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ADHERENCE TO ANTIRETROVIRAL THERAPY AND ASSOCIATED FACTORS AMONG HIV POSITIVE ADULTS ATTENDING TREATMENT AT NEKEMTE REFERRAL HOSPITAL, WEST ETHIOPIA, 2019

BACK GROUND Antiretroviral therapy has a remarkable clinical effect in decreasing the viral replication, reducing the progress of AIDS and deaths related to AIDS. The clinical outcome of ART depends on the strict adherence to antiretroviral medication. However; only a few studies have been done on the adherence status of ART and its determinant factors in Ethiopia and this study could provide an opportunity to identify obstacles to taking medication. Therefore, the purpose of this study was to assess adherence status and associated factors among HIV infected patients on ART attending Nekemte referral hospital, West Ethiopia. METHODS Institutional based cross-sectional study was conducted on 311 HIV/AIDS patients, from March 01 to March 30, 2019. The study participants were selected by simple random sampling method and were interviewed using structured questionnaires. The data were coded, checked, cleaned and entered into Epi data version 3.1 and then exported to SPSS window version 20.0 for analysis. Multivariable logistic regression was used to find the independent variables which best predict adherence. Association and statistical significance were measured using odds ratio at 95% confidence interval and p-value less than 0.05.

improve knowledge through health education, and encourage HIV/AIDS patient to disclose their HIV status.

Introduction
Human immune deficiency virus is one of a chronic disease which affects human immune systems and increases vulnerability of individuals to infections [1]. Globally, 36.7 million people were living with HIV/AIDS at the end of 2015 with approximately 70% (25.7 million) residing in Sub-Saharan Africa [2]. In Ethiopia, the Federal HIV/AIDS Prevention and Control Office (EFHAPCO) indicates that there are over 718,550 people (> 1.18%) living with HIV [3]. Antiretroviral therapy has a remarkable clinical effect in decreasing the viral replication and viral load, reduces the progress of AIDS, and reduces deaths related to AIDS [4]. The availability of ART has essentially improved the survival rates of HIV patients, reduction of the new number of HIV infection and prevention of HIV related comorbidities [5]. The availability of this ART drugs changed the disease course to chronicity which arise the issue of adherence. However, the clinical outcome of ART depends on the strict adherence of HIV patients to antiretroviral medication. Strict adherence to antiretroviral therapy is important to decrease the multiplication of the virus and improve disease outcomes [6 & 7].
Several studies indicate that > 95% adherence to therapeutic regimen is required for HIV infected patient to reach full viral suppression [8 -11]. Maintaining over 95% adherence level is a crucial to maintain viral suppression, to minimize HIV related morbidity and mortality. In Ethiopia, the rate of adherence to ART is 88.2%, which is low compared to WHO Standard [12]. Poor adherence to antiretroviral therapy reduces the effectiveness of ART and hastens viral distribution and drug resistance [13 & 14]. Poor adherence is linked to higher mortality rates, higher rates of decrease in CD4 cell count, lower therapeutic success and increased hospital days [15]. Studies have shown that adherence to ART medication among people living with HIV/AIDS is affected by factors related to the patient, therapeutic regimen, psychosocial environment and health care related factors. Hence, factors such as socio-demographic and socio-cultural factors, side effects of ARVs, ART regimes, duration on ART, and psychosocial factors such as stress, depression and anxiety have also been associated with ART adherence [16 & 17]. It is essential to assess the number of people living with HIV/AIDS drop out of treatment programmes and factors affecting adherence to ART. Since most of the Ethiopian setting is resource limited, there are no routine assessments for ART adherence among PLHIV in Ethiopia. In addition, only a few studies have been done on the adherence status of ART and its determinant factors in Ethiopia and this study could provide an opportunity to identify obstacles to taking ART medication which may help to prevent development of drug resistance and treatment failure. Therefore, this study was aimed to assess adherence status and associated factors among HIV infected patients.

