Antiretroviral therapy adherence among patients enrolled after the initiation of the Universal Test and Treat strategy in Dessie town: a cross-sectional study

Abstract

Poor adherence was the major challenge in providing treatment, care, and support for people living with HIV (PLHIV). Evidence of adherence to antiretroviral therapy (ART) after initiation of the Universal Test and Treat (UTT) strategy was limited in Ethiopia. So, this study aimed to determine the proportion of ART adherence after the initiation of UTT strategy and associated factors among adult PLHIV in Dessie town using two adherence measurements. A cross-sectional study was conducted on 293 PLHIV selected using a systematic sampling technique. The data were collected by face-to face-interview using a pretested questionnaire; chart review was also used to collect the data. The proportion of ART adherence measured by using the Morisky scale and seven-day recall was 49.3% (95% CI: [43.5%, 54.8%]) and 95.9% (95% CI: [93.2%, 98.2%]), respectively. Being urban in residence (AOR = 3.72, 95% CI: [1.80, 7.68]), the absence of depression (adjusted odds ratio [AOR] = 3.72, 95% CI: [1.22, 11.35]), taking one tablet per day (AOR = 3.26, 95% CI: [1.64, 6.49]), and the absence of concomitant illness (AOR = 0.23, 95% CI: [0.09, 0.59]) were factors associated with ART adherence. The proportion of ART adherence measured by the Morisky scale was very low; however, adherence measured by seven-day recall was higher and consistent with World Health Organization recommendations. Residence, depression, and the number of tablets taken per day had a positive association with good ART adherence whereas having concomitant illness had a negative association with good ART adherence. Efforts should be made to improve adherence and interventions should be given to overcome factors linked with poor adherence.

Keywords

Antiretroviral therapy adherence HIV/AIDS Universal Test and Treat Dessie

Introduction

Human immunodeficiency virus (HIV) continues to be a major global public health issue. Since the start of the epidemic, an estimated 74.9 million people have become infected with HIV and 32 million people have died of Acquired Immune Deficiency Syndrome (AIDS)-related illnesses. In 2018, an estimated 37.9 million people were living with HIV worldwide, with an estimated 68% living in sub-Saharan Africa (SSA); 1.7 million people were newly infected, and 770,000 people died of AIDS-related illnesses.¹ In the same year, the prevalence of HIV among adults aged from 15 to 64 years in urban Ethiopia was 3.0%.²

World Health Organization (WHO) recommends that an adherence level of at least 95% of antiretroviral therapy (ART) doses is required to have a sustained viral suppression and good treatment outcome;³ however, poor adherence to ART medication becomes the major bottleneck in providing HIV/AIDS care and support. Many of the studies conducted in developed countries indicated that the level of adherence was less than 75% with a range from 20 to 100%, whereas, in developing countries, it was greater than 75% with a range from 45 to 100%.⁴ In SSA, the average ART adherence score was estimated at 72.9%⁵ and in Ethiopia, it ranged from 63.8 to 95.5%.^6–16

Sub-optimal adherence imposes a significant impact on the health of people living with HIV (PLHIV). It results in the development of detectable viral loads (VLs), declining CD4 cell counts, disease progression, drug resistance, and subsequent treatment failure. For example, a longitudinal study conducted in Veterans University Hospital indicated that PLHIV with adherence of ≥95, 80–94.9, and <80% had a virologic failure rate of 22, 61, and 80%, respectively.¹⁷ PLHIV with sub-optimal adherence tend to develop poor health outcomes with increased morbidity and mortality as a result of disease progression.^18,19

As studies showed, socio-demographic factors,^8,13,20,21 medication-related factors,^11,20,21 disease-related factors,^8,11 health system factors,^13–15 and psycho-social and behavioral factors^7,8,11 affect adherence to ART medication.

