HIVManagment.org - Adherence Literature Review

**Interventions to improve patient adherence to medication courses: Meta-analyses and reviews from the general literature¹**
Author	Methods	Results
Haynes 124	Systematic review of unconfounded, randomised controlled trials of interventions to support medication adherence.	Haynes 124 Systematic review of nonblinded, randomised controlled trials of interventions to support medication adherence. Suitable packages include the provision of care which is convenient for patients, education and counselling, medication alerts, social support, self-assessment, family therapy, and reinforcement during follow-up. Suggests that complex care packages are required in chronic therapy. Notes that even where these measures were most effective they did not result in substantial improvements in adherence, suggesting a need for further research and the evaluation of novel interventions.
Roter 125	Roter 125 Meta-analysis of 153 studies of interventions to improve patient adherence published between 1977 and 1994. Interventions categorised as either educational, behavioural, or affective, and assessed for effect on health outcomes (e.g. blood pressure); direct indicators (e.g. weight change); indirect indicators (e.g. pill count); subjective reports (e.g. patient reports); and utilization (e.g. appointment-making). Interventions produced the greatest effect on direct and indirect indicators, and smaller effects on health outcomes and utilization. Patients with chronic disease, and those with mental health problems especially benefited from interventions. No single intervention was found more effective than others. Comprehensive interventions involving cognitive, behavioural and affective elements were more effective than single-focus interventions.	Roter 125 Meta-analysis of 153 studies of interventions to improve patient adherence published between 1977 and 1994. Interventions categorised as either educational, behavioural, or affective, and assessed for effect on health outcomes (e.g. blood pressure); direct indicators (e.g. weight change); indirect indicators (e.g. pill count); subjective reports (e.g. patient reports); and utilisation (e.g. appointment-making). Interventions produced the greatest effect on direct and indirect indicators, and smaller effects on health outcomes and utilisation. Patients with chronic disease, and those with mental health problems especially benefited from interventions. No single intervention was found more effective than others. Comprehensive interventions involving cognitive, behavioural and affective elements were more effective than single-focus interventions.

**Interventions to improve adherence to antiretroviral therapy: Evidence from randomised, controlled trials**¹
Author	Methods	Results
Tuldra 126	Comparison of a multi-faceted 'psychoeducative' intervention with standard follow-up in patients beginning a new HAART regimen. The intervention was designed to increase self-efficacy around taking medication, and involved explaining rationale for taking HAART and role of adherence in preventing resistance; 'solving doubts' about medication intake; involving patient in designing a medication schedule, and in development of strategies to manage problems relating to forgetting or delaying doses, side-effects, and changes in daily routine. Telephone support was available between clinic visits. During follow-up visits, the need for high adherence was reinforced, and problems were reviewed and coping strategies proposed. Strategies most commonly involved modification of dosing schedules, encouragement of habits to spur medication intake, and supporting patients to manage side-effects. Improved adherence levels (% taking >95% of prescribed doses), and treatment responses (% with viral load below 400 copies) were observed in the intervention group after 48 weeks follow-up. There were no differences between the two arms until this point, suggesting that long-term support is required to support long-term effectiveness. Initial adherence levels in both arms were relatively high, but fell off in the control arm by 48 weeks, suggesting initial success may not be maintained without ongoing support.	Strategies most commonly involved modification of dosing schedules, encouragement of habits to spur medication intake, and supporting patients to manage side-effects. Improved adherence levels (% taking >95% of prescribed doses), and treatment responses (% with viral load below 400 copies) were observed in the intervention group after 48 weeks follow-up. There were no differences between the two arms until this point, suggesting that long-term support is required to support long-term effectiveness. Initial adherence levels in both arms were relatively high, but fell off in the control arm by 48 weeks, suggesting initial success may not be maintained without ongoing support.
Rigsby 127	Randomised 55 people (predominantly male, black and with a history of heroin or cocaine use) on stable antiretroviral therapy to receive either weekly nondirective inquiry about adherence (control); 'cue-dose training' designed to enable development of personalised cues to medication taking, with feedback from MEMS pill bottle cap; or cue-dose training plus cash payment for correctly timed pill bottle opening. Adherence measured using MEMS and defined as opening the pill bottle two hours before or after a predetermined time. Over a four week period, adherence was significantly improved in recipients of cash payments, but not in those receiving cue-dose training alone, compared with the control arm. Eight weeks after the intervention, adherence returned to baseline levels in the cash payment group.	Over a four week period, adherence was significantly improved in recipients of cash payments, but not in those receiving cue-dose training alone, compared with the control arm. Eight weeks after the intervention, adherence returned to baseline levels in the cash payment group.
