Chung 2011.

Methods	Randomized controlled trial
Participants	The study location was Coptic Hope Center for Infectious Diseases in Nairobi, Kenya Patients were randomized as follows: 100 patients to counseling,100 patients to the alarm device, 100 patients to counseling plus the alarm device, and 100 patients to the control group The inclusion criteria were a CD4 count < 250 cells/mm3, World Health Organization (WHO) clinical stage IV disease, or a CD4 count < 350 cells/mm3 with WHO clinical stage III disease. In addition, patients had to be 18 or older, antiretroviral naive, agree to home visits, and plan to live in Kenya for at least 2 years
Interventions	Intervention: COUNSELING In the adherence counseling intervention, trained counselors administered 2 counseling sessions to participants prior to HAART initiation and a third session one month after HAART initiation. Counseling sessions around HAART initiation were based on a model of successful antiretroviral adherence promotion at a large University of Washington‐affiliated HIV treatment program in Seattle, Washington. All counseling sessions followed a written standardized protocol and lasted between 30 and 45 minutes. In the first session, counselors explored personal barriers to good adherence and taught participants about HIV, the virus that causes AIDS, antiretroviral medications, and the risks of treatment failure due to poor adherence. The second session occurred on a separate day and involved a review of a participant's understanding and readiness to begin antiretroviral medications. The third session allowed the counselor to examine practical and personal issues that the participant may have encountered on HAART. The adherence counseling intervention had been previously used and adapted at the same site in Kenya for over 2 years and was delivered in English and Kiswahili Intervention: COUNSELING PLUS ALARM Participants in counseling plus alarm group received both adherence counseling and alarm reminders. 3 adherence counseling sessions (2 prior to HAART initiation and 1 after HAART initiation) were conducted. All counseling sessions followed a written standardized protocol and lasted between 30 and 45 minutes. In the first session, counselors explored personal barriers to good adherence and taught participants about the HIV, the virus that causes AIDS, antiretroviral medications, and the risks of treatment failure due to poor adherence. The second session occurred on a separate day and involved a review of a participant's understanding and readiness to begin antiretroviral medications. The third session allowed the counselor to examine practical and personal issues that the participant may have encountered on HAART. The counseling session was delivered in English and Kiswahili. In addition, participants were given a small pocket digital alarm, which the individual was to carry at all times for 6 months. The device was programmed by the study staff to beep and flash twice a day at a time convenient to the participant when medications were to be taken. The digital alarm could not be reprogrammed or inactivated by the individual and was utilized for 6 months after HAART initiation before being disabled by study staff Intervention: ALARM DEVICE Participants in the alarm device intervention received a small pocket digital alarm which the individual was to carry at all times for 6 months duration. The device was programmed by the study staff to beep and flash twice a day at a time convenient to the participant when medications were to be taken. The digital alarm could not be reprogrammed or inactivated by the individual and was utilized for 6 months after HAART initiation before being disabled by study staff Control: USUAL CARE "At HAART initiation, the study pharmacist explained the side effects of medications and problems associated with poor adherence in a 15‐min session prior to dispensing drugs. All participants, including those in the control arm, received this educational message. Participants randomized to the control group did not receive adherence counseling or an alarm device." (pg 2)
Outcomes	The measures of adherence were pill counts and pharmacy refill visits. After initiating HAART, participants returned to the study clinic monthly with their pill bottles to pick up antiretroviral medications. At each monthly visit, the study pharmacist counted and recorded the number of pills remaining in the bottle, the visit date, whether the participant took his or her morning dose, and the number of pills dispensed that day. Adherence was calculated as the percentage of dispensed doses that were taken since the previous visit to the study pharmacy. Total time between the last date the participant visited the pharmacy and the participant's subsequent pharmacy visit included any missed visits to the pharmacy or time when the participant was not attending the clinic. This calculated adherence was assumed to be constant and the same as daily adherence throughout this time period. Continuous adherence and time to monthly adherence < 80% and < 95% were calculated The patient outcomes were viral failure, mortality, and change in CD4 count. Participants had blood drawn at 6, 12, and 18 months. RNA was measured using the Gen‐Probe quantitative HIV‐1 viral load assay. CD4 counts were determined using flow cytometry. Viral failure was defined as the first plasma HIV‐1 RNA level greater than or equal to 5000 copies/ml measured at least 4 months after HAART initiation
Notes	―
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	(pg 2) "In a 262 factorial design, participants were randomized in a 1:1:1:1 ratio to one of four arms prior to initiating HAART: (1) adherence counseling alone; (2) alarm device alone; (3) both adherence counseling and alarm device together; and (4) a control group that received neither adherence counseling nor alarm device. Randomization was performed at enrollment by the study nurse who opened a sealed envelope containing a computer‐generated block randomization code that was developed by the study biostatistician."
Allocation concealment (selection bias)	Low risk	Randomization was performed at enrollment by the study nurse who opened a sealed envelope containing a computer‐generated block randomization code that was developed by the study biostatistician. Study investigators and participants were not blinded to the interventions
Selective reporting (reporting bias)	Low risk	All relevant results appear to be reported; protocol is available
Other bias	Unclear risk	The authors note several limitations of the study but insufficient information is provided to make a judgment
Blinding of outcome assessment (detection bias) Adherence measure	Low risk	(PRIMARY) PHARMACY REFILL RECORDS ‐ Not blinded, but refill records are unlikely to be biased
Blinding of outcome assessment (detection bias) Patient outcome	Low risk	(PRIMARY) CD4 CELL COUNT AND VIRAL LOAD ‐ This an objective outcome
Blinding of participants (performance bias) Adherence measure	Unclear risk	(PRIMARY) PHARMACY REFILL RECORDS ‐ No mention of blinding of study participants. Possible bias that participants might discard medicine instead of taking it
Blinding of participants (performance bias) Patient outcome	Low risk	(PRIMARY) CD4 CELL COUNT AND VIRAL LOAD ‐ This an objective outcome
Blinding of personnel (performance bias) Adherence measure	Unclear risk	(PRIMARY) PHARMACY REFILL RECORDS ‐ No mention of blinding of study personnel
Blinding of personnel (performance bias) Patient outcome	Low risk	(PRIMARY) CD4 CELL COUNT AND VIRAL LOAD ‐ This an objective outcome
Incomplete outcome data (attrition bias) Adherence measure	Unclear risk	(PRIMARY) PHARMACY REFILL RECORDS ‐ Missing data appear relatively balanced across groups but insufficient information provided to make a judgment
Incomplete outcome data (attrition bias) Patient outcome	Unclear risk	(PRIMARY) CD4 CELL COUNT AND VIRAL LOAD ‐ Losses to follow‐up relatively balanced across the groups