Three types of adherence to HIV antiretroviral therapy

ORIGINAL RESEARCH ARTICLE

Three types of adherence to HIV antiretroviral therapy and their association with AIDS diagnosis, medication side-effects, beliefs about antiretroviral therapy, and beliefs about HIV disease Lena Nilsson Scho¨nnesson PhD*, Mark L Williams Pamela M Diamond PhD- and Blair Keel MPH-

-

PhD

, Michael W Ross

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PhD MPH

,

*Infectious Disease Clinic/Gay Men’s Health Clinic, Karolinska University Hospital, Stockholm, Sweden; -School of Public Health, University of Texas Health Science Center at Houston, Houston, TX, USA

Summary: One hundred and ninety-three adults with HIV taking antiretroviral therapy completed a questionnaire on demographics, health beliefs, medication side-effects, and adherence to dose, schedule, and dietary instructions. Three health beliefs indices were identified: antiretroviral therapy (ART) benefits, ART adherence self-efficacy, and beliefs about future HIV-related health concerns. Patients who experienced medication side-effects reported strong beliefs that HIV infection would cause them future health problems or distrust in the benefits of ART. AIDS diagnosis obtained through medical records or medication side-effects were not related to any of the three types of adherence. Beliefs about future HIVrelated health concerns were associated with suboptimal dose adherence. Beliefs about ART benefits were associated with suboptimal schedule and dietary instructions adherence. Older age and partner were protective factors of schedule adherence. Data suggest that health beliefs may vary across type of adherence and that adherence behaviours may be a coping strategy to adjust antiretroviral therapy to one’s daily living. Keywords: HIV infection, adherence, health beliefs, AIDS, medication side-effects

INTRODUCTION With the introduction of combination antiretroviral therapy (ART) for HIV infection in 1996, HIV-related morbidity and mortality have dramatically decreased. The aim of ART is to suppress replication of HIV to undetectable levels (o50 copies/mL),1 and successful medication outcome depends largely on medication adherence. While dose adherence must be above 95% to maintain undetectable viremia (HIV1 RNA),2,3 in general, rates of dose adherence vary between 26% and 85%.4–6 Low ART adherence places the individual at risk of disease progression and eventually the development of antiretroviral resistance, rendering potent ART regimens ineffective.1 Resistant virus can be transmitted to uninfected people, thereby limiting future therapeutic options in those newly HIV-infected.1 Correspondence to: Dr Lena Nilsson Scho¨nnesson, Gay Men’s Health Clinic/Venha¨lsan, So¨dersjukhuset, SE-118 83 Stockholm, Sweden Email: [email protected]

Individual health beliefs are important for performing treatment behaviours.7 Leventhal’s Self-Regulatory Model of Illness8 proposes that medication adherence is influenced by illness and treatment beliefs.9 Beliefs are in turn influenced by experienced illness symptoms and/or adverse medication side-effects.8,10,11 Perceived adherence self-efficacy, i.e. the belief that one can take medications as prescribed, is another important component of the adherence process.12 The influence of illness and treatment beliefs on medication adherence is a little researched area of HIV infection. Existing studies have focused on beliefs about the efficacy of ART,13–16 adherence self-efficacy,10,17–20 the effect of medication side-effects, and HIVrelated complications on health beliefs and their associations with adherence.16,21–23 These studies defined adherence only in terms of dose adherence.24 Optimal ART efficacy also requires adherence to proper scheduling of doses and to dietary instructions that accompany some medications. 4,25–28 To our knowledge, there are no published studies examining the associations between health beliefs and adherence to schedule and dietary instructions. This study uses the self-regulatory International Journal of STD & AIDS 2007; 18: 369–373

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model8 as a framework to: (1) determine whether beliefs about ART and beliefs about HIV disease depend on AIDS diagnosis and adverse medication side-effects; (2) examine how adherence to dose, schedule, and dietary instructions vary with AIDS diagnosis and medication side-effects; and (3) examine the effect of demographics, beliefs about ART and HIV disease on adherence to dose, schedule, and dietary instructions.

