Peer-led counselling with problem discussion therapy for adolescents living with HIV in Zimbabwe: A cluster-randomised trial.

BACKGROUND: Adolescents living with HIV have poor virological suppression and high prevalence of common mental disorders (CMDs). In Zimbabwe, the Zvandiri adolescent peer support programme is effective at improving virological suppression. We assessed the effect of training Zvandiri peer counsellors known as Community Adolescent Treatment Supporters (CATS) in problem-solving therapy (PST) on virological suppression and mental health outcomes. METHODS AND
FINDINGS: Sixty clinics were randomised 1:1 to either normal Zvandiri peer counselling or a peer counsellor trained in PST. In January to March 2019, 842 adolescents aged 10 to 19 years and living with HIV who screened positive for CMDs were enrolled (375 (44.5%) male and 418 (49.6%) orphaned of at least one parent). The primary outcome was virological nonsuppression (viral load ≥1,000 copies/mL). Secondary outcomes were symptoms of CMDs measured with the Shona Symptom Questionnaire (SSQ ≥8) and depression measured with the Patient Health Questionnaire (PHQ-9 ≥10) and health utility score using the EQ-5D. The adjusted odds ratios (AORs) and 95% confidence intervals (CIs) were estimated using logistic regression adjusting for clinic-level clustering. Case reviews and focus group discussions were used to determine feasibility of intervention delivery. At baseline, 35.1% of participants had virological nonsuppression and 70.3% had SSQ≥8. After 48 weeks, follow-up was 89.5% for viral load data and 90.9% for other outcomes. Virological nonsuppression decreased in both arms, but there was no evidence of an intervention effect (prevalence of nonsuppression 14.7% in the Zvandiri-PST arm versus 11.9% in the Zvandiri arm; AOR = 1.29; 95% CI 0.68, 2.48; p = 0.44). There was strong evidence of an apparent effect on common mental health outcomes (SSQ ≥8: 2.4% versus 10.3% [AOR = 0.19; 95% CI 0.08, 0.46; p < 0.001]; PHQ-9 ≥10: 2.9% versus 8.8% [AOR = 0.32; 95% CI 0.14, 0.78; p = 0.01]). Prevalence of EQ-5D index score <1 was 27.6% versus 38.9% (AOR = 0.56; 95% CI 0.31, 1.03; p = 0.06). Qualitative analyses found that CATS-observed participants had limited autonomy or ability to solve problems. In response, the CATS adapted the intervention to focus on empathic problem discussion to fit adolescents' age, capacity, and circumstances, which was beneficial. Limitations include that cost data were not available and that the mental health tools were validated in adult populations, not adolescents.
CONCLUSIONS: PST training for CATS did not add to the benefit of peer support in reducing virological nonsuppression but led to improved symptoms of CMD and depression compared to standard Zvandiri care among adolescents living with HIV in Zimbabwe. Active involvement of caregivers and strengthened referral structures could increase feasibility and effectiveness. TRIAL REGISTRATION: Pan African Clinical Trials Registry PACTR201810756862405.

Introduction

Common mental disorders (CMDs) such as anxiety and depression are highly prevalent among adolescents living with HIV [1]. CMDs affect quality of life directly and are associated with impaired adherence to antiretroviral therapy (ART) and, therefore, with the increased resistance, morbidity, and mortality. Adolescents living with HIV have poorer virological suppression than any other age group [2].

The World Health Organisation (WHO) updated recommendations on service delivery for the treatment and care of people living with HIV [3] make a strong recommendation that psychosocial interventions should be provided to all adolescents and young adults living with HIV. One of the programmes underpinning this recommendation is Zvandiri, a WHO best practice programme [4] for adolescents living with HIV in Zimbabwe. The core of the Zvandiri approach is Community Adolescent Treatment Supporters (CATS). CATS are young people aged 18 to 24 years living with HIV who are trained and mentored to provide peer counselling and support. A cluster-randomised controlled trial (CRT) showed that the Zvandiri programme was more effective than standard of care at improving HIV virological suppression of adolescents but was not more effective for treating CMDs [5]. In qualitative interviews, participants reported that they found aspects of the intervention beneficial for mental health.

Friendship Bench is a counselling programme delivered by trained lay health workers, with a focus on problem-solving therapy (PST). PST is a cognitive-behavioural approach, which develops cognitive tools for problem solving, and builds adaptive skills and an enhanced sense of agency [6]. Friendship Bench was developed for adults and has been adapted for youth. In adults, it has been proven effective at improving mental health outcomes compared to standard of care [6]. The Friendship Bench program focuses on exploration and understanding of the clients’ situational context through talk therapy, mentalization, positive relational experience through being listened to, and intrapersonal growth towards strength and ability through goal-oriented learning.

The aim of the current trial was to evaluate whether enhancing the counselling skills of CATS to provide PST reduces virological nonsuppression and improves mental health among adolescents living with HIV in Zimbabwe, compared with standard Zvandiri care.

Methods

The study design and methods have been fully described in a protocol paper [7]. Briefly, the Zvandiri programme was operational in 60 clinics (clusters), 6 in each of 10 districts across Zimbabwe. The clinics had previously been selected for a scale-up of the Zvandiri programme. In each district, the 6 clinics were randomly allocated 1:1 to the Zvandiri-PST arm or the Zvandiri arm by an independent statistician using a prewritten randomisation code. There was no allocation concealment.

All participants attending clinics allocated to the Zvandiri arm received Zvandiri standard care, consisting of HIV care following Ministry of Health and Child Care (MoHCC) guidelines [8], plus counselling and home visits from trained, mentored CATS, monthly support groups, and weekly text messages and home visits. Participants at the Zvandiri-PST clinics received the same, plus additional sessions based on the CATS’ PST training. The CATS in the Zvandiri-PST arm met a Zvandiri mentor at least once every 2 weeks to review individual cases.

The PST consisted of a series of steps described in the Friendship Bench manual [9]. The first step is “kuvhura pfungwa” (opening up the mind), in which the client makes a list of all their problems. In the next step, “kusimudzira” (uplifting), the counsellor helps the client choose one manageable, relevant problem, establish a goal, and brainstorm solutions. The third step, “kusimbisa” (strengthening), focuses on selecting a detailed solution and devising a specific, measurable, achievable, realistic, and timely (SMART) action plan to carry it out. Finally, in the fourth step, “kusimbisisa” (further strengthening), clients are invited to join a support group.

Adolescents living with HIV aged 10 to 19 years who were taking ART were screened using the 14-item Shona Symptom Questionnaire (SSQ), a locally developed and validated instrument to assess symptoms of CMD [10,11]. Those scoring ≥7/14 who did not meet any of the exclusion criteria (unable to comprehend the nature of the study in either English, Shona, or Ndebele, currently in psychiatric care, end stage AIDS, current psychosis, intoxication, and/or cognitive disability) were enrolled after obtaining written consent from the caregiver and assent from the adolescent (or consent from the adolescent if aged 18 to 19). Those who were too unwell to participate or unable to give informed consent were excluded. The trial was registered with the Pan African Clinical Trials Registry (PACTR201810756862405) and approved by the ethics committees of the Medical Research Council of Zimbabwe and the London School of Hygiene & Tropical Medicine.

Quantitative data collection and analysis

The primary outcome was the proportion of participants with virological failure (defined as ≥1,000 copies/ml) or death at 48 weeks after enrolment (plus or minus 8 weeks). Viral load was obtained from a dried blood spot (DBS) sample. Secondary outcomes were the proportion of participants with symptoms of CMD, defined as a score of ≥8/14 on the SSQ [11], and proportion with symptoms of depression, defined as a score of ≥10/27 on the Patient Health Questionnaire (PHQ-9) [11]. Poor quality of life was assessed as a secondary outcome using the EQ-5D scale converted to an index using validated Zimbabwe utility scores [12,13] and analysed as a binary variable (1 versus <1), as the highly skewed distribution of scores did not allow for analysis as a continuous outcome. Severity of mental health symptoms was assessed using the SSQ and PHQ-9 as continuous scores.

The sample size of 840 participants recruited from 60 clusters provided 85% power to detect a difference in virological nonsuppression of 43% among participants in the Zvandiri arm versus 30% in the Zvandiri-PST arm assuming 20% loss to follow-up and a coefficient of variation (k) between clusters of 0.25. For secondary outcomes, the sample size provided 87% power to detect a difference in the proportion with CMD symptoms at 12 months of 16% in the Zvandiri arm and 8% in the Zvandiri-PST arm. The predicted outcomes in the Zvandiri arm were based on baseline results of a previous trial [5].

At baseline, data collection was predominantly paper based. A private company (Datalyst) completed double entry and validation of data. At endline, data were collected using a preprogrammed form in ODK on Android tablets. Data were exported to Stata 15.1 for cleaning and analysis, following a prespecified analytical plan. Statisticians were blinded to study arm until analysis was complete. Data were collected by CATS, so it was not possible to blind them to study arm.

Analysis used intention-to-treat principles, retaining participants in the arm to which they were randomised. In a prewritten analytical plan (S1 Text), an a priori decision was made to adjust for baseline values of the relevant outcome measure and for key variables that were deemed imbalanced between arms at baseline or were associated with missing outcome data. The primary analysis was complete case. For binary outcomes, logistic regression random effects models were used to estimate adjusted odds ratios (AORs) and 95% confidence interval (CI), with a random effects term to allow for clustering by clinic. A quadrature check was performed to evaluate the model fit. For continuous outcomes, analogous mixed effects linear regression models were used to estimate adjusted mean differences (AMDs) and 95% CI. Prespecified effect modification by age group at baseline of the intervention effect on the primary and secondary outcomes was assessed by fitting separate models for the 10 to 14 and 15 to 19 age groups.

Qualitative data collection and analysis

To better understand how the CATS experienced implementing the intervention, including its feasibility and any necessary modifications, we collected qualitative data to capture concurrent and retrospective accounts of the CATS (Table 1). Case reviews between 20 individual CATS and their mentors were conducted each month over the 12-month trial duration. Two focus group discussions (FGDs) were held with 20 CATS at the end of the trial. Conducted by Zvandiri researchers at the Africaid offices in Harare, the FGDs involved a range of activities to facilitate reflective discussion. All data collection was conducted in the local languages and audio recorded. Data were transcribed and translated into English. A thematic analytical approach was adopted [14]. Analytical memos and weekly analytical team meetings were also used in the development of themes and identification of patterns related to CATS experiences across the datasets [15]. See S1 CONSORT Checklist.

Table 1

Description of qualitative data collection.

Method	Outline of method	Purpose of data collection
Case reviews	Individual supervisory discussions (between CATS and mentors) about client cases	CATS’ experiences of provision of support and support needs in real time
FGDs	Group discussion between CATS	Retrospective reflections of CATS’ on their experiences
Audio diaries	Recorded interviews between CATS and mentors about the CATS’ experiences of delivering the intervention and participants’ problems	Participatory insights into the types of problems participants presented with and the experiences of implementation

CATS, Community Adolescent Treatment Supporters; FGD, focus group discussion.

Results

Quantitative findings

Between 2 January and 21 March 2019, 1,573 adolescents were screened for eligibility and 863 were eligible. The most common reason for noneligibility was an SSQ score below 7 (N = 690). In addition, 11 adolescents were excluded because they lived out of the study area, 6 because they were younger than 10 or older than 19 years, 2 because of disability, and 1 because they were at boarding school. Of the 863 eligible adolescents and their caregivers who were asked for consent or assent, 12 (1.3%) participants and 9 (1.0%) of caregivers refused. Of the 842 enrolled participants, 421 participants were randomised to each arm (Fig 1).

Fig 1

Enrolment flow chart.

CATS, Community Adolescent Treatment Supporters; PST, problem-solving therapy; SSQ, Shona Symptom Questionnaire.

The mean number of participants per clinic was 14.0 (standard deviation 2.7, range 6 to 22). At baseline, 35.1% (292/833) of participants had a viral load ≥1,000 copies/ml, with 9 missing viral loads. The prevalence of virological nonsuppression by district ranged from 20.2% to 55.4%. There was little imbalance between arms in any of the prespecified variables (Table 2).

Table 2

Descriptive characteristics of participants at baseline by trial arm.

		Zvandiri-PST, n (%)	Zvandiri, n (%)
	N	421	421
Sex	Male	184 (43.7)	191 (45.4)
	Female	237 (56.3)	230 (54.6)
Age (years)	10–11	77 (18.3)	75 (17.8)
	12–13	72 (17.1)	92 (21.9)
	14–15	78 (18.5)	101 (24.0)
	16–17	109 (25.9)	68 (16.2)
	18–19	85 (20.2)	85 (20.2)
Education (7 missing)	Below grade 7	150 (36.1)	151 (36.0)
	Grade 7	153 (36.8)	133 (31.7)
	Secondary or higher	113 (27.2)	135 (32.2)
HIV status disclosure	Does not know status	87 (21.8)	71 (18.3)
	Knows status, has not disclosed	177 (44.3)	196 (50.5)
	Knows status, has disclosed	136 (34.0)	121 (31.2)
	Missing	21	33
Orphan (2 missing)	Both parents alive	207 (49.3)	215 (51.2)
	Single orphan	136 (32.4)	109 (26.0)
	Double orphan	77 (18.3)	96 (22.9)
Viral load (9 missing)	≥1,000 copies	151 (36.4)	141 (33.7)
	<1,000 copies	264 (63.6)	277 (66.3)
SSQ score	No red flag	265 (63.0)	282 (67.0)
	Red flag	156 (37.1)	139 (33.0)
SSQ score	Median (IQR)	8 (7–9)	8 (7–10)
PHQ-9 score (1 missing)	Minimal (0–4)	81 (19.3)	82 (19.5)
	Mild (5–9)	201 (47.9)	181 (43.0)
	Moderate (10–14)	106 (25.2)	116 (27.6)
	Moderately severe/Severe (15–27)	32 (7.6)	42 (10.0)
PHQ-9 score	Median (IQR)	8 (5–11)	8 (5–11)
EQ5D index score	Median (IQR) 1 = best	0.84 (0.74–1)	0.81 (0.74–1)

IQR, inter-quartile range; PHQ, Patient Health Questionnaire; PST, problem-solving therapy; SSQ, Shona Symptom Questionnaire.

Endline interviews were completed between 4 to 31 January 2020, with the exception of one interview completed on 26 February 2020. Three participants died during the follow-up period, all in the Zvandiri-PST arm, of causes unrelated to the intervention. In addition, 22 participants moved away from the area, and 52 were lost to follow-up for unknown reasons. Follow-up was 89.6% in the Zvandiri-PST arm and 92.2% in the Zvandiri arm. The proportion lost to follow-up by district ranged from 2.4% to 16.7%. Fourteen participants had an endline interview but no endline viral load result, owing to challenges with lab testing as a result of the COVID-19 lockdown in Zimbabwe. Therefore, 88 participants (10.5%) had no primary outcome (excluding the 3 who died).

The mean time between baseline and follow-up interviews was 49.6 weeks in the Zvandiri-PST arm (range 44 to 56) and 49.4 weeks in the Zvandiri arm (range 42 to 56). All endline visits were within the prespecified visit window of 48 weeks ± 8 weeks. There was no evidence of an association between loss to follow-up and baseline values of virological nonsuppression, SSQ score or PHQ-9 score. Follow-up was similar by arm (89.1% versus 90.0% for the primary outcome; 89.6% versus 92.2% for other outcomes). Participants lost to follow-up were on average older than those with an endline measurement, and after adjusting for age, there was no association of loss to follow-up with any other factors (S1 Table). Therefore, we adjusted for baseline age in all analysis.

At endline, there was no evidence of an intervention effect on the primary outcome of virological nonsuppression or death (14.7% versus 11.9% in the Zvandiri-PST arm versus Zvandiri arm; AOR = 1.29; 95% CI 0.68, 2.48; p = 0.44) (Table 3). However, there was evidence of an apparent intervention effect on prevalence and severity of common mental health outcomes (SSQ ≥8: 2.4% versus 10.3%; AOR = 0.19; 95% CI 0.08, 0.46; p < 0.001; AMD = −1.14; 95% CI −1.80, −0.49; p = 0.001; PHQ-9 ≥10: 2.9% versus 8.8%; AOR = 0.32; 95% CI 0.14, 0.78; p = 0.01; AMD = −1.14; 95% CI −2.01, −0.27; p = 0.01) (Table 3). The proportion of participants with an EQ-5D score below 1 was lower in the Zvandiri-PST arm than in the Zvandiri arm, but with weak evidence of effect (27.6% versus 38.9%; AOR = 0.56; 95% CI 0.31, 1.03; p = 0.06). Crude results, unadjusted for baseline outcome or age, were similar (S2 Table).

Table 3

Intervention effect on primary and secondary outcomes at 48 weeks.

	Zvandiri-PST	Zvandiri
Binary	n/N (%)	n/N (%)	AOR (95% CI)	p-value	ICC
Primary outcome
Viral load ≥1,000	55/375 (14.7)	45/379 (11.9)	1.29 (0.68, 2.48)	0.44	0.15
Secondary outcomes
SSQ≥ 8	9/377 (2.4)	40/388 (10.3)	0.19 (0.08, 0.46)	<0.001	0.17
PHQ-9 ≥10	11/377 (2.9)	34/388 (8.8)	0.32 (0.14, 0.78)	0.01	0.18
EQ-5D index score <1	104/377 (27.6)	151/388 (38.9)	0.56 (0.31, 1.03)	0.06	0.22
Continuous	Mean (SD)	Mean (SD)	AMD (95% CI)	p-value
SSQ score	2.22 (2.15)	3.38 (3.02)	−1.14 (−1.80, −0.49)	0.001	0.18
PHQ-9 score	2.40 (3.01)	3.48 (3.83)	-1.14 (−2.01, −0.27)	0.01	0.19

AMD, adjusted mean difference; AOR, adjusted odds ratio; ICC, intracluster correlation; PHQ, Patient Health Questionnaire; SSQ, Shona Symptom Questionnaire.

All analysis adjusting for baseline value of the outcome, baseline age, and clinic as a random effect.

There was evidence of a difference in effectiveness of the intervention on virological nonsuppression or death by age (p = 0.01 for interaction), with stronger evidence of an intervention effect in 15- to 19-year-olds (18.5% versus 9.8%; AOR = 2.65 95% CI 0.97, 7.23; p = 0.06) than for 10 to 14-year-olds (10.6% versus 13.6%; AOR = 0.68, 95% CI 0.35, 1.31; p = 0.24) (S3 Table). There was no evidence of effect modification by age for secondary outcomes. Intracluster correlation was below 0.2 for all outcomes.

Five participants in the Zvandiri-PST arm had no PST sessions logged, and 4 of these did not have endline data. The mean number of PST sessions was 5 (maximum 11) (Table 4). On average, Zvandiri-PST participants received more text messages (mean difference = 6.50; 95% CI 0.57, 12.43, p = 0.03) and fewer support group sessions (mean difference = −1.88; 95% CI −3.51, −0.25), p = 0.02) than Zvandiri arm participants, with no evidence of a difference between arms in the mean number of facility visits, outreach visits, or contacts with caregivers.

Table 4

Description of care received by arm.

	Zvandiri-PST, mean (SD), range	Zvandiri arm, mean (SD), range	MD (95% CI)	p-value
PST sessions	5.0 (1.7), 0–11	0
CKT sessions	4.1 (2.6), 0–20	0
Facility visits	10.6 (3.9), 1–23	9.8 (4.4), 1–25	0.94 (−0.75, 2.62)	0.28
Text messages	21.9 (16.0), 0–107	15.2 (10.3), 2–63	6.50 (0.57, 12.43)	0.03
Support groups	7.1 (3.7), 0–17	8.9 (3.7), 0–16	−1.88 (−3.51, −0.25)	0.02
Outreach visits	7.5 (3.9), 0–25	7.0 (7.5), 0–120	0.50 (−1.58, 2.59)	0.64
Caregiver contact	10.8 (4.9), 0–29	10.4 (6.1), 2–36	0.32 (−2.15, 2.79)	0.80

CKT, Circle Kubatana Tose support group; MD, mean difference; PST, problem-solving therapy.

Adjusting for clinic as a random effect.

According to self-reported data, 74 participants switched ART regimen during follow-up (11.7% of 632 who knew their status and were asked the question). The most common reported reason for switching regimen was that viral load was high (n = 32, 43.2%). In the Zvandiri-PST arm, 43 (13.9%) reported switching regimen compared to 31 (10.2%) in the Zvandiri arm.

Qualitative findings

The 2 FGDs were held during the endline data collection period (January 2020). Each comprised 10 CATS and lasted approximately 90 minutes. Of the 240 planned case reviews (20 CATS have one per month for a year), 200 were conducted. Case report transcripts generally ranged from 500 to 1,000 words.

Trial participants and CATS reported that the PST intervention was difficult to implement, with challenges reflecting the relational context of adolescents’ lives. Their problems tend to be a product of how entangled and dependent they are on their relationships with others, which limits the agency that youth have to resolve their problems themselves. Consequently, there was low fidelity to the later steps in the model, which involved developing SMART action plans to address an identified problem. Instead, the CATS focused on the earlier steps of the model (problem discussion), which participants found to be affirming and constructive in enabling them to cope.

The analysis is presented through 3 key themes: fidelity impeded by relational nature of adolescents’ problems; the value of peer-led problem discussion therapy; and role for others in developing mental health support networks (Table 4).

Fidelity impeded by relational nature of adolescents’ problems

The CATS were able to encourage participants to discuss their problems, although it often took several sessions for them to feel confident to talk openly. This reticence indicates how unusual it is for adolescents to have a dedicated forum to talk about their problems, as well as the time taken to establish the expertise of the CATS in the eyes of the participants and their caregivers. This reflects a prevailing view articulated by adolescents, caregivers, and the CATS themselves that young people exercise very limited influence over their situations if they do not have adult support (Table 5, Subtheme 1a). As a CATS describes:

Table 5

Qualitative themes and indicative quotes on fidelity of delivering the intervention.

Themes	Subthemes	Indicative quotes
1. Impeded fidelity
	1a. Scepticism of the capacity of young people to affect their peers’ problems
	“It’s still very difficult because some participants are still failing to open up because they will be thinking that how will I help them because I am also a child myself so it will be useless for them to share with me their problems.” (Matobo)“Some of the challenges are that some adolescents do not cooperate, they just look at you to the extent that it becomes very difficult to assist them. It is still very difficult to see whether PST is working or not. There is a problem of not understanding each other, it is difficult for a child to tell you their problem. Other participants think that it is very difficult to disclose their problems to another adolescent and still think they might not get assistance from the CATS.”—Matobo“Caregivers now understood and accepted us. At times you would reach a point when we would be chased by caregivers and you would actually see that it was difficult to get to the caregivers. But with time we were being treated nicely and welcomed. Caregivers allowed us to meet their children.” (Gokwe South)“The first day we arrived with aunty the child tried to run away and we saw the child after a long time. After we had waited at the child’s home and then aunty talked to the child and it helped the child. When l visited the child for the second, third time alone we were now getting along well.”—Kwekwe
	1b: Limited agency of youth to resolve relationally entangled problems
	“His father married a wife who was his stepmother and this was another challenge the client faced. He says there was never a good relationship between the two. The client was unhappy at home because the stepmother was not supportive of him.”—Beitbridge“The problem she mentioned is that her stepmother punishes her by depriving her food even for little offences and giving her punishments. The help that is required is to find someone, a mature and respectable person to have a diplomatic chat with her stepmother such that she can be enlightened on the need for her child to have adequate food and not be overburdened with work. So with such an intervention her situation can improve.”—Zaka“She won’t be able to solve them because she is still very young. As a child she cannot do anything about her parents’ conflicts and fights. When it comes to paying her own school fees she can’t do that because she cannot be employed at her young age.”—Murewa“The SMART action did not work, the father was willing to assist but the mother refused.”—Gwanda“She mentioned that she was always insulted by her grandmother over the death of her parents, which then leads her to be depressed to such an extent that she does not take her medication. …. . .Her goal was not to be insulted by her grandmother over the death of her parents..… It had no time frame as she wanted to talk to her grandmother’s friend first because she was the one who would then decide when she will be able to talk to her grandmother but she managed to do that the Sunday after we met.. …. . .The plan did not work out because the grandmother’s friend refused to talk to the grandmother claiming that she wouldn’t understand her. …. . . The challenge that I faced was that the participant was not able to air out her thoughts, and spend most of the time crying.”—Murewa“His father married a wife who was his stepmother and this was another challenge the client faced. He says there was never a good relationship between the two. The client was unhappy at home because the stepmother was not supportive of him.”—Beitbridge“With the older ones you could talk to them and they would understand, but the younger ones did not understand and could not tell what was affecting them and you would give them a paper to draw.”—Beitbridge“Problem identification is mostly useful when discussing with a mature person. This beneficiary was young, she was slow in brainstorming that sometimes she could stop and tell me that she needs to think it through then come back later.”—Chivi“These [problem solving] steps are helpful in some scenarios but in others they are a bit difficult. For example about this beneficiary, she told me that she can go and look for firewood but looking at her age it was not possible for her to look for firewood to sell and be able to buy what she needed.”—Zaka“The problem she mentioned is that her stepmother punishes her by depriving her food even for little offences and giving her punishments. The help that is required is to find someone, a mature and respectable person to have a diplomatic chat with her stepmother such that she can be enlightened on the need for her child to have adequate food and not be overburdened with work. So with such an intervention her situation can improve.”—Zaka“The SMART action did not work, the father was willing to assist but the mother refused.”—Gwanda
2. Value of peer-led problem discussion therapy
	“I think [talking about problems] is helping because if the children have problems at home they are afraid to discuss with the adults but it is very easy when they share their problems with their peers.”—Matobo“The child is now able to open up when talking even when he meet others he is now able to open up and share challenges which will be troubling them. I can see that this has changed even his life at school for the better, he was stigmatising himself considering himself as a sick person but this changed.”—Chivi“I feel elated because even those who used to wear weary faces, they are now wearing happy faces. They are now happy… there is a great improvement since we can now freely talk and interact with each other which are a thing that was not possible before.”—Murewa
3. Including others in developing broader mental health support networks
	3a. Support for clients from significant adults
	“The problem is difficult and the solution might not work. It was a family issue so I could not directly involve myself.”—Murewa“I need an older person who can help facilitating the disputes between the participant’s mother and the aunt.”—Chiredzi“I think if possible there can be a friend of the beneficiary to whom she is free to talk to or any close relative whom she can openly disclose what is troubling her, if such a people could be present during the session l think this could help.”—Chivi“I think if we can make his/her caregiver be available during the PST sessions this may help because he/she sometimes may not speak out solutions because he/she is young.”—Gokwe South“As CATS we want help so that parents are communicated with so that beneficiaries will be able to communicate with them.”—Kwekwe
	3b. Support for CATS
	“When discussing with them about their problems it is difficult at times but as a CATS I am not supposed to be overwhelmed by it as I am supposed to help the beneficiaries in their various problems.”“The challenges are that when they discuss their problems with me they expect me to solve their problems or maybe give them that thing that they are in need of e.g. money to buy what they need.”—Zaka“It was difficult conducting counselling with young mothers because some of them talked about deep issues such as marriage life.”—Zaka“The main challenge that we have is that it is very difficult for a client to just open up because they judge you not knowing that you might be facing greater challenges, so you end up discussing your problems with them so that they are also free to open up their problems with you.”—Matobo“The beneficiary is requiring me to give him solutions to solve his problem, yet we encourage that the child should chose his/her own solutions to solve his problem.”—Chivi“I need you [the supervisor] to help me with ideas and skills on how to deal with very complicated problems during PST sessions.”—Chiredzi“The assistance that I need as a CATS is that the nurses should assist me in identifying problems since they are adults some children might be able to open up their problems with them; that is my wish.”—Murewa“I feel happy and that l have assisted someone, even though sometimes l feel unstable due to the problems that are shared.”—Kwekwe

CATS, Community Adolescent Treatment Supporters; PST, problem-solving therapy; SMART, specific, measurable, achievable, realistic, and timely.

“Some participants look at my age and they tend to judge me and think I know nothing, or I am too young to help solve their problems. So, at times they don’t open up to me about all their challenges.”—Chiredzi

The steps of the model, which involved identifying an action plan to address a particular problem, were less evenly implemented. Younger participants particularly struggled with the tasks of brainstorming problems and solutions within the time frame of each session. However, the primary factor that constrained the CATS was a recognition, borne out of their discussions with participants, which the adolescents had relatively little capacity to resolve their problems.

“She couldn’t make a decision on which problem to tackle first: that of her parents fighting, or failure to afford school fees. She could not solve either of these problems by herself. So, it was extremely difficult for her to even choose the problem to deal with. It took her some time to finally speak up regarding the problem that she wanted to work on.”—Murewa)

Consistently, the problems identified by participants were embedded within their relationships (e.g., bereavement or abuse) or related to structural conditions of poverty. Both the drivers and solutions to their problems were inextricably connected to someone else, usually a significant adult in their lives. The participants increasingly trusted the influence and advice of the CATS, but neither the participants nor the CATS expected that the problems could be resolved without the intervention of significant adults. A CATS described a common challenge: “There are some problems that were not within the participant’s ability to solve”—Chiredzi

When participants developed a SMART plan, they remained reliant on others to implement solutions. It was common for these plans to fail due to a lack of engagement or capacity from those they depended upon to instigate such actions (Table 5, Subtheme 1b).

“He told them [grandmother and maternal aunties] but they did not take any action. He continued to be sent home (from school due to no fees). The caregivers are refusing to look for money to pay for his school fees.”—Gokwe South

The emphasis on identifying solutions within the model was ill-suited to many adolescents’ relational context. The CATS had limited experience to draw on to guide the participants in identifying feasible solutions. Without further support to develop and instigate an effective action plan the experience could at times be intimidating and disempowering. The dissonance between what they were expected to achieve in these sessions and what they felt was feasible caused some distress to participants. The CATS, who tended to be dedicated practitioners and took great pride in accomplishing their roles, were keen to emphasise that their limited capacity to implement all the steps in the model should not be interpreted as a failure to correctly engage.

“Some [problems] due to the situation they cannot be dealt with. For example [a client] thought if she sees where her mother was buried it can help her in her life but because of a lack of resources she could not go and see where her mother was buried.”—Kwekwe

Value of peer-led problem discussion therapy

Despite these challenges, most CATS considered that the intervention had been valuable. The primary benefit they described was that it had created a rare forum for adolescents to legitimately discuss their problems, beyond being asked about HIV and their treatment adherence, and to be listened to with empathy by a trusted peer. The opportunity to have their problems recognised and validated helped to reduce the perceived harm of the problem. As one CATS put it, “They no longer had to suffer alone.”—Gokwe South. This suggests that the intervention operated as a form of problem discussion therapy, which was beneficial even if the problems could not be resolved. For additional quotes, see Table 5, Theme 2.

“The community used to discriminate her, and through our sessions she understood that people are always saying something: good or bad she will take her medication.”—Kwekwe

Including others in developing broader mental health support networks

The third key theme was the need to extend the mental health support network provided for the adolescents beyond the CATS. Given the uneven relational power characterising many of the problems encountered by participants, the CATS emphasised that it was necessary to include significant others, especially caregivers, in the intervention. This would not only expedite the development of trust and rapport, but also strengthen caregivers’ engagement in the action plans (Table 5, Subtheme 3a).

“Challenges encountered by the beneficiary are beyond their ability to mention or answer to without a parent being present. You may find that the parent’s fight is the reason behind the problem that the child is facing, the parent is the one whom we need to talk to before talking to the child so that we can help the child.”

Some CATS who included caregivers in their sessions described the benefits: “It was difficult doing PST sessions only with children but when we were allowed to work with caregivers it now became easy.”—Gokwe South

Even with this potential avenue of support, many problems were also beyond the remit of the participant’s immediate community to resolve. CATS described this as “overwhelming” at times, indicating the need for investment in robust referral systems to professional social welfare or psychological review:

“When we discuss bigger problems, we will be needing help from mentors and nurses at the hospital so that it will be easier for us as CATS in our discussions.”—Zaka

The CATS described the work as gruelling at times and highlighted the need for ongoing supervision from adult mentors to support them emotionally and professionally and protect them from potential occupational harm (Table 5, Subtheme 3b).

“I thought by this time I would say it is easy but each time I meet the participants they are always revealing something new. ….. Supporting someone with a common mental disorder feels like you have to carry them around in order for them to cope with life.”—Hwange

Discussion

Among adolescents with HIV and comorbid symptoms of CMD, peer mental health counselling showed no evidence of an impact on the primary outcome of virological nonsuppression but did show apparent evidence of improved mental health. To our knowledge, this is the first trial to show evidence of improved mental health in this population group. Those who received care from a PST-trained CATS had substantially lower prevalence of CMD and depression symptoms after 1 year, compared to those receiving care from a CATS without PST training. There was weak evidence of improved quality of life (EQ-5D). Mental health outcomes improved over time in both trial arms.

This trial adds to the sparse literature on mental health interventions for adolescents living with HIV in low- and middle-income settings (LMIC). A recent systematic review identified only 3 such studies [16]. Two were pilot studies that were not powered to assess effectiveness [17,18], and the third was an analysis of the baseline characteristics of trial participants [19].

The results of the current trial extend those of our previous trial, which was conducted among adolescents living with HIV and was not restricted to those with symptoms of CMD. In that trial, which compared the Zvandiri programme delivered by CATS (i.e., the control arm in the current trial) with standard HIV care, 20.4% of participants had an SSQ score ≥8 at enrolment. We found an intervention effect on virological nonsuppression or death but not on mental health outcomes [5]. Prevalence of virological nonsuppression or death was 24.9% in the Zvandiri arm versus 35.9% in the standard HIV care arm after 2 years (adjusted prevalence ratio = 0.58; 95% CI 0.36 to 0.94).

In our present trial, there was a substantial reduction in virological nonsuppression in both arms (33.7% to 11.9% in the Zvandiri arm, 36.4% to 14.7 in the Zvandiri-PST arm). There was no evidence of added benefit of PST on virological nonsuppression. There may not be scope for further reduction of virological nonsuppression below the low level achieved with Zvandiri care, particularly given that some nonsuppression is due to ART resistance rather than suboptimal adherence. Evidence of the extent of ART resistance in Zimbabwe is limited, but there are reasons to believe it is particularly high among adolescents. A study of 102 children and adolescents in Harare with virological failure in 2012 found that 68% of them had at least one clinically significant mutation [20].

This model integrates mental healthcare for adolescents into HIV care, as recommended in a recent review [21] and identified as a priority area by the Adolescent HIV Implementation Science Alliance [22]. Our finding that PST, as originally envisaged, was not appropriate or feasible for an adolescent population is in line with the literature. Adolescents have very limited agency to resolve their own problems and rely on others to help them [23]. An important element of PST is for the counsellor to help the client choose a problem that is both meaningful and within their power to change [9]. The extent of challenges that adolescents faced may have made it less feasible to help them to focus on “smaller” problems that were in their control. In our study, younger adolescents became tired over the course of a session and also had trouble brainstorming solutions within the time. The intervention was equally effective on mental health outcomes for younger adolescents as older ones, but this could be because the CATS adapted it towards “problem discussion therapy.”

Caregivers have a role to play in adolescent mental health and HIV interventions [24]. In our trial, CATS pointed out that the minimal involvement of caregivers limited the capacity of the adolescent and CATS to resolve problems. The ZENITH trial in Zimbabwe showed improvement in HIV virological suppression of children aged 6 to 15, from a family-centred home-based support programme by lay workers [25,26].

This study supports previous evidence that young people gain fulfilment from being CATS [27], but it can also be challenging and emotionally draining, particularly when CATS are faced with problems that they do not have the resources or experience to handle. The needs of young peer supporters have been laid out in the TRUST framework [23], comprising Training, Referral pathways, Understanding the remit of their role, Supervision, and recognition that Talking helps.

The strengths of the trial are that it was well powered with low intracluster correlation, the sample was representative of the whole country [7], follow-up was good (90.9% overall), and the qualitative evaluation enabled correct interpretation of the quantitative results. Limitations included that cost data were not available and that the mental health tools were validated in adult populations, not adolescents. The ways that the intervention was adapted may limit external application of the findings.

Conclusions

Virological nonsuppression is common among Zimbabwean adolescents with mental health problems living with HIV. This trial provides additional supporting evidence of the effect of Zvandiri on virological suppression. Training in counselling for peer supporters can have beneficial effects on mental health. We recommend that PST for adolescents should be less structured than the SMART plan for adults, with shorter sessions (especially for young adolescents) over a longer time frame. Counsellors should be trained to help clients identify problems that are within their power to affect. Creating a space for discussion and the sharing and discussion of problems, rather than solving them, should also be valued. Finally, ways to involve caregivers, such as family therapy approaches, should be explored.

(DOCX)

Click here for additional data file.

Trial analytical plan.

(PDF)

Click here for additional data file.

Association of baseline characteristics with missing primary outcome.

(DOCX)

Click here for additional data file.

Unadjusted intervention effect on primary and secondary outcomes at 48 weeks.

(DOCX)

Click here for additional data file.

Effect modification of baseline age on trial outcomes at 48 weeks.

(DOCX)

Click here for additional data file.

28 Jun 2021

Dear Dr Simms,

Thank you for submitting your manuscript entitled "Effect of peer-led counselling on viral load and mental health of adolescents living with HIV in Zimbabwe: a cluster-randomised trial" for consideration by PLOS Medicine.

Your manuscript has now been evaluated by the PLOS Medicine editorial staff and I am writing to let you know that we would like to send your submission out for external assessment.

However, we need you to complete your submission by providing the metadata that is required for full assessment. To this end, please login to Editorial Manager where you will find the paper in the 'Submissions Needing Revisions' folder on your homepage. Please click 'Revise Submission' from the Action Links and complete all additional questions in the submission questionnaire.

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Richard Turner, PhD

Senior Editor, PLOS Medicine

rturner@plos.org

7 Aug 2021

Dear Dr. Simms,

Thank you very much for submitting your manuscript "Effect of peer-led counselling on viral load and mental health of adolescents living with HIV in Zimbabwe: a cluster-randomised trial" (PMEDICINE-D-21-02706R1) for consideration at PLOS Medicine.

Your paper was discussed among the editors and sent to independent reviewers, including a statistical reviewer. The reviews are appended at the bottom of this email and any accompanying reviewer attachments can be seen via the link below:

[LINK]

In light of these reviews, we will not be able to accept the manuscript for publication in the journal in its current form, but we would like to invite you to submit a revised version that addresses the reviewers' and editors' comments fully. You will appreciate that we cannot make a decision about publication until we have seen the revised manuscript and your response, and we expect to seek re-review by one or more of the reviewers.

In revising the manuscript for further consideration, your revisions should address the specific points made by each reviewer and the editors. Please also check the guidelines for revised papers at http://journals.plos.org/plosmedicine/s/revising-your-manuscript for any that apply to your paper. In your rebuttal letter you should indicate your response to the reviewers' and editors' comments, the changes you have made in the manuscript, and include either an excerpt of the revised text or the location (eg: page and line number) where each change can be found. Please submit a clean version of the paper as the main article file; a version with changes marked should be uploaded as a marked up manuscript.

In addition, we request that you upload any figures associated with your paper as individual TIF or EPS files with 300dpi resolution at resubmission; please read our figure guidelines for more information on our requirements: http://journals.plos.org/plosmedicine/s/figures. While revising your submission, please upload your figure files to the PACE digital diagnostic tool, https://pacev2.apexcovantage.com/. PACE helps ensure that figures meet PLOS requirements. To use PACE, you must first register as a user. Then, login and navigate to the UPLOAD tab, where you will find detailed instructions on how to use the tool. If you encounter any issues or have any questions when using PACE, please email us at PLOSMedicine@plos.org.

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Please let me know if you have any questions, and we look forward to receiving your revised manuscript.

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rturner@plos.org

-----------------------------------------------------------

Requests from the editors:

Please quote aggregate demographic details for study participants in the abstract.

Please quote study dates in the abstract.

Please add a new final sentence to the "Methods and findings" subsection of your abstract, beginning "Study limitations include ..." or similar and quoting 2-3 of the study's main limitations.

At line 52 and elsewhere in the elements of discussion in the paper, please quote the null findings on the study's primary endpoint prior to mentioning other findings.

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Throughout the text, please adapt reference call-outs to the following style (noting the absence of spaces within the square brackets): "... symptoms of CMD [10,11].".

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Comments from the reviewers:

*** Reviewer #1:

Statistical review

This paper reports a cluster randomised trial comparing a peer-led counselling intervention on HIV-positive adolescents with mental health problems.

Generally the results are reported well. I have some minor comments on the statistical methods and reporting, which are listed below.

1. Abstract conclusions - I would recommend flipping the sentence around to emphasise the primary outcome was not met but that there were some significant secondary outcomes. The same goes for the first paragraph in the discussion.

2. Methods page 5 - can more be said about the randomisation procedure, was it a block randomisation or was there any stratification?

3. Methods - I'd recommend having the outcomes listed first and then the sample size section.

4. Page 6 - the primary outcome here is given as 1000 copies per microlitre, whereas the protocol says 100 copies per millilitre - these are different by a couple of orders of magnitude - can the authors clarify? The secondary outcomes also have slightly different thresholds to those given in the protocol.

5. Results, page 9 - for the subgroup analysis I would mention the significant interaction p-value as otherwise it might be puzzling to the reader how the two non-significant subgroup p-values are evidence of a significance.

James Wason

*** Reviewer #2:

This is an excellent paper, and an important study. It compares a well-evidenced NGO program to support adolescents living with HIV, to an enhanced version with additional mental health components based on another well-evidence-based program. It is encouraging to see a commitment to building the evidence-base and optimising interventions, and to see two research groups working together (which doesn't happen as often as it should).

The original Zvandiri program has strong evidence of improving viral load suppression. The original Friendship Bench program has strong evidence of reducing common mental health disorders. This study shows that a combined program can do both, even with some complexities and challenges. This is of enormous value to programming for this group of exceptionally vulnerable adolescents.

The methods are robust, and the program delivery was done through existing government clinics, suggesting scaleability. Good measures are used. I had no comments on the methods or write-up, which are both excellent. I'm not familiar with a quadrature check for model fit, but the other analytical approaches all look strong.

The qualitative findings were extremely valuable - and it would be helpful to know whether these have contributed to any adjustments to the mental health component of the program. In retrospect, it may have been useful to have done the qualitative evaluation before the trial, to allow adjustments to be made, but it is also absolutely commendable to have accompanied the quantitative trial with qualitative study, and in the wider implementation science approach these are all iteratively feeding into program improvements.

I was struck by the importance of including caregivers, and at some point it could be of value to think about synergies between these approaches and the growing evidence-base on parenting programs for families of adolescents - which have not always shown good impacts on adolescent mental health, but have helped with some of the structural challenges mentioned, such as family budgeting, violence prevention, reducing conflict and improving family relationships.

My only minor comments are:

1. Exclusion criteria included intoxication or psychosis. There is a lot of logic to this, but in most of the countries most affected by HIV, there would be very limited other services for these adolescents, and so it would be valuable also to see whether the combined program would help even in quite extreme cases.

2. It would be helpful to have a bit more information about the delivery of the combined program.

3. I know that there is a lot described in the protocol paper, but perhaps some more information could be uploaded into the supplementary material to this paper, so that it is easy for the reader to access.

But these are very minor. This is clearly a paper of real importance to the field, and a novel and extremely important study. Congratulations to the team.

Lucie Cluver.

*** Reviewer #3:

PLOS Medicine review

The authors conducted a clinic-randomized trial (n=60 clinics) to assess the impact of adding "training in Problem-Solving Therapy (PST)" to an established peer counselling intervention on mental health and viral suppression outcomes among adolescents with HIV.

Mental health is a predictor of adherence and retention in HIV care as well as an important health outcome in its own right. Adolescents with HIV face unique mental health challenges and this population is growing as vertically-infected children age into adolescence (e.g. Maskew et al. 2019, Lancet HIV).

Whereas the (standard of care) established counselling intervention was previously shown to be effective in increasing viral suppression, it had no impact on mental health. Hence the effort to amend the intervention with PST.

PST appears to be the missing link. Although the authors find no impact of the PST-augmentation on viral suppression (perhaps due to ceiling effects), they find large reductions in depression and other adverse mental health outcomes. (One can infer that relative to "no counselling", the combination of PST with the original intervention would therefore be expected to lead to improvements on both mental health and viral suppression.)

The study is important and appears carefully executed (with carefully described procedures). The combination of qualitative data is a major asset in interpreting the study findings, although I think it can be better used (see below).

General comments:

1) RATIONALE. I think the study would be strengthened by a clearer explication of the intervention rationale (why PST?). The content of PST-training (Friendship Bench) is described. However, what are the theoretical constructs that PST is designed to address? And how did the authors identify these constructs (based on their prior work) as needing to be addressed? My initial sense is that the intervention was designed to (a) give people a sense of agency and control in their lives and (b) to provide cognitive tools to assist with problem solving and give opportunities for practice using these tools. I infer that a major source of mental morbidity is a sense of lack of control which may be exacerbated by having HIV. And building up a sense of agency as well as problem solving skills could theoretically support ART adherence too. (But these were my own speculations based on the paper. Further details here would help the reader understand the nature of the problem that needs to be solved. In fact, the bottom of p10 suggests a different interpretation based on coping and validation rather than agency.)

2) FIDELITY, FEASIBILITY, and ACCEPTABILITY. There is a bit of whiplash as the authors present large intervention effects and then present qualitative data indicating that the intervention was actually rather difficult to implement (low feasibility, acceptability) and had low fidelity in implementation. So, which is it? If the data indicate that the intervention was not really implemented faithfully, should we interpret this as evidence that the highly significant effects on mental health occurred by chance? Or should we rather interpret this as evidence that the particular components of the intervention that were implemented turned out to be important in this context?

I love the combination of qual and quant. But as it is, my feeling is that the qual results undercut the quant findings, rather than adding validity and nuance. The qual results are framed as providing information on "what was wrong about the intervention implementation." But this is immaterial. The question in the reader's mind after the quantitative results is "what was RIGHT about the intervention implementation", i.e. what led to the big mental health impacts observed?

