Simoni, Jane M PhD*; Huh, David MS*; Frick, Pamela A PharmD, MPH†; Pearson, Cynthia R PhD‡; Andrasik, Michele P PhD§; Dunbar, Peter J MB, ChB¶; Hooton, Thomas M MD∥
Widespread adoption of highly active antiretroviral therapy (HAART) has significantly extended the lives of persons living with HIV/AIDS,1,2 with 1 report estimating that the potent therapies have saved at least 3.0 million years of life in the United States alone.3 Consistent strict adherence remains key to successful viral suppression.4 However, in both resource-rich and resource-constrained settings, the majority of patients on HAART struggle to maintain optimal levels of adherence.5,6
Two meta-analyses indicated that various behavioral strategies can be efficacious in promoting adherence and improving clinical outcomes.7,8 Successful behavioral strategies include couples-based counseling9; modified directly observed therapy10; and cognitive-behavioral, problem-solving, and motivational interviewing techniques.11 Research on peer support and electronic reminders12 is more limited, with mixed findings. However, both strategies are potentially cost effective, culturally adaptable, and easily translatable and, therefore, merit further investigation.
The present study builds upon preliminary work of a peer support intervention13 that indicated nonsignificant between-group findings but a dose response effect among participants within the peer support arm. The current study supplemented the peer support program with messaging from a programmable pager. Moreover, this follow-up study involved a larger and more restricted sample, a lengthier follow-up assessment period, and monetary incentives to encourage greater engagement in the peer support intervention.
Data were collected from March 30, 2003 to May 30, 2007 at the adult HIV primary care outpatient clinic at Harborview Medical Center, a public institution affiliated with the University of Washington in Seattle, WA. Advertisements for the study were posted in the clinic waiting room, and all providers were informed of the study. Referrals came from clinic providers, the patients themselves, and a nurse at the clinic dedicated to soliciting research participants. The nurse approached all potentially eligible patients at each clinic session.
Eligible participants were (a) at least 18 years of age, (b) proficient in English, (c) living within the service area of the pager, and (e) initiating or changing at least 2 medications of a HAART regimen. Some of the changes were prescribed because of poor response, but in other cases, new formulations were prescribed to reduce pill burden and/or side effects. Individuals who were cognitively impaired, actively psychotic, or had a known history of harming others were excluded. Study staff provided detailed information about the scope of the trial to all eligible patients referred to them and scheduled a baseline appointment to obtain written informed consent and enroll participants. The baseline appointment was scheduled to coincide as closely as possible with the day patients were to initiate their HAART regimen.
At the baseline appointment, participants first completed an approximately 1-hour computer-assisted self-interview assessing adherence and other psychosocial and attitudinal variables (ie, knowledge about treatment, adherence self-efficacy, side effects, substance use, sexual risk behaviors, social support, coping, negative affective states, and quality of life). Next, they were randomly assigned to 1 of the 4 study arms: peer support, pager, both peer and pager, or usual care. Allocation concealment involved the use of sequentially numbered, opaque, sealed envelopes containing the study arm assignment, which the study staff opened at the moment of randomization. An external statistician had used a computerized random number generator to select random permuted blocks of 4. Due to the nature of the intervention, participants, study staff, and data analysts could not be completely blinded to study arm assignment.
Electronic drug monitors (EDM; ie, the Medication Event Monitoring System; http://www.aardex.ch) were provided to all participants for the duration of the trial. EDM technology consists of a plastic pill vial and modified cap containing a microprocessor capable of recording the precise date and time of each vial opening as a presumptive dose. Each participant was given 1 EDM to use with the most frequently dosed antiretroviral.
