Behavioral Economics Incentives to Support HIV Treatment Adherence (BEST) in Uganda

There will be two intervention arms, both of which will use lottery-based incentives. In Treatment Group 1 (T1), clients will be eligible for quarter-yearly lotteries with small prizes based on timely drug refills and annual large prize lotteries if they demonstrate viral suppression. In Treatment Group 2 (T2), clients will be eligibility for quarterly small prize lotteries and annual larger prize lotteries based on high adherence as measured by electronic devices known as medication event management systems (or MEMS-caps). The control group will receive care as usual, including any adherence support mechanisms that are present within usual care practices. All participants including those in the control group will receive MEMS-caps.

There will be two intervention arms, both of which will use lottery-based incentives. In Treatment Group 1 (T1), clients will be eligible for quarter-yearly lotteries with small prizes based on timely drug refills and annual large prize lotteries if they demonstrate viral suppression. In Treatment Group 2 (T2), clients will be eligibility for quarterly small prize lotteries and annual larger prize lotteries based on high adherence as measured by electronic devices known as medication event management systems (or MEMS-caps). All participants including those in the control group will receive MEMS-caps.

Treatment Group 1: Lottery eligibility based on timely drug refills at each clinic visit and achieving viral suppression at the annual lottery

Prize drawings at each clinic visit to encourage study engagement: In this low-cost arm, participants will be eligible to participate in prize drawings whenever they come to the clinic as scheduled. Scheduled clinic visits coincide with picking up drug refills as all Mildmay clients receive their medication for free at the Mildmay pharmacy. Drug refills are needed for high adherence (as late pick-ups would lead to not having enough drugs), and have been found to be highly correlated with viral outcomes. When the client comes to the clinic, the study coordinator will check whether the clinic appointment was kept using the client’s clinic booklet and/or medical records. If the client qualifies, s/he is invited to draw a number out of a bag without looking. In the bag are four laminated cards of identical size with numbers 0 through 3 on them; if the ‘0’ is drawn, the client wins nothing, but if any of the numbers 1-3 are drawn s/he wins a prize and can then take the prize home immediately.

Annual prize drawings: The T1 group is eligible for the annual lottery conditional on showing viral suppression at their annual viral load measure, which requires long-term behavioral change. Approximately one year after recruitment, each study client will be due for their annual viral load test. Once the test results are available, the study coordinator assesses eligibility for the annual lottery based on whether the client has a detectable viral load. For eligible clients, the drawing for the larger prize (worth roughly $10 USD with a 10% chance of winning) will take place at the subsequent clinic visit. We will classify a viral load as ‘undetectable’ using the cut-off of HIV RNA <200 copies/mL. The AIDS Clinical Trials Group (ACTG) defines virologic failure as a confirmed viral load >200 copies/mL—a threshold that eliminates most cases of apparent viremia caused by viral load blips or assay variability.

Treatment Group 2: Lottery eligibility based on measured adherence using MEMS-caps

Prize drawings at each scheduled clinic visit: When participants in this group learn about their treatment assignment, they will be informed that if they take 90% or more of their medication by their next their next clinic visit, they will be eligible for the lottery. The lottery will have the same setup as for T1. They will also be informed that for the next 24 months, they will continue being eligible for the lottery if they continue to adhere to their medication at or above this level. Each time the client comes for a scheduled clinic visit, the study coordinator will use the client’s MEMS-cap to perform a reading. When the client is found eligible (>90% adherence), s/he is invited to participate in the prize drawing as described for the T1 group above.

Annual prize drawings for T2 to encourage continuous health behavior change: We will conduct an annual drawing where eligibility is based on observed mean adherence over the course of the year. The study coordinator will check the participant’s record for continued adherence over 90% (we will create a separate file for each client so that this check is easily performed), and determine if the client is eligible for each drawing.

Control Group: Usual care

The control group will receive care as usual, including any adherence support mechanisms that are present within usual care practices. All clients receive intensive ART orientations and adherence education when they first start ART, but for long-term ART clients there is no systematic adherence support mechanism; however, adherence counseling is available to patients who are referred by their providers to a counselor. All control group participants are encouraged to come to the study offices at each clinic visit in order to make sure that they spend an equal amount of time with the study coordinator as those in the intervention groups. During that visit, we check the MEMS-device and ask about any difficulties using it.

2018-04-12

2022-03-01

We will have one biological primary outcome and one behavioral primary outcome, namely viral suppression, and the percent of prescribed medication taken (mean adherence), respectively.