STUDY SETTING AND POPULATION
This study was conducted in Nekemte referral hospital from March 01 to March 30, 2019. Nekemte referral hospital if found in Nekemte town which is one of the largest towns found in western part of Ethiopia at about 325 kilometers from a capital city Addis Ababa. The institutional based crosssectional study design was employed. All ART patients on treatment follow up at Nekemte referral hospital was the source population and the sampled ART patients who had treatment follow up during the study period was the study population. Patients whose ages are 18 years and above were included in this study. Patients who are eligible but not willing to take part in the study were excluded.

SAMPLE SIZE DETERMINATION AND SAMPLING TECHNIQUES
The sample size of the study was calculated using the formula for estimation of a single population proportion with the assumptions of 95 % Confidence Level (CL), marginal error (d) of 0.05. Adherence level of 0.74 (74.0 %) was taken from previous study done in Addis Ababa [18], and by adding a nonresponse rate of 5%, a total of 311 ART patients were enrolled in the study. Simple random sampling method was used to select the study participants.

DATA COLLECTION TOOL AND PROCEDURES
Data was collected using a structured questionnaire and face-to-face interview was used for data collection. The dependent variable of the study was adherence to ART and the independent variables were socio-demographic, psychosocial and medication related characteristics. Adherence status was assessed based on the number of pills reported to have been taken one month prior to the data collection period divided by the number of prescribed pills multiplied by 100%. Patients who reported an intake of ≥ 95% of the prescribed medication were considered adherent; those with a reported intake of < 95% were classified as non-adherent [19]. Socio-demographic factors, psychosocial and medication related characteristics were measured as explanatory variables. Data was collected by three trained BSc nurses and one supervisor for duration of approximately one month.

DATA PROCESSING AND ANALYSIS
The data were coded, checked, cleaned and entered into Epi data version 3.1 and then exported to SPSS window version 20.0 for analysis. Bivariate analysis was done to find association between each independent variable with adherence. Finally, multivariable logistic regression was used to find out the independent variables which best predict adherence. Association and statistical significance were measured using odds ratio at 95% confidence interval and p-value less than 0.05.

DATA QUALITY CONTROL
The questionnaire was translated to the local language and then translated back to English by expertise for consistency. Five percent (5 %) of the questionnaire was pre-tested on ART patients having treatment follow up at Gimbi general hospital which is found about 87-kilometer distance from Nekemte referral hospital. One-day training was also given for data collectors and supervisor.

SOCIO-DEMOGRAPHIC CHARACTERISTICS OF PARTICIPANTS
Out of the total of 311 study participants sampled, 305 were participated; making a response rate of 98.07 %. From the total of 305 participants, 140 (45.9 %) were male, and 165 (54.1 %) were females.

CLINICAL AND BEHAVIORAL CHARACTERISTICS OF PARTICIPANTS
Majority of the study participants, 212 (69.5 %) had no co-morbidity of other chronic diseases. Two hundred-one (65.9 %) had knowledge about HIV and its treatment. Majority of the study participants, 207 (67.9 %) had disclosed their HIV status to their family. One hundred forty (45.9 %) had CD4 count  Table 2).

LEVEL OF ADHERENCE TO MEDICATION AMONG THE STUDY PARTICIPANTS
Adherence status was assessed based on the number of pills reported to have been taken one month prior to the data collection period divided by the number of prescribed pills multiplied by 100%.
Patients who reported an intake of ≥ 95% of the prescribed medication were considered adherent; those with a reported intake of < 95% were classified as non-adherent. Accordingly, out of the total of 305 study participants, 223 (73.1 %) were adhered to their medication and 82 (26.9 %) were not adhered to their medication ( Figure 1).

BIVARIATE LOGISTIC REGRESSION ANALYSIS
In bivariate analysis, socio-demographic characteristics such as sex, age, marital status, educational status, occupation, income and living companion showed significant association with adherence at Pvalue less than 0.25. Clinical variables such as HIV stage, side effects of ARV medication, treatment duration, knowledge about HIV and its treatment and comorbidity of other chronic diseases showed significant association with adherence to medication at P-value less than 0.25. Behavioral variables such as family/social support, substance use, family disclosure status and perceived social stigma showed significant association with adherence at P-value less than 0.25. (Table 3).