All participants continued to receive medical care at the clinic and were asked to return for assessments at 2 weeks (for a brief interview) and 3, 6, and 9 months (for full follow-up assessments). At each full assessment, EDM data were uploaded, and blood was drawn to determine HIV-1 RNA viral load (VL) and CD4 lymphocyte count. Participants were reimbursed $60 for the baseline interview, $20 for the 2-week interview, and $35 for the 3-month, 6-month, and 9-month interviews, with a $25 bonus if they completed all 5 assessments and returned the EDM. Tracking efforts included unscripted reminder phone calls 1 week and 1 day before each scheduled interview appointment and mailed correspondence in the face of nonresponse to phone calls.
Peer Support Arm
Clinic patients who were HIV positive and currently on HAART served as “peers” who provided medication-related social support in the peer support arm. Medical providers in the clinic assisted study staff in identifying appropriate peers from among current patients who reported consistently high levels of adherence, attended clinic appointments regularly, were socially skilled, and were able to participate in an initial training and commit to ongoing supervision. Research staff (ie, the principal investigator, psychology doctoral candidates, and clinical staff including a pharmacist, medical provider, nutritionist, and case manager) provided approximately 15 hours of training to a total of 17 peers during the course of the study. During the trainings, peers learned how to assess for negative affective states and other barriers to adherence and to sensitively provide emotional, informational, and affirmational social support. Other topics covered in the training included an overview of HIV and HAART, how to maintain appropriate limits on the peer relationship, overcoming potential barriers to the acceptance of support, harm reduction approaches to substance use, appropriate referrals for medical inquiries, and strategies for working with diverse participants. Peers received $25-$40 twice monthly as an incentive for their involvement based on the number of participants (1-3) to whom they were assigned as peers. On average, peers remained actively involved for approximately 1 year.
The 3-month peer support intervention consisted of 2 parts: (a) 6 twice monthly 1-hour gatherings (ie, “peer meetings”) held at the clinic, consisting of all peers and actively enrolled participants in the peer support arm and (b) weekly phone calls from peers to participants. At the time of enrollment, participants were assigned to individual peers by study staff based on peer availability and presumed compatibility (ie, whenever possible, an effort was made to match peers to participants based on race/ethnicity, sex, and sexual orientation). In the group setting, participants had the opportunity to interact face-to-face with their assigned peer and meet the other peers and participants, with the goal of benefiting from the discussion of the shared experiences of the group. The meetings were designed to identify barriers to HAART adherence and generate problem-solving strategies to overcome them. Other emerging themes included life issues that impact adherence, including HIV status disclosure, dating, substance use, and struggles with mental health issues. One of several research staff members (each with graduate training in psychology) coordinated the groups by making reminder phone calls, preparing the meeting room, and providing refreshments. With assistance from the peers, they facilitated the meetings by refocusing the discussion on adherence-related topics when appropriate. Otherwise, they refrained from interfering with the group process and the exchange of support among peers and participants, resulting in predominantly peer-led groups. Participants received a $15 incentive for attending each of the 6 sessions. All were welcomed to continue attending thereafter but were provided neither reminder phone calls nor monetary incentives for additional meetings.
Between group meetings, peers were instructed to call each of their study participants weekly to provide more in-depth one-on-one attention and feedback. Phone calls also were better suited for participants with confidentiality concerns and those who had difficulty traveling to the clinic or had scheduling conflicts with the set meeting times. Peers were instructed not to initiate contact with participants after the 3-month intervention period, but they were allowed to respond to requests for contact from the participants at their own discretion.
To preserve and monitor intervention fidelity, peers were evaluated at the end of the training to ensure they acquired competency in their respective tasks. Peers also received ongoing supervision from the group facilitator after each group meeting and at twice monthly telephone check ins. Additionally, they completed a 1-page log for each telephone and face-to-face contact with a participant. These logs were reviewed with project staff during supervision.