Our behavioral primary outcome will be electronically-monitored adherence. MEMS-data will be collected continuously over the course of the 24-month study period allowing us to investigate daily adherence and its timing, as well as for twelve months after the intervention ends. We will create a variable that captures the share of prescribed pills that were actually taken (i.e. number of actual bottle openings divided by the prescribed bottle openings).

Our biological primary outcome will be a binary indicator for whether the participant has an undetectable viral load. The AIDS Clinical Trials Group (ACTG) defines virologic failure as a confirmed viral load >200 copies/mL. We will indicate a viral load measure as undetectable if it is below 200 copies/mL. Viral load is the primary measure used to assess level of viral activity in a person’s blood, as well as response to ART. Although other factors besides adherence contribute to viral load, undetectable viral load is widely considered a strong indicator of good ART adherence. Furthermore, given the limitations of measures of behavioral adherence, viral load is considered by some to be the best indicator of adherence, and at the very least a valuable complement to behavioral adherence measures. Viral load measurements are now part of routine clinical care at Mildmay and will be chart abstracted. They are taken when a person tests HIV-positive, six and twelve months thereafter, and then every 12 months. We will line up recruitment so that all participants have a viral load measure taken at baseline, around month 12, and around month 24.

Viral Load as continuous variable, and measure of adherence (90%)

First, as an additional measure of viral load, we will analyze viral load as a log-transformed continuous variable instead of a binary variable indicating detectable/undetectable. Second, as an additional measure of adherence, we will create a binary indicator for whether the client opened 90% or more of the openings that were prescribed. We will also create an indicator for treatment interruptions of more than 48 hours, which is an important predictor of virologic failure.

This study will use a three-armed randomized controlled trial (two intervention groups and one control group), with 1:1:1 randomization at the individual level. The intervention will last for 24 months. The study will be conducted at Mildmay Uganda, an NGO with headquarters in Uganda’s capitals Kampala. Mildmay Uganda specializes in the provision of comprehensive HIV and AIDS prevention, care, and treatment services.

This study will use a three-armed randomized controlled trial (two intervention groups and one control group), with 1:1:1 randomization at the individual level. The intervention will last for 24 months. The study will be conducted at Mildmay Uganda, an NGO with headquarters in Uganda’s capitals Kampala. Mildmay Uganda specializes in the provision of comprehensive HIV and AIDS prevention, care, and treatment services.

Random treatment assignment will occur after participants are recruited, but before they complete a baseline survey using a 1:1:1 ratio. We will stratify random assignment on age (under-25 or over-25 years of age), gender, marital status (married/cohabiting or unmarried), low CD4 count (below 200 or above 200), and viral load (detectable or undetectable). Stratified randomization is achieved by generating a separate block for each combination of covariates identifying which clients fall into each block. We will then randomize treatment assignment within each block. We will use the randtreat package in Stata15 to carry out the randomization procedure.

Client-level (i.e. individual)

No

330 treatment-mature clients and 70 treatment-initiating clients

330 treatment-mature clients and 70 treatment-initiating clients

110 clients per arm, plus 70 treatment initiators in the T2 arm eligible for prize drawings conditional on high MEMS-cap measured adherence

We have calculated the size of effects that our sample will be able to detect with 80% power (2-tailed test) with regard to outcomes at month 12 and 24, and 10% attrition every year (we observed 5% attrition over 20 months in our previous studies so this is a conservative estimate). For the primary outcome of viral suppression, we use a conservative estimate of 70% of clients in the control group showing suppression based on discussions with the Mildmay team. Our sample size of 110 participants in each of the three arms (total n=330) will be able to detect a 7 percentage point difference for joint comparison of T1 and T2 against the control at month 12, and about an 8.5 percentage point difference between the two intervention arms (a ‘subgroup analysis’). The corresponding differences at month 24 are 8 and 9 percentage points, respectively. These are considered small effect sizes (Cohen’s d of between .15 and .185) that we will be able to detect. For adherence, in our previous study we observed mean adherence rates of ~ 75% as measured by MEMS-caps; our sample size of 110 in each of the intervention arms and the control group will provide sufficient power to detect about a 6.5 percentage point difference in mean adherence between the two intervention arms (combined) and the control group. To test for differences in adherence between the two intervention arms, our study is powered to detect about a 7.5 percentage point effect as measured by MEMS- caps. Again, this means we will be able to detect small-sized effects. The corresponding differences we will be able to detect at month 24 are about 7 and 8 percentage points, respectively.