Isoniazid preventive therapy utilization rate and associated factors in adult HIV/AIDS patients in Jimma University Specialized Hospital ART clinic: 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. IPT is one of the several key interventions recommended by the world health organization (WHO) for the prevention of TB in patients infected with HIV. Hence, the present study aimed to determine the IPT utilization rate and to explore the determinant factors among PLHIV under follow-up, Health care providers (HCP’s) and TB/HIV coordinators working in Jimma University Specialized Hospital (JUSH) ART clinic, Ethiopia. Methods: An Institution based cross-sectional study was conducted in JUSH ART clinic, Oromia region, Ethiopia. The target groups were enrolled by a systematic sampling technique from the registered medical records of JUSH HIV care. Semi-structured questioners and in-depth interviews were designed for quantitative analysis from PLHIV, HCP’s and TB/HIV coordinators working in JUSH, ART clinic. All statistical analysis was compiled by Epi data 3.1 and SPSS 20. Results: The overall estimated IPT utilization rate in JUSH ART clinic was 59.2%.Demographic and clinical factors are not significant, but ethnicity was highly significant with IPT use in PLHIV. All respondents, HCP’s and TB/HIV coordinators were interviewed on identifying the factors and barriers that increase the utilization of IPT. The results of in-depth interviews are grouped into three core categories as patient perceptions, HCP’s and TB/HIV coordinator perspectives. Discussion and conclusion:PLHIV, HCP’s 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. Higher attention should be provided in linking all HIV patients to the nearest health facilities for receiving free service packages and medical care. Administrative managers could improve the capacity building by increasingthe number of

health care professionals, maintaining data base on patient records and continuous supply of pyridoxine and IPT for all PLHIV. HCP's and TB/HIV coordinators responded that disclosure to the patient families and occupational independence will increase the acceptance and implementation of IPT in large scale.
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. PLHIV are at least 26 times more likely to develop TB disease than people without HIV [2]. 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. Ethiopia is one of the 22 high TB burden countries ranking 9th in the world and 3rd in Africa with the prevalence of TB burden was estimated at 261 and 394 per 100,000 populations, respectively [3,4]. According to WHO report the rate of TB patients who were found to be co-infected with HIV in Ethiopia was between 10% and 15% and nearly 88% of TB patients who were co-infected with HIV were placed on ART [5].Multiple strategies are existing in the prevention of TB disease such intensified case finding (ICF), isoniazid preventive therapy (IPT) and TB infection control (IC), along with ART [6]. Earlier research reports recommend the use of IPT with ART in reducing the burden of TB among PLHIV [7,8,9]. 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 [10,11,12]. Earlier research findings emphasised 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 on 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 [13,14]. In controversy, 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 [15]. A research study done in sub-Saharan Africa recommended that IPT can be prescribed safely during the early course of HIV disease [16] . 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
To determine IPT utilization rate and determinant factors among adult HIV infected patients at JUSH ART clinic, Oromia region, Ethiopia.

Specific Objectives
To determine the IPT utilization rate among adult HIV infected patients enrolled in HIV Care at JUSH ART clinic.

Inclusion criteria for Participants
HIV infected patients enrolled in the ART clinic during our study period were screened through medical records and included the patients who are using IPT.
PLHIV under follow up programme, HCP'S and TB /HIV coordinators willing to participate in the assessment of IPT associated factors and in-depth interviews are included as our study participants.

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 excluded in the analysis.

Sampling method
The sample size was calculated by single population proportion formula n = Zα / 2 p (1p) /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 [14,17] . The calculated sample size was 264 and with 10% s expected loss and non-response rate, the final sample size was 290. Our respondents were selected by systematic sampling technique with every study subjects are 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 IPT as dependent variable and knowledge, education, occupation, residence, disclosure of HIV status, pill burden, Level of CD4, WHO clinical stages, nutritional status, alcohol use and comorbidity as independent variables.
We used convenient sampling technique for semi-structured questioners and in-depth interviews from the patients who were included in the study (from both those who took IPT and those who did not take IPT) and have a visit to the ART clinic during the study time, health care workers at TB/HIV clinics and TB/HIV program managers working in JUSH, ART clinic. The questioners are developed according to standard WHO 6 health system frames [18], and in-depth interviews were used till saturation of ideas/ responses have occurred.
The core ideas originated as barriers and factors that increase the IPT implementation are 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 are initiated on INH (isoniazid) 300mg daily as IPT and who are either taking during data collection or 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 of

Results
The present study includes quantitative and qualitative data's collected from medical records, and respondents including PLHIV, HCP's and TB/HIV coordinators in JUSH ART clinic, Ethiopia.   Table -3.
In the logistic regression model, Oromo and Amhara ethnic groups were more likely to use IPT than SNNP groups (for Oromo ethnicity, P≤ 0.03 and Amhara, P≤ 0.025) and other variables like age, occupation, residence, type of HIV care and its duration, previous TB, CD4 count and hemoglobin were not found to be statistically significant with IPT (Table -4).

Discussion
The present research aimed to define the IPT utilization rate and to identify the factors influence use among PLHIV, HCP's and TB/HIV TB/HIV coordinators in JUSH ART clinic, Ethiopia. The overall IPT utilization rate among patients enrolled in ART clinic was 59.2%.
Our results are in accordance with other studies that recommended IPT use in combination with ART could effectively reduce TB risk in HIV-infected adults. [16,22,23] also recommended that IPT in combination with ART were effective in reducing TB risk in HIVinfected adults.
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 [ 17] . 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, occupation, educational level and residence were not found to be statistically significant with IPT use. Our findings are supported by earlier reports that age and sex had no significant association with IPT [24]; the only ethnicity was statistically significant with IPT use. Oromo and Amhara ethnics are 3.6 and 8.8 folds more likely to use IPT when compared to SNNP group (Oromo: P< 031; Amhara: P<025). However, there were no quantitative studies done to evaluate the ethnic effect on IPT use.
We also 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 as lack of awareness, no proper counselling about the benefits of IPT, unwillingness to disclose the disease, pill burden, misinformation and fear of side effects. Almost 89% of HIV patients reported that counselling was beneficial by adhering to HIV treatment and to change their perception about the disease. 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 [25,26,27,18].
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 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 without active TB was 42% in Oromia Region [28,29]. They highlighted some major barriers as lack of knowledge among the respondents on adverse effect of TB and the benefits of IPT, fear on drug toxicity, pill burden and misinformation about IPT use. HCPs' suggested their solution to improve IPT implementation by increasing public awareness through health education, regular counseling, launching advanced TB screening techniques and increasing sufficient number of HCP's at ART clinics.
TB/HIV coordinators of JUSH ART clinic responded that IPT implementation was monthly monitored by HIV coordinators and every quarterly period by CDC focal person which is further supervised by Oromia regional and National Health Bureau representatives. TB/HIV coordinators responded that their ultimate target was to achieve the highest implementation of IPT. Coordinators also replied that some patients refuse to use IPT and

Strength and Limitations of the study
Our finding is one of the fewer studies conducted in a clinical care setting where patient management protocols are standardized and executed in practice. This is the first study in Oromia region integrating the perspectives and implementation of IPT among PLHIV, HCP's and TB/HIV coordinators. So, the findings of our study could be used as a baseline for scale-up program in the community level and stake holder's extension packages. Our limitations are relatively small sample size, and we adapted the existing facilities because of resource limitation. Our only sampling site is JUSH, ART clinic which may limit the generalizability of our findings to other regions of Ethiopia. However, our results serve as a pilot trial to focus our upcoming research on finding innovative medical approaches and quantifying the effect of IPT to control TB in PLHIV.

Conclusion And Recommendation
The overall IPT utilization rate among patients enrolled in HIV care was 59.2%. The    Note: df = degrees of freedom Note: df = degrees of freedom, *P < 0.05 is statistically significant