Isoniazid preventive therapy utilization rate and associated factors in adult HIV/AIDS patients in Jimma University Specialized Hospital ART clinic, Oromia Region, Ethiopia: A cross-sectional study.

Background: Tuberculosis (TB) is the most frequent life-threatening infection and a common cause of death for people living with HIV (PLHIV). The influence of TB and HIV infection has enhanced the magnitude of both epidemics. Several clinical interventions recommended early diagnosis in PLHIV and treating latent TB infection (LTBI) with Isoniazid preventive therapy (IPT) along with antiretroviral therapy (ART). IPT is one of the key interventions recommended by the world health organization (WHO) for the prevention of TB in patients infected with HIV. Hence, this study aimed to determine IPT utilization rate among adult HIV infected patients enrolled in HIV care and qualitative analysis, which explore the factors that influence IPT use among PLHIV under follow-up, Health care providers (HCPs) and TB/HIV coordinators working in Jimma University Specialized Hospital (JUSH) ART clinic. Methods: An Institution based mixed cross-sectional study was conducted in JUSH ART clinic. Adult HIV infected patients were enrolled by a systematic sampling technique from the registered medical records of JUSH HIV care. PLHIV who were on follow-up and eligible for IPT during the study period, permanent HCPs and TB/HIV coordinators working in ART clinic were included in the qualitative investigation using semi-structured questioners and in-depth interviews. All statistical analysis was compiled by Epi data 3.1 and SPSS 20. Results: Demographic and clinical factors are not significantly associated with IPT use but ethnicity (P≤ 0.02**) was highly significant with IPT use in logistic regression model. Overall, 59.2% of the patients have been prescribed and taken at least one-month course of IPT. The results of in-depth interviews are grouped into three core categories as patient perceptions, and TB/HIV coordinator perspectives. Discussion and conclusion: PLHIV, HCPs and TB/HIV coordinators suggested their overall response as periodic counseling for target groups, educating the benefits of IPT and increasing public awareness on TB prophylaxis in PLHIV will increase the acceptance and implementation of IPT in large scale. Higher attention should be provided in linking all HIV patients to the nearest health facilities for receiving free service packages and medical care.


Background
TB and Human Immunodeficiency Virus (HIV) are the two opportunistic infections that cause high morbidity and mortality in the world [1]. HIV infection is one of the greatest risk factors in developing TB disease [2,3]. PLHIV are at least 26 times more likely to develop TB disease than people without HIV [4]. HIV suppresses the immune system by reducing CD4 count and increases the risk of developing TB infection among PLHIV. Therefore, prevention of TB is one of the most important measures needed to reduce morbidity and mortality among PLHIV, especially in countries with a high TB and HIV burden. A report rendered by WHO, 2012 stated that Ethiopia is one among 22 high TB burden countries ranking top five in African countries and ninth in the world. The incidence and prevalence of TB was about 261 and 394 per 100,000 populations and TB-related mortality rate for the same year is 35/100,000 population [5,6]. The rate of TB patients co-infected with HIV was between 10% and 15% in Ethiopia and nearly 88% of TB/HIV confected patients were found on ART regimen [7]. Multiple strategies are existing in the prevention of TB disease such as intensified case finding (ICF), isoniazid preventive therapy (IPT) and 4 TB infection control (IC), along with ART [8]. Earlier research reports recommend the use of IPT with ART in reducing the burden of TB among PLHIV [9,10,11].
WHO strongly recommends providing at least 6 months of IPT for PLHIV without active TB, including those receiving ART and those who have successfully completed TB treatment conditionally recommends providing isoniazid for 36 months for PLHIV [12,13,14]. Earlier research findings emphasized various factors that hinder the implementation of IPT such as complexities observed in organizing national and regional TB / HIV programs, lack of confidence on IPT, fear of drug resistance and pill burden. Moreover, lack of counselling for target groups, work burden, fear of stigma, lack of money for travelling long distance to the health centres, prolonged waiting time for investigation and misinformation about IPT are some of the highlighted factors that inhibit the utilization of IPT among PLHIV [15,16]. In controversy, the report of a pilot study conducted in Vietnam among HIV infected patients reported that acceptability and completion rate was high (80%; 91.8%) and no adverse effects were reported on IPT use [17]. A research study was done in sub-Saharan Africa recommended that IPT can be prescribed safely during the early course of HIV disease [18]. Therefore, determining the IPT use and suggestions to improve IPT implementation in representative population increases the strength of further TB/HIV programs conducted on large scale.

Objectives
The general objective of the study were to investigate the IPT utilization rate and determinant factors among adult HIV infected patients at JUSH ART clinic, Oromia region, Ethiopia.

Specific Objectives 5
The specific objectives of this study are the following:

Inclusion criteria for Participants
Adult PLHIV enrolled in the HIV care at JUSH. We included the adult PLHIV who were eligible for IPT from the medical records, including patients who were taking IPT.
Adult PLHIV who were on follow-up and eligible for IPT during our study period, permanent HCPs and TB/HIV coordinators working in JUSH HIV care, who showed voluntary participation for semistructured questioners and an in-depth interviews were included as a participants in the qualitative study.

Exclusion criteria
Patients whose symptoms are positive in TB screening, identification of active TB, acute/chronic hepatitis, alcoholics, peripheral neuropathy, prior allergy or intolerance to isoniazid were excluded from the analysis.

Sampling method
The sample size was calculated by single population proportion formula n = Zα / 2 p (1-p) /d 2 using (p = 22%; 95% CI and 5% precision) the prevalence of IPT use in HIV-infected patients in ART clinic, Black lion hospital, Addis Ababa [16,19]. We considered that 10% of the patient as expected loss and the final sample size were 287. The respondents were selected by systematic sampling technique. More explicitly, study subjects were at the 24th interval in the sampling frame and the initial respondent being the first patient in HIV care. We excluded 9 patients who had active TB disease, and 2 had a history of chronic alcoholism for which we recruited an additional 11 patients to reach our sample size. We considered that IPT utilization as continuous a dependent variable and sex, age, marital status, education, ethnicity, religion, occupation, residence, BMI, WHO Clinical stages, duration of HIV care, types of HIV care, duration of HAART care, CD4 count, comorbidity, previous TB treatment, patients taking medication, baseline availability of LFT, RFT, Hgb, HBsAg and Anti HCV as an independent variables.
To achieve the objectives of the study, we used a convenient sampling technique for semi-structured questioners and an in-depth interview from the patients who were included in the study (from both those who took IPT and those who did not take IPT).
In addition, we made a visit to the ART clinic during the study time, and interviewed the health care workers at TB/HIV clinics and TB/HIV coordinators working in JUSH, ART clinic. The questionnaires were developed according to standard WHO 6 health system frames [20], and in-depth interviews were imployed till data saturation occurred. The core ideas originated as barriers and factors that increase the IPT implementation were grouped into three categories as patient-related factors, HCP's and TB/HIV coordinator perspectives. All questionnaires were pre-coded and target group interviews were audio recorded and cross-checked for completeness prior to computation.

Definition of variables
IPT users/utilizers: PLHIV who were initiated on INH (isoniazid) 300mg daily as IPT and who were either taking during data collection or PLHIV who were prescribed IPT for one month and whose status after initiation is known or unknown.
Previous TB treatment: patients who took the standard anti-TB drugs for ≥ 1months and not taking the drugs during the study time despite the treatment outcomes Adult PLHIV: defined as PLHIV whose age ≥15 years as this cut of age is used for classification of adult and pediatric clinics in JUSH and other governmental hospitals in Ethiopia.

Ethical Consideration
Ethical clearance was acquired from Institutional Review Board (IRB) of the College 8 of Health science and Ethical review committee of JUSH (Ref. No: RPGC/14/2016). As per HIV programme protocols, the resident Physicians are permitted to collect the data for evaluating the strength and weakness of the program and to act accordingly. Written consent was obtained from each subject and passive parental consent from the parent (or) guardian was received for the patients < 18 years. All interview script was coded, and none of the patient identifiers as included in data assessment.

Statistical analysis
All quantitative data were coded through Epi Data 3.1 and then exported to SPSS version 20 for indepth analysis. Descriptive statistics, χ2 test and bivariate analysis were done to sort variables for logistic regressions having value P ≤ 0.25. A stepwise logistic regression model was used to generate factors strongly associated with the dependent variable. A value of P < 0.05 was considered as significant to declare the associations. Qualitative data were subjected to thematic analysis which involves identifying, coding, analyzing and clustering recurring factors into overarching themes with respective sub-themes. Additionally, data's collected from the patients, HCP's and TB/HIV coordinators for the IPT utilization were described based on their categories to add depth and richness to the findings.

Results
The present study constitutes a baseline information collected from PLHIV enrolled in JUSH HIV care, clinical data from medical records, and qualitative data from PLHIV who were on follow-up and eligible for IPT, HCPs and TB/HIV coordinators working in JUSH ART clinic, Ethiopia. Accordingly, Almost 29.6% of the respondents were government employees; 19.2% were merchants; 13.6% of the target groups were farmers; 14.6% were housewives, 9.8% were daily labors; 5.6% were students and 7.7% were others. 62.4 percent of the study populations were residing in the urban area, and 37.6% of patients' are live in the rural area.
According to the clinical data collected from medical records (Table-2 of respondents were prescribed with pyridoxine. The data collected through questionnaire and medical record ( Table-3 In the logistic model, Oromo and Amhara ethnic groups were more likely to use IPT (Table-4) than SNNP groups (**P< 0.02) and other variables like age, marital status, occupation, residence, duration of HIV care, previous TB treatment, CD4 and hemoglobin were not found to be statistically significant with IPT.
In qualitative analysis and in-depth interviews 60% and 40% of the respondents were females and males respectively. In addition the mean age of the respondents were 33± 4.Around40% of HCP's permanently working JUSH were included in the indepth interviews which comprises20% nurses (age: 27 ± 5.7) and 20% ART physicians (age: 26 ± 1.7) respectively. Average service days of HCP's were 92± 3.1 for nurses and 36± 3.2 for ART physicians. Nearly 10% of participants are TB/HIV coordinators (age: 41 ± 3.5), and their mean working experience was about 20 years in JUSH.
The result of the data ( Table-5

Discussion
The present research aimed to define the IPT utilization rate and to identify the factors that influence IPT use among PLHIV, HCP's and TB/HIV coordinators in JUSH 12 ART clinic, Ethiopia. With this regard the overall IPT utilization rate among PLHIV in ART clinic was 59.2%. The ffindings are 3 -4 fold increase in IPT implementation compared with 30% implementation in Addis Ababa [21,22] and 19.6% in Northern Ethiopia [23]. Thecurrent research finding shows that in accordance with other studies that recommended IPT use in combination with ART could effectively reduce TB risk in HIV-infected adults (18,24,25]. According to TB/HIV surveillance annual report, nearly 18.2% of HIV patients with no clinical symptoms of TB received IPT, which varied by 5.6% in SNNP, 16% in Oromia and 55.9% in Harari regions, respectively [19]. However, the government intention is to reach the target goal as 100% in HIV care users. We investigated the demographic and clinical factors associated with IPT use in PLHIV. Accordingly age, marital status, occupation, residence, duration of HIV care, previous TB treatment, CD4 and hemoglobin were not found to be statistically significant with IPT use. Astonishingly, the findings reveals that the age and sex had no significant association with IPT [26]; the only ethnicity was statistically significant with IPT use. Accordingy, Oromo and Amhara ethnics are (**P < 0.020) more likely to use IPT when compared to SNNP group However, there were no quantitative studies done to associate ethnicity on IPT use and we used this findings to investigate a successive trials to evaluate the ethnic effect on IPT use.
Besides, wealso collected the baseline information through semi-structured questionnaires and evaluated the factors that determine IPT use from PLHIV, HCP's and TB/HIV coordinators' perspectives. PLHIV who have not used IPT were interviewed to mention the reasons or barriers that made them not use IPT and they responded that, lack of awareness, inefficiency of proper counselling about the benefits of IPT, unwillingness to disclose the disease, pill burden, misinformation 13 and fear of side effects.Accordingly, almost 89% of HIV patients reported that counselling was beneficial by adhering to HIV treatment and to change their perception about the disease. In addition, they further responded that counselling motivate them to live a planned life. Nearly 60% of patients supported that disclosure was important which helped them to protect from infections and to have safer sex with their partners and knowing their health status will at least help them not to have sex with them. In controversy, 40% of respondents argued that disclosure to other family members would result in stigma and discrimination in rural areas. All participants agreed that an increase in CD4 count and medications would prolong their life and protect them from TB/HIV disease. 35% of patients mentioned that they are fearful about the adverse effect of the drug and resistant capacity despite they believed that taking more medications are not good for their body. The group of IPT users mentioned the factors that motivated are counselling, fear of death from TB disease, concern for their family; maintain routine daily life and the trust that IPT can cure their disease. Some of the major constraints observed in non-IPT users are lack of counselling and awareness on IPT, unwillingness to disclose their disease, pill burden, misinformation and fear of side effects. Our findings are similar in previous studies done in Tanzania, Northern Thailand, South Africa and Addis Ababa [27,28,29,20].
HCPs responded that implementation of IPT is one of the effective ways to prevent TB in PLHIV and they are a volunteer to prescribe for all eligible individuals with HIV. They underlined that, the IPT completion rate was very high and side effects are rare because it was given with pyridoxine for all patients. The positive attitude of HCP's observed in our study was supported by a report stated that IPT use

Declarations
Ethics approval and consent to participate All participants involved in the study were provided with information on the risks and benefits of the project. A written consent form was received from the target groups and all respondents know that they had the right to withdraw at any stage of the study without giving any notification.

Consent for publication
A Written consent was obtained from BMC Central Consent Form and is available on request from the Editor.

Availability of data and materials
All the data's analyzed during this study are included in this published article and the raw data are available from the corresponding author on reasonable request.