Previously, PLHIV started ART treatment according to CD4 cell count and WHO clinical stage.²² However, nowadays the Universal Test and Treat (UTT) strategy has gained significant attention from international agencies as an important public health approach to control the HIV epidemic.^23,24 It involves offering HIV voluntary counseling and testing to the entire population and providing immediate ART to those testing positive without considering clinical stage or CD4 cell count. It reduces HIV transmission,²⁵ progression of the disease, and mortality rate as a result of opportunistic infection in a high prevalence setting.²⁶ UTT strategy also had a significant role for achieving the Joint United Nations Programme on HIV/AIDS 90–90–90 targets by 2020 (90% of PLHIV know their HIV status, 90% of PLHIV who know their HIV-positive status are accessing treatment, and 90% of PLHIV on treatment have suppressed VLs).²⁷ The rationale underpinning UTT strategy is that high HIV transmissions occur in index cases that are not on ART because they have not been diagnosed HIV-positive; diagnosed, but are not yet eligible for ART, or are eligible but have not yet started on ART.²⁸ However, in a UTT program, starting ART at the early stages of HIV infection may lead to poor adherence²⁹ since many of those who started ART may have had no clinical symptoms associated with their HIV infection²⁸ and experience adverse drug reactions when they initiate ART at high CD4 cell counts.³⁰ The Ethiopian government adopted this strategy in 2016 and began to implement it in ART clinics of Dessie town since December 2016. However, information on adherence to ART after the new strategy is limited in Ethiopia. So, this study aimed to determine the proportion of ART adherence after initiation of UTT strategy and associated factors among PLHIV who attended ART clinics of Dessie town in 2018.

Methods

Study design, setting, and participants

A cross-sectional study was conducted in ART clinics of Dessie town from 15 April to 5 June 2018. Currently, a total of 926 adult patients enrolled after the initiation of the UTT strategy was on ART in Dessie town ART clinics.³¹ All PLHIV enrolled after the initiation of UTT strategy and attended ART clinics of Dessie town were taken as the source population, whereas all systematically selected patients enrolled after the initiation of UTT strategy and attended ART clinics of Dessie town during the study period were considered as the study population. Patients aged greater than or equal to 18 years and who took ART for at least three months since 12 December 2016 were included in this study.

Sample size and sampling procedure

The sample size was calculated using Epi Info version 7.1 with the assumption of 83.6% ART adherence among patients with CD4 cell count ≥ 350 cells/mm³ and 3.7 odds ratio taken from a study done in Northern Ethiopia²⁰ by taking the following assumptions: 1:1 ratio of exposed to unexposed 80% power and 95% confidence level. Thus, the required sample size after adding a 10% non-response rate was 293. After proportional allocation of the sample size to each ART clinics, study participants were selected using systematic sampling until reaching the final sample size.

Data collection instrument and measurements

Face-to-face interview with a structured and pretested questionnaire was used to collect socio-demographic, psycho-social and behavioral, disease, medication, and health-care related characteristics of study participants. Medical records were also reviewed to assess CD4 cell count, WHO clinical staging, current ART regimen, and duration of treatment. Data were collected by five trained nurses with supportive supervision of one supervisor and principal investigator.

In this study, ART adherence was measured by using both seven-day recall and eight-item Morisky Medication Adherence Scale (MMAS). In the seven-day recall method, the patient was asked a question ‘did you miss in taking your ART drug in the last seven days?’. Patients who answered ‘yes’ to this question were classified as poor adherence and patients who answered ‘no’ to this question were classified as good adherence.^11,13 In the MMAS approach, eight questions were designed to assess medication adherence. The first seven questions were with yes or no response options coded as 1 or 0, respectively. The eighth question was with five response options coded as 0= always, 1= usually, 2= sometimes, 3= once a while, and 4= never. Then, those patients who scored less than or equal to the median value were classified as poor adherence, whereas patients who scored greater than the median value were classified as good adherence.³² The model was fitted by using eight-item MMAS.

Depression was assessed using the Patient Health Questionnaire-9 checklist. The checklist has nine questions with four response options coded as 0= not at all, 1 = several days, 2= more than half a day, and 3 = nearly every day. Then, patients who scored greater than or equal to the median value were classified as having depression and patients who scored less than the median value were classified as having no depression.⁸

The reliability of MMAS was determined by pretesting 15 adult PLHIV enrolled after the initiation of the UTT strategy who met the study inclusion criteria in Kombolcha Health Center which has similar characteristics to the study area. As a result, an alpha of 0.893 was obtained.

Data processing and analysis

The data were coded and entered into Epi Data version 3.1 and exported to SPSS version 23 for cleaning and analysis. Descriptive statistics like frequency, proportion, and median with interquartile range were computed. Bi-variable binary logistic regression analysis was done and those variables with a p-value less than 0.2 were entered into a multiple logistic regression model. Multi-collinearity was checked using standard error and the p-value of the model fitness of the test was 0.23. Variables with a P-value less than 0.05 and adjusted odds ratio (AOR) with a 95% confidence interval (CI) non-inclusive of one were considered as statistically significant predictors of ART adherence in the final model.

