to them”. I am not sure these conclusions can be made based on the 3 scales of depression, anxiety and stigma presented. Do you have specific data not presented to support this. Otherwise, perhaps it is more accurate to say it is possible that being open to life experiences non-judgmentally, developing self-compassion, and learning how to make choices in ways that bring meaning may be the mechanism by which participants in the intervention arm experienced less mental distress and reduced internal stigma at post-intervention.

3. Any concern of spillover of intervention content between AWH who received the intervention compared to those in the control group given they all attend the same clinic?

4. Consider Simms PMID 34986170, Dow PMID 32887558, in the references of line 392 regarding other psychotherapeutic approaches to improve the MH of adolescents living with HIV in LIC.

Reviewer #3: General comments:

This study reports the results of a mental health intervention for adolescents in Uganda with HIV.

Regarding the study design, I have specific comments below regarding aspects of the study. One major comment I have is, since the intervention was delivered in small groups, I believe this is an individual randomized group treatment trial (IRGT doi: 10.2105/AJPH.2007.127027). In IRGTs, the composition of the groups could influence the participant's outcome; in other words, within group responses may be correlated. The sample size calculations and analyses do not appear to have taken into account this correlation in the analyses. Unfortunately, this is a shortcoming of the power analyses and, depending on the magnitude of the correlation and the small number of subgroups, may mean the study is underpowered.

Regarding the methods, you need to make changes to the analyses to address the correlation between participants in the same subgroup in order for the analyses to be robust. Most likely, this involves switching to a mixed model.

It is also not entirely clear to me whether the regression models analyze change scores or the responses at each survey. There is quite a bit of literature on changes scores and, unfortunately, a good portion of it came out before the widespread availability of methods to fit longitudinal models. The efficiency of change scores can be quite low (e.g., https://doi.org/10.1136/bmj.323.7321.1123). I strongly encourage you not to analyze change scores and instead analyze both pre- and post-test measurements together in a mixed model. That means two rows for each person who completed both assessments and then using a random effect to control for the correlation between those observations.

I also think, if the clinical threshold outcomes are important enough to have a table (Table 6) and devote a portion of the discussion to, multivariable analyses need to be performed on them. It seems strange to not have regression analyses of the clinical threshold outcomes.

The reporting in Table 5 is very confusing (see specific comments below). I also believe more discussion is needed on the magnitude of the decreases. What do the beta coefficients mean? How clinically relevant are these decreases? Continuous scale outcomes are nice from a research perspective because they provide greater power, but I think the changes need to be described more fully.

I think the language of saying that your study "contradicts" other studies (line 351) is too strong.

Specific comments:

1. (line 153) "protocal" should be "protocol".

2. (lines 168-169) Please indicate the program utilized for randomization and the random number algorithm.

3. (line 254) I have many questions about the power analysis. Is the mean decrease of 4.09 based on BDI or all measures? Why did you choose 4.09? What is the relevance of that mean decrease? What did you assume as a variance or standard deviation estimate?

4. (lines 254-255) What did you use for your power calculations, e.g., formulas, software packages, etc.?

5. (lines 262-264) These two statements do not make sense together since an ITT approach assumes anyone randomized gets analyzed. You are following a per protocol (PP) or according to protocol (ATP) approach by excluding all people who withdrew before the end of the protocol.

6. (Table 1) Significance testing in these situations is generally frowned upon because a non-significant p-value does not indicate that groups are the same. For info on the topic in relation to baseline imbalance in randomized trials see Altman, https://doi.org/10.2307/2987510 and Senn, https://doi.org/10.1002/sim.4780131703. My recommendation is to remove the significance testing from table 1 and use standardized difference to assess differences (see Austin, https://doi.org/10.1080/03610910902859574).

7. (Table 4) I don't believe there was a mention of using Cohen's effect size in the methods section. This needs to be described in the methods section. Also, I'm not sure what this adds beyond the information in tables 3 and 5.

8. (Table 5) What is the first row, the one labeled "Coefficient"? Are these the model intercepts? Also, why does the Stigma coefficient not have a CI?

9. (Table 5) Also, the coefficients and CIs are confusing in almost all situations. A first example is the comparison between intervention and control for the anxiety outcome is reported as "-.326 (12.240- (-2.770))" with a p-value of .002. The lower CI limit is greater than the upper CI limit. Since the CI covers zero, the p-value should not be <0.05. A second example is the intervention versus control for the stigma outcome. That is reported as

"-.371 (-1.046 -3.036)". The point estimate is not contained within the CI limits, which is illogical. This table is very problematic and requires a thorough review.

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Reviewer #1: Yes: Dr Ruth Verhey

Reviewer #2: No

Reviewer #3: No

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Effectiveness of a mindfulness and acceptance-based intervention for improving the mental health of adolescents with HIV in Uganda: An open-label trial

PONE-D-23-25851R1

Dear Dr. Musanje,

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Thank you for taking the time to thoroughly respond to the reviewers' comments. 

Reviewers' comments: