Kunutsor 2011.

Methods	Randomized controlled trial
Participants	The study location was Jinja Hospital HIV clinic, Jinja District, Uganda 87 participants were randomized to the intervention group and 87 participants were randomized to the control group The inclusion criteria were adults (at least 18 years old), currently receiving ART, receiving the standard adherence intervention package including the existing routine adherence counseling support and education provided by the HIV clinic, and if they were all agreeable to have a treatment supporter
Interventions	Intervention: TREATMENT SUPPORTER (TS) INITIATIVE Patients in the TS arm received both the TS intervention and the standard adherence intervention package. Elements of the standard intervention package consisted of self monitoring of medication taking using adherence diaries; regular individual and group education by peer‐workers using patient education leaflets and tabletop flip‐charts; and late attendee tracing. The treatment supporters were usually family members—usually a partner, mother, daughter, sister, brother, friend, or neighbor/friend—who were chosen by the patient with the assistance of the health workers, had accepted the patient's HIV status and were confidantes. These individuals were committed to support the patient with ART for a long time, had gained the patient's trust over time, and commanded respect. Patients were asked to bring their chosen treatment supporter to the ART clinic for the health worker to explain about ART, adherence and treatment support. This includes commitment, confidentiality, knowledge on HIV and ART related needs, and perhaps emergency resource needs such as money, help with household, and children. Treatment supporters were educated with the following WHO Integrated Management of Adolescent and Adult Illness (IMAI) educational materials: Patient Education Flipchart, Patient Education Cards, and Caregiver Booklets. They were also educated on how to remind the patient to take their medicine, be present at the follow‐up appointments, remember all important test results and clinic history over time, and to accompany patient to support group meetings if possible. Treatment supporter meetings were also held at the clinic every 2 or more weeks to deal with issues of burn out, patient non‐adherence and other barriers to treatment and adherence Control: STANDARD ADHERENCE INTERVENTION Patients randomized to the control arm did not have a treatment supporter but otherwise received the same standard adherence intervention package including the ongoing existing health education and adherence counseling support that all patients received during routine monthly clinic visits. These existing interventions are typical for HIV/ AIDS treatment programs in Uganda and the rest of sub‐Saharan Africa
Outcomes	The measures of adherence were an adherence assessment. Each client who reported to the health facility for their 4‐weekly refill of ARV drugs had a clinic‐based pill count conducted. Clients also answered an adherence assessment form. Zero adherence was awarded to patients who missed visits and were known not to have collected medications from the pharmacy, and those patients who were incapacitated or sick and were known not to have taken their medications The patient outcome was confirmed deaths
Notes	―
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Patients were randomized to a standard adherence intervention package plus treatment supporter (TS) intervention group versus the standard intervention package (non‐TS) control group at a 1:1 allocation ratio (see Figure 1, trial profile). Randomization was performed using a computer‐generated allocated sequence
Allocation concealment (selection bias)	Unclear risk	Not mentioned of allocation concealment in the article. (pg 1796) Patients were randomized to a standard adherence intervention package plus treatment supporter (TS) intervention group versus the standard intervention package (non‐TS) control group at a 1:1 allocation ratio (see Figure 1, trial profile). Randomization was performed using a computer‐generated allocated sequence
Selective reporting (reporting bias)	Unclear risk	No protocol available
Other bias	Unclear risk	The author indicate the following limitations: (pg1800) "Though informative, our study had some limitations which merit consideration. Our study was originally powered to detect a 15% increase in adherence after the intervention, but then adherence levels were higher than anticipated for the control group thereby rendering the small but 'real' increase in adherence between the two groups statistically non‐significant. It is possible this study was likely underpowered for adherence outcomes. Considering the fact that very high levels of adherence were exhibited by both treatment groups, any small difference could be of clinical and substantive importance. We were not able to corroborate attendance and adherence monitoring with more objective indicators such as immunological, virological or clinical outcomes because of financial constraints particularly the cost of additional laboratory monitoring in this setting. The clinic‐based pill count measure though less objective compared to Medication Event Monitoring System (MEMS) caps and HIV viral loads, it has been reported to be correlated with viral loads. Considering the fact that all participants were willing to identify treatment supporters, i.e. they all reported disclosure before enrollment, it is possible this could have attenuated potential benefits of treatment supporters since disclosure alone is a major predictor of adherence; it may be that we collected data from a cohort of highly motivated people who were prepared to gain the most from ART. The data was derived from a single site and so the results may not be generalizable to the whole country. Despite the various limitations, our study findings are very important and lend support to the results reported by Taiwo et al. in their randomized trial on treatment partners, that the use of patient‐selected treatment supports is associated with improved adherence."
Blinding of outcome assessment (detection bias) Adherence measure	Unclear risk	(PRIMARY) PILL COUNT ‐ Blinding not mentioned
Blinding of outcome assessment (detection bias) Patient outcome	High risk	(PRIMARY) CLINIC ATTENDANCE ‐ Author's note: adherence assessors were not blinded. Quite impossible to blind in such operational research studies where patients receive usual care
Blinding of participants (performance bias) Adherence measure	High risk	(PRIMARY) PILL COUNT ‐ Participants not blinded due to the nature of the intervention
Blinding of participants (performance bias) Patient outcome	High risk	(PRIMARY) CLINIC ATTENDANCE ‐ Patients aware of intervention and measurement due to the nature of intervention
Blinding of personnel (performance bias) Adherence measure	Unclear risk	(PRIMARY) PILL COUNT ‐ Blinding not mentioned
Blinding of personnel (performance bias) Patient outcome	High risk	(PRIMARY) CLINIC ATTENDANCE ‐ Author's note: high risk of bias as key study personnel were not blinded
Incomplete outcome data (attrition bias) Adherence measure	Unclear risk	(PRIMARY) PILL COUNT ‐ Missing data matched between the groups but reasons for missing data are not the same, therefore marked unclear
Incomplete outcome data (attrition bias) Patient outcome	Unclear risk	(PRIMARY) CLINIC ATTENDANCE ‐ Missing data matched between the groups but reasons not the same