Influencing medication adherence among women with AIDS

Influencing medication adherence amongwomen with AIDS

D. L. JONES,1 M. ISHII,2 A. LAPERRIERE,2 H. STANLEY,2

M. ANTONI,3 G. IRONSON,3 N. SCHNEIDERMAN,3 F. VAN

SPLUNTEREN, A. CASSELLS,4 K. ALEXANDER,4 Y. P. GOUSSE,4

A. VAUGHN,4 E. BRONDOLO,6 J. N. TOBIN4,5 & S. M. WEISS

2

1Barry University, 2University of Miami School of Medicine, 3University of Miami, 4Clinical

Directors Network, New York City, 5Department of Epidemiology and Social Medicine, Albert

Einstein College of Medicine, New York City & 6Department of Psychology, St. John’s University,

New York City, USA

Abstract This study examined the effects of a ten-session cognitive-behavioural stress management/

expressive supportive therapy (CBSM�/) intervention on adherence to antiretroviral medication.

Although the intervention was not designed to influence adherence, it was theorized that improved

coping and social support could enhance adherence. Women with AIDS (N�/174) in Miami, New

York and New Jersey, USA, were randomized to a group CBSM�/ intervention or individual control

condition. Participants were African American (55%), Latina (18%) and Caribbean (18%) with

drug (55%) and/or alcohol (32%) histories. Participants were assessed on self-reported medication

adherence over seven days, HIV-related coping strategies and beliefs regarding HIV medication.

Baseline overall self-reported adherence rates were moderate and related to coping strategies and HIV

medication beliefs. Low adherent (80%) participants in the intervention condition increased their

mean self-reported medication adherence (30.4% increase, t44�/3.1, pB/0.01), whereas low

adherent women in the control condition showed a non-significant trend (19.6% increase, t44�/

2.0, p�/0.05). The intervention did not improve adherence in this population; conditions did not

differ significantly on self-reported adherence. Low adhering intervention participants significantly

decreased levels of denial-based coping (F1,88�/5.97, pB/0.05). Results suggest that future

interventions should utilize group formats and address adherence using coping and medication-

knowledge focused strategies.

Introduction

Recent advances in medical treatment for HIV offer the potential for increased longevity,

improved quality of life, and the treatment of HIV as a chronic, rather than terminal, illness

(Kalichman et al ., 1998). Since the advent of highly active antiretroviral therapy (HAART),

Address for correspondence: Deborah Jones, Department of Psychology, Barry University, 11300 NE 2nd

Avenue, Miami Shores, Florida 33161-6695, USA. E-mail: [email protected]

AIDS CARE (August 2003), VOL. 15, NO. 4, pp. 463�/474

ISSN 0954-0121 print/ISSN 1360-0451 online/03/040463-12 # Taylor & Francis Ltd

DOI: 10.1080/0954012031000134700

the current standard of care for HIV treatment (Carpenter et al ., 1996, 1997), medication

adherence has become extremely important to achieving successful clinical outcomes (Hogg et

al ., 2000). HAART has revolutionized HIV treatment and reduced morbidity and mortality

(Carpenter et al ., 1996), but demands strict compliance to a complex combination of

medications (Senak, 1997) to limit the potential for the development of viral resistance

(Bangsberg et al ., 2000). Adherence to medication regimens has been associated with

clinically significant viral load reductions (e.g. in a recent study, 81% of subjects had complete

viral suppression at �/95% adherence compared with 64% at 90�/95% adherence, 50% at

80�/90% adherence, 25% at 70�/80% adherence and 6% at B/70% adherence (Paterson et al .,

2000)).

Inadequate adherence

The primary factors associated with non-adherence to HAART include side effects,

forgetting, sickness, being away from home, running out of medication and regimen

complexity (Catz et al ., 2000; Chesney & Ickovics, 1997). In previous research with

zidovudine (AZT), non-compliance was associated with dosing schedule, the extended

duration of its prescription, unpleasant side effects (Chesney & Folkman, 1994; Muma et al .,

1995; Wall et al ., 1995) and skepticism regarding the efficacy or value of the medication

(Horne et al ., 1999; Wall et al ., 1995; Besch, 1995). Compliance to HAART’s more

demanding multiple dosing schedules has ranged from 20�/80% (Volberding, 1998),

providing effective viral load suppression in less than 50% of those living with HIV.

Factors that interfere with medication adherence include chronic asymptomatic illness,

non-curative treatment and worsening or improvement of physical symptoms (Ickovics &

Meisler, 1995). Psychological distress in the form of depression, anxiety and self-blaming

coping have been related to less than adequate adherence in various medical populations*/

HIV (Ickovics & Meade, 2002), heart disease (Blumenthal et al ., 1995; Dunbar, 1990), burn

injury (Chesney & Folkman, 1994; Kiecolt-Glaser & Williams, 1987). Patients have also

reported anxiety, isolation and lack of information regarding treatment efficacy as barriers to

adherence (Chesney & Folkman, 1994). An assumption underlying adherence interventions is

that improving adherence will result in adhering patients achieving control of their illness and

a reduction of symptoms. For many persons living with HIV, taking medication may result in

unpleasant physical symptoms and psychological distress and may prove ineffective,

decreasing perceptions of personal control and self-efficacy.

Previous studies by investigators from this research team with Hispanic and non-

Hispanic white gay men have shown that psychosocial status plays an important role in health

outcomes for these populations (Antoni et al ., 1991). These investigators utilized a group

cognitive behavioural stress management (CBSM) intervention to enhance personal control

over life stressors and encourage the use of active coping strategies to reduce the deleterious

affective and behavioural sequelae of HIV infection (Antoni et al ., 1992; Lutgendorf et al .,

1997a,b). Supportive-expressive group therapy has been effective in improving coping skills in

chronic illness populations*/HIV (Diamond et al ., 1997) and breast cancer (Spiegel &

Yalom, 1981). Cognitive-behavioural interventions have assisted individuals with HIV in

illness self-management, improvement of quality of life (Chesney & Folkman, 1994) and

reduction of anxiety and depression (Fawzy et al ., 1989; Lutgendorf et al ., 1997a). CBSM

interventions have been associated with improved coping (Lutgendorf et al ., 1997b) and

changes in maladaptive behaviour (Schneiderman et al ., 1997) in men living with HIV. Given

the association between depression, distress and unproductive coping and non-adherence, we

reasoned that a CBSM�/ intervention might alleviate psychosocial distress and improve

464 D. L. JONES ET AL.

coping (Bandura, 1986), to provide a self-management skill foundation for enhancing

adherence. Although the CBSM�/ intervention was not specifically designed to improve

adherence and did not include any specific medication adherence strategies aimed at

improving adherence, we reasoned that such an intervention might have salutary effects on

adherence through improving selected areas of psychological functioning (Weiss et al .,

submitted), reducing distress (LaPerriere et al ., 1999) and increasing coping skills. In this

study, we sought to determine what factors influence adherence in HIV-positive women, and

whether medication adherence by women in our trial might be improved by our CBSM�/

intervention.

Methods

Participants

Beginning in 1997, participants were recruited from the three major epicentres in the USA for

women living with HIV/AIDS: Miami-Dade County, New York City and the New Jersey

metropolitan area. Study candidates were drawn primarily from hospital outpatient clinics,

community health centres/agencies and via participant referrals. Of those recruited, 28% did

not meet eligibility requirements for the following reasons: 44% had significant cognitive

impairment, 10% were substance dependent, 22% met the diagnostic criteria for major

depression, 8% for psychosis and 15% did not meet the diagnostic criteria for case defined

AIDS or failed to appear for scheduled screening appointments. Participants (N�/174) were

women, 18 years or older, who met the CDC guidelines for case-defined AIDS, i.e. CD4 cell

count below 200/mm3 and/or one opportunistic infection (CDC, 1998). Women were

administered both pre- and post-medication adherence assessments and provided verification

of current medication regimen (randomized participants: Miami, n�/78; New York City/New

Jersey, n�/96; total, n�/92 group condition, n�/82 individual condition). Participants in the

group condition participated in ten weekly two-hour CBSM�/ sessions and those in the

individual control condition received time and content equivalent information on stress

management and coping with AIDS. Participants were followed in the study over a 15-month

period (pre-intervention assessment to 12-month follow-up).

Participants’ mean age was 379/10 years. Most women (76%) were unemployed and

receiving government assistance. The majority of women (54%) were African American, 18%

were Hispanic, 18% were from the Caribbean, 7% were Caucasian and 3% were of other

ethnic backgrounds, including Native American and Pacific Islander. Forty-eight per cent of

the participants reported having completed less than a 12th grade high school education; 48%

had never been married. The majority of women had histories of drug (55%) and/or alcohol

(32%) dependence. Among the three sites, no differences were found between the group and

individual conditions on these demographic variables (Tobin et al ., 1999).

Outcome measures

Adherence. Adherence was evaluated at pre- (baseline) and post- (ten weeks) intervention

using the Adherence to Medication Scale (AMS). The AMS is a 14-item self-report measure

adapted from the ACTG (AIDS Clinical Trials Group) Questionnaire for Adherence to Anti-

HIV Medication (four days) (Chesney & Ickovics, 1997; Chesney et al ., 2000; Golin et al .,

1999; Wenger et al ., 1999). The ACTG Questionnaire is a widely used questionnaire

correlated with virological outcome, designed to provide a behavioural assessment of HIV

INFLUENCING MEDICATION ADERENCE 465

medication compliance and has been adapted in previous research to increase the information

obtained (e.g. length of time adherent (Chesney & Ickovics, 1997; Golin et al ., 1999; Wenger

et al ., 1999). The AMS was adapted to assess: (1) level of adherence and non-adherence to

medication over the last seven days (skipping medication, compliance with medication

schedule and special instructions), (2) additional reasons for non-adherence, (3) amount of

instruction received on taking medication, and (4) level of basic knowledge and beliefs about

HIV and medication. The AMS yields a percentage score on amount of adherence over seven

days, using a 1�/10 scale. The level of instruction score is the total number of persons

endorsed as having provided instruction on medication consumption, and in what form

(verbal, written, both). The level of basic knowledge and beliefs about HIV is a total score of

six ‘true, false, don’t know’ questions and two general HIV knowledge questions. For the

purpose of analyses, adherence scores reported were ‘What percentage of time have you taken

all your medication’, percentage of total adherence and change in percentage of total

adherence, pre- to post-intervention.

Coping with stress. As the CBSM intervention used in this study was designed to increase active

coping/social support and decrease maladaptive coping, the COPE (Carver et al ., 1989), a 38-

item scale, was used to determine the strategies participants used to cope with AIDS-related

stressors over the past month. The COPE has been used with varied medical populations

(Ingledew et al ., 1996) and has demonstrated reliability (Cronbach’s alpha]/0.61). COPE

sub-scales are theoretically derived and measure preferential use of hypothesized problem-

focused and emotion-focused coping strategies. Eight of the 11 COPE sub-scales were

selected to assess the cognitive appraisal process: active coping, planning, instrumental and

emotional support, denial, social and behavioural disengagement, self-distraction, substance

use and self-blame. ‘Active coping’ is an adaptive coping strategy that has been associated

with lower distress in several studies of patients with HIV. In our previous work, ‘denial’ has

been shown to significantly relate to emotional distress and to disease progression (Ironson et

al ., 1994). Thus, intervention-related changes in adherence related to these COPE sub-scales

were of particular interest.

Additional measures

Disease status. Viral load was assessed using the reverse transcriptase polymerase chain

reaction Amplicor HIV Monitor Ultrasensitive Kit Assay (Roche Diagnostics Corporation) to

quantitate blood HIV-1 RNA levels. This assay has been applied to the evaluation of

nucleoside analogue therapy in drug combination clinical trials. The amplified product is

detected by hybridization and quantitation based on an internal control added to each

specimen to yield the number of HIV-RNA copies/ml in the original sample.

Procedure

Interested candidates were screened by telephone to determine potential eligibility and

interest in the study. Candidates who were deemed eligible (by age, education and AIDS

status) were invited to complete an informed consent form and screening assessments (see

exclusion criteria under Participants above for details). Eligible participants completed

additional psychosocial questionnaires, including the adherence assessment, and were then

randomized into the group or individual conditions. Study assessors and investigators were

‘blind’ to participant condition assignment, and did not participate in provision of the

466 D. L. JONES ET AL.

intervention. In addition, participants were asked not to reveal information regarding their

assignment to assessors during their post-intervention assessment.

CBSM�/ group condition. The CBSM�/ condition (n�/92) was a group intervention of ten

weekly sessions, each of two-hour duration (90-minute stress management and 30-minute

relaxation components). Sessions included didactic components explaining the physiological

effects of stress, cognitive-behavioural interpretation of stress and emotions, identification of

cognitive distortions and automatic thoughts, rational thought replacement, coping skills

training, cognitive reframing, assertiveness training, anger management, and identification of

social supports, combined with group processing of personal issues as conceptualized within

the CBSM framework (Lutgendorf et al ., 1997a; Meichenbaum & Turk, 1987). An expressive

supportive therapy component (EST; Diamond et al ., 1997; Spiegel & Spira, 1991) was

integrated into the CBSM intervention to make the intervention less didactic and to provide

an opportunity for greater emotional expressiveness and less structured sharing of

experiences, problems and solutions. Therapists were trained in the protocol using training

tapes and sessions, acted as co-therapists with senior facilitators and ultimately progressed to

senior therapists. Therapists were assessed by audiotape for fidelity to the CBSM�/ protocol

(audiotapes were randomly selected, one per 20 sessions) and provided with weekly

supervision. Participants were asked to practise relaxation and CBSM techniques between

sessions.

Individual control condition. The individual control condition (n�/82) was a ten-session

individual format of ten weekly 120-minute sessions (45-minute informational/educational

videotape component supplemented by a 75-minute entertainment videotape). The

information videotapes related to similar topics covered in the group sessions (e.g., stress

management/relaxation training and coping with HIV/AIDS) and were supplemented by

entertainment tapes to minimize dropout and provide time exposure equivalence.

Statistical analyses

This study used a repeated measures design with condition (group CBSM�/, individual

control) as the between-subjects factor and time (ten weeks; pre- and post-intervention) as the

within-subjects factor. Pre-intervention differences between group and individual participants

were assessed using the AMS to evaluate differences between the two conditions, and all

analyses were based on randomization, according to ‘intent to treat’. Pearson r correlation

coefficients were computed between adherence scores and other outcome measures. All

correlations were cross-sectional, and were assessed at pre- and post-intervention. All

comparisons (N�/174) used an alpha (two-tailed) of 0.05 for statistical significance tests.

Percentage of time adherent to medication regimen was used in all adherence-related

analyses.

Results

Control measures: baseline

At study entry, members of the CBSM�/ group and individual control conditions were

compared on possible confounding variables, including baseline differences in levels of

adherence, cognitive functioning (Mini-Mental Status Exam, MMSE; Folstein et al ., 1975),

HIV Dementia Scale (HDS; Power et al ., 1995) and ADL level (Karnofsky Scale; Karnofsky

INFLUENCING MEDICATION ADERENCE 467

et al ., 1948). Analysis of variance indicated there was no significant difference between

conditions on these potentially confounding variables at study entry, respectively (F1,172�/

1.41, p �/0.05; F1,168�/0.34, p �/0.05; F1,169�/0.20, p �/0.05). Thus, it appeared that any

confounding effects of these factors on adherence, after exclusion criteria were met, were

randomly distributed between conditions. Self-reported adherence was correlated with viral

load (cross-sectional, r�/0.26, p B/0.05). Of the study sample (N�/174), 14% were

prescribed non-nucleoside reverse transcriptase inhibitors (NNRTIs), 63% protease inhibi-

tors and 84% nucleoside analogues. The modal frequency in both conditions was three types

of antiretroviral medications. Among the entire sample (N�/174), greater participant

knowledge regarding HIV, medication and the immune system was related to higher

adherence (r�/0.25, p B/0.01) at baseline, while coping by denial (r�/�/0.27, p B/0.01),

substance use (r�/�/0.25, p B/0.01) and behavioural disengagement (r�/�/0.21, p B/0.01)

were associated with lower adherence. Analysis of variance indicated there were no significant

differences between group and individual conditions at study entry on coping variables and

medication beliefs.

At baseline, participants reported 68% mean adherence. Although ]/95% adherence is

required to obtain clinically significant viral load reduction (Paterson et al ., 2000), we chose

to identify women adhering ]/80%, the traditional standard for adherence used for other

chronic illnesses (Epstein & Cluss, 1982; Mehta et al ., 1997). In addition, we hoped to

identify increases in both low and high adherers, though we were primarily interested in

whether our intervention would increase adherence in non-adherent women. A large number

of women reported ]/80% adherence, while half of the sample qualified as ‘low adherers’

(range�/10�/100% adherent). Ninety women (52% of the total sample: n�/45 group

CBSM�/ condition; n�/45 individual control condition) had been less than or equal to

80% adherent over the last seven days, thereby forming a ‘low adherent’ group. These low

adhering women averaged 48% adherence. Among women adhering ]/80% of the time,

greater adherence was associated with a previous history of drug dependence (r�/0.31, p B/

0.01). Analysis of variance indicated there were no significant differences between high and

low adherent women on demographic variables at study entry.