I think the discussion of fidelity would be greatly improved if it were organized around key questions that guide interpretation of the quantitative results. E.g., (a) can the authors provide some evidence that study participants in the treatment group actually received something different than participants in the control group? (b) can the authors be more explicit about WHAT exactly was different? E.g. if it seems that the earlier stages of PST were emphasized, then that's valuable to know. (c) How do the findings on fidelity shape interpretation of the theoretical model? i.e. if the intervention was designed to affirm the experiences of subjects, to build locus of control, and to build cognitive problem-solving skills… but if only the first of these was actually implemented, then that is pretty important for interpretation. But the authors should set this up ex ante that the intervention was designed to target different constructs. And (d) how can this evidence guide future development of the intervention and inform scale-up?

Smaller stuff:

ABSTRACT

- I found the intervention content and rationale to be unclear. The abstract states that the comparison was between peer-counselling and peer-counselling where the counsellor was trained in Problem-Solving Therapy. However, it would be helpful to know: (a) how did PST differ from the standard of care counselling; (b) did the counsellors actually deliver PST or were they just trained in PST; (c) what was the theoretical motivation for PST relative to standard of care, i.e. what was the problem that PST was introduced to solve?

- In the description of results, it is unclear what 14.7% and 11.9% refer to. Are these prevalences of viral non-suppression? Or percent reductions in non-suppression? Or percentage point reductions in non-suppression?

- Conclusion "Active involvement of caregivers and strengthened referral structures could increase feasibility and effectiveness" doesn't seem to follow from the study results.

METHODS

- "An a-priori decision was made to adjust for baseline values of the relevant outcome measure and for key variables that were deemed imbalanced between arms at baseline or were associated with missing outcome data." The authors should also present crude/unadjusted results. And the decision rules for how variables were determined to be "key" and therefore adjusted for should be stated.

RESULTS

- "The proportion of participants with an EQ-5D score below 1 was slightly lower in the Zvandiri-PST arm than in the Zvandiri arm (27.6% vs 38.9%; AOR=0.56; 95%CI 0.31, 1.03; p=0.06)." The term "slightly lower" is inaccurate. The PST arm proportion was >40% lower than control! The p-value was "slightly higher" than conventional cut-offs for statistical significance (but the CI is all that matters anyway).

CONCLUSIONS

- "Our finding that PST, as originally envisaged, was not appropriate or feasible for an adolescent population is in line with the literature." I don't understand. It feels like the authors are saying that the intervention didn't work. But it DID work! (unless I misunderstand)

Final word:

The availability of both qualitative and quantitative (trial) data is a major asset to this study. However, while each component (quant and qual) was well done, the current manuscript does not integrate the two very well. It feels like a trial results paper on the success of an intervention, followed by a qual study on how the intervention failed. This contradiction led to a great deal of confusion in this reader as to whether the trial results were credible and missed opportunities to explicate the reasons for the large trial effects. A cluster-randomized trial is higher quality evidence (per GRADE standards) and should dictate the overall conclusions of the study. I strongly recommend the authors cut the qual section by 50% and use the qual section to answer very specific questions that will help the reader interpret what went well (leading to large effects) in the intervention and what components of the PST intervention to emphasize going forward if it is brought to scale.

***

Any attachments provided with reviews can be seen via the following link:

[LINK]

30 Sep 2021

Submitted filename: Zvandiri-PST review response.docx

Click here for additional data file.

22 Oct 2021

Dear Dr. Simms,

Thank you very much for submitting your revised manuscript "Effect of peer-led counselling on viral load and mental health of adolescents living with HIV in Zimbabwe: a cluster-randomised trial" (PMEDICINE-D-21-02706R2) for consideration at PLOS Medicine.

Your paper was re-seen by our referees and discussed among the editors. The reviews are appended at the bottom of this email and any accompanying reviewer attachments can be seen via the link below:

[LINK]

In light of these reviews, we will not be able to accept the manuscript for publication in the journal in its current form, however we would like to like to invite you to submit a further revised version responding fully to the reviewers' and editors' comments. We cannot make a decision about publication until we have seen the revised manuscript and your response, and we expect to seek re-review by one or more of the reviewers.

In revising the manuscript for further consideration, your revisions should address the specific points made by each reviewer and the editors. Please also check the guidelines for revised papers at http://journals.plos.org/plosmedicine/s/revising-your-manuscript for any that apply to your paper. In your rebuttal letter you should indicate your response to the reviewers' and editors' comments, the changes you have made in the manuscript, and include either an excerpt of the revised text or the location (eg: page and line number) where each change can be found. Please submit a clean version of the paper as the main article file; a version with changes marked should be uploaded as a marked up manuscript.

In addition, we request that you upload any figures associated with your paper as individual TIF or EPS files with 300dpi resolution at resubmission; please read our figure guidelines for more information on our requirements: http://journals.plos.org/plosmedicine/s/figures. While revising your submission, please upload your figure files to the PACE digital diagnostic tool, https://pacev2.apexcovantage.com/. PACE helps ensure that figures meet PLOS requirements. To use PACE, you must first register as a user. Then, login and navigate to the UPLOAD tab, where you will find detailed instructions on how to use the tool. If you encounter any issues or have any questions when using PACE, please email us at PLOSMedicine@plos.org.

We hope to receive your revised manuscript by Nov 12 2021 11:59PM. Please email us (plosmedicine@plos.org) if you have any questions or concerns.

***Please note while forming your response, if your article is accepted, you may have the opportunity to make the peer review history publicly available. The record will include editor decision letters (with reviews) and your responses to reviewer comments. If eligible, we will contact you to opt in or out.***

We ask every co-author listed on the manuscript to fill in a contributing author statement, making sure to declare all competing interests. If any of the co-authors have not filled in the statement, we will remind them to do so when the paper is revised. If all statements are not completed in a timely fashion this could hold up the re-review process. If new competing interests are declared later in the revision process, this may also hold up the submission. Should there be a problem getting one of your co-authors to fill in a statement we will be in contact. YOU MUST NOT ADD OR REMOVE AUTHORS UNLESS YOU HAVE ALERTED THE EDITOR HANDLING THE MANUSCRIPT TO THE CHANGE AND THEY SPECIFICALLY HAVE AGREED TO IT. You can see our competing interests policy here: http://journals.plos.org/plosmedicine/s/competing-interests.

Please use the following link to submit the revised manuscript:

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Your article can be found in the "Submissions Needing Revision" folder.

To enhance the reproducibility of your results, we recommend that you deposit your laboratory protocols in protocols.io, where a protocol can be assigned its own identifier (DOI) such that it can be cited independently in the future. Additionally, PLOS ONE offers an option to publish peer-reviewed clinical study protocols. Read more information on sharing protocols at https://plos.org/protocols?utm_medium=editorial-email&utm_source=authorletters&utm_campaign=protocols

Please ensure that the paper adheres to the PLOS Data Availability Policy (see http://journals.plos.org/plosmedicine/s/data-availability), which requires that all data underlying the study's findings be provided in a repository or as Supporting Information. For data residing with a third party, authors are required to provide instructions with contact information for obtaining the data. PLOS journals do not allow statements supported by "data not shown" or "unpublished results." For such statements, authors must provide supporting data or cite public sources that include it.

Please let me know if you have any questions, and we look forward to receiving your revised manuscript.

Sincerely,

Richard Turner PhD

Senior editor, PLOS Medicine

rturner@plos.org

-----------------------------------------------------------

Requests from the editors:

Noting reviewer 3's comments, we ask you to explain how the modification of the intervention fits in with the conduct and findings of the trial - did this happen before or, as apparently the case, during the study, for example?

We reserve judgement about the suggested restructuring of the paper pending resolution of the previous question.