Pager Messaging Arm
The 3-month pager intervention consisted of a customized pager system that combined the communicating abilities of the world-wide web and 2-way pagers. A computer program allowed for the timing of all text messages to be specified up front and then sent automatically without any further intervention from study staff. At randomization, the study coordinator distributed a 2-way pager and customized a message schedule to the participant's daily medication regimen, which was confirmed by the clinic pharmacist. In addition to dose reminders (which included medication names familiar to the patient and number of pills to be taken), 3 other types of text messages were sent: (1) educational (referring to side effects and their management, medication benefits, understanding laboratory values, the importance of adherence, drug interactions, proper medication storage, resistance, and self-advocacy); (2) entertainment (jokes or thoughts for the day); and (3) adherence assessments. There was some flexibility in the frequency and content of messages to accommodate participants' differing needs and schedules, but there was a minimum of 3 pager messages sent daily to participants for the first 2 months. Pages gradually tapered in the last month of the 3-month intervention to avoid a rebound in nonadherence. A confirmation return page was requested for every message sent. Project staff periodically reviewed the return page log and if no responses were received, the participant could be called to determine if they were having any problems with the pager.
Between the first contact and the end of the 3-month intervention, the participants were asked to wear the pager at all waking moments. Participants had to use the study pagers and could not substitute with their own pager or cell phone. They were instructed not to use the devices for personal use. Participants could select from a variety of auditory alarms or a vibrate-only option if desired. If the pager was lost or failed, it was promptly replaced at no cost to the subject.
Before initiation of HAART, all clinic patients who are naive patients or off HAART for more than 6 months are required to complete the HAART Protocol, a clinic-based program designed to provide education regarding HAART and adherence and to identify and correct adherence barriers before HAART initiation. The HAART protocol involves a series of 3 separate appointments with a pharmacist, nutritionist, and case manager after an initial meeting with a provider and before a final meeting when the provider decides whether to prescribe HAART. During these preliminary interviews, patients are given social and mental health referrals as appropriate, a daily medication schedule, and information on medication side effects and techniques to help manage them. All participants in each of the study's 4 arms participated in the HAART protocol if they had not received it in the last 6 months. There were no time or attention-control activities.
The primary outcome measures were self-reported and EDM-based medication adherence at 3 months (immediate postintervention) and at 6 and 9 months (postintervention follow-ups). The secondary outcomes were the clinical laboratory biomarkers of CD4 lymphocyte count and VL at 3, 6, and 9 months.
Self-reported medication adherence was assessed with 1 item from the Simplified Medication Adherence Questionnaire14 assessing the number of doses missed during the previous week (none of the time, 1-2 times, 3-5 times, or 6-10 times). A dichotomous variable for past week 100% adherence was created with participants classified as perfectly adherent if they missed zero doses and nonadherent if they missed 1 or more doses.10,15 We computed a continuous EDM adherence variable, defined as the number of bottle openings recorded by the Medication Event Monitoring System cap during the 7 days before each assessment date divided by the number of prescribed doses. The EDM adherence outcome was analyzed as a continuous variable and as dichotomous variables with cut offs at 80, 85, 90, 95, and 100% at each assessment point and across all 3 follow-up assessments.
Study staff abstracted VL and CD4 lymphocyte counts from patient medical records if they were available within 30 days of the baseline, 3-month, 6-month, and 9-month interviews; otherwise, blood draws for VL and CD4 counts were conducted the day of the interview. As VL data were not normally distributed, we conducted a log transformation and used the transformed values in all further analyses. Clinical outcomes were analyzed as continuous variables and as dichotomous variables with cut offs for VL of undetectable, 1000, and 10,000 and for CD4 of 350 at each assessment point and across all 3 follow-up assessments.
Initial power analyses were based on a dichotomous measure of adherence as the outcome and 0.80 power to detect a 15%-20% difference in the percentage of 100% adherent patients. An analysis “at the margins” was planned whereby all patients treated with 1 intervention are compared with all patients not treated with the intervention. For example, in evaluating the peer support intervention, all participants in the peer support arm and those in the peer support and pager arm would be compared with those in the pager only and usual care arms. This method maximizes the statistical power for detecting intervention effects when analyzing a factorial trial.16 These power calculations indicated that 120 patients were required to receive each intervention, resulting in a total sample of 240.