The reasons given by participants for non-adherence were consistent with existing

research (Chesney, 1997). Low adherence among all participants at baseline was reported in

the following categories (participants were able to endorse one or more reasons for non-

adherence at pre- and post-intervention); forgetfulness (39%), side effects (27%), being too

busy (27%), just not wanting to take pills (20%), difficulty with instructions (11%),

depression (9%), running out (9%), too many pills (7%) and not wanting others to know

HIV status (1%). Post-assessment, reasons for non-adherence had decreased across all

categories. Changes in reasons for non-adherence at post-intervention may have reflected

improved coping strategies, as well as improvements in the tolerability of antiretrovirals,

reduction in the level of dosing per medication and the introduction of combined medication

in a single dose (e.g. Combivir†). Randomization of study participants was used to assure

equivalent distribution individual variability (e.g. medication regimen).

Effects of the intervention on adherence

Outcome measures: post-intervention. The CBSM�/ group and individual control conditions did

not differ significantly at post-intervention on their self-reported level of adherence; thus the

intervention did not improve adherence in this population. Women (n�/90) who were

adherent less than 80% of the time (‘low adherent’) were selected for statistical analysis. High

468 D. L. JONES ET AL.

and low adherent women did not differ significantly on psychosocial variables at post-

intervention. Tests of reported adherence among low adherent women revealed a significant

increase in adherence in the CBSM�/ group condition (30.4% increase over baseline, t44�/

3.08, p B/0.01), while women in the individual control condition showed a non-significant

trend (19.6% increase over baseline, t44�/1.96, p �/0.05) in adherence. The main time effect

of a repeated measures analysis of variance, condition (group CBSM�/, individual control) by

time (pre- and post-intervention), was significant (F1,88�/12.35, p B/0.01) with no significant

interaction by intervention. Among those low adherers whose level of adherence increased,

35% increased to 95% adherence or greater in both group and individual conditions. In

contrast, 73% (group) and 70% (individual) of high adherers maintained their level of

adherence, while approximately 25% decreased their level of adherence (group, 75%;

individual, 76%) (see Table 1).

Additional analyses identifying two levels of low adherence, very low (0�/40%) and

moderately low (41�/80%), compared levels of adherence at pre-and post-intervention. The

greatest adherence gains were among those at lowest initial levels of adherence in both

conditions (group, t17�/4.97, p B/0.001; individual, t11�/3.21, p B/0.01), while the

moderately low adhering women remained unchanged (group, t32�/0.21, p �/0.05; indivi-

dual, t26�/�/0.42, p �/0.05). Intervention and control conditions did not differ significantly

on self-reported adherence.

Relationships between coping strategies, medication beliefs and adherence measures pre- to post-

intervention

The interaction effect of a repeated measures analysis of variance, condition (group CBSM�/,

individual control) by time (pre- and post-intervention), was significant (F1,86�/5.97, p B/

0.05) among low adhering women. The CBSM�/ group and individual control conditions did

not differ significantly at post-intervention on substance use or behavioural disengagement

coping strategies. Lower levels of adherence were associated with use of denial (r�/�/0.211,

p B/0.05), substance use (r�/�/0.266, p B/0.01), behavioural disengagement (r�/�/0.246,

p B/0.05) and self blame (r�/�/0.293, p B/0.01) as coping strategies. Participant knowledge

about HIV and medication (r�/0.393, p B/0.001) was positively associated with higher levels

of adherence. Type of medication (NRTI, PI, NNRTI) was not associated with level of

adherence, although in the group condition, use of a greater number of types of antiretroviral

medications was associated with higher levels of adherence (r�/0.322, pB/ 0.05).

Table 1. Percentage adherence pre- and post-intervention

Pre-intervention Post-intervention

CBSM�/ group condition

�/20% adherers 959/1.38 769/26.19

5/80% adherers 469/28.4 609/27.7

41�/80% adherers 669/13.09 669/22.04

0�/40% adherers 169/16.25 529/33.39

Individual control condition

�/20% adherers 959/1.02 759/27.62

5/89% adherers 519/25.7 619/32.2

41�/80% adherers 669/12.71 679/28.12

0�/40% adherers 119/12.94 459/38.46

INFLUENCING MEDICATION ADERENCE 469

Discussion

Overall, participants were moderately adherent (68%) at study entry. Identifying women with

low adherence at baseline, though the intervention was not specifically designed to affect

adherence, we found medication adherence improved in those participating in the CBSM�/

intervention. However, as the group condition did not significantly differ from the individual

condition, the intervention did not improve adherence in this population. Negative HIV-

related coping strategies and lack of knowledge regarding HIV medication and the immune

system were related to decreased adherence, while women participating in the group

condition decreased their levels of denial-based coping.

The intervention did not produce increases in adherence among more highly adherent

women, most likely due to a ceiling effect, i.e. lower potential score variability available to

those reporting higher levels of adherence. In fact, more highly adherent women’s adherence

decreased, in keeping with the observed decrease in adherence over longer periods of time

(Epstein & Cluss, 1982). Half of the participants reported high levels of adherence, which

may confirm previous research on significant overestimates of adherence using patient self-

report of seven days of medication (e.g. 50% self-report of 100% adherence versus 22% of

perfect adherence obtained by pill bottle cap monitor (Golin et al ., 1999)).

Accurate HIV-related medication knowledge and belief in medication efficacy was

consistently associated with higher levels of adherence. These findings highlight the

importance of assessing beliefs regarding medication (Horne et al ., 1999) and are consistent

with recent research (Sipler et al ., 1999). Results emphasize the need to clarify HIV-related

confusion and inadequate or inaccurate knowledge regarding HIV, medication and disease

outcomes (Stein et al ., 1991), as well as to address negative attitudes concerning the efficacy

of HIV medication (Muma et al ., 1995; Stein et al ., 1991). The increase in adherence in the

group condition at post-intervention may have been related to the reduction in HIV-related

denial-based coping. The group intervention is designed to provide the opportunity to

confront HIV-related issues with other women living with the virus. The CBSM�/

intervention may influence adherence by discouraging unproductive disengagement and

denial (Ironson et al ., 1994) and pessimism about HIV disease (Kirscht & Rosenstock, 1977).