METHODS Patients Patients receiving ART for at least six months, who were fluent in Swedish, not using illicit substances, and not suffering from a diagnosed psychiatric disorder or dementia, were approached by clinic nurses at two HIV clinics in Stockholm, Sweden, and asked to participate in the study. Patients who agreed to participate in the study were fully informed and asked to sign an informed consent form. Seventy-four percent of the patients approached (203/274) agreed to participate. An institutional ethics committee reviewed and approved study procedures and research instruments.

Statistical analyses Principal component analysis with Varimax rotation was used to group the eight ART-related statements into categories forming treatment belief indices. Walkey and McCormack’s (1985) criterion for scale derivation was used to assess scale coherence. Factors derived from principal component analysis were tested for internal reliability using Cronbach’s alphas. One-way analysis of variance was utilized to address the first research question. Beliefs about ART and about HIV disease served as dependent variables, and the independent variables were AIDS diagnosis and medication sideeffects. The second research question was assessed using chi-square tests. Multivariate logistic regression analysis was utilized to examine the third question. The three types of adherence served as the dependent variables, and the independent dichotomized variables entered stepwise were demographics (gender, age, education, partner status) and beliefs about ART and HIV disease. All tests of statistical significance were two tailed, Po0.05. Data were analysed using SPSS 11.0 for Windows.

RESULTS Procedures Following informed consent, patients were given a selfadministered questionnaire that could be completed in the clinic or at home. The questionnaire was sealed in an envelope and forwarded or mailed to the principal investigator.

Measures One section of the questionnaire included eight statements related to beliefs about ART. Belief about HIV disease was measured by the statement ‘HIV infection will cause me health problems over the years’. Patients were asked to rate how much they agreed or disagreed with each of the nine statements on a four-point Likert-type response scale (0 ¼ strongly disagree to 3 ¼ strongly agree). AIDS diagnosis, obtained through patients’ medical records, was based upon whether the patient had been diagnosed with an AIDS-defining illness. Medication adverse side-effects were measured by asking the patients if they currently experienced adverse medication side-effects (yes/no). Adherence to dose, schedule, and dietary instructions for each medication a patient was reported to be taking in the past four days were measured by patients’ self-reports, using a somewhat modified version of the adult AIDS Clinical Trials Group (AACTG) adherence instruments.28 All adherence measures were initially conceptualized as multi-category variables. Because of low responses in some categories and highly skewed distribution, the three adherence measures were dichotomized into 100% adherence versus suboptimal adherence.29

One hundred and ninety-three patients completed the questionnaire (95% return rate). All patients were Caucasian Swedes and the majority was bi- and homosexual men between 34 and 53 years. Sixty percent were married or partnered in a relationship like marriage. Over a half had a university degree or professional training. All patients were infected with HIV sexually, and most were diagnosed before 1995. Eighteen percent of patients had an AIDS diagnosis. Close to two-thirds reported taking three to five antiretroviral medications and had been on ART for an average of 47 months (range 6–96 months, median ¼ 51). Sixty-nine percent reported adverse medication side-effects (Table 1). Two ART factors emerged from the principal component analysis, explaining 54% of the variance (Table 2). Factor 1, beliefs about ART benefits (Cronbach’s alpha ¼ 0.72), is composed of items measuring the benefits that the patient expected to get from taking ART. Factor 2, ART adherence self-efficacy, is made up of items measuring the patient’s perceived ability to follow a medication regimen. Although adherence necessity was one of three items making up ART adherence self-efficacy, Cronbach’s alpha increased when this item was excluded (from alpha ¼ 0.42–0.60). Adherence necessity was thus excluded from the analysis. The measurement of beliefs about HIV disease is labelled ‘beliefs about future HIV-related health concerns’. The mean and standard deviation of beliefs about ART benefits, adherence self-efficacy, and belief about future HIV-related health concerns on total sample, AIDS diagnosis, and medication side-effects are presented in Table 3. Twenty-three patients (12%) reported suboptimal dose and 72 (34%) reported suboptimal schedule adherence behaviour in the four days prior to filling out the questionnaire. Among the 103 participants who reported


Nilsson Scho¨nnesson et al. Types of adherence to HIV antiretroviral therapy 371 ...................................................................................................................................................................................... Table 1

Patient characteristics (n=193)

Characteristics

No.