All participants who were randomly assigned were included in the analyses (ie, an intent-to-treat approach), with adjustments made only in the case of 2 participants who were dropped from the study when they were determined during the baseline interview to be ineligible. Missing data were set equal to zero for the primary adherence outcomes and the detection limits for the secondary biomarker outcomes.
To evaluate efficacy, repeated measures analyses were conducted using generalized estimating equations (GEEs).17 In these analyses, each outcome was regressed on peer support arm, pager arm, peer support × pager arm, time (assessment point), all arm × time interactions, and previous experience with HAART as a control variable (ie, HAART naive or not). Time was partitioned into contrasts of 2-week assessment point (or, in the case of the biomedical outcomes, baseline) against each follow-up (ie, 2 weeks versus 3, 6, and 9 months). The statistical tests of the intervention effects were the peer support × time and pager support × time interactions. A logit link function was utilized for the binary outcomes and Gaussian link function for continuous outcomes. An unstructured working correlation structure was specified to account for correlated outcome data across assessments.
To assess whether an analysis “at the margins” was appropriate, the full factorial models were compared with models that excluded any interaction effects between the pager and peer support interventions. Wald tests were performed to evaluate whether the peer support × pager and peer support × pager × time terms were collectively significant for each primary and secondary outcome. Analyses conducted at the margins were comparable with the full factorial models for 3 of the 4 outcomes, so results from the analyses “at the margins” are reported. All trend-level findings at P < 0.12 are reported for interpretive purposes.
Additional post hoc analyses evaluated whether dichotomous versions of the primary (EDM adherence) and secondary (VL, CD4 count) outcomes would be associated with the interventions. In the first set of analyses, we substituted dichotomous version of EDM adherence, VL, and CD4 count in the GEE analyses. In the second set of analyses, we used a stricter dichotomous outcome that required meeting the dichotomous outcome across all follow-up assessments (eg, EDM adherence >80% at 3, 6, and 9 months). In these analyses, the strict dichotomous outcome (ie, meeting the cut off at all follow-up assessments) was regressed on peer support, pager support, and previous experience with HAART and baseline levels as control variables.
In further post hoc analyses, we examined whether the number of mandatory peer support meetings attended or pager response rate was associated with intervention effectiveness among those in the experimental arms. In these quasi dose response analyses, each outcome was regressed on dose, time (assessment point), dose × time, and previous experience with HAART and baseline levels as control variables. The statistical test of the dose response effect for each outcome was the dose × time interaction.
Flow of Participants
As seen in Figure 1, of the 909 patients screened for eligibility, 308 (34%) did not meet study eligibility criteria, mainly because they were not currently prescribed HAART, not switching at least 2 medications, or were severely psychologically or cognitively impaired. A minority (232; 26%) of eligible patients approached declined to participate. The primary reasons cited for refusal were lacking interest, being too busy, having transportation difficulties that made it difficult to accommodate the additional study-related clinic visits, and feeling uncomfortable in groups. Other participants (143; 16%) were excluded because they died or could not be recontacted before enrollment. Across the 4 assessment points, 79% of participants had complete data, 13% missed a single assessment, and 9% missed 2 or more assessments. No significant differences were found in retention by study arm.
Description of Participants
The final analytic sample of 224 patients ranged in age from 19 to 60 years (M/SD = 40.0/8.2) at baseline and were mostly (76%) male. On average, participants had been diagnosed with HIV for 9 years; 62% were HAART naive at baseline, and 38% were switching or restarting an antiretroviral therapy regimen. The sample was 30% of African American, 11% of Hispanic, 47% of white, and 12% of “other” or “mixed” racial heritage. The sample was fairly well educated (71% had a high school degree or general education degree (GED) and 9% had a college degree), and 81% were employed full time or part time. Nearly half (44%) reported injection drug use at some point in the past.