Result

Socio-demographic characteristics

In this study, 292 adult PLHIV enrolled after the initiation of UTT were involved giving a response rate of 99.6%. The median age of participants was 36 years with an interquartile range of 12 years. One hundred and forty (47.9%) participants were males and 178 (61%) were married, and 218 (74.7%) resided in urban areas, respectively. Seventy-one (24.3%) participants had no formal education, 31 (10.6%) were government employed, and 277 (94.9%) had a family size of less than or equal to five, respectively (Table 1).

Table 1.

Socio-demographic characteristics of PLHIV enrolled after the initiation of UTT strategy in Dessie town ART clinics, 2018.

Variable	Frequency (n = 292)	Percentage
Gender
Male	140	47.9
Female	152	52.1
Marital status
Single	45	15.4
Married	178	61
Widowed	13	4.4
Divorced	56	19.2
Ethnicity
Amhara	275	94.2
Others^a	17	5.8
Religion
Christian^b	102	34.9
Muslim	190	65.1
Residence
Urban	218	74.7
Rural	74	25.3
Level of education
No formal education	71	24.3
Grade 1–8	116	39.7
Grade 9–12	78	26.7
College and above	27	9.3
Occupation
Government employed	31	10.6
Private employed	36	12.3
Housewife	52	17.8
Merchant	55	18.8
Farmer	62	21.3
Daily laborer	39	13.4
Others^c	17	5.8
Family size
≤5	277	94.9
≥6	15	5.1
Frequency of meals
<3 meals/day	8	2.7
≥3 meals/day	284	97.3
With whom patient lives
Family	77	26.4
Partner	179	61.3
Alone	36	12.3
Wealth quintile
Lowest	50	17.1
Second	87	29.8
Middle	32	11
High	62	21.2
Highest	61	20.9

ART: antiretroviral therapy; UTT: Universal Test and Treat.

^aOromo and Tigray.

^bProtestant and orthodox tewahido.

^cStudent and jobless.

Psycho-social and behavioral characteristics

Two hundred and eighty-five (97.6%) participants used reminders to take their ART medication, 212 (72.6%) felt comfortable while taking medication in front of others, and 270 (92.5%) had disclosed their HIV status to somebody else, respectively. Thirty-six (12.3%) participants had multiple sexual partners in the last six months, 189 (64.7%) had good knowledge of HIV/AIDS and its treatment, and 35 (12%) had depression, respectively (Table 2).

Table 2.

Psycho-social and behavioral characteristics of PLHIV enrolled after the initiation of UTT strategy in Dessie town ART clinics, 2018.

Variables	Frequency (n = 292)	Percentage
Using reminders
Yes	285	97.6
No	7	2.4
Feel comfortable in taking medication in front of others
Yes	212	72.6
No	80	27.4
Disclosure status
Yes	270	92.5
No	22	7.5
Getting support
Yes	21	7.2
No	271	92.8
Taking alcohol
Yes	34	11.6
No	258	88.4
Smoking cigarettes
Yes	7	2.4
No	285	97.6
Chewing chat
Yes	17	5.8
No	275	94.2
Multiple sexual partners
Yes	36	12.3
No	256	87.7
Knowledge of ART
Good	189	64.7
Poor	103	35.3
Stigma
Yes	84	28.8
No	208	71.2
Depression
Yes	35	12
No	257	88

ART: antiretroviral therapy; UTT: Universal Test and Treat.

Disease-related characteristics

One hundred and ten (37.7%) participants had no VL test result, 156 (53.4%) had a VL of <1000 copies/ml, and 26 (8.9%) had a VL of ≥1000 copies/ml, respectively. Sixty-five (22.3%) participants had a baseline CD4 cell count < 200 cells/mm³, 237 (81.2%) had baseline WHO clinical stage I, 279 (95.5%) had current WHO clinical stage T₁, and 34 (11.6%) had a concomitant illness in the last year, respectively (Table 3).

Table 3.

Clinical characteristics of PLHIV enrolled after the initiation of UTT strategy in Dessie town ART clinics, 2018.

Variables	Frequency (n = 292)	Percentage
Viral load
Not done	110	37.7
<1000 copies/ml	156	53.4
≥1000 copies/ml	26	8.9
Baseline CD4 cell count (cells/mm³)
<200	65	22.3
200–350	92	31.4
351–500	84	28.8
>500	51	17.5
Recent CD4 cell count (cells/mm³)
<200	44	15.1
200–350	88	30.1
351–500	87	29.8
>500	73	25
Baseline WHO stage
I	237	81.2
II	33	11.3
III	14	4.8
IV	8	2.7
Current WHO stage
T1	279	95.5
≥T2	13	4.5
Concomitant diseases
Yes	34	11.6
No	258	88.4
Opportunistic diseases
Yes	11	3.8
No	281	96.2

ART: antiretroviral therapy; CD4: cluster differentiation 4; UTT: Universal Test and Treat; WHO: World Health Organization.

