All patients who attended the clinic on June 6th 2009 and met the eligibility criteria (n = 24), were approached for participation in the study and all agreed. However, one patient, a long-distance truck driver, withdrew from the study immediately after consenting because he judged the use of the MEMS-bottle to be incompatible with his travelling schedule. Hence, 23 ART users completed the three-month study period and were interviewed.
Fourteen (61%) participants were married, three (13%) were single, one (4%) was divorced, and five (22%) were widowed. All married participants had disclosed their HIV status to their spouses. The median age was 44 (interquartile range (IQR): 39-48). The period of ART use by the time of enrollment ranged from 6 to 48 months. At enrolment, the CD4 cell count was less than 200 cells/μL in one patient (4%), between 201 and 300 cells/μL in six patients (26%), between 301 and 500 cells/μL in ten patients (44%), and above 500 cells/μL in six patients (26%). The patient characteristics are summarized in Table .
Demographic and disease characteristics of participants who completed the study (N = 23)
Acceptability of MEMS-design
The first indicator of the acceptability of the MEMS-bottle was the patients' willingness to participate in this study and use the MEMS-bottle. As reported, all eligible patients accepted study participation, but one withdrew from the study immediately after consenting. The majority of participants (21/23) indicated to have no problem with the color and size of the MEMS-bottle. A female participant (36 years) narrated: "The shape is good; it looks like a make-up bottle." Another female (41 years) stated: "This container looks like a body lotion-it is not easy for people to know that I am carrying the pills." A man of 52 years remarked: "This medication bottle is better than ordinary pill bottles, its shape and size are OK." Another man (30 years) said: "If you put this bottle on the table, no one will know what it is for. Its size has no problem, and its color-no problem."
Common feedback was that the MEMS-bottles, contrary to the regular medication bottles, do not have labels that reveal its content. This was perceived as highly beneficial. For example, a female of 39 years remarked: "This container is very good. No one would immediately know what it is for. The normal pill bottles are labeled so when someone sees it, it is recognized quickly." Another female (41 years) said: "This one is cool. With the other type, people read it and start bombarding you with questions."
Upon inquiring about what patients think the ideal shape of a MEMS-bottle would be, two participants proposed that a flat-shaped container would be easier to carry in one's pocket. A long-distance truck driver (male, 50 years) said: "I would prefer a container with a flat shape like a small mobile phone because it will be easy to put in the pocket."
Feasibility of using MEMS according to guidelines
None of the patients reported to have had difficulties with following the guidelines for accurate MEMS-use: 1] to put the MEMS-cap on the pill bottle after use and close it properly, 2] always take all pills from the MEMS-bottle, and 3] prevent the bottle from being opened by a family member. Moreover, no one complained about the condition not to open the pill-bottle between medication intakes. A widower (44 years) said "I keep it on my table, it's easy. I have my time for medication intake, so I open it during that time. On travel occasions, I move with it." When asked if a family member or child might have opened the MEMS-bottle, most patients reported to have kept the MEMS-bottle out of reach from others. A woman (41 years) remarked: "I did not have any problem whatsoever. I keep it in my bedroom and put it in a drawer to avoid it being opened by children. I have no problem with it, the instruction is not difficult." One participant (male, 50 years) said: "I hide my container in my suitcase. I don't want children or any other person to open it or ask me about it, this is my secret."
Four participants talked about the challenges of always using all their medication from the MEMS-bottle. These challenges were mainly related to travelling. The patients considered it unsafe to travel with the bottle as they feared that it could be stolen or lost. For example, a long-distance truck driver (male, 50 years) indicated: "When I was traveling, I left it at home and took the medication along. I was afraid the device could be stolen." A female (39 years) confessed: "I left my MEMS-bottle at home during my travel away from home and I transferred my pills into an ordinary medication bottle." A mason (man, 50 years) said: "I had to travel to Arusha for construction work for one and a half month. I left my MEMS-bottle at home and instead transferred my pills into another bottle. I feared my MEMS-bottle could be stolen or misplaced at the construction site."