With respect to baseline medication, 59% of participants were on a once daily regimen, and 41% were on a twice daily regimen. Participants were prescribed between 2 and 5 antiretroviral products, either individual or combination tablets (M/SD = 3.0/0.8), with 64% on a protease inhibitor-based regimen, 32% on a nonnucleoside reverse transcriptase inhibitor-based regimen, 4% on both protease inhibitors and a nonnucleoside reverse transcriptase inhibitor, and 1% using a fusion inhibitor.
Baseline comparison of participants in the 4 arms demonstrated that randomization was successful. No important differences were found on any sociodemographic, regimen, or outcome variable except that participants in both the pager (M/SD = 7.7/6.9, t (111)= 1.99, P = 0.05) and peer support arms (M/SD = 7.0/5.6, t (112) = 2.77, P = 0.01) received their HIV diagnosis fewer years ago than those receiving standard of care (M/SD = 10.3/6.9).
Among the 111 participants randomized to the 2 arms including the peer intervention, attendance at the twice monthly meetings ranged from 0 to all 6 meetings (M/SD = 2.8/2.2); 54% attended 3 or more of the 6 required meetings. An additional 36 participants attended from 1 to 12 of the additional voluntary meetings as well (M/SD = 1.5/1.9).
Among the 110 participants randomized to the 2 arms including the pager intervention, the average number of pages received ranged from 0 to 343 (M/SD = 157.0/71.0). The average response rate was 41% (SD = 31.1%) as measured by the proportion of messages that participants acknowledged receipt of the total received. A total of 8 participants in the pager arm did not use the pager at all.
To assess for differences between participants with complete self-report data (79%), those who missed a single assessment (13%), and those who missed 2 or more assessments (9%), χ2 tests and one-way analysis of variances were conducted on categorical and continuous sociodemographic characteristics, respectively. No significant differences were found among these 3 groups. Missing EDM adherence data were tabulated separately as this data could be available even if a self-report assessment was missing. For EDM adherence, 88% of participants had complete data, 5% were missing a single assessment, and 8% were missing 2 or more assessments. No significant differences were found among these 3 groups.
Self-reported and EDM adherence data at 2 weeks and 3, 6, and 9 months are presented in Table 1. Note these are the findings for each of the experimental arms, but in the analyses of intervention effects, these groups were combined “at the margins” as described above. Overall, average adherence was low at initiation and slowly declined over time with 70% of participants at 2 weeks, 58% at 3 months, 51% at 6 months, and 49% at 9 months self-reporting 100% adherence in the past 7 days. Descriptive data from the “at the margins” analyses indicated that among those in the 2 peer intervention arms, the percentage self-reporting 100% adherence in the past 7 days at 2 weeks and 3, 6, and 9 months was 67%, 63%, 49%, and 47%, compared with 73%, 52%, 53%, and 51% for those not receiving the peer intervention. Among those in the 2 pager intervention arms, the percentage self-reporting 100% adherence in the past 7 days at 2 weeks and 3, 6, and 9 months was 75%, 64%, 49%, and 55%, compared with 64%, 52%, 53%, and 44% for those not receiving the pager intervention.
With respect to EDM data, the mean percentage of doses taken in the past 7 days was 63% at 2 weeks, 44% at 3 months, 38% at 6 months, and 33% at 9 months. Among those in the 2 peer intervention arms, the percentage of doses taken in the past 7 days at 2 weeks, 3, 6, and 9 months was 62%, 49%, 36%, and 32%, compared with 63%, 40%, 39%, and 33% for those not receiving the intervention. Among those in the pager intervention arms, the percentage of doses taken in the past 7 days at 2 weeks, 3, 6, and 9 months was 63%, 46%, 36%, and 34%, compared with 62%, 43%, 39%, and 31% for those not receiving the intervention.