In contrast with previous literature on the association of race (Malow et al ., 1998; Sipler

et al ., 1999; Wenger et al ., 1999), gender (Malow et al ., 1998) and low income (Sipler et al .,

1999) with low adherence, low-income multi-ethnic women with AIDS reported high levels of

adherence. In addition, histories of drug dependence were also associated with higher levels of

adherence. Many of these women were participating in 12-step programmes that encourage a

commitment to self-care. Previous studies have shown women and non-whites to have less

access to AZT, PCP prophylaxis (Stein et al ., 1991) and antiretroviral medications (Balano et

al ., 1997) than the recommended standard of care, though sociodemographic variables have

not been found to predict adherence (Ickovics & Meade, 2002). These findings suggest that

multi-ethnic low-income women make equally appropriate candidates for antiretroviral

combination therapy when compared with studies of self-reported adherence in other

populations (Crespo-Fierro, 1997; Stall et al ., 1996). In fact, in the group condition, women

receiving larger numbers of medications were more highly adherent.

Study outcomes had several limitations, the first being that the study was not designed to

influence adherence and measures of adherence were restricted. Three important factors

related to long-term adherence were not measured in the present study: (1) study participants

did not share the same start date for beginning treatment, and duration of medication dosing

negatively influences adherence (Meichenbaum & Turk, 1987); (2) the complexity of

medication regimen adds to the adherence burden, and participants had a variety of

470 D. L. JONES ET AL.

regimens; and (3) adherence should be assessed for a longer duration to evaluate the efficacy

of the intervention over time. In this study, the first two factors were controlled for by

randomization, but may be a variable for investigation in future research. In addition, self-

reported adherence measures may overstate levels of adherence (Golin et al ., 1999).

Participants may wish to ‘look good’ in the study, resulting in a response bias. It is reasonable

to assume that subjects volunteering to participate have greater motivation to appear adherent

to medication regimens than those who might be unwilling to participate (Klaus & Grodesky,

1997). There is additional evidence that persons identifying themselves as less adherent are

more likely to respond to an intervention aimed at increasing adherence (Haynes et al ., 1979).

In this study, the assessment measure may have served to identify those individuals most likely

to improve. Finally, screening criteria (e.g. depression, substance dependence) employed may

limit the generalizability of these findings.

Previous research on the hierarchy of methods of monitoring adherence has found pill

counts to overestimate adherence (Haynes, 1976), followed by verbal reports and written logs,

which are similarly inaccurate. The adherence measure used in this study encouraged patients

to share their behaviour in relation to taking medication, while giving them permission to tell

the truth (Chesney, 1997). A complementary method of monitoring adherence is the

microelectronic monitoring system (MEMS, Aprex Corporation) Trackcap, a pill bottle cap

monitor. Future research should continue to use a combination of methods (Bangsberg et al .,

2000; Melbourne et al ., 1999 (e.g. MEMS Trackcap, viral monitoring and self-report, etc.) to

obtain valid and reliable data on adherence.

In most studies concerning adherence, the ]/80% threshold has been considered

adequate for obtaining clinically meaningful outcomes. Current research has suggested that

the goal for HIV medication adherence must approximate 95�/100% to achieve complete viral

suppression (Paterson et al ., 2000). These findings suggest that among HIV-positive

individuals who do not adequately adhere to medication regimens, group and individual

behavioural interventions can be designed to have a favourable impact on variables related to

adherence. Although adherence among low adhering participants in our study increased,

adherence levels for many still fell far short of levels needed for adequate viral suppression (i.e.

�/90%), emphasizing the urgency for adherence-focused interventions to attain effective

clinical outcomes. Future interventions designed to improve adherence should include

strategies such as clarification of medication regimens, medication education, plans for

responding to side effects, attention to lifestyle issues and barriers to taking medication

(Chesney, 1997; McPherson-Baker et al ., 2000; Reiter et al ., 2000). Finally, given the

importance of adherence to HIV medication schedules, the development of improved

medications (i.e. longer acting medications with fewer side effects) and regimens (i.e. fewer

medications with simpler dosing schedules) remains essential.

Acknowledgements

We would like to thank the following referral sites, medical practitioners and staff: (Miami)

Broward House, Broward Wellness Center, Center One, The Center for Positive Connec-

tions, Community Health Initiative, Family Health Center, Health Crisis Network, Liberty

City Health Center, Mercy Hospital, MOVERS (Mt. Tabor Baptist Church, Reverend

George McCrae), North Dade Health Center, Overtown Health Center, SMART Project,

South Shore Hospital, Stanley C. Myers Health Center, Special Immunology Corridor D and

the Maternal Addiction Program: University of Miami/Jackson Memorial Hospital, Vincent

Jarvis, Mark Csete, Deborah Holmes, Terrence Ibbs, Deshratn Asthana, Victoria Busta-

mante, Mahendra Kumar, Thomas Mellman, Bryan Page, Rene Nasajon, Amy Trachter,

INFLUENCING MEDICATION ADERENCE 471

Alison Goldstein, Robert Malow, Rosalind Mathis, Yael Wiesner, Sandra Abrams and Maxine

Etienne. (New York/New Jersey): Betances Health Unit, Community Family Planning

Council, Community Healthcare Network, Community Research Initiative on AIDS, Morris

Heights Health Center, St. Vincent Hospital, William F. Ryan Community Health Center,

Inc./NENA, Eric B. Chandler Health Center, Newark Community Health Center-Ludlow,

Jersey City Family Health Center, Community Health Center at Vauxhall and Overlook

Hospital, Majorie Ubiera, Shellon Munoz-D’Andrea, Marc Zuckerman, Cezarina Coma,

Barbara Dorsey, Robin Masheb, Alison Thomas-Cottingham, Patricia Whelan, Sandra

Colon, Milagos Harris, Fran Hoey, Nabilian uhamed-Ismail, Erinn Musser, Nyz Ittai,

Suzanne Ornstein, Beatriz Alvarez-Nuniez, Louis Caraballo, Erinn Haswell, Sterling

Alexander, Tamara Buckley and Varzi Jeanbaptiste.