The proportion of ART adherence

The proportion of ART adherence measured by using eight-item MMAS and seven-day recall was 49.3% (95% CI: [43.5%, 54.8%]) and 95.9% (95% CI: [93.2%, 98.2%]), respectively (Figure 1).

Figure 1.

ART adherence measured by Morisky scale (a) and seven-day recall (b) among patients enrolled after UTT strategy at Dessie town ART clinics, 2018.

Factors associated with ART adherence

In this study, both bi-variable and multivariable binary logistic regression analyses were done. As a result, adult PLHIV who live in urban areas were 3.72 times more likely to have better adherence than those who live in rural areas (AOR = 3.72 95% CI: [1.80, 7.68]). The odds of having good adherence among adult PLHIV who did not experience depression were 3.71 times greater than the odds of adult PLHIV who experienced depression (AOR = 3.71 95% CI: [1.22, 11.3]).

Similarly, adult PLHIV who took one tablet per day were 3.26 times more likely to have better adherence than those patients who had taken three tablets per day (AOR = 3.26 95% CI: [1.64, 6.50]). However, participants without concomitant illness were 77% less likely to adhere to their ART medication as compared to those with concomitant illness (AOR = 0.23 95% CI: [0.09, 0.60]) (Table 4).

Table 4.

Factors associated with ART adherence among PLHIV enrolled after the initiation of UTT strategy in Dessie town ART clinics, 2018.

Variables	Adherence (n = 292)		COR (95% CI)	AOR (95% CI)
Variables	Good	Poor	COR (95% CI)	AOR (95% CI)
Age	144	148	1.04 (1.008–1.06)*	1.02 (0.98, 1.06)
Marital status
Single	16	29	1	1
Married	86	92	1.69 (0.86, 3.34)	1.78 (0.53, 6.03)
Widowed	10	3	6.04 (1.45, 25.2)*	5.66 (0.79, 40.6)
Divorced	32	24	2.42 (1.08, 5.42)*	2.50 (0.67, 9.33)
Residence
Urban	115	103	1.73 (1.01, 2.97)*	3.72 (1.8, 7.68)***
Rural	29	40	1	1
Alcohol
Yes	11	23	1	1
No	133	125	2.23 (1.04, 4.75)*	2.14 (0.80, 5.79)
Multiple sexual partners
Yes	10	26	1	1
No	134	122	2.86 (1.32, 6.16)**	1.78 (0.61. 5.18)
Stigma
Yes	28	56	1	1
No	116	92	2.52 (1.49, 4.28)***	1.66 (0.79, 3.51)
Depression
Yes	7	28	1	1
No	137	120	4.57 (1.93, 10.8)***	3.71 (1.22, 11.3)*
Satisfaction
Yes	140	132	4.24 (1.38, 13.0)*	2.94 (0.77, 11.3)
No	4	16	1	1
No. of tablets
1	103	70	3.05 (1.76, 5.29)***	3.26 (1.64, 6.5)***
2	14	22	1.32 (0.59, 2.97)	1.30 (0.50, 3.42)
3	27	56	1	1
Recent CD4 count (cells/mm³)
<200	27	17	1	1
200–350	35	53	0.416 (0.20, 0.87)*	0.79 (0.30, 2.09)
351–500	46	41	0.71 (0.34, 1.48)	1.74 (0.60, 5.03)
>500	36	37	0.61 (0.29, 1.31)	1.71 (0.56, 5.22)
Concomitant disease
Yes	22	12	1	1
No	122	136	0.49 (0.23, 1.03)	0.23 (0.09, 0.60)**
Opportunistic disease
Yes	9	2	1	1
No	135	146	0.21 (0.04, 0.97)*	0.38 (0.04, 3.56)

AOR: adjusted odds ratio; ART: antiretroviral therapy; CD4: cluster differentiation 4; CI: confidence interval; COR: crude odds ratio; UTT: Universal Test and Treat.

*Significant at P < 0.05; **significant at P < 0.01; ***significant at P ≤ 0.001 in the bi-variable and multivariable logistic regression analysis.

Discussion

The proportion of ART adherence among PLHIV who were enrolled after initiation of UTT strategy using the Morisky scale and seven-day recall was 49.3 and 95.9%, respectively. The absence of depression, being urban in residence, and taking one tablet per day were factors positively associated with good ART adherence, whereas the absence of concomitant illness was negatively associated with good ART adherence.