Evaluation of Intervention Effects
With respect to the dichotomous self-report 100% adherence outcome, GEE at-the-margins analyses revealed a significant peer support × time (2 weeks versus 3 months) interaction indicating a 2-fold increase in the odds of 100% adherence for those receiving versus not receiving peer support at postintervention [odds ratio (OR) = 2.10, SE = 0.69, 95% confidence interval (CI) = 1.10 to 4.01, P = 0.02]. This effect was partially supported by findings from the EDM dose adherence continuous outcome measure, for which there was a trend toward a peer support × time (2 weeks versus 3 months) interaction suggesting that peer support (versus no peer support) was associated with 9% higher adherence at postintervention (estimate = 8.88, SE = 5.60, 95% CI = −2.09 to 19.85, P = 0.11). The findings for the efficacy of peer support at postintervention did not persist at the 6-month and 9-month follow-ups for either self-reported (P > 0.77) or EDM adherence (P > 0.74); nor were there any peer intervention effects for the secondary outcomes of VL (P > 0.70) or CD4 (P > 0.66).
According to the self-report measure, pager support did not predict improved odds of 100% adherence at 3 or 9 months (P > 0.74). However, pager support was associated with a marginally significant “decrease” in 100% adherence at 6 months (OR = 0.50, SE = 0.18, 95% CI = 0.24 to 1.03, P = 0.06). Analyses with the EDM dose adherence continuous outcome measure also indicated no effect for pager support at 3, 6, or 9 months (P > 0.54). There were no intervention effects (ie, pager support × time interactions) at any time point for either of the secondary outcomes of log10 VL (P > 0.17) and CD4 count (P > 0.12) as continuous variables.
Post Hoc Analyses
Analyses of the primary EDM adherence and secondary VL and CD4 outcomes as dichotomous variables revealed no intervention effects for peer support at each time point (P > 0.19) or when the outcome was evaluated more strictly across time points (P > 0.50).
Dose response analyses indicated that attendance at the peer meetings did not predict differences in either the self-report or EDM adherence outcomes (P > 0.50). However, associations emerged between attendance and the secondary clinical outcomes. Greater attendance had a marginal association with reduced log10 VL at 3 months (Est = −0.13, SE = 0.08, 95% CI = −0.28 to 0.02, P = 0.08) and 6 months (Est = −0.17, SE = 0.09, 95% CI = −0.34 to 0.01, P = 0.06). At 9-month assessment, greater attendance predicted significant reductions in log10 VL (Est = −0.22, SE = 0.08, 95% CI = −0.38 to −0.06, P = 0.01). Attendance had a marginal association with elevated CD4 count at 3 months (Est = 12.35, SE = 6.67, 95% CI = −0.72 to 25.42, P = 0.06).
Analyses of the clinical outcomes revealed effects for pager support when (1) CD4 count was analyzed at each time point using a 350 cells per cubic millimeter cut off and (2) VL was evaluated using the strict criteria of remaining below 1000 copies per milliliter across all 3 follow-up time points, controlling for baseline. With respect to the dichotomous CD4 measure, there was a 2-fold greater odds (OR = 2.20, SE = 0.78, 95% CI = 1.10 to 4.42, P = 0.03) of possessing a CD4 count above 350 cells per cubic millimeter for those receiving versus not receiving pager support at postintervention. At 9-month follow-up, pager participants were marginally more likely to have CD4 count above 350 cells per cubic millimeter (OR = 1.94, SE = 0.74, 95% CI = 0.92 to 4.08, P = 0.08). With respect to VL as a dichotomous measure, pager participants had a nearly 2-fold greater odds of reporting VL less than 1000 copies per milliliter at all 3 follow-ups (OR = 1.78, SE = 0.50, 95% CI = 1.03 to 3.09, P = 0.04) than those not receiving a pager.