This study was made by possible by grants from the National Institute of Mental Health/

National Institutes of Health, RO1MH55463 and T32MH18917.

References

ANTONI, M.H., BAGGETT, L., IRONSON, G., AUGUST, S., LAPERRIERE, A., KLIMAS, N., SCHNEDERMAN, N. &

FLETCHER, M.A. (1991). Cognitive behavioral stress management intervention buffers distress responses and

immunologic changes following notification of HIV-1 seropositivity. Journal of Consulting and Clinical Psychology ,

59 , 909�/915.

ANTONI, M., IRONSON, G., HELDER L., LUTGENDORF, S., LAPERRIERE A., FLETCHER, M. & SCHEIDERMAN, N.

(1992). Stress management intervention reduces social isolation and maladaptive coping behaviors in gay men

adjusting to an HIV-1 seropositive diagnosis. Annual Meeting of the Society of Behavioral Medicine, New York.

BALANO, K., LILJESTRAD, P., GOLDSCHMIDT, R., LEOUNG, G. & LEGG, J. (1997). Antiretroviral usage trends: data

from the National HIV Telephone Consultation Service. 4th Conference on Retroviruses and Opportunistic

Infections, Washington, 22�/26 January.

BANDURA, A. (1986). Social foundations of thought and action: a social cognitive theory. Englewood Cliffs, NJ: Prentice

Hall.

BANGSBERG, D.R., HECHT, F.M., CHARLESBOIS, E.D., ZOLOPA, A.R., HOLODNIY, M., SHEINER, L., BAMBERGER, J.D.,

CHESNEY, M.A. & MOSS, A. (2000). Adherence to protease inhibitors, HIV-1 load, and development of drug

resistance in an indigent population. AIDS , 14 , 357�/366.

BESCH, C.L. (1995). Compliance in clinical trials. AIDS , 9 , 1�/10.

BLUMENTHAL, J.A., WILLIAMS, R., WALLACE, A., O’CONNOR, HINDERLITER, A., FATH, K, HEDGE, S. B., MILLER,

G., PUMA, J., SESSIONS, W., SHEPS, D. & ZAKHARY, B. (1995). Physiological and psychological variables predict

compliance to prescribed exercise therapy in patients recovering from myocardial infarction. Psychosomatic

Medicine , 44 , 519�/527.

CARPENTER, C.C.J., FISCHL, M.A., HAMMER, S.M., HIRSCH, M.S., JACOBSEN, D.M., KATSENSTEIN, D.A.,

MONTANER, J.S.G., RICHMAN, D.D., SAAG, M.S., SCHOOLEY, R.T., THOMPSON, M.A., VELLA, S., YENI, P.G. &

VOLBERDING, P.A. (1996). Antiretroviral therapy for HIV infection in 1996. Recommendations of an international

panel. International AIDS Society-USA. Journal of the American Medical Association , 10 , 146�/154.

CARPENTER, C.C.J., FISCHL, M.A., HAMMER, S.M., HIRSCH, M.S., JACOBSEN, D.M., KATSENSTEIN, D.A.,

MONTANER, J.S.G., RICHMAN, D.D., SAAG, M.S., SCHOOLEY, R.T., THOMPSON, M.A., VELLA, S., YENI, P.G. &

VOLBERDING, P.A. (1997). Antiretroviral therapy in adults: updated recommendations of the international AIDS

society-USA panel. Journal of the American Medical Association , 283 , 381�/390.

CARVER, C., SHEIER, M. & WEINTRAUB, J.D. (1989). Assessing coping strategies: a theoretically based approach.

Journal of Personality and Social Psychology , 56 , 267�/283.

CATZ, S.L., KELLY, J.A. & BOGART, L.M. (2000). Patterns, correlates, and barriers to medication adherence among

persons prescribed new treatments for HIV disease. Health Psychology , 19 , 124�/133.

CENTERS FOR DISEASE CONTROL AND PREVENTION (1998). HIV/AIDS Surveillance Report , 9 , 1�/44.

CHESNEY, M.A. (1997). New antiretroviral therapies: adherence challenges and strategies. Evolving HIV Treatments:

Advances and Challenges of Adherence, 37th ICAAC Symposium Toronto, Canada, September.

CHESNEY, M.A. & FOLKMAN, S. (1994). Psychological impact of HIV disease and implications for intervention.

Psychiatric Clinics of North America , 17 , 163�/182.

CHESNEY, M. & ICKOVICS, J. FOR THE RECRUITMENT, ADHERENCE AND RETENTION COMMITTEE OF THE ACTG

(1997). Presented at the Annual Meeting of the AIDS Clinical Trials Group, July, Washington, DC.

CHESNEY, M.A., ICKOVICS, J.R., CHAMBERS, D.B. ET AL. (2000). Self-reported adherence to antiretroviral medications

among participants in HIV clinical trials: the AACTG Adherence Instruments. AIDS Care , 12 (3), 255�/266.

472 D. L. JONES ET AL.

CRESPO-FIERRO, M. (1997). Compliance/adherence and care management in HIV disease. Journal of the Association of

Nurses in AIDS Care , 8 , 43�/54.

DIAMOND, S, GORE-FELTON, C, GALE, D.A., CLASSEN, C. & SPIEGEL, D. (1997). Supportive-expressive group therapy

for persons with HIV infection: a treatment manual. Stanford: Stanford University Press.

DUNBAR, J. (1990). Predictors of patient adherence: patient characteristics. In: SHUMAKER, S., SHRON, E., OCKENE, J.