In this study, two measurements were used to measure adherence to ART. As a result, the proportion of ART adherence measured by using the Morisky scale was much lower than the proportion of ART adherence in this study as well as other studies measured by using a seven-day recall.^11,13 The reason behind this difference could be seven-day recall overestimates adherence since it is highly affected by social desirability bias³³ and measures adherence using a single ‘yes’ or ‘no’ question in contrast to MMAS which assesses medication intake history indirectly using a set of eight questions.

It was also lower than the study conducted in the Bale Zone, which was measured by using four-item MMAS.⁸ It could be due to the original four-item MMAS having a low Cronbach’s alpha value (0.61), sensitivity (81%), and specificity (44%) to detect adherence. However, the modified eight-item MMAS is one of the most sensitive (93%) and specific (53%) methods to detect adherence and had high Cronbach’s alpha value (0.83) as compared to four-item MMAS.³⁴ Similarly, the reliability (Cronbach’s alpha) of the eight-item MMAS was found to be high in this study.

The proportion of ART adherence measured by using the Morisky scale was also lower than ART adherence in a study done in India, which was measured by eight-item MMAS.³² The reason behind this could be due to the difference in the study population’s socio-demographic characteristics and study setting.

However, the proportion of ART adherence measured by seven-day recall was in line with the current WHO recommendation and a study done in Debre Berhan Hospital.¹⁶

In this study, being urban in residence was positively associated with good ART adherence similar to other literature.⁶ The reason could be patients who live in urban areas have adequate knowledge of HIV/AIDS^35,36 secondary to better education and good media exposure. Moreover, patients who live in urban areas might have better access to transportation and the health care service, which enables them to collect more drug before they run out at any time during their follow-up.

The absence of depression was positively associated with good ART adherence similar to other literature.^10,11,20 The possible reason for this might be those non-depressed patients did not experience hopelessness and demoralization so that they follow their regular treatment.

The absence of concomitant illness has been negatively associated with good ART adherence similar to a study conducted in the Bale Zone.⁸ The reason behind this could be patients without concomitant illness might not take their medication because they felt well. On the other hand, patients with concomitant illness might take their ART medication strictly due to fear of death as a result of both HIV/AIDS and other illness and due to having good knowledge about the importance of adhering medication secondary to the counseling service they obtained from different health care providers.

Taking one tablet per day was positively associated with good ART adherence similar to a study done in Eastern Ethiopia.¹¹ The reason behind this could be taking a single tablet might be associated with a decreased level of adverse drug reactions and reduced pill burden that might improve treatment adherence. Using multiple adherence measurement approaches and one-week recall to minimize recall bias were the strengths of this study. However, overestimation of adherence in case of using seven-day recall and the issue of recall bias in using the Morisky scale were the main limitations of the study.

Conclusion

In this study, the proportion of ART adherence using the Morisky scale was low. However, the proportion of ART adherence using seven-day recall was high and consistent with the current WHO recommendation. Being urban in residence, absence of depression, and taking one tablet per day had a positive association with better ART adherence, whereas the absence of concomitant illness had a negative association with good ART adherence. Adherence counseling should target patients without concomitant illness, patients who take more than one tablet per day, and patients who live in rural areas. Health care providers should screen patients for depression and provide medical as well as psychological support with mental health professionals. Further study with a longitudinal study design was recommended.

Footnotes

Acknowledgments

We would like to express our heartfelt thanks to Dessie city Administrative Health Office and ART clinics of Dessie town for their permission and study subjects, data collectors, and supervisors for their cooperation during the data collection period.

Authors’ contribution

YD: initiated the research concept, wrote the research proposal, involved in the data collection processes, did data entry and analysis; FT: involved in statistical analysis and write up of the manuscript. All authors read and approved the final manuscript.

Availability of data and material

The data set used in the current study is available from the corresponding author on reasonable request.

Declaration of conflicting interests

The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Ethical approval and consent to participate

The actual data collection was carried out after getting ethical approval from the Ethical Review Committee of Wollo University, College of Medicine and Health Sciences and after getting permission from the Administrative Health Office of Dessie town and each health facility administration. Verbal informed consent was obtained from each participant, and they were informed that participating in the study is voluntary and refusal to participate would not compromise the medical care they receive. Privacy of the client and confidentiality of information was secured at all levels.

Funding

The authors received no financial support for the research, authorship, and/or publication of this article.

ORCID iD

Yitayish Damtie

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