Simoni 2009.

Methods	Randomized controlled trial
Participants	The study location was Harborview Medical Center, Seattle, Washington, USA 57 participants were randomized to peer support; 56 to pager messaging; 56 to pager messaging and peer support; and 57 to the control group The inclusion criteria were (a) at least 18 years of age, (b) proficient in English, (c) living within the service area of the pager, and (d) initiating or changing at least 2 medications of a HAART regimen The exclusion criteria were cognitively impaired, actively psychotic, or had a known history of harming others
Interventions	Intervention: PEER SUPPORT The 3‐month peer support intervention consisted of 2 parts: (a) 6 twice‐monthly, 1‐hour gatherings held at the clinic, consisting of all peers and actively enrolled participants in the peer support arm and (b) weekly phone calls from peers to participants. At the time of enrollment, participants were assigned to individual peers by study staff based on peer availability and presumed compatibility. In the group setting, participants had the opportunity to interact face‐to‐face with their assigned peer and meet the other peers and participants, with the goal of benefiting from the discussion of the shared experiences of the group. The meetings were designed to identify barriers to HAART adherence and generate problem‐solving strategies to overcome them. Other emerging themes included life issues that impact adherence, including HIV status disclosure, dating, substance use, and struggles with mental health issues. One of several research staff members co‐ordinated the groups by making reminder phone calls, preparing the meeting room, and providing refreshments. With assistance from the peers, they facilitated the meetings by refocusing the discussion on adherence‐related topics when appropriate. Otherwise, they refrained from interfering with the group process and the exchange of support among peers and participants, resulting in predominantly peer led groups. Participants received a USD 15 incentive for attending each of the 6 sessions. All were welcomed to continue attending thereafter but were provided neither reminder phone calls nor monetary incentives for additional meetings. Between group meetings, peers were instructed to call each of their study participants weekly to provide more in‐depth one‐on‐one attention and feedback. Phone calls also were better suited for participants with confidentiality concerns and those who had difficulty traveling to the clinic or had scheduling conflicts with the set meeting times. Peers were instructed not to initiate contact with participants after the 3‐month intervention period, but they were allowed to respond to requests for contact from the participants at their own discretion. Intervention: PAGER MESSAGING The 3‐month pager intervention consisted of a customized pager system that combined the communicating abilities of the world‐wide web and 2‐way pagers. A computer program allowed for the timing of all text messages to be specified up front and then sent automatically without any further intervention from study staff. At randomization, the study co‐ordinator distributed a 2‐way pager and customized a message schedule to the participant's daily medication regimen, which was confirmed by the clinic pharmacist. In addition to dose reminders, 3 other types of text messages were sent: (1) educational; (2) entertainment (jokes or thoughts for the day); and (3) adherence assessments. There was some flexibility in the frequency and content of messages to accommodate participants' differing needs and schedules, but there was a minimum of 3 pager messages sent daily to participants for the first 2 months. Pages gradually tapered in the last month of the 3‐month intervention to avoid a rebound in non‐adherence. A confirmation return page was requested for every message sent. Project staff periodically reviewed the return page log and if no responses were received, the participant could be called to determine if they were having any problems with the pager. Between the first contact and the end of the 3‐month intervention, the participants were asked to wear the pager at all waking moments. Participants had to use the study pagers and could not substitute with their own pager or cell phone. They were instructed not to use the devices for personal use. Participants could select from a variety of auditory alarms or a vibrate‐only option if desired. If the pager was lost or failed, it was promptly replaced at no cost to the subject Control: USUAL CARE Before initiation of HAART, all clinic patients who are naive patients or off HAART for more than 6 months are required to complete the HAART protocol, a clinic‐based program designed to provide education regarding HAART and adherence and to identify and correct adherence barriers before HAART initiation. The HAART protocol involves a series of 3 separate appointments with a pharmacist, nutritionist, and case manager after an initial meeting with a provider and before a final meeting when the provider decides whether to prescribe HAART. During these preliminary interviews, patients are given social and mental health referrals as appropriate, a daily medication schedule, and information on medication side effects and techniques to help manage them. All participants in each of the study's 4 arms participated in the HAART protocol if they had not received it in the last 6 months. There were no time or attention‐control activities