ET AL. (Eds), The handbook of health behavior change (pp. 348�/360). New York: Springer.

EPSTEIN, L.H. & CLUSS, P.A. (1982). A behavioral medicine perspective on adherence to long-term medical regimens.

Journal of Consulting and Clinical Psychology , 50 , 950�/971.

FAWZY, I., NAMIR, S. & WOLCOTT, D. (1989). Group intervention with newly diagnosed AIDS patients. Psychiatric

Medicine , 7 , 35�/46.

FOLSTEIN, M.F., FOLSTEIN, S.E. & MCHUGH, P. (1975). Mini-Mental Status Exam: a practical method for grading

the cognitive state of patients for the clinician. Journal of Psychiatric Research , 12 , 189�/198.

GOLIN, C., LIU, H., HAY, R, ICKOVICS, H., BECK, K., MILLER, L., KAPLAN, A. & WENGER, N. (1999). Self-reported

adherence to protease inhibitors substantially overestimates objective measure. 6th Conference on Retroviruses and

Opportunistic Infections, Chicago, 31 January�/4 February.

HAYNES, R.B. (1976). A critical review of the ‘determinants’ of patient compliance with therapeutic regimens. In:

SACKETT, D. L. & HAYNES, R. B. (Eds), Compliance with therapeutic regimens (pp. 193�/279). Baltimore, MD: Johns

Hopkins University Press.

HAYNES, R.B., TAYLOR, D.H. & SACKETT, D.L. (Eds) (1979). Compliance in health care . Baltimore, MD: Johns

Hopkins University Press.

HOGG, R.S., YIP, B., CHAN, K., O’SHAUGHNESSY, M.V. & MONTANER, J.S.V. (2000). Non-adherence to triple

combination is predictive of AIDS progression and death in HIV positive men and women. 7th Conference on

Retroviruses and Opportunistic Infections, 30 January.

HORNE, R., WEINMAN, J. & HANKINS, M. (1999). The beliefs about medicines questionnaire: the development and

evaluation of a new method for assessing the cognitive representation of medication. Psychology and Health , 12 , 1�/

24.

ICKOVICS, J.R. & MEADE, C.S. (2002). Adherence to HAART among patients with HIV: breakthroughs and barriers.

AIDS Care , 14 , 309�/338.

ICKOVICS, J.R. & MEISLER, A.W. (1995). Adherence in AIDS clinical trials: a framework for clinical research and

clinical care. Journal of Clinical Epidemiology , 50 , 385�/391.

INGLEDEW, D.K., HARDY, L., COOPER, C.L. & JEMAL, H. (1996). Health behaviours reported as coping strategies: a

factor analytical study. British Journal of Health Psychology , 1 , 263�/281.

IRONSON, G., FRIEDMAN, A., KLIMAS, N., ANTONI, M., FLETCHER, M. A., LAPERRIERE, A., SIMONEAU, J. &

SCHNEIDERMAN, N. (1994). Distress, denial, and low adherence to behavioral interventions predict faster disease

progression in gay men infected with human immunodeficiency virus. International Journal of Behavioral Medicine ,

90�/105.

KALICHMAN, S.C., RAMACHANDRAN, B. & OSTROW, D. (1998). Protease inhibitors and the new AIDS combination

therapies: implications for psychological services. Professional Psychology: Research and Practice , 29 , 349�/356.

KARNOFSKY, D., ABELMANNN, W., CRAVER, L. & BURCHENAL, J. (1948). The use of the nitrogen mustards in the

palliative treatment of carcinoma. Cancer , 1 , 634�/652.

KIECOLT-GLASER, J. & WILLIAMS, D. (1987). Self-blame, compliance, and distress among burn patients. Journal of

Personality and Social Psychology , 58 , 187�/193.

KIRSCHT, J.P. & ROSENSTOCK, I.M. (1977). Patient adherence to antihypertensive medical regimens. Journal of

Community Health , 4 , 113�/124.

KLAUS, B.D. & GRODESKY, M.J. (1997). Assessing and enhancing compliance with antiretroviral therapy. Nurse

Practitioner , 212 , 211�/219.

LAPERRIERE, A., IRONSON, G., ANTONI, M.H., JONES, D., GOLDSTEIN, A., STANLEY, H., SCHNEIDERMAN, N.,

CASSELLS, A., TOBIN, J. & WEISS, S. (1999). CBSM�/ group intervention decreases depression and anxiety in

women with AIDS. American Psychological Association Convention, Boston, 4�/6 August.

LUTGENDORF, S.K., ANTONI, M.H., IRONSON, G., KLIMAS, N., KUMAR, M., STARR, K., MCCABE, P., CLEVEN, K.,

FLETCHER, M.A. & SCHNEIDERMAN, N. (1997a). Cognitive-behavioral stress management decreases dysphoric

mood and herpes simplex virus-type 2 antibody titers in symptomatic HIV-seropositive gay men. Journal of

Consulting and Clinical Psychology , 65 , 31�/43.

LUTGENDORF, S.K., ANTONI, M.H., IRONSON, G., STARR, K., COSTELLO, N., ZUCKERMAN, M., KLIMAS, N.,

FLETCHER, M.A. & SCHNEIDERMAN, N. (1997b). Changes in cognitive coping skills and social support during

cognitive behavioral stress management intervention and distress outcomes in symptomatic HIV-seropositive men.

Psychosomatic Medicine , 60 , 204�/214.

INFLUENCING MEDICATION ADERENCE 473

MALOW, R., MCPHERSON, S, KLIMAS, N., ANTONI, M.H., SCHNEIDERMAN, N., PENEDO, F., ZISKIND, D., PAGE, B. &

MCMAHON, R. (1998). Adherence to complex combination antiretroviral therapies by HIV-positive drug abusers.

Psychiatric Services , 49 , 1021�/1022.