MULTIVARIATE LOGISTIC REGRESSION ANALYSIS
In the final model of logistic regression, social/family support, adverse drug reaction, Knowledge about HIV and its treatment, family disclosure status and comorbidity of other chronic diseases were significantly associated with adherence to medication. Study participants who had good family/social support were 7.36 times more likely to adhere to their medication than those who had poor family/social support (AOR=7.36, 95% CI: 2.07, 26.10). Study participants who had knowledge about HIV and its treatment were 8.13 times more likely to adhere to their medication than those who had no knowledge about HIV and its treatments (AOR=8.13, 95% CI: 3.06, 21.61). Respondents who didn't develop adverse drug reactions were 5.62 times more likely to adhere to their medication than those who develop adverse drug reaction (AOR=5.62, 95% CI: 2.11, 14.93). Study participants who hadn't other comorbid chronic diseases were 5.46 more likely to adhere to their medication than those who had other comorbid chronic illness (AOR=5.46, 95% CI: 1.86, 16.02).
Study participants who disclosed their HIV status to their family were 5.27 times more likely to adhere to their medication than those who don't disclosed their HIV status to their family (AOR=5.27, 95% CI: 2.20, 12.62). (Table 4).

Discussion
This study examined the level of adherence to ART and associated factors among HIV/AIDS patients in  [12].
The finding of this study also showed that study participants who had knowledge about HIV and its treatment were more adhered to their medication than those who had no knowledge about HIV and its treatment. This is due to the fact that knowledge on HIV and its treatment might increase their awareness and access to HIV therapy which might further increase adherence to medication. This finding is consistent with study done in Gonder, North West Ethiopia [12], but not supported with many other studies [20, 22, 23, 24, 27, 28 and 29].
In this study, study participants who disclosed their HIV status to their families were more adhered to their medication than who didn't disclosed their HIV status. This is similar with study done in China and Togo [30]. When there is no self-disclosure about HIV status, the persons may fear to take their treatments and miss the medication. Participants who did not disclose their HIV status put more pressure on themselves in terms of taking regular medication and might skip their medication. On the other hand, non-disclosure might impede the participants from obtaining social support and patients with lower social support might to show poor adherence to their medication.
Respondents who had comorbidity of other chronic illness was less adherent to their medication than those who had no comorbidity of other chronic illness. The possible reason might be that when patients had co-morbidities, they might have pill burden. When a number of pill increases, the patient might experience more adverse effects from the medications which potentially lead them to skip their

LIMITATION OF THE STUDY
Causality cannot be confirmed since the research design was cross-sectional. Adherence was assessed based on data taken during the previous one month. So, the participants might be subjected to recall bias.

Conclusions
In this study, the level of adherence to antiretroviral therapy was found low compared to the WHO standard. Social/family support, adverse drug reaction, knowledge about HIV and its treatment, disclosure status and comorbidity of other chronic diseases were significantly associated with adherence. The clinician should emphasize adverse drug reaction, early detect and treat co-morbidities, improve knowledge through health education, and encourage HIV/AIDS patient to disclose their HIV status to improve medication adherence. The study was reviewed and approved by the Institutional Review Boards of Wollega University Ethical review board. The purpose of the study was explained to medical director and staffs of the hospital and permission was obtained. All participants of the study were provided written consent, clearly stating the objectives of the study and their right to refuse. Filled out questionnaires were carefully handled and all access to results was kept strictly within the author.

Availability of data and materials
The data used during this study are available on request.

Competing Interests
I declare that I have no competing interests.

Funding
No funding was received for this research work.

Authors' Contributions
Overall activities of this study (conceptualization of the study, designing, result writing, analyzing the finding and writing and approving the manuscript) were carried out by the author MA.

Acknowledgment
I would like to acknowledge Nekemte referral hospital medical director and staffs for their cooperation. I am also grateful to the study participants who voluntarily agreed to be interviewed and participated in the study.

5.
ART failure and strategies for switching ART regimens, Report of the WHO expert consultation Copenhagen, 7 December 2007.