Outcomes	The measures of adherence were self reported adherence and Electronic Drug Monitor‐based adherence, measured at 3 months, 6 months, and 9 months. Self reported adherence was measured with 1 item from the Simplified Medication Adherence Questionnaire assessing the number of doses missed during the previous week. The measure was taken via a computer‐assisted self interview. Participants were provided with an EDM for the duration of the trial. Each participant was given one EDM to use with the most frequently dosed antiretroviral. The EDM adherence was calculated by the number of bottle openings recorded during the prior 7 days before each assessment divided by the number of prescribed doses The patient outcomes were HIV‐1 RNA viral load (VL) and CD4 lymphocyte count. Patients were assessed at 3, 6, and 9 months. At each assessment, blood was drawn to determine HIV‐1 RNA viral load (VL) and CD4 lymphocyte count. Study staff abstracted VL and CD4 lymphocyte counts from patient medical records if they were available within 30 days of the baseline, 3‐month, 6‐month, and 9‐month interviews; otherwise, blood draws for VL and CD4 counts were conducted the day of the interview. Clinical outcomes were analyzed as continuous variables and as dichotomous variables with cut offs for VL of undetectable, 1000, and 10,000 and for CD4 of 350 at each assessment point and across all 3 follow‐up assessments
Notes	―
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	"An external statistician had used a computerized random number generator to select random permuted blocks of 4." (pg 466)
Allocation concealment (selection bias)	Low risk	"Allocation concealment involved the use of sequentially numbered, opaque, sealed envelopes containing the study arm assignment, which the study staff opened at the moment of randomization." (pg 466)
Selective reporting (reporting bias)	Unclear risk	No protocol available; although it appears that everything was reported it is difficult to determine this without a protocol
Other bias	Low risk	The study seems to be free of other types of bias
Blinding of outcome assessment (detection bias) Adherence measure	Low risk	(PRIMARY) EDM ‐ MEMS type measure, unlikely staff would bias the results
Blinding of outcome assessment (detection bias) Adherence measure	Low risk	(PRIMARY) SELF REPORT ‐ QUESTIONNAIRE ‐ Self interview, staff unlikely to bias responses
Blinding of outcome assessment (detection bias) Patient outcome	Low risk	(PRIMARY) VIRAL LOAD ‐ This is an objective measure of outcome
Blinding of participants (performance bias) Adherence measure	High risk	(PRIMARY) EDM ‐ "Due to the nature of the intervention, participants, study staff, and data analysts could not be completely blinded to study arm assignment." (pg 466)
Blinding of participants (performance bias) Adherence measure	High risk	(PRIMARY) SELF REPORT ‐ QUESTIONNAIRE ‐ "Due to the nature of the intervention, participants, study staff, and data analysts could not be completely blinded to study arm assignment." (pg 466) This is a subjective outcome measure
Blinding of participants (performance bias) Patient outcome	Low risk	(PRIMARY) VIRAL LOAD ‐ This is an objective measure of outcome
Blinding of personnel (performance bias) Adherence measure	Low risk	(PRIMARY) EDM ‐ This is an objective measure of outcome
Blinding of personnel (performance bias) Adherence measure	Low risk	(PRIMARY) SELF REPORT ‐ QUESTIONNAIRE ‐ Self interview, staff unlikely to bias responses
Blinding of personnel (performance bias) Patient outcome	Low risk	(PRIMARY) VIRAL LOAD ‐ This is an objective measure of outcome
Incomplete outcome data (attrition bias) Adherence measure	Low risk	(PRIMARY) SELF REPORT ‐ QUESTIONNAIRE ‐ "To assess for differences between participants with complete self report data (79%), those who missed a single assessment (13%), and those who missed 2 or more assessments (9%), x2 tests and one‐way analysis of variances were conducted on categorical and continuous sociodemographic characteristics, respectively. No significant differences were found among these 3 groups." (pg 469)
Incomplete outcome data (attrition bias) Adherence measure	Low risk	(PRIMARY) EDM ‐ "Missing EDM adherence data were tabulated separately as this data could be available even if a self report assessment was missing. For EDM adherence, 88% of participants had complete data, 5% were missing a single assessment, and 8% were missing 2 or more assessments. No significant differences were found among these 3 groups." (pg 469)
Incomplete outcome data (attrition bias) Patient outcome	Unclear risk	(PRIMARY) VIRAL LOAD ‐ Not enough information given on the reasons for dropouts. These were not evenly spread across groups