%

Gender Female Male

48 145

25 75

29 83 52 29

15 43 27 15

Sexual preference Homosexual Bisexual Heterosexual

111 7 75

57 4 39

Education High school Some college University degree or professional training

19 61 112

10 32 58

78 81 34

40 42 18

AIDS diagnosis Yes No

34 159

18 82

Number of medications Less than 3 3–5 6

72 117 2

37 62 1

Duration of antiretroviral therapy 6–12 months 13–23 months X24 months

6 7 180

3 4 93

Medication side-effects Yes No

133 60

69 31

Age (years) 24–33 34–43 44–53 X54

Year of HIV diagnosis 1983–1989 1990–1994 1995–2000

being prescribed dietary instructions, over half (n ¼ 60, 58%) reported suboptimal dietary instructions adherence. Low to moderate associations were found between dose and schedule adherence (r ¼ 0.26, Po0.01) and schedule and dietary instructions adherence (r ¼ 0.34, Po0.01). There was no association (Table 3) between AIDS diagnosis and health beliefs. However, patients reporting medication side-effects scored significantly lower on ART benefits or higher on perceived future HIV-related health concerns. None of the three types of adherence was significantly associated with AIDS diagnosis or medication side-effects. The odds of reporting suboptimal dose adherence were close to three times greater for patients with strong beliefs about future HIV-related health concerns than the odds for those with low scores (odds ratio [OR] ¼ 2.74; 95% confidence interval [CI] ¼ 1.01–6.83). The odds of reporting suboptimal schedule adherence were two times greater for patients with strong beliefs about ART benefits than the odds for those with low scores (OR ¼ 2.38; 95% CI ¼ 1.04–5.46). Older age (OR ¼ 0.44; 95% CI ¼ 0.23–0.83) and patients in a stable relationship had significantly higher odds of adhering to schedule adherence (OR ¼ 0.52, 95% CI ¼ 0.28–0.98) over the preceding four days. The odds of reporting suboptimal dietary instructions adherence were close to four times greater for those with strong beliefs about ART benefits than the odds for those with low scores (OR ¼ 3.94; CI ¼ 1.12–13.82).

DISCUSSION To our knowledge, this is the first study to examine the associations between AIDS diagnosis, medication sideeffects, beliefs about ART, beliefs about HIV disease, and adherence to medication dose, schedule, and dietary instructions. Our data did not indicate significant

Table 2 Varimax rotated component matrix obtained by principal component analysis and Spearman’s rank order correlation coefficient between the two health belief indices Factor 1, ART benefits Factor 1 I do not believe that HIV medication will make me sicker I am not afraid of (to get more) medical side-effects I do not feel sicker now than I did before I started HIV medication HIV medication prolongs my life HIV medications have a positive impact on my health Factor 2 I do my best to adhere to the medical regimens I am convinced I will be able to manage my HIV medications in the future Unless I take my medication exactly as prescribed, the virus will become resistant towards HIV medication Eigenvalue Percentage of variance explained Correlation with Factor 2/ART adherence self-efficacy

Factor 2, ART adherence self-efficacy

0.778 0.738 0.677 0.660 0.597

0.775 0.610 0.592 2.854 33.66 0.17

ART=antiretroviral therapy


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...................................................................................................................................................................................... Table 3 Means and standard deviations of health belief indices and effects of AIDS diagnosis and medication side-effects on health belief indices

Health beliefs

Total sample n=193

ART benefits Adherence self-efficacy Future HIV-related health concerns

2.4370.55 2.6070.57 1.5071.08

AIDS diagnosis

Medication side-effects

Yes (n=34)

No (n=159)

F

Yes (n=133)

No (n=60)

