Sorensen 2007.

Methods	Randomized controlled trial
Participants	The study location was 2 urban clinics in San Francisco, California, USA: the San Francisco General Hospital Opiate Treatment Outpatient Program (OTOP) and Bay Area Addiction Research and Treatment (BAART), Market Street Clinic 34 participants were randomized to the intervention group and 32 participants were randomized to the control group The inclusion criteria were for the initial baseline phase: (a) enrolled in outpatient methadone maintenance treatment, (b) HIV antibody seropositive as indicated by clinic records, and (c) prescribed an antiretroviral medication for treatment of HIV/AIDS for at least 1 month, evidenced by prescription or prescription bottle The exclusion criteria were for the initial baseline phase: (a) participating in other adherence improvement research or clinical programs or (b) living in a controlled environment that dispensed residents' HIV medications. Before beginning the actual trial, participants who were 80% adherent or greater during the baseline phase were excluded from the study
Interventions	Intervention: VOUCHER INTERVENTION Patients in the voucher intervention group began with a 4‐week baseline phase, where they received a MEMS monitor for one of their HAART medications. Patients met with a registered nurse or trained research assistant who provided medication coaching once during the baseline phase and then every 2 weeks throughout the study. Patients were provided with a hard copy of their MEMS data throughout the study. During baseline, patients met a research assistant twice weekly to provide the MEMS data. At the end of the baseline phase, patients in the voucher phase continued to meet twice weekly with a research assistant, for a total of 24 visits. When patients opened their medication caps as scheduled, they received vouchers that were exchangeable for goods and services for each correctly taken medication dose. The value of the voucher increased for each correctly taken dose in a row, but reset to the original value if a dose was missed. Patients could earn up to USD 1172.40 if they took all their medication correctly throughout the study Control: COMPARISON Patients in the comparison group began with a 4‐week baseline phase, where they received a MEMS monitor for one of their HAART medications. Patients met with a registered nurse or trained research assistant who provided medication coaching once during the baseline phase and then every 2 weeks throughout the study. Patients were provided with a hard copy of their MEMS data throughout the study. During baseline, patients met a research assistant twice weekly to provide the MEMS data. During the intervention phase, comparison group participants continued to meet twice weekly with the research assistant, for a total of 24 visits, and received medication coaching every 2 weeks. As several of the initial comparison group participants expressed dissatisfaction with their treatment compared to the voucher group, a reward system was implemented for the comparison group. A fishbowl prize system was used to reinforce attendance at scheduled interviews. Patients could pick a number from the fishbowl, which would give them either a small or large prize
Outcomes	The measures of adherence were MEMS, a medication adherence and side effects questionnaire, and pill counts. For MEMS, one selected HAART medication was selected to monitor as the primary adherence outcome measure. On‐time MEMS cap openings were expressed as the percentage of scheduled dosing times when the cap was opened "on‐time", defined as taking place in a 4‐hour window around the scheduled dosage time, that is, per cent observed openings/per cent expected openings. MEMS records were used to calculate on‐time openings and the longest documented days of continuous on‐time openings. The medication adherence questionnaire was a self report of patient's adherence for the previous day and the past 3 days for each medication. This measure was administered weekly throughout the study. Pills were counted for one selected HAART medication at baseline to reflect the initial stock, then weekly to track adherence, and after refills to account for new pills added to the bottle. All adherence measures were collected by research assistants during in‐person meetings with participants The patient outcome was the SF‐36, a 36‐item self administered instrument that evaluates health‐related quality of life in 8 dimensions, including: physical functioning, role functioning, bodily pain, general health, vitality, social functioning, mental health, and reported health transition. It provides 2 summary measures; a Mental Health Summary Scale and a Physical Health Summary Scale, which were utilized as the primary outcome measures of self reported health. The SF‐36 was administered monthly (baseline, weeks 4, 8, 12, 16, and 20). Plasma HIV‐1 RNA (viral load) was quantified from monthly blood draws using the Quantiplex bDNA Assay. Viral load results typically are widely variable, therefore they present raw results and log‐10 transformed values. A decrease of at least 0.5 in log 10 viral load is considered consistent with improvement and not within the range of laboratory error. CD4+ lymphocyte counts, a type of white blood cells or T‐cells vital to immune function, was obtained at baseline, weeks 12 and 20 from blood samples sent to the hematology section of San Francisco General Hospital clinical laboratories. HIV infection leads to a progressive reduction in the number of T‐cells with CD4 receptors, and the CD4 count is used as a staging indicator for treatment decisions. When there are fewer than 200 CD4+ T‐cells per microliter of blood, a person is diagnosed with AIDS. Weight was measured in pounds on a physician mechanical balance beam scale at baseline and at 20‐week follow‐up. Urine specimens were collected monthly and analyzed by Quest Diagnostics Inc., using enzyme multiplied immunoassay technique (EMIT), and positive screens were re‐analyzed using thin‐layer chromatography (TLC). Reported results included alcohol, amphetamines, barbiturates, benzodiazepines, cannabinoids, cocaine, and opiates; however, due to low frequencies of positive tests for most substances only cocaine and opiates were analyzed in the current report
Notes	―
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	A computer‐generated random sequence was used for randomization. "Eligible participants were randomly assigned to receive vouchers or a comparison intervention (medication coaching only) according to a computer generated list. Assignment was stratified by baseline CD4 lymphocyte count (i.e., greater than or equal to 200 cells/UL versus less than 200 cells/UL) because more medically compromised patients were likely to have more severe medical problems during the study. The research assistant opened a sealed envelope of intervention group assignments generated by the project statistician." (pg 56)
Allocation concealment (selection bias)	Unclear risk	It does not specify opaque envelopes. "The research assistant opened a sealed envelope of intervention group assignments generated by the project statistician." (pg 56)
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) MEMS ‐ unlikely to be affected by the blinding status of the RA collecting the data
Blinding of outcome assessment (detection bias) Patient outcome	Unclear risk	(PRIMARY) SELF REPORTED HEALTH (SF 36) ‐ This is a subjective measure; there is no information on blinding
Blinding of participants (performance bias) Adherence measure	High risk	(PRIMARY) MEMS ‐ Participants in the intervention group were given vouchers based on opening their medication caps. Participants could have opened the caps without actually taking any medication
Blinding of participants (performance bias) Patient outcome	Unclear risk	(PRIMARY) SELF REPORTED HEALTH (SF 36) ‐ This is a subjective measure; there is no information on blinding
Blinding of personnel (performance bias) Adherence measure	Low risk	(PRIMARY) MEMS ‐ unlikely to be affected by the blinding status of the personnel
Blinding of personnel (performance bias) Patient outcome	Unclear risk	(PRIMARY) SELF REPORTED HEALTH (SF 36) ‐ This is a subjective measure; there is no information on blinding
Incomplete outcome data (attrition bias) Adherence measure	Unclear risk	(PRIMARY) MEMS ‐ Reasons for dropout given but not which group they were in. Not completely balanced across the conditions
Incomplete outcome data (attrition bias) Patient outcome	Unclear risk	(PRIMARY) SELF REPORTED HEALTH (SF 36) ‐ Dropouts uneven across groups; it does not indicate which dropouts were in each group