In the response to referees you mention that the intervention delivered was "problem discussion therapy" rather than "problem-solving therapy" per se, and it seems that judicious changes need to be made in the text, for example around line 140, to reflect this.

We ask you to adapt the title to better match journal style, and suggest: "Peer-led counselling with problem discussion therapy for adolescents living with HIV in Zimbabwe: A cluster-randomised trial".

In the abstract and elsewhere in the paper, please soften the language describing secondary outcome findings, e.g., "... evidence of an apparent effect"

In the author summary, please present the primary outcome findings before those of the secondary outcomes.

Please avoid claims of "the first", e.g., at line 92, and where necessary add "to our knowledge" or similar.

Please substitute "sex" for "gender" where appropriate, e.g., in table 2.

Please update reference 23.

Comments from the reviewers:

*** Reviewer #1:

Thank you to the authors for addressing my previous comments. Regarding the primary endpoint cut-point, this is denoted as 1000 copies/mL on page 2 line 35 and 1000 copies/µl (which I understand as microlitre rather than millilitre) on page 8 line 170. Otherwise I am happy with the paper and have no issues to raise.

*** Reviewer #2:

I am happy with the authors responses to the reviewer and editor comments. Recommend acceptance. Lucie Cluver.

*** Reviewer #3:

Thank you for the opportunity to re-review this paper. I appreciate the clarifications that the authors have made in response to my comments. However, several of the underlying issues remain unaddressed.

1) The authors have clarified that "The intervention as originally envisaged was not appropriate or feasible. It was modified in practice. The modified version worked."

In light of authors' feedback, it is not clear what the intervention was. The intervention is described in the abstract as "training peer counsellors in PST". Yet if PST was not delivered, then it is not at all clear that training counsellors in PST was the key element of the intervention. What WAS the intervention? And how would someone replicate this intervention in another setting? Inasmuch as research is about creating generalizable knowledge, the intervention needs to be well-defined in order for the reader to draw any conclusions about it. This is a major limitation of the study.

I still believe the study is interesting and important. But...

(A) The authors should change how they present the intervention. They might consider labelling the study a "pilot" of a new, situationally-adapted mental health counseling intervention based on PST principles and training. They may also specify that this was a community-engaged intervention development approach, with peer counselors providing ongoing feedback and shaping the design of the intervention as it was implemented. And that the goals of the intervention were to engage counsellors in an effort to design wraparound mental health services, in which they had discretion to develop their own protocols.

(B) The authors should invert the paper, describing the intervention development process, process outcomes, and intervention content (as implemented) first, BEFORE showing the data on impact of the intervention on the primary and secondary outcomes. As currently organized, it was hard for the reader to interpret the results without a clear understanding of the intervention first.

(C) Relatedly, the role of the qualitative data collection and analysis in the overall project needs to be specified. (I.e. the mixed methods design) Inasmuch as the qualitative research guided intervention development, it should be labeled as "formative research" and presented before the data on the trial results. Alternatively, if it was "explanatory research" of process outcomes, then it should be labeled as such and STILL presented before the other outcomes.

2) The authors did not respond to my request for further information on the theoretical constructs that the friendship bench intervention was designed to target, why these were relevant to the adolescent HIV population, and which of these constructs the ADAPTED version of the intervention (i.e. not PST) still targeted. Given that there was poor fidelity to the planned intervention, understanding what constructs were actually targeted successfully and which were not is critical for any kind of generalizability to other settings. A lot of this comes out in the qualitative results. But it would be advantageous to spell out at the beginning of the paper / in the methods section what constructs were being targeted.

3) The authors did not adequately address my comment #6. I requested crude/unadjusted results from the RCT. These are always appropriate whether pre-specified or not. Further, I requested information on how the authors determined what variables to include in the adjusted model. In the reply, it is unclear whether in fact there were pre-specified decision rules or not. They write "there were no specific decision rules" and then "the decision was made prior to analysis". If there was a pre-analysis protocol defining what was adjusted for, the authors can link to that. But if they chose variables as they went along based on their associations with the trt and outcome non-response, then they should show robustness checks with other adjustment variables. Basically, they need to convince the reader that they did not "choose" their preferred specification and that the benefits of randomization were preserved.

I remain convinced that this is an important study. However, I cannot recommend it for publication in its current form based on the methodological concerns highlighted above.

***

Any attachments provided with reviews can be seen via the following link:

[LINK]

18 Nov 2021

Submitted filename: Zvandiri-PST review response 181121.docx

Click here for additional data file.

28 Nov 2021

Dear Dr. Simms,

Thank you very much for re-submitting your manuscript "Peer-led counselling with problem discussion therapy for adolescents living with HIV in Zimbabwe: a cluster-randomised trial" (PMEDICINE-D-21-02706R3) for consideration at PLOS Medicine.

I have discussed the paper with editorial colleagues and it was also seen again by one reviewer. I am pleased to tell you that, provided the remaining editorial and production issues are fully dealt with, we expect to be able to accept the paper for publication in the journal.

The remaining issues that need to be addressed are listed at the end of this email. Any accompanying reviewer attachments can be seen via the link below. Please take these into account before resubmitting your manuscript:

[LINK]

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Sincerely,

Richard Turner PhD

Senior Editor, PLOS Medicine

rturner@plos.org

------------------------------------------------------------

Requests from Editors:

In your data statement (submission form), can you substitute a specific webpage address for data from the present study?

Is there a duplicate parenthesis at line 48 (abstract)?

At line 52, please adapt "was beneficial" to indicate how this was judged.

At line 56, please avoid "further reduction" (in favour of "... did not add to the benefit of peer support in reducing virological suppression" or similar).

Please remove the duplicated full point at line 142.

At line 257, please revisit "anadjusted".

Please add a further sentence, say, to the section on limitations (line 447). For example, perhaps the adaptation of the intervention might limit external application.

Comments from Reviewers:

*** Reviewer #3:

I thank the authors for their thoughtful responses and clarifications. I appreciate the addition of the crude RCT results. And I think the authors' justifications regarding manuscript organization are reasonable.

A final suggestion: to avoid the feeling of whiplash that I experienced in reading this article the first time, I would urge the authors to assist the reader a bit by defining the intervention a bit more broadly than PST, e.g. "discussion based therapy by peer counsellors trained in PST", and foreshadowing that there was no further intervention to ensure that peer counselors were staying close to PST protocols and that the counselors were free to use and interpret their training as they saw fit. ...or something like that. So that when you get to the process outcomes, the focus is on "why did it work" rather than on "looks like it didn't really work".

I believe it's a strong paper that will push the field forward.

***

Any attachments provided with reviews can be seen via the following link:

[LINK]

1 Dec 2021

Submitted filename: response.docx

Click here for additional data file.

9 Dec 2021

Dear Dr Simms,

On behalf of my colleagues and the Academic Editor, Dr Bor, I am pleased to inform you that we have agreed to publish your manuscript "Peer-led counselling with problem discussion therapy for adolescents living with HIV in Zimbabwe: a cluster-randomised trial" (PMEDICINE-D-21-02706R4) in PLOS Medicine.

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Prior to final acceptance, please update the data URL in the submission form; and convert nested parentheses (abstract) into square brackets.

In the meantime, please log into Editorial Manager at http://www.editorialmanager.com/pmedicine/, click the "Update My Information" link at the top of the page, and update your user information to ensure an efficient production process.

PRESS

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To enhance the reproducibility of your results, we recommend that you deposit your laboratory protocols in protocols.io, where a protocol can be assigned its own identifier (DOI) such that it can be cited independently in the future. Additionally, PLOS ONE offers an option to publish peer-reviewed clinical study protocols. Read more information on sharing protocols at https://plos.org/protocols?utm_medium=editorial-email&utm_source=authorletters&utm_campaign=protocols

Thank you again for submitting to PLOS Medicine. We look forward to publishing your paper.

Sincerely,

Richard Turner, PhD

Senior Editor, PLOS Medicine

rturner@plos.org