Dose response analyses indicated that increased percentage of pager response was associated with lower EDM adherence at 6 months (Est = −0.30, SE = 0.13, 95% CI = −0.34 to 0.01, P = 0.06). Greater pager response predicted significant reductions in log10 VL at 3 months (Est = −0.01, SE = 0.01, 95% CI = −0.024 to −0.004, P = 0.01) and 9-months (Est = −0.01, SE = 0.01, 95% CI = −0.025 to 0.003, P = 0.01). Additionally, pager response predicted significant increases in CD4 count at 3 months (Est = 1.84, SE = 0.39, 95% CI = 1.08 to 2.60, P < 0.001), 6 months (Est = 1.15, SE = 0.53, 95% CI = 0.11 to 2.20, P = 0.03), and 9 months (Est = 2.38, SE = 0.52, 95% CI = 1.37 to 3.39, P < 0.001).
In an effort to address the widespread problem of nonadherence to antiretroviral medication, we developed peer and pager support interventions and evaluated them among a sample of 224 men and women on HAART in a publicly funded clinic in Seattle, WA. Findings from intent-to-treat, missing equals failure analyses indicated a 2-fold greater odds of self-reported 100% medication adherence at immediate postintervention among individuals receiving peer support versus not receiving peer support. EDM data partially supported this finding. However, neither effect was maintained at the follow-ups, and there was no effect of the peer intervention on the secondary outcomes of CD4 count or VL at any time point. Post hoc analyses indicated that, among participants receiving the peer intervention, increasing attendance at the peer meetings was associated with some clinical benefit (but not improved adherence).
These findings suggest that receiving informational, emotional, and affirmational support from peers might promote adherence, but that effect did not persist when the support was discontinued. Ongoing social support, perhaps from individuals more integrated into the participants' lives, may hold greater promise in promoting and sustaining long-term adherence. Indeed, Remien et al9 demonstrated that incorporating a partner in a 4-week couples-based intervention led to increases in adherence over usual care. It is likely that the more intensive and structured intervention in that study, delivered by a highly skilled counselor, contributed as well to its efficacy. The lack of peer support's impact on clinical outcomes, despite associated improvements in adherence, may be due to its small and short-lived effects.
In contrast, the pager messaging intervention was associated with some clinical improvement, which partially persisted over time, even though it did not seem to be successful in promoting adherence at any time point. Dose response post hoc analyses indicated that, among pager participants, greater response to pagers was associated with better clinical outcomes. Although the pager message could serve as a reminder to take a dose at the scheduled time of the dose, this assistance alone apparently was not enough to improve adherence. Adherence involves a complex set of behaviors that includes maintaining a supply of medication that is available at the prescribed dosing time and being in a situation at that time in which medication ingestion is feasible. The success of the pager as well depends on the participant's maintaining the pager in working order (with operating batteries) and carrying it at all times. Moreover, the pagers were not used in this study to link participants to study personnel; they functioned as high technology reminder systems. It is possible that more individualized pages from a known study staff member might solidify a personal connection and be more effective in promoting long-term adherence. Any of these factors may explain the inconsistent findings in the literature regarding the efficacy of reminder devices to promote adherence.12,18
How do we explain the post hoc findings of an association between both peer meeting attendance and pager messaging on clinical outcomes in the absence of improvements in adherence? One possibility lies in the difficulty of reliably and validly capturing adherence behavior. Although adherence is generally associated with VL,15 it is possible that our operationalization of adherence did not capture improvements in adherence that led to better clinical outcomes. For instance, perhaps a more finely tuned assessment of the timing of medication taking or the extent of drug holidays may have captured the benefits of the pager intervention that led to improved VL and CD4 count.
One caveat involves the trend for worsened adherence at 6 months among participants in the pager arms versus others. Although the pagers were tapered to reduce an iatrogenic rebound effect, these data suggest the need for greater attention to compensatory strategies when such alarms are removed. Alternatively, alarm interventions might be viewed as continuously needed, at least until the participants themselves opt to discontinue their use. Note this strategy was used successfully in the peer intervention, where participants were allowed to continue attending group meetings after the 3-month period at their own discretion.