Impact of MEMS-use on patient behavior
Nearly 75% of patients (17/23) had informed other family members that they had a new medication container. As one of the respondents said: "I have informed my family and children that this bottle records pill taking behavior every time you open, so I strictly forbid them to touch it because it will be revealed when false openings are done to the pills bottle." All participants who had told their family members about the MEMS-bottle said that their family members became more supportive in reminding them to take the medication. One participant (female 45 years) said: "Because my family members don't want me to have a bad record on my medication, they are very supportive in reminding me about the time to take pills."
On the question about how patients felt that their behavior was being monitored by the MEMS-cap, a typical response was: "I have no problem with that." A female (45 years) answered: "That is very good because it motivates me to remember to take pills." A man (30 years) remarked: "I have become more conscious in taking medication. I am now more systematic and I don't forget to take my pills because I know that I am been monitored. With other containers I could take pills any time and skip taking pills at will." Similarly, another man (45 years) said: "Because I know that I am being recorded, I make every effort to take my medication as prescribed." A women (45 years) stated: "In the past I used to skip pills even for about 20 days, sometimes I found myself with two containers full of pills, but with this new container, I don't skip a day."
Corroborating interview responses with MEMS-data
Examination of the MEMS-reports revealed that there was no evidence of systematic overdosing by any of the patients. Bottles were typically opened twice a day at regular intervals. Sporadically, MEMS-bottles were opened three times a day instead of two. This was usually on clinic visit days when the bottle was refilled. Hence, these data confirm patients' reports that they only opened the pill-bottle for medication intake.
There were six patients whose MEMS-data showed periods of more than three days of missed medication (observed range was 12 to 71 days). Two of these patients reported during the initial interviews that they had left the MEMS-bottle at home when travelling, fearing that it might be stolen. Hence, they were not considered as non-adherent, but as not using the MEMS-cap. Two of the four remaining patients, who reported in the initial interviews to have always used the MEMS-cap as prescribed, showed up too late for collecting their medication in that period. Their missing MEMS-data was therefore considered to accurately describe their medication intake (i.e., non-adherence). Of the two remaining patients, who did not self-report inaccurate MEMS-use and were on time for collecting their medication, one could be re-contacted to explain the data. This patient reported to have left the MEMS-bottle at home when travelling for a period of six weeks. The non-monitored period was indeed 6 weeks, and this was thus considered to be non-MEMS-use rather than non-adherence. Hence, the MEMS-caps seemed to have been used accurately by all patients, except by three patients who did not use it during long-distance travels.
The interviews suggest that patients were, on average, highly adherent. Moreover, they suggest that patients changed their medication intake behavior because they were being monitored, an effect that has also been recognized in the Western literature. However, this monitoring effect is expected to reduce over time [16
]. As a final step, we therefore explored the patients' monthly adherence scores, namely the percentage of doses taken (taking adherence) and the percentage of doses taken within a 9-15 hour interval (timing adherence), and explored whether adherence decreased over time also in this study. For the three patients who travelled and used their medication from another bottle, their period of non-MEMS-use was set to 'missing'. Monthly adherence scores were only computed for these three patients if they provided at least two weeks of continuous MEMS-data.
The adherence scores are summarized in Table and reveal that adherence levels were fairly high and declined somewhat over time. Seventy-four percent (17/23) of the patients took more than 95% of their medication during the first month, 63% (14/22) in month 2 and 62% (13/21) in month 3. Wilcoxon's Signed Rank tests revealed that for taking and timing adherence there was a statistically significant decrease in adherence between month 1 and 3 (both p < 0.05), but not between month 1 and 2, or 2 and 3.
One additional finding was that MEMS-data frequently revealed 3-5 days of non-adherence before a clinic visit. Upon exploring the cause of this pattern, it became clear that whereas the time between two consecutive visits in this clinic ranges from 30 to 35 days, patients were only provided with medication for 30 days. Hence, even the most motivated patients could not always be fully adherent due to mismanagement at the clinic level.