The magnitude of opportunistic infections and associated factors in HIV-infected adults on antiretroviral therapy in southern zone Tigray, Ethiopia: a cross-sectional study

Introduction Greater than twenty known opportunistic infections have been associated with HIV infection and usually patients experience co-infections during the stage of illness, HIV-related opportunistic infections are associated with significant morbidity and mortality. Methods A hospital-based retrospective study was conducted in HIV-infected adult patients on antiretroviral (ART) from April to June 2017; secondary data were collected from review of clinical records. A total of 400 study participants selected through a systematic sampling technique and a pre-tested checklist was used to collect data from records of study subjects. The data was entered and analyzed using SPSS version 22. Results A total of 400 patients included in the study, in which more than half (51.0%) were females. The mean age of patients was 34 (standard deviation [SD] ±1.96) years. The overall of opportunistic infections (OIs) among HIV/AIDS patients on ART was 55.3%. The highest rates of OIs observed were oral candidacies 11.0%, followed by herpes zoster (10.8%) and tuberculosis (TB) (9.5%). The odds of having college and above educational levels were less likely to developed OIs compared to illiterate (AOR=0.007; 95% CI=0.053, 0.634). The odds of having OIs in WHO clinical stage I were less likely to have OIs compared to WHO clinical stage III and V (AOR=0.001; 95% CI=0.000, 0.015 and AOR=0.00; 95%CI=0.00 respectively). Conclusion There was a high prevalence of OIs observed in this study. Illiterate educational level and advanced WHO clinical stages were found to be predictors of OIs. Interventions were aimed at promoting early HIV testing and ART enrollment of HIV-infected.


Introduction
The clinical symptoms of HIV infection encompass a spectrum ranging from primary infection and prolonged non-symptomatic state to advanced disease [1,2]. Most of the opportunistic infections (OIs), usually manifest at a terminal stage of the illness, are the commonest causes of morbidity and mortality among HIV/AIDS infected patients.
Despite the existence of prevention and treatment modalities, opportunistic infections continued to be the leading causes of morbidity and mortality among people living with HIV/AIDS [1,3]. The risk for the development of OIs in HIV patients depends on exposure to potential pathogens, the virulence of the pathogens, the degree of host immunity, and the use of antimicrobial prophylaxis [4]. HIV causes progressive depletion of the CD4 T cells, which leads to lifethreatening opportunistic infections (OIs) or malignancies during the natural course of the disease greater than 90% of them are responsible for the development of AIDS morbidities and mortalities [5].
The World Health Organization (WHO) reports the number of people living with HIV/AIDS has increased from 33.3 million in 2010 to 36.7 million in 2015 including 2.1 million newly infected people. Developing countries share 69% of the global HIV burden [5]. Greater than 20 specific opportunistic infections have been associated with HIV infection and usually, patients experience co-infections during their illness [6,7]. Stage II infections such as herpes zoster (HZ) and other skin infections occur in early World Health Organization (WHO) clinical stages (stages I and II) [2,7,8] whereas critical, life-threatening infections such as CNS toxoplasmosis and cryptococcal meningitis come in later WHO clinical stages (stages III and IV) with severe immunity suppression. Some life-threatening infections, such as pneumonia and tuberculosis (TB), may occur in early as well as in later WHO clinical stages [9][10][11][12]. The most common opportunistic diseases in HIV patients in Ethiopia are tuberculosis (TB), oral candidacies, Pneumocystis Carini Pneumonia (PCP), bacterial pneumonia, kaposi´s sarcoma and lymphoma [13,14].
HIV/AIDS-related opportunistic infections are the predominant causes of morbidity and mortality and virtually cannot be a cure, except lifelong suppressive therapy after an acute infection. Prevention of such illness through primary prophylaxis is, therefore, compelling [15].
Although nationally representative and comprehensive data regarding the magnitude of opportunistic infections lack in Ethiopia, the same regional studies have shown the prevalence ranging from 19.7% to 48% [15][16][17]. Antiretroviral therapy (ART) increases the length and quality of life and work productivity of patients by improving survival and decreases the incidence of OIs in HIV-infected people through reduction of the viral load and increasing the level of CD4 cells [18].
The widespread use of ART has had the most profound influence on reducing OI-related mortality in HIV-infected persons in those countries in which these therapies are accessible and affordable.
Worldwide, it is estimated that between 250,000 and 350,000 deaths were averted in 2005 as a result of increased treatment access, however, OIs continued to cause morbidity and mortality in HIV/AIDS patients even after receiving ART. This mortality occurs because some patients do not have a sustained response to antiretroviral agents for multiple reasons including poor adherence, drug toxicities, drug interactions or initial acquisition of a drug-resistant strain of HIV-1 [7,19]. The adult HIV prevalence of Ethiopia was estimated to be 1.1% in 2015, where more than 691 thousand people are near to be suffering from the disease. It is the second leading cause of death in Ethiopia resulting in the death of greater than 26 thousand people in 2015. More than 90% of HIV/AIDS deaths are contributed to opportunistic infections and malignancies [20]. The type of opportunistic infection which affects people living with HIV/AIDS different from region to region [21].

Methods
The study area, design and period south zone Tigray is located in the northern part of Ethiopia, which is 821 kilometers away from the capital city Addis Ababa. It had a projected total population of people in the year 2016. There are four hospitals and ten health centers in the zone (Tigray regional health bureau state health bureau, variables. Crude and adjusted odds ratios (CORs and AORs, respectively) with 95% confidence intervals (CIs) were used to describe the strength of association between the selected study variables. The criterion for significance was set at P, 0.05 based on a two-sided test.

Discussion
This study assessed the prevalence and associated factors of OIs among HIV-positive patients taking ART. The resulting study found that about 48.75% of HIV/AIDS patients on ART had one or more OIs.
This finding was comparable to the 47.6% and 48% reported in a study conducted in Taiwan 12 and Eastern Ethiopia [14,21]. However, it is higher than two recent, similar studies carried out in Ethiopia in Debre Markos and Gondor, which reported 19.7% and 33.3% prevalence, respectively [16,22]. This difference might be due to the accessibility of higher health facilities and methodological differences in selecting study subjects. Similar studies were conducted among HIV patients taking ART for five and more years. The risk of developing an OI for a person receiving ART is highest during the initial month of therapy, shows that 39% after 12 months of initiation of ART [21].
There were 55 co-infections of different OIs observed in the current study.
Of these, 58.3% (n=44/55) were oral candidacies with ulcers -