F

2.5670.45 2.5070.71 1.7571.16

2.4170.57 2.6270.54 1.4571.05

2.14 1.24 2.05

2.3370.56 2.5770.55 1.7171.03

2.6670.45 2.6670.61 1.0071.01

16.16** 0.97 19.07***

**Po0.01; ***Po0.001 ART=antiretroviral therapy

associations between AIDS diagnosis and health beliefs, which might be explained by the low number of patients having been diagnosed with AIDS. On the other hand, patients who reported medication side-effects expressed distrust in the benefits of ART. It is quite possible that patients who have relatively good health prior to beginning ART may be sceptical about the benefits of ART, as sideeffects may be perceived as causing a deterioration in their health. Medication side-effects also correlated with beliefs about future HIV-related health concerns, which, within this context, may be related to the actual side-effects rather than to the HIV disease. In contrast to other studies, neither AIDS diagnosis16,22 or medication side-effects16,17,30–33 were associated with suboptimal adherence. But patients were less likely to take their medication doses if they perceived a risk of future HIV-related health concerns. The finding can be interpreted within Leventhal’s self-regulatory framework. Suboptimal dose adherent patients may perceive a lower sense of coherence between medical messages that medications improve health and their experience of medication sideeffects. Suboptimal adherent behaviour may thus be a way of coping with the perceived risks associated with ART. Strong beliefs about ART benefits were associated with suboptimal schedule and dietary instructions adherence. Patients may have the experience of no negative effects from suboptimal schedule or dietary instructions and thus have no reason to not trust the benefits of ART. This may also be the result of patients attempting to exert personal control over their health. Clinical experiences suggest that patients frequently feel as if their medications control their lives and may be trying to exert control by ignoring schedule and dietary instructions. Less than optimal schedule and dietary instructions adherence may be a coping strategy to regain a sense of control. Being older and being within a stable relationship appeared to increase optimal schedule adherence. The study has limitations. The inclusion criteria and the use of a convenience sample limit generalizability to other populations. Moreover, this kind of study may attract patients who do not have major concerns about their treatment or problems with adherence. Additionally, compared to Swedish transmission data, gay men and women were over-represented in the sample. Secondly, concurrent HIV-related medical problems, specific medication side-effects, and the perceived intensity of each were not examined. It is possible that these may have had an effect on health beliefs and adherence. Thirdly, self-reported

measures of adherence may be subject to social desirability.33 However, as adherence data were not collected in a monitored clinical trial setting or by the primary physician or nurse, it is likely that social desirability was negligible. The dose adherence data are in concordance with other studies.5,6,34–37 The data are cross-sectional and causality cannot be inferred. For example, we presuppose that health beliefs influence adherence, but it may be that patients who reported suboptimal adherence endorsed beliefs that ‘justify’ their behaviour. Thus, future research warrants longitudinal prospective designs, not only to clarify causal relations but also to assess changes of health beliefs and adherence over time. An important implication of the study findings is that clinicians should ask patients about different aspects of adherence to ART rather than relying on a single indicator of adherence in the efforts to endorse and reinforce maintenance of adherence to ART. To improve dose adherence, our data propose that health-care providers find individually tailored medication regimens that minimize medication side-effects, which in turn may reduce the associated distrust in ART benefits and pessimistic HIV disease beliefs as manifested in a strong belief in future HIV-related health concerns. With regard to suboptimal schedule and dietary instructions adherence, it seems important to add that, although short-term failure to adhere may not result in negative effect on ART efficacy, it may do so in the long run. Our data clearly imply the necessity for health-care providers to invest time and effort in eliciting patients’ beliefs about antiretroviral therapy and HIV disease, educating patients about their disease and treatment, and alleviating potential treatment and HIV disease concerns.

ACKNOWLEDGEMENTS

We extend our gratitude to those women and men who participated in the study for their contribution. We also thank the nurses, in particular Eva-Lena Fredriksson and Britt-Marie Johansson, at Gay Men’s Health Center, So¨der Hospital, and HIV Clinic, Karolinska Hospital, for administering the questionnaire. This study was supported by grants from the Swedish Foundation for Health Care Sciences and Allergy Research; Department of Research, Education, and Development, Stockholm City Council; the Magn Bergvall’s Foundation; and the Swedish Physicians against AIDS Research Foundation, Sweden, and the National Institute on Drug Abuse, USA, R03 DA 12328.


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(Accepted 2 August 2006)