Knobel 128	Randomised 170 people (2:1) taking AZT/3TC/IDV to receive standard care or to receive detailed information on their therapy and for it to be adapted to their lifestyle. Adherence measured by structured interview and pill counts. Patients who took more than 90% of their doses were defined as adherent.	After 24 weeks, there was a significant difference in adherence between groups (76.7% intervention versus 52.7% control), but no difference in proportions with viral load below 50 copies.
Gifford 129	Randomised 168 people taking multi-drug antiretroviral therapy to either a group-based patient education programme (SME); a social support control (SS) or printed materials control (PM). SME was led by a trained nurse and peer educator and taught adherence and self-care skills over six two hour sessions. Adherence was measured by self-report and summarised as excellent (100%); fair (80-99%); or poor (<80%).	Self-report was associated with serum drug levels. Immediately after the intervention, adherence levels were better in SME compared to PM, but no different to SS, regardless of baseline level. After six months follow-up there was no difference in adherence level between the three groups at any baseline adherence level. The authors conclude that benefits gained from adherence interventions may not persist over the longer-term without reinforcement.
Goujard 130	Randomised 365 HAART recipients to take part in a Treatment Education Programme (TEP) or to a control arm which received standard follow-up (Goujard). The TEP included four face-to-face educational sessions of one hour each, conducted by doctor or a nurse, using a toolkit called Ciel Bleu, designed to teach patients about HIV pathogenesis, disease progression, the rationale for anti-HIV therapy, and the importance of adherence. TEP patients also received a beeper pillbox, and a number of devices to aid treatment scheduling. Every six months, study participants self-reported adherence over the previous week via a questionnaire. At entry, mean viral load was 2.42 log, mean duration of prior treatment was 4.0 years, 57% had viral load below 200 copies, and adherence levels were comparable across the two arms, with 46% belonging to the upper level adherence stratum.	Over six months follow-up, adherence levels improved in the TEP group, and fell in the control arm. There was no appreciable change in viral load and CD4 count in either group.
Collier 131	Randomised 282 individuals enrolled in a comparative antiretroviral therapy trial (ACTG 388) to standard adherence care versus standard care plus scripted telephone calls (16 calls over 96 weeks). Adherence measured at clinic visits by self-report over previous four days.	73% of phone calls were completed successfully. >64% of subjects in each arm reported >95% adherence, and >61% reported 100% adherence. 34% of subjects met criteria for virological failure. There was no difference in time to virological failure between arms. The authors conclude that within a clinical trial setting, telephone calls did not improve high levels of reported adherence, or virological outcome.
Wall 132	Randomised 27 individuals undergoing methadone maintenance treatment with low adherence to AZT monotherapy to receive either eight weeks of weekday supervised dispensing of therapy, or to receive standard care. Adherence was measured by self-report, erythrocyte mean corpuscular volume (MCV), MEMS and pills counts.	MCV levels were significantly higher in the intervention group during the intervention period, and MEMS demonstrated higher adherence in the intervention group on weekdays during this period, though not at weekends. There were no significant differences regarding the other measures, and no differences in any measure after one month of follow-up.
Samet 133	Randomised 151 people with a history of alcohol problems who were receiving antiretroviral therapy to usual follow-up or an intervention (4 meetings with a nurse trained in motivational interviewing: addressed alcohol problems; provided a programmable watch; enhanced perception of treatment efficacy). Adherence measured by self reported 30 day recall.	After 13 months follow-up, there were no differences in adherence between the two groups, or in other outcome measures (CD4 count, viral load, alcohol consumption.
Safren 134	After a two week period where adherence to antiretroviral therapy was monitored using an electronic pill cap, 71 people who recorded <90% adherence were randomised to continued monitoring or to receive a pager (MediMom, an internet-based paging system). Adherence level at randomisation was 56%.	The pager was associated with improved adherence at week 2 (70% versus 56% in the non-pager group), and at week 12 (64% versus 52% respectively. It is noted that adherence in this population remained inadequate even following the intervention.