One possible explanation for the lack of stronger intervention effects may be the intensive usual care provided by the clinic. Before initiating their HAART regimens, all HAART-naive patients or those off medications for more than 6 months are required to undergo a series of appointments with various staff at the clinic to identify and address potential barriers to adherence. There is some evidence that this approach itself might lead to improvements in adherence,19 setting a high standard that the intervention arm could not surpass. Relatedly, postintervention interviews indicated that some participants in the usual care arm reported benefiting from the sustained contact with study staff and considered their EDM device to be a potent visual reminder to take their medications.
Another possibility is that not all participants got a full “dose” of either intervention, because they failed to attend peer support group meetings, return the phone calls of their peers, or consistently use their pagers. It should be noted that peer support participants who attended more group meetings and pager participant who responded more consistently to their pagers had improved clinical outcomes. This suggests that the peer support intervention was less effective when participants missed the group meetings and pager messaging requires active participation. However, to be successful, any adherence intervention must limit the burden to patients who are often already overwhelmed with caring for their HIV disease and other life responsibilities.
The findings are consistent with recent reviews of the field. In 2 meta-analyses, behavioral interventions to improve HAART adherence have been shown to have positive though minor effects on adherence and clinical outcomes that diminish over time.7,8 Perhaps interventions need to be more highly tailored and, like adherence behavior itself, dynamic over time. Perhaps, offering individuals a choice of intervention strategies would be more beneficial as well.
There were some limitations to the present study. Our eligibility criteria were relatively broad. For example, we did not exclude participants who were already resistant to medications, which would make it difficult to demonstrate effects on VL even among participants who were adherent to their medications. Also, we did not exclude individuals whose adherence was already satisfactory; these participants may have been less motivated to fully engage in the interventions and would affect our power to find a significant intervention effect. Indeed, in their meta-analysis, Amico et al7 noted that interventions targeting participants with known or anticipated problems with antiretroviral therapy adherence demonstrated larger effects on adherence than interventions that did not. With respect to methodology, adherence assessment strategy seemed to influence our estimates of intervention effects, with self-reported data indicating a larger effect size than did EDM data for the peer intervention. It is possible that participants in the intervention arm were subject to a “social desirability” bias and, after receiving an intervention obviously designed to enhance their adherence, would be more likely to report improved adherence than participants in the usual care arm. Given this possibility, future studies would do well to employ triangulation approaches to adherence, as we did, using multiple methods and avoiding reliance solely on self-report. Also, our post hoc analyses suggesting improvements in clinical outcomes for pager participants suggests that creating more stringent outcome measures (ie, the achievement of a predetermined cut off at each of successive assessment points) may capture small effects. This would be especially helpful in the presence of ceiling effects, which are common in self-reported adherence.
The findings can likely generalize to other outpatient HIV clinic populations in the United States, although our participants included fewer ethnic minorities and were more highly educated than most HIV-positive individuals in the United States. In international settings, peers may be even more influential given the greater stigma of HIV that inhibits disclosure. For example, one study in Mozambique utilizing peer-delivered modified directly observed therapy led to significantly higher adherence.10 Also, almost one third of eligible patients declined to participate in our intervention, suggesting that the findings may be generalizable to a subgroup of patients who are open to disclosing their HIV infection and receptive to social support. Perhaps, targeting such individuals would result in greater adherence to the intervention and more positive effects.
Optimal intervention designs might involve conducting needs assessments at baseline and offering a range of potentially appealing and useful strategies to enhance adherence. Maintaining optimal adherence requires a set of complex and dynamic behaviors that may necessitate interventions of equal sophistication with personnel trained and dedicated to providing them on an ongoing basis.
We thank clinic staff Carol Glenn, Robert Harrington, and Bobby Santucci; all other research assistants and staff; and all participants-especially the trained peers.
© 2009 Lippincott Williams & Wilkins, Inc.