Simoni 2011.

Methods	Randomized controlled trial
Participants	The study location was Ditan hospital, Beijing, China 36 participants were randomized to the intervention group and 34 participants were randomized to the control group The inclusion criteria were mandarin speaking, above 18 years of age, CD4 counts lower than 350 cells /mm3,otherwise eligible for ART, willing to or capable of attending follow‐up visits at the hospital The exclusion criteria were cognitive impairment, actively psychotic
Interventions	Intervention: ENHANCED INTERVENTION ARM Patients assigned to the intervention arm could choose an alarm device, counseling, or both. The alarm device was either a cell phone (if the patient so chose) or a small battery‐powered electronic alarm device. In either case, the project staff helped the patient set up the device of their choice. Counseling was delivered by a bachelor level nurse. In accordance with a manualized protocol, the counseling sessions involved a cognitive‐behavioral and problem‐solving approach to: (1) enhancing motivation for treatment continuation, (2) learning about antiretroviral medication and the prescribed regimen, (3) keeping appointments, (4) communicating with healthcare providers, (5) formulating a daily medication schedule, (6) storing medications, (7) setting reminder strategies, (8) coping with side effects, (9) securing family and social support, (10) handing adherence lapses, and (11) addressing additional barriers. Participants could also invite a treatment partner to attend the counseling sessions with them. A ''treatment partner'' was defined as someone to whom the participant had already disclosed their HIV status and who was available to assist the participant on a daily basis. Participants who opted to have counseling, either individually or with a treatment adherence partner, had 3 counseling sessions of up to 1 hour each with the study nurse. The first session occurred either at the enrollment interview or within the first 2 weeks of initiating ART; additional counseling sessions occurred at 5 and 9 weeks. If necessary, the later sessions were replaced with counseling provided over the telephone Control: MINIMAL INTERVENTION ARM At the baseline appointment and before initiation of ART, all participants completed a 1‐hour interviewer‐administered paper‐and‐pencil baseline survey. They then participated in a 30‐minute educational session facilitated with a flip‐chart, which was designed to provide information regarding their treatment plans, likely side effects, and the importance of adherence. All patients also were given a daily medication schedule, a plastic pill box to organize daily doses, and a referral card to the hospital‐based peer support group. Participants assigned to the minimal intervention were to receive no further adherence‐promotion intervention beyond the usual care at the clinic, which involved monthly medication pick‐ups and any conversations patients initiated with their healthcare providers. All participants continued to receive medical care as usual at the clinic
Outcomes	The measures of adherence were self reported and electronic drug monitoring device (EDM), using 7‐day and 30‐day assessment intervals. Adherence outcomes were computed for 7 weeks, 13 weeks, and 19 and 25 weeks. Self reported 7‐day adherence was based on a single item ''How many of your HIV medication doses did you miss in the last 7 days?'' for which we computed a dichotomous outcome of 100% versus less than 100% adherence. A similar variable based on data covering a 30 day time frame was also calculated. An electronic drug monitoring device known as Medication Event Monitoring System or MEMS was provided to all participants for the duration of the trial. EDM technology consists of a plastic pill vial and modified cap containing a microprocessor capable of recording the precise date and time of each vial opening as a presumptive dose. Each participant was given one EDM to use with nevirapine or efavirenz. Based on EDM data, 2 continuous adherence variables for each assessment point, defined as the number of bottle openings recorded by the EDM cap during the 7 days and the 30 days before each assessment was computed date divided by the number of prescribed doses according to medical record review. Doses were spaced 12 hours apart and EDM openings 11 to 13 hours after the previous dose were counted for on‐time adherence estimates. The patient outcomes were CD4 lymphocyte count and viral load, which were assessed via blood draws at baseline, 13 weeks, and 25 weeks. As viral load data were not normally distributed, a log10 transformation of viral load data were conducted and used the transformed values in all analyses. CD4 and viral load were analyzed as continuous variables to enhance power
Notes	―
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Randomization was not described in detail. "...sequentially numbered, opaque, sealed envelopes containing the intervention assignment, which the staff member opened at the moment of randomization." (pg 921)
Allocation concealment (selection bias)	Low risk	No information was provided about how allocation was handled
