Hospitalization and Predictors of Inpatient Mortality among HIV-Infected Patients in Jimma University Specialized Hospital, Jimma, Ethiopia: Prospective Observational Study

Despite the number of patients enrolled in ART is increased, HIV/AIDS continues to constitute a significant proportion of medical admissions and risk of mortality in low- and middle-income countries. As one of these countries, the case in Ethiopia is not different. The aim of this study was thus to assess reasons for hospitalization, discharge outcomes, and predictors of inpatient mortality among people living with HIV (PLWH) in Jimma University Specialized Hospital (JUSH), Jimma, Southwest Ethiopia. Prospective observational study was conducted in medical wards of JUSH from February 17th to August 17th, 2017. In this study, 101 PLWH admitted during the study period were included. To identify the predictors of mortality, multiple logistic regression analysis was employed. Of the 101 hospitalized PLWH, 62 (61.4%) of them were females and most of them (52.5%) were between 25 and 34 years of age. A majority (79.2%) of the study participants were known HIV patients, before their admission. Tuberculosis (24.8%), infections of the nervous system (18.8%), and pneumonia (9.9%) comprised more than half of the reasons for hospitalization. Moreover, drug-related toxicity was a reason for hospitalization of 6 (5.9%) patients. Outcomes of hospitalization indicated that the overall inpatient mortality was 18 (17.8%). The median CD4 cell counts for survivors and deceased patients were 202 cells/μL (IQR, 121–295 cells/μL) and 70 cells/μL (IQR, 42–100 cells/μL), respectively. Neurologic complications (AOR = 13.97; 95% CI: 2.32–84.17, P = 0.004), CD4 count ≤ 100 cells/μl (AOR = 16.40; 95% CI: 2.88–93.42, P = 0.002), and short hospital stay (AOR = 12.98, 95% CI: 2.13–78.97, P = 0.005) were found to be significant predictors of inpatient mortality. In conclusion, opportunistic infections are the main reason of hospitalization in PLWH.


Introduction
Globally, close to 35 million people are believed to live with HIV. Sub-Saharan Africa, worst affected region, in particular accounts for 71% of HIV infections [1]. Life expectancy for patients infected with HIV has improved significantly in the era of highly active antiretroviral therapy (HAART) [2]. e decline in hospitalization due to HAART, however, has been unevenly distributed and inconsistent. Despite the global decrease in AIDS-related death and improvement of access to HAART, eastern and southern Africa remain the most HIV-affected regions [3]. In such low-and middle-income countries, HIV and its associated immunosuppression (AIDS) continue to constitute a significant deal of morbidity and mortality in adults. In some of these countries, the problem is acute [4][5][6].
In resource-poor settings, between 20% and 52% of hospital beds in medical wards are occupied by HIV-infected patients at any given time, mostly with opportunistic infections [7] and ended up with longer hospital stays [8]. Furthermore, it is reported that non-HIV-related hospitalizations of HIV-infected patients is increasing, globally [9].
Most reports of hospitalization from HIV infection in the era of HAART are from the developed countries [10][11][12][13]. is is mainly because publications reporting HIV-related hospitalization from developing countries are infrequent.
Data on the spectrum of both HIV-and non-HIV-related illnesses that result in hospital admission are essential for policymakers and stakeholders to plan actions in reducing morbidity, mortality, and further hospitalization [14]. Recently, Negera and Mega [15] reported that body mass index (BMI) of less than 18.5 is a significant predictor of inpatient mortality in Ethiopia. However, with the paucity of published data on HIV/AIDS in Ethiopia, little is known about other reasons for hospitalizations, discharge outcomes, and predictors of inpatient mortality in hospitalized patients with HIV. us, this study aimed to assess reasons for hospitalization, discharge outcomes, and predictors of inpatient mortality among people living with HIV in Jimma University Specialized Hospital (JUSH), Jimma, Southwest Ethiopia.

Study Area and Period.
is study was conducted from 17 th February to 14 th August 2017 in medical wards of JUSH, which is the only teaching and referral hospital in Southwest Ethiopia. e hospital provides services for approximately 9000 inpatient and 80,000 outpatient attendants a year from the catchment population of about 15 million people. It has more than 450 beds. In this hospital, the HIV test was performed using the HIV 1/2 STAT-PAK1 RDT (Chembio Diagnostics, Medford, NY, USA) kit. In JUSH, Mycobacterium tuberculosis diagnosis was made using the Xpert assay (Cepheid Xpert MTB/RIF ® ).

Study Design and Participants.
A hospital-based prospective observational study was employed. e study population included 101 patients who met the following criteria: HIV seropositive (either known prior to hospitalization or tested positive following hospitalization), adult patients (≥15 years), admitted to medical wards of JUSH in the study period, willing to participate in the study, and stayed for at least 24 hours in the inpatient wards. To confirm HIV status of patients, every hospitalized patient underwent provider-initiated counseling and testing (PICT).

Data Collection and Data
Quality. Patient demographics, anthropometric measurements, reason for hospitalization, comorbidities, complications, laboratory profile, and HAART status were collected using a predesigned data collection form. All CD4 cell counts included in study analyses were either done during hospitalization or within the previous 1 month before hospitalization. e clinical staging of patients was carried out using WHO guidelines for the clinical staging of HIV/AIDS for adults.
Adherence to HAART was assessed for 46 patients who were on HAART for at least 6 months prior to their admission. Adherence was estimated from patients' self-report of missed doses out of 30 doses of their prescribed medication and reported as good (≥95%), fair (85 to 95%), or poor (<85%) if and only if they missed 2 and less, 3 to 5, or 6 and more doses, respectively [16]. Data were collected by hospital pharmacists, working in medical wards, after being trained on interview techniques, data collection methods, and techniques of measurements. Moreover, to determine the outcomes of hospitalization, they followed the patients prospectively until discharged or died.

Data
Processing and Analysis. Data were coded, entered, cleaned, and analyzed using SPSS version 20 statistical package. Bivariate and multivariate logistic regression analyses with 95% confidence interval were employed in order to infer associations and predictions. In bivariate analysis, all explanatory variables that are associated with the outcome variable (inpatient mortality) with a P value of <0.2 were included in the final logistic model. P value < 0.05 was considered as statistically significant for all the independent variables in the final model.

Ethical Consideration. Letter of ethical clearance was obtained from the Ethical Review Board of College of Public
Health and Medical Sciences, Jimma University. Informed, voluntary, written, and signed consent/assent was obtained from each study participants/caregivers. Privacy and confidentiality were strictly maintained throughout the study.

Sociodemographic Characteristics of the Study Population.
Of 101 hospitalized PLWH enrolled in the study, 62 (61.4%) of them were females and 53 (52.5%) of the patients were between 25 and 34 years of age. Most of the study participants were urban residents (64.4%) and unemployed (62.4%). As it is illustrated in Table 1, the measured mean BMI of patients was 17.63 ± 3.24 kg/m 2 . Slightly more than one-third of the patients (34.8%) had severe malnutrition (BMI < 16 kg/m 2 ).

Clinical Characteristics of the Participants.
Clinical characteristics and laboratory findings of the patients are presented in Tables 2 and 3, respectively. e result showed that 21 (20.8%) of participants were newly diagnosed HIVpositive patients (tested on hospitalization). For known HIV patients (79.2%), the median duration of time since their diagnosis was 24 months (IQR, 6-60). Majority (82.2%) of the patients were in WHO clinical stage 4 and 44.6% of them had complications. e main (46.7%) complication of the hospitalized patient was severe neurologic dysfunctions. More than a quarter (27.7%) of the participants had a history of prior hospitalization in the last 12 months, and opportunistic infections were the leading (53.6%) reasons for their previous hospitalization (Table 2).

Antiretroviral erapy Regimen of Patient on HAART.
Among 80 known HIV patients, 65 (81.2%) of them were on HAART with the median duration of 19.00 (IQR, 3.25-40.25) months and majority (89.2%) of them were on first-line regimen. About a third (16; 34.8%) of the patients,who were assessed for adherence, had a poor (<85%) HAART adherence. Among 19 (29.2%) patients who had regimen changes, treatment failure was found to be the leading (36.8%) reason for treatment switch (Table 4).

