Predictors of mortality among adult patients enrolled on Antiretroviral Therapy in Hiwotfana specialized University Hospital, Eastern Ethiopia: Retrospective Cohort study

Objective: Mortality of HumanImmunodefi ciency Virus (HIV)infected patients have been reduced substantially since the introduction of Antiretroviral Therapy (ART). However, many studies have shown high mortality. But the factors associated with this high mortality are poorly characterized. So this retrospective cohort study aims to determine mortality and identify predictors of it among patients on ART at Hiwotfana specialized university Hospital (HFSUH). Result: A total of 61 (11.9%) deaths were observed giving an overall mortality rate of 2.8 per 100 person years. Advanced WHO stages (hazard ratio (HR) =3.44, 95% CI: 1.73 6.85), baseline CD4 count less than 200cells/mm3 (HR=3.18, 955 CI: 1.6716.06), regimen changed (HR=23.62, 95% CI: 9.95 56.05), and being anemic (HR=3.23, 95% CI: 1.71 6.11) were the independent predictors of mortality. Patients who started AZT based initial regimen had a lower risk of mortality (HR=0.29, 95% CI=0.13 0.64) when compared with the D4T based regimen. Research Article Predictors of mortality among adult patients enrolled on Antiretroviral Therapy in Hiwotfana specialized University Hospital, Eastern Ethiopia: Retrospective Cohort study Endalkachew Mekonnen Eticha1* and Ashenafi Beru Gemeda2 1Department of Pharmacy, College of Health and Medical Science, Haramaya University, Harar, Ethiopia 2Department of clinical nursing, college of Medicine and Health Science, Jigjiga University, Jigjiga, Ethiopia Received: 10 September, 2018 Accepted: 09 November, 2018 Published: 10 November, 2018 *Corresponding author: Endalkachew Mekonnen Eticha, Department of Pharmacy, College of Health and Medical Science, Haramaya University, Harar, Ethiopia, Tel: +251967344420; E-mail:

There has been a dramatic decline in morbidity and mortality in patients with HIV disease in all demographic subpopulations with the advent of highly active antiretroviral therapy (HAART) [2][3][4]. Global mortality peaked in 2005 at 1.8 million and subsequently fell by 5·5% per year to 1.2 million in 2015 [1]. According to UNAIDS/Ethiopia report, approximately 20,000 HIV related deaths [5]. Despite the increased availability of ART and promising effi cacy, early mortality has been high after initiating ART [6,7]. Factors contributing to the high fatality rate and reduced quality of life in poor countries are poorly understood.
Multiples of factors have been associated with mortality among clients on ART [7][8][9][10]. However, those factors which contribute to the deaths of HIV-infected patients while on ART are not well explored particularly in eastern Ethiopia. Therefore, this study aimed to investigate the predictors of mortality among adult ART users in HFSUH, eastern Ethiopia.

Study period, setting and participants
The present study was conducted from January to June 2016 in HFSUH located eastern part of Ethiopia. The hospital starts ART service in 2005 and since then it has been providing, free of charge ART to eligible HIV-infected patients.
The treatment protocol for Ethiopia is implemented using World Health Organization (WHO) ART treatment guideline for HIV infection in adults and adolescents [11] and national guidelines for HIV prevention, care and treatment: Federal Democratic Republic of Ethiopia [12]. According to the current treatment guidelines, HIV infected adults are eligible to start ART if their CD4cell count is < 500cells/mm 3 irrespective of CD4 count or WHO clinical stage 3 or 4 irrespective CD4 cell count.
Breast feeding women, pregnant women, and sero-discordant Based on this, random sample of 513 patient's medical records was drawn for data collection. Regarding the sampling technique, patients' medical card numbers were generated from the computer database according to their entry time and adult patients were fi ltered using eligibility criteria, then we give a unique number for the remaining records and select each record for our study using systematic random sampling.
Pregnant women started ART for prevention of mother to child transmission (PMCT), regimen change, and transfer in were excluded from the study.

Data collection and quality control
A Standard checklist containing study variables were developed from the patient registry card which was developed by the Ethiopian Federal Ministry of Health (FMOH). During data collection, the most recent laboratory results before starting ART were generally used as baseline values. If there is no pretreatment laboratory test, however, the results obtained within one month of ART initiation were used. The data collection/ extraction process was supervised by the principal investigator.
Two trained data collectors were involved in the study; both were nurses working in the ART clinic. All completed data were examined for clarity and consistency on a daily basis.

Statistical analysis
The collected data were cleaned, categorized, coded, entered and analyzed by using STATA 12. Kaplan-Meier survival analysis was used to estimate survival probability. We applied Cox-proportional hazards regression to identify risk factors associated with outcome variable (time of regimen change).
Variables found to be associated with the outcome in the univariate analysis assuming a signifi cance threshold of 20% were included in the multivariate analysis. The multivariate analysis results showed a signifi cant effect on the outcome considering the signifi cance thresholds of 5% were described.

Ethical consideration
Ethical clearance was obtained from Ethical clearance board of Haramaya University, college of Health and Medical science (reference number sop 792/1/2016) and data access permission was obtained from the medical director of HFSUH. We simply extracted anonymized data from the patient's medical registry and no participant was involved in the study.    [13][14][15]. In contrary, studies from other regions of Ethiopia, Nekemte Referral Hospital (7.2%) and
The estimated survival probability of our cohort at 6, 12, 18 and 24 months were 94.6%, 93.5%, 92.3% and 89.7%, respectively. This shows a better survival compared with Ethiopian Somali [13] and Malawi studies [20]. This better survival in our cohort group may be due to majority of this cohort started HAART at WHO stage I or II (51.66%) and at a CD4 count > 200 cells/mm 3 (57.5%).
Previous studies done in Ethiopia show that advanced WHO clinical stage was one of the major predictors of mortality for patients enrolled on ART [17][18][19]. This study was consistent with those fi ndings. A Cohort study from Cameroon [20], indicated patients with stage III (2 times) and stage IV (3.79 times) more likely to die than patients with stage I or II.
Previous studies in Africa, Tanzania, South Africa and Senegal [7,21,22] also showed that advanced stage of the disease was associated with more than doubling in the hazard of death.
In this cohort study, clients with baseline CD4 count < 200 cells/mm 3 had higher hazard of mortality than patients with CD4 count >200 cells/mm 3 . Cohort study in university of Gondar indicated patients presented with CD4 count < 200cells/mm 3 had 5 times higher risk of mortality than those with >200cells/ mm 3 [23]. In line with the present study, different studies found twice or more risk of mortality among patients with CD4 count of < 200 cells/mm 3 (7,8,24). Advanced immunodefi ciency was associated with opportunistic infection, thereby increasing the likelihood of death Patients who were anaemic at baseline were 3 fold higher risk of mortality than those who doesn't have. Previous studies done across many parts of Africa and in industrialized countries reported that anaemia at baseline was independently associated with higher mortality among patients enrolled on ART [7,20,25]. A Similar study from Ethiopia by Tadesse and colleagues [15], mortality was higher among patients with anaemia than their comparator. Although there is no concrete evidence on causal association between anaemia and mortality, the incidence of anemia, increased with the progression of HIV disease [7,26,27].
The initial regimen change was a signifi cant predictor of mortality in this cohort study. Different studies confi rm that ART regimen change causes diminishing the clinical and immunological benefi t of treatment [28,29] failing virological suppression, increase drug resistance [30] and thereby increase morbidity and mortality due to HIV/AIDS [30,31]. This cohort also showed that patients on Zidovudine based regimens were shown to have less risk of mortality (HR: 0.34; 95% CI: 0.16 -0.76) than D4T based regimen.

Conclusion
This study has revealed an overall low mortality rate, but the high mortality rate in the fi rst six months of HAART initiation. Advanced WHO stages, lower CD4 count, ART regimen changed, D4T based regimen and anemia were the independent predictors of mortality. For this reason, early enrolment of patients on HIV care service and treatment is very crucial to improve patients' survival.

Limitations of the study
We acknowledge the limitations of the current study, including: 1) This study includes only patients' medical records with complete baseline information, so this might have made a selection bias; 2) all deaths documented were considered as HIV/ AIDS related deaths due to lack of available records on the cause of death; 3) it also shares limitations of retrospective studies.