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	High risk	Same nurses were involved in the care of both groups; therefore there was a chance of diffusion of intervention. "The nurse intervener was supervised twice a month by telephone by study investigators to ensure fidelity to the intervention protocol, which included completion of a checklist and a progress note after each session. Note that the study nurse as well as the other nurses, all trained in the intervention, continued to see other patients at the hospital, including those in the minimal intervention arm. It was difficult, therefore, to limit the diffusion of the intervention." (pg 922)
Blinding of outcome assessment (detection bias) Adherence measure	Low risk	(PRIMARY) MEMS ‐ This is an objective measure of outcome
Blinding of outcome assessment (detection bias) Adherence measure	Unclear risk	(PRIMARY) SELF REPORT ‐ QUESTIONNAIRE ‐ "Study staff administering surveys, but not the participants and the intervention nurse, were generally blinded to study arm assignment." (pg 921)
Blinding of outcome assessment (detection bias) Patient outcome	Low risk	(PRIMARY) CD4 COUNT AND VIRAL LOAD DATA ‐ This is an objective measure of outcome. "Study staff administering surveys, but not the participants and intervention nurse, were generally blinded to study arm assignment." (pg 921)
Blinding of participants (performance bias) Adherence measure	High risk	(PRIMARY) SELF REPORT ‐ QUESTIONNAIRE ‐ This is a subjective measure
Blinding of participants (performance bias) Adherence measure	High risk	(PRIMARY) MEMS ‐ No mention of patient blinding. Patients could have been aware of the intervention
Blinding of participants (performance bias) Patient outcome	Low risk	(PRIMARY) CD4 COUNT AND VIRAL LOAD DATA ‐ This is an objective measure of outcome
Blinding of personnel (performance bias) Adherence measure	Unclear risk	(PRIMARY) SELF REPORT ‐ QUESTIONNAIRE ‐ No information on blinding given. There is insufficient information to permit judgment of 'Low risk' or 'High risk'
Blinding of personnel (performance bias) Adherence measure	Low risk	(PRIMARY) MEMS ‐ This is an objective measure of outcome
Blinding of personnel (performance bias) Patient outcome	Low risk	(PRIMARY) CD4 COUNT AND VIRAL LOAD DATA ‐ This is an objective measure of outcome
Incomplete outcome data (attrition bias) Adherence measure	Unclear risk	(PRIMARY) SELF REPORT ‐ QUESTIONNAIRE ‐ It is unclear because there is a significant difference between the number of people who dropped out in the control group and the intervention group. However, the percentage retention in the minimal intervention group is above 8%. One of the reasons for dropout is ceasing ART because of severe side effects. "During the course of the trial, 6 of 34 participants enrolled in the minimal intervention arm dropped out due to moving to other provinces, ceasing ART because of severe side effects, losing interest in the study, or transferring to another institution for HIV care. None of the participants in the enhanced arm of the study dropped out. This difference was statistically significant (18% vs. 0%), Fisher's exact v2(1) = 6.95, P = 0.01. According to v2 tests and one‐way ANOVAs, participants across arms with complete selfreport data (79%) did not differ from those who missed one or more assessments (21%) on any of the main sociodemographic, psychosocial, or biological variables as assessed at baseline." (pg 923)
Incomplete outcome data (attrition bias) Adherence measure	Unclear risk	(PRIMARY) MEMS ‐ It is unclear because there is a significant difference between the number of people who dropped out in the control group and the intervention group. However, the percentage retention is the study is above 80% in the minimal intervention arm. One of the reasons for dropout is ceasing ART because of severe side effects. "During the course of the trial, 6 of 34 participants enrolled in the minimal intervention arm dropped out due to moving to other provinces, ceasing ART because of severe side effects, losing interest in the study, or transferring to another institution for HIV care. None of the participants in the enhanced arm of the study dropped out. This difference was statistically significant (18% vs. 0%), Fisher's exact v2(1) = 6.95, P = 0.01." (pg 923)
Incomplete outcome data (attrition bias) Patient outcome	Unclear risk	(PRIMARY) CD4 COUNT AND VIRAL LOAD DATA ‐ It is unclear because there is a significant difference between the number of people who dropped out in the control group and the intervention group. However, the percentage retention is the study is above 80% in the minimal intervention arm. One of the reasons for dropouts is ceasing ART because of severe side effects. "During the course of the trial, 6 of 34 participants enrolled in the minimal intervention arm dropped out due to moving to other provinces, ceasing ART because of severe side effects, losing interest in the study, or transferring to another institution for HIV care. None of the participants in the enhanced arm of the study dropped out. This difference was statistically significant (18% vs. 0%), Fisher's exact v2(1) = 6.95, P = 0.01." (pg 923)