MCPHERSON-BAKER, S., MALOW, R.M., PENEDO, F., JONES, D., SCHNEIDERMAN, N. & KLIMAS, N. (2000).

Enhancing adherence to combination antiretroviral therapy in non-adherent HIV-positive men. AIDS Care , 12 (4),

399�/404.

MEHTA, S., MOORE, R.D. & GRAHAM, N.M.H. (1997). Potential factors affecting adherence with IV therapy. AIDS ,

11 , 1665�/1670.

MEICHENBAUM, D. & TURK, D.C. (1987). Facilitating treatment adherence: a practitioner’s guidebook . Boston, MA:

Plenum Press.

MELBOURNE, K.M., GELETKO, S.M., BROWN, S.L., WILLEY, C., CHASE, S. & FISHER, A. (1999). Medication

adherence in patients with HIV infections: a comparison of two measurement methods. AIDS Reader , 9 , 329�/338.

MUMA, R., ROSS, W., PARCEL, G. & POLLARD, R. (1995). Zidovudine adherence among individuals with HIV

infection. AIDS Care , 7 , 439�/448.

PATERSON, D., SWINDELL, S., MOHR, J., BRESTER, M., VERGISI, E., SQUIERI, C., WAGENER, M., SINGH, N.,

PATERSON, D.L., SWINDELS, S., MOHR, J. ET AL. (2000). Adherence to protease inhibitor therapy and outcomes in

patients with HIV infection. Annals of Internal Medicine , 4 , 21�/30.

POWER, C., SELNES, O., GRIM, J. & MCARTHUR, J. (1995). HIV dementia scale: a rapid screening test. Journal of

Acquired Immune Deficiency Syndromes and Human Retrovirology , 8 , 273�/278.

REITER, G.S., STEWART, K.E., WOJTUSIK, L. ET AL. (2000). Elements of success in HIV clinical care: multiple

interventions that promote adherence. Topics in HIV Medicine , 8 (5).

SCHNEIDERMAN, N., ANTONI, M.H. & IRONSON, G. (1997). Cognitive behavioral stress management and secondary

prevention in HIV/AIDS. Psychology & AIDS Exchange , 22 , 1�/8.

SENAK, M. (1997). Predicting antiviral compliance. Journal of the International Association of Physicians with AIDS

Care , June , 45�/48.

SIPLER, A.M., CROSS, J.T., LANE, D.R., DAVIS, T.C., WILLIAMS, L.M., YARNOLD, P.R., LINDAU, S.T. & BENNETT,

C.L. (1999). The relationship between literacy, race, and adherence to potent antiretroviral therapies. 6th

Conference on Retroviruses and Opportunistic Infections, Chicago, 31 January�/4 February.

SPIEGEL, D. & SPIRA, J. (1991). Supportive-expressive group therapy: a treatment manual of psychosocial intervention

for women with recurrent breast cancer. Stanford, CA: Psychosocial Treatment Laboratory, Department of

Psychiatry and Behavioral Sciences.

SPIEGEL, D. & YALOM, I. (1981). Group support for patients with metastatic breast cancer. Archives of General

Psychiatry , 38 , 527�/533.

STALL, R., HOFF, C., COATES, T., PAUL, J., PHILLIPS, K.A., EKSTAND, M., KEGELES, S., CATANIA, J., DAIGLE, D. &

DIAZ, R. (1996). Decisions to get tested and to accept antiretroviral therapies among gay/bisexual men: implications

for secondary prevention efforts. Journal of Acquired Immune Deficiency Syndromes and Human Retrovirology , 11 ,

151�/160.

STEIN, M.D., PIETTE, N., MOR, V., WACHTEL, T.J., FLEISHMAN, J., MAYER, K.H. & CARPENTER, C.C. (1991).

Differences in access to zidovudine (AZT) among symptomatic HIV-infected individuals. Journal of General Internal

Medicine , 6 , 35�/40.

TOBIN, J.N., WEISS, S.M., SCHNEIDERMAN, N., IRONSON, G., BRONDOLO, E., VAUGHN, A.C., CASSELLS, A.,

GOUSSE, Y.P., ALEXANDER, K., LAPERRIERE, A., STANLEY, H., ISHII, M., DEVIEUX, J., JONES, D., ANTONI, M.,

ASTHANA, D., BUSTAMANTE, V., KUMAR, M., MALOW, R., PAGE, B., VAN SPLUNTEREN, F., GOLDSTEIN, A.,

NASAJON, R. & WIESNER, Y. (1999). Psychosocial, behavioral and clinical characteristics of women with AIDS

enrolled in a behavioral medicine clinical trail: the SMART/EST women’s AIDS intervention study (symposium).

Society for Behavioral Medicine Conference, San Diego, 12�/15 March.

WALL, T.L., SORENSEN, J.L., BATKI, S.L., DELUCCI, K.L., LONDON, J.A. & CHESNEY, M.A. (1995). Adherence to

zidovudine (AZT) among HIV infected methadone patients: a pilot study of supervised therapy and dispensing

compared to usual care. Drug and Alcohol Dependence , 37 , 261�/269.

WEISS, STEPHEN, M., TOBIN, J., BRONDOLO, E., SCHNEIDERMAN, N., ANTONI, M. & IRONSON, G. (submitted).

Empowering women living with AIDS: the SMART/EST Women’s Project. American Psychological Association

Convention, Boston, 3�/5 August.

WENGER, N., GIFFORD, A., LIU, H., CHESNEY, M., GOLIN, C., CRYSTAL, S., BERR, S., COPLAN, P., BOZZETTE, S. &

SHAPIRO, M. (1999). Patient characteristics and attitudes associated with antiretroviral (AR) adherence. 6th

Conference on Retroviruses and Opportunistic Infections, Chicago, 31 January�/4 February.

VOLBERDING, P.A. (1998). Nonadherence to HIV treatment is high. Journal of International Association of Physicians

AIDS Care , 4 , 32�/35.

474 D. L. JONES ET AL.