ADHERENCE TO ANTIRETROVIRAL THERAPY

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© JAPI • DECEMBER 2012 • VOL. 60

Original Article

Adherence to Antiretroviral Therapy Anant Gokarn*, Meenakshi Gangadhar Narkhede**, Geeta Shrikar Pardeshi***, Mohan Kondiba Doibale**** Abstract Introduction: The goal of HAART is to achieve maximal and durable suppression of virus replication. Adherence plays a very important role in success of antiretroviral therapy. Aims and Objectives: To find out the rate of adherence and factors that influence adherence to antiretroviral therapy (ART). Material and Methods: The present study was conducted in the Department of Medicine in a tertiary care hospital from November 2007 to September 2009. Patients attending ART centre OPD and started on ART for at least 6 months were included in the study. A pretested proforma and MMAS adherence questionnaire of every patient was used for data collection. Univariate and multivariate logistic regression analysis was done to identify factors associated with adherence. Observations and Results: A total of 300 patients attending ART OPD and satisfying inclusion criteria were studied. Adherence rate of >95% was reported by 290 (97%) patients. On MMAS scale 78% of the patients were found adherent to the treatment. On multivariate analysis factors such as age, addictions, difficulty in remembering treatment, finding treatment to be difficult, taking traditional medicines and having no one to remind about medicines were found to be associated with nonadherence. The most common reason for nonadherence were missing pills while travelling or being out of home. Conclusions: Adherence to antiretroviral treatment in the ART centre is high. During counseling sessions giving up addictions, avoiding traditional medicines, addressing the apprehensions about treatment, and identifying reminder systems should be emphasized. The patients should be advised to carry medications while traveling and when away from home.

O

Introduction

ver the last 5 years, there has been a rapid change in treatment strategies for HIV infection. With the advent of newer antiretrovirals, treatment has moved from monotherapy and bi-therapy to triple drug therapy or Highly Active Antiretroviral Therapy (HAART) which consists of three or more antiretroviral medicines to be taken in combination.1 In order to achieve the goal of antiretroviral therapy of undetectable levels of the virus in the blood, patients are required to maintain more than 90 – 95 % adherence.1 Adherence to the HAART regimen appears to be the single most important variable that predicts a patient’s ability to achieve and maintain suppression of HIV viraemia to below the level of detection and is thus critical for success of HAART.2 The definition of adherence used by the World Health Organization (WHO) is, “the extent to which a person’s behavior – taking medication, following a diet, and/or executing lifestyle changes, corresponds with agreed recommendations from a health care provider”.3 Adherence is the ability to take prescribed drugs in the recommended dosages and schedules and following any special instructions e.g. empty stomach, after meals etc.4 There are multiple factors that influence adherence: patient factors (e.g. socioeconomic, education, literacy etc.), treatment regimen, disease characteristics, patient – provider relationship Observer Department of Hematology, AIIMS, Delhi; **Associate Prof Medicine, ***Assistant Prof., ****Prof. & HOD, Department of PSM, Government Medical College, Nanded. Received: 08.03.2011; Accepted: 03.10.2011

*

and clinical settings. Little information is available about the levels of adherence to ART among people living with HIV/ AIDS in India. We studied the adherence rate and the factors that influence adherence to antiretroviral therapy (ART).

Material and Methods Study setting This cross sectional observational study was conducted at the Antiretroviral therapy (ART) centre in the out-patient department of a tertiary care hospital in Aurangabad between November 2007 and September 2009. This centre was established in July 2006. The ART centre is run under Maharashtra State AIDS Control Society, National AIDS Control Organization (NACO) under the National Aids Control Programme by Government of India. Every patient, before starting ART, undergoes three sessions of adherence counseling by adherence counselor. If the patients miss medication or do not report on time to collect medications, adherence counseling is repeated. Group counseling is also conducted daily during OPD hours using audio visual aids, comprising of a television set playing educational information regarding HIV and drug adherence, in the patients waiting area. Patients who fail to come to OPD on scheduled day are contacted telephonically. Those who are lost to follow up are visited at their homes by outreach workers. Sampling List of patients fulfilling the inclusion criteria was updated

© JAPI • DECEMBER 2012 • VOL. 60

Table 1 : Individual questions of MMAS and its summary score MMAS items Have reminder system for medicines Have sometimes forgotten medications Have forgotten medicines when traveling Consider it a difficult treatment Have reduced doses without the doctors knowledge Have forgotten medicines during the last two weeks Took medicines yesterday Have had treatment interruptions because he/she considers the infection under control Never Occasionally Difficulty in remembering Sometimes treatment Usually Always 5-8 Summary score 9-10 11-13

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No. of patients

Percentage

172

57.33%

86

28.66%

51

17%

50

16.66%

23

7.66%

19

6.33%

12

4%

3

1%

233 38 28 0 1 17 50 233

77.66% 12.66% 7.33% 0 0.33% Mean summary score is 11.42

from the OPD register and the patients to be included in the study sample were selected by simple random sampling method. Sample size The sample size was based on adherence rate of 81 % amongst patients receiving free ART in the study conducted in India.5 The sample size of 237 was calculated with a confidence level of 95 percent, absolute precision of 5 percent points to have sufficient variation in the population characteristics (e.g., sex, education, economic status) that may influence adherence. All patients who were aged 18 years or above, and had taken ART for a duration of at least 6 months were included in the study. Informed consent was taken from all the patients. An institutional ethical committee approval to conduct the study was obtained on October 20th 2007. Tools of data collection Adherence was measured using self-reported data. The nine questions Morisky Medication Adherence Scale (MMAS) with scores ranging from 1 to 13 was used to measure adherent behavior.6 Score > 11 indicates adherence to medication.7 In addition, a closed ended self assessment questionnaire in local language was used to collect data regarding number of medications taken, number of doses missed, socio-demographic information, family support, and reasons for not taking medications as prescribed. Patients who attended the ART centre OPD, during study period, and satisfied inclusion and who were willing to participate in the study were given the adherence assessment questionnaire. Data analysis Adherence Rate was calculated by dividing number of pills actually taken by the number of pills prescribed during one month multiplied by 100.4 Adherence rate is equal to

Number of pills expected to be taken – Number of pills missed x 100 Number of pills expected to be taken Adherence was defined as value > 95 %.8 Logistic regression analysis was undertaken to explore the factors associated with lower adherence (MMAS score of ≤ 11) to provide odds ratios (OR) and 95 per cent confidence intervals (CI). Variables found to be associated with lower adherence on univariate analysis were included in multivariate analysis. A P value of <0.05 was considered significant.

Results A total of 300 patients were included in the study. Adherence rate of more than 95% (i.e. proportion of adherent patients) was reported by 290 patients (96.6%). The mean adherence rate of the study population using the adherence formula was 98.74 with a range of zero (two patients had missed medications for the entire month to 100%. A total of 262 patients (87.3%) had 100% adherence to medication over last 1 month while 10 patients (3.33%) were non adherent (adherence < 95 %). On the MMAS scale, 233 (77.66%) patients had a summary score of > 11(i.e. adherent) in the month prior to the study. The range of summary score was from 5 to 13, with a mean summary score of 11.42 (sd = ± 1.47). Table 1 describes the patient’s responses on individual questions in the MMAS scale. It was observed that 57.33% of the patients were having some reminder system for medicines while 28.66 % of the respondents confessed to have sometimes forgotten medications and 6.33 % had forgotten pills in the 2 weeks before interview. Most of these were reminded to take pills by family members. A few used alarm watches or alarm on their mobile phones to remind themselves. A total of 51 patients (17%) had not taken medication while they were travelling. In addition, 12 patients had not taken medications a day before being interviewed, 172 (57%) patients had to be reminded to take medications, 23 (7.66%) had reduced medications without telling their doctor, while 3 patients did not take medications because they felt better and thought that disease was now under control. Table 2 describes the univariate and multivariate logistic regression analysis of factors related to adherence among the socio demographic factors, on univariate analysis, age and marital status were significantly associated with adherence. Patients who had difficulty in remembering treatment and those who considered treatment to be difficult were more likely to have poor adherence. Patients who were simultaneously taking some traditional medicines, those who had not disclosed HIV status to anyone, those without support from family/friends/NGO, those who did not discuss about medication with any friend/relative and those who did not have a friend/relative who reminds them to take medication were more likely to be nonadherent. On multivariate analysis, age was significantly associated with adherence. Patients aged equal to or less than 40 years were less adherent than older patients. Patients who had difficulty in remembering treatment were 48 times more likely to be nonadherent to treatment than patients who did not report such difficulty. Patients who felt that the treatment was difficult were 21 times more likely to be non adherent than patients who did not feel the treatment to be difficult. Patients who were taking some traditional medicines simultaneously were 22 times more at risk of non adherence. Patients who had no one to remind them of the medication were 13 times more at risk of non adherence and patients with any kind of addictions were 5 times more at

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© JAPI • DECEMBER 2012 • VOL. 60

Table 2 : Univariate and Multivariate analysis of factors related to adherence Variables Age (in years)

Non Adherence Adherence 7 (12.28) 50 (87.72) 60 (24.69) 183 (75.31)

>40 years ≤ 40 years

Sex Occupation Income (Annual family income) Education Marital status

Male

45 (24.46)

139 (75.54)

Female

22 (18.97)

94 (81.03)

Employed

62 (22.14)

218 (77.86)

Unemployed >8000 ≤8000 Secondary school and above Up to primary Married Single

5 (25.00) 49 18

15 (75.00) 153 80

45 (22.38)

156 (77.62)

22 (22) 66 (23.57) 1 (5.00)

78 (78) 214 (76.43) 19 (95.00)

X2 4.56# 1.26

0.72 (0.41-1.28)

NA

1.98

1.12 (0.96 -1.30)

NA

1.35

0.70 ( 0.38-1.294)

NA

0.009

0.97 ( 0.55 - 1.73)

NA

4.9#

0.17 (0.022-1.30)

0.0683 (0.00 -12.45)

1.2

0.72(0.40-1.28)

NA

6.11#

1.73 (1.09 - 2.73)

4.94 (1.58 - 15.41)

1.46

1.00 (0.995-1.00)

NA

0.96

1.32 (0.76-2.29)

NA

88.13#

19.62(10.01- 38.45)

48.09 (9.70 -238.52)

Urban

34 (33.66)

67 (66.34)

Rural Yes No <200 >200 ART ART +others Yes

43 (20.57) 31 (36.90) 36 (16.51) 19 (22.89) 58 (25.89) 26 (19.70) 41 (24.40) 45 (67.16)

166 (79.43) 53 (63.10) 182 (83.49) 64 (77.11) 166 (74.11) 106 (80.30) 127 (75.60) 22 (32.84)

No

22 (9.44)

211 (90.56)

Yes No Yes Take any traditional medicine No Yes Have not disclosed about HIV status No Yes Have no support No Yes Have not told about medicines No Yes Have no one to remind about medication No Yes Anyone else in family taking ART No

45 (61.64) 22 (9.69) 51 (70.83) 16 (7.02) 29 (28.43) 38 (19.19) 43 (31.16) 24 (14.81) 39 (32.77) 27 (15.00) 42 (33.07) 25 (14.45) 17 (19.32) 50 (23.58)

28 (38.36) 76.97# 205 (90.31) 21 (29.17) 120.56# 212 (92.98) 73 (71.57) 5.51# 160 (80.81) 95 (68.84) 11.52# 138 (85.19) 80 (67.23) 13.71# 153 (85.00) 85 (66.93) 14.04# 148 (85.55) 71 (80.68) 0.01 162 (76.42)

Locality Addictions CD4 Regimen Problem in remembering Find treatment to be difficult

Table 3 : Reasons for non adherence Reason Were out of home/were traveling Too busy in other work Side effects of medication Forgot to take pills Felt better hence did not take pills Did not want others to know Was asked by a doctor to stop medications No improvement on medications Fear of side effects Too many pills Other reasons

No. of patients Percentage 51 17% 29 9.66% 16 5.33% 12 4% 8 2.66% 4 1.33% 4

1.33%

3 1 1 41

1% 0.33% 0.33% 13.66%

risk of non adherence. Disclosure about HIV status,support from family/friends/NGO and discussion about medication with family/friends were not significantly associated with adherence. Not being able to take medications because of being out of

Unadjusted OR (95% CI) Adjusted OR (95% CI) 2.34 (1.01 - 5.44) 8.90 (1.51- 52.62)

14.98 (7.86-28.54)

21.46 (6.05- 76.17)

34.99(16.87-72.53)

21.92 (6.66- 72.18)

1.97(1.12-3.46)

2.57 (0.80 - 8.24)

2.60 (1.48-4.57)

0.79 ( 0.22 - 2.8)

2.83(1.62 – 4.95)

0.61 ( 0.18- 2.04)

2.87 (1.63-5.03)

12.80(3.27 - 50.07)

0.97 (0.53 -1.75)

NA

home or while travelling was the commonest reason for missing medications (17%) (Table 3). While 29(9.66%) of the patients were too busy with some other work when they missed their medications and 16 patients (5.33%) stopped medication because of side effects.Gastrointestinal side effects like nausea, vomiting, and decreased appetite were most commonly reported. Tingling and numbness in feet, rashes, fatigue, body ache and change in facial appearance (lipoatrophy) were also seen. Giddiness and weakness developed in a few patients, which they attributed to medications and had hence stopped taking ART pills. A total of 3 patients had stopped medications because they did not find any improvement after starting ART, while 8 patients (2.66%) stopped pills because they felt better and 12 patients (4%) said they ‘forgot’ to take pills, without stating any reason. Other reasons for missing tablets included guests in house, death or illness in family and reporting late to ART center to collect tablets.

Discussion This study focuses on adherence to ART provided free of cost to the patients. The MMAS test measures adherent

© JAPI • DECEMBER 2012 • VOL. 60

behavior rather than dose adherence. Internal consistency reliability (measured by Crohnbach α) has been reported to be 0.89 for the MMAS.6 MMAS has been used internationally to measure adherence to antiretroviral treatment.9,10 Score > 11 indicates adherence to medication and corresponds to 95 % dose adherence.7 This definition is based on how patients theoretically would have completed the MMAS if they had taken at least 95 % of prescribed doses.7 MMAS scale was chosen over widely used AACTG scale because of studies which suggested superiority of MMAS due to lesser internal attrition,11 less complexity12 and also association between MMAS and viral load.11 In the present study the adherence rate, as calculated by adherence formula was 96.6 % over last one month and mean adherence rate was 98.74 %. The proportion of adherent patients as assessed by MMAS scale was 77.6 %. The adherence rate calculated by MMAS was lower than that by adherence formula. This could be because MMAS measures adherence behavior rather than absolute dose adherence rate.9 Moreover adherence is lower over longer periods of recall.13 Adherence formula calculates adherence over the last one month before interview, while MMAS scale measures adherence since beginning of ART. The level of adherence in the HIV population is higher than in most other chronic diseases.14 In international literature the percentage of HAART doses taken as prescribed varies between 63-93% according to different assessments.15-20 In many of the other studies majority of the study population had to bear the financial burden of medication. The adherence rate to ART was high in our study population as compared to other studies. This could be because all patients in this study were receiving free ART and also special adherence counselors are appointed for adherence counseling in the ART center. Every time patient attends OPD to collect their monthly medication they have to first meet the counselors. In a study from Cameroon the authors found great disparity between adherence rates in those receiving free drugs and those paying for ART. Adherence rate was high in patients receiving free ART.21 The most common reasons for missing pills were being out of home or travelling, being busy in some other work and side effects. In a study, it was found that forgetting, change in daily routine and being away from home were the most common causes of missing pills19 while another study reports financial constraints and forgetting as the most common reason for omitted drugs.18 Women were less adherent than men in some studies22 however we did not find any statistically significant relation between gender and adherence. In the present study age was found to be significantly associated with adherence. Age has been found to be significantly associated with adherence in other studies too.7,23-27 In the present study, level of education and income were not found to have statistically significant association with adherence. This may be because treatment was provided free of cost. Income and education have been shown to have an impact on adherence in other studies.28-30 There are three key aspects to regimen complexity which need to be considered: the drug regimens, number of doses, and total number of pills. The crucial factor in regimen complexity may not be the number of medications but the number of doses that have to be taken every day. This is borne out in HIV therapy in many studies,5,34 although no association between either number of doses or number of pills was found in some studies.35 In our study we did not find statistically significant relation between

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either the regimen or number of doses and adherence. Living alone and a lack of support have been associated with non-adherence to ART.36 Social isolation is predictive of non adherence.37 According to Eraker, et al., 1984 not living alone, having a partner, social or family support, peer interactions and better relationships are characteristics of adherent patients.38 In our study merely being married or having support from friends /family was not significantly associated with adherence while being reminded by a family member /friend to take medications was significantly associated with adherence. Addictions have been identified as significant factor related to non adherence in this study. Having drug and alcohol addictions have been reported to reduce the level of adherence in other studies too.30,39 To conclude more attention should be paid to patients with addictions during counseling sessions. In patients who have trouble in remembering medications specific individual should be identified who could remind the patient about the medicines. Perception of treatment regimen in terms of finding the treatment difficult and difficulty in remembering treatment needs to be addressed during counseling sessions.

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10. Viswanathan H, Anderson R, Thomas J, 3rd. Evaluation of an antiretroviral medication attitude scale and relationships between medication attitudes and medication nonadherence. AIDS Pat Care STDS 2005;19:306-16. 11. Sodergard B, Halvarsson M, Brannstrom J, et al. A comparison between AACTG Adherence Questionnaire and the 9-item Morisky Medication Adherence Scale in HIV-patients. Eighth International Congress on Drug Therapy in HIV Infection, Glasgow, UK; 2006. 12. Schneider J, Kaplan SH, Greenfield S, et al. Better physician-patient relationships are associated with higher reported adherence to antiretroviral therapy in patients with HIV infection. J Gen Intern Med 2004;19:1096-103.

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