Reasons for Hospitalization and Treatment
Outcome of Hospitalized Patients. Tuberculosis (TB) was the most common diagnosis that accounted for 25 (24.8%) of the reasons for hospitalization (Figure 1). e median duration of hospital stay for the patients was found to be 13 days (IQR, 8-20 days). As it is revealed in Figure 2, 82.2% of the admitted patients survived: 69 (68.3%) discharged, 10 (9.9%) of them discharge against medical advice (DAMA), and 4 (4.0%) transferred cases. e remaining 18 (17.8%) were deceased, of whom 12 (66.7%) died within the first 7 days of their hospital stay.

Factors Associated with Inpatient
Mortality. Both univariate and multivariate logistic regression analyses (

Discussion
In this study, opportunistic and other infectious diseases were dominant attributes of hospitalization. e spectrum of opportunistic infection is in agreement with previous reports on hospitalized HIV/AIDS patients from other parts of Ethiopia [17][18][19] and other low-and middle-income countries [3,5,[20][21][22][23]. Our study, however, reported a relatively lower proportion of TB. is could be because of the better availability of free HAART, which determines the frequency and severity of opportunistic infections such as active TB disease [7,18,24]. e prevalence of CNS infections observed during our study period was 18.8%. is is in line with a similar study conducted in Kenya [25] and lower than other studies [26,27]. e common CNS infections identified were cryptococcal meningitis (36.8%), bacterial meningitis (31.6%), and cerebral toxoplasmosis (31.6%). is proportion of CNS infections was consistent with other studies [3,15,20,[28][29][30]. HAART-related toxicity was also among the commonly occurred reasons for hospitalization. Proper counseling about the adverse effects of antiretroviral drugs and aggressive monitoring of patients before and within the first few weeks of commencement of HAART will help to reduce morbidity associated with the use of these drugs. e overall inpatient mortality in our study population was 17.8%, similar to previous reports [3,23,31]. Our finding, nevertheless, was higher than previous studies in India [6] and France [30]. e high mortality is probably reflective of the advanced nature of the disease during hospitalization [10,20]. Although there were differences in study design, a higher mortality rate was reported in other studies [16,20,21,32].
Logistic regression analysis showed that presentation with neurologic complications, low CD4 count (≤100 cells/ μl), and short duration of hospital stay (<7 days) were predictors of inpatient mortality. Multiple studies reported a statistically significant association of low CD4 cell counts as the predictor of inpatient mortality [20,33]. HIV patients hospitalized with neurologic complications were almost 14 times more likely to die inpatient compared with those without neurologic complications. is is in accordance with findings from other studies from Ethiopia by Berhe et al. [34] and elsewhere by Gill et al. [35].

AIDS Research and Treatment
Our study has some limitations that should be considered while interpreting the findings. ey include the following: certain disease conditions might have been overestimated or underestimated due to inadequate diagnostic facilities. Outcome measures for our study depended on the survival status at last contact with our patient in the hospital; we cannot exclude an underrepresentation of mortality rate as some DAMA patients might have died outside our hospital.

Conclusion
Tuberculosis, infections of the nervous system, and pneumonia were the top three leading reasons for hospitalization. Furthermore, our study disclosed that presentation with neurologic complication, low CD4 count, and short hospital stay were found to be predictors of inpatient mortality.

AIDS:
Acquired immunodeficiency syndrome CNS: Central nervous system COPD: Chronic obstructive pulmonary disease DAMA: Discharge against medical advice DVT: Deep venous thrombosis HAART: Highly active antiretroviral therapy HIV: Human immunodeficiency virus IQR: Interquartile range JUSH: Jimma University Specialized Hospital PLWH: People living with HIV TB: Tuberculosis.

Data Availability
e data used to support the finding of this study are available from the corresponding author upon request.

Disclosure
is study was done for the partial fulfillment Mr. Mishore's master's degree in clinical pharmacy.

Conflicts of Interest
e authors declare that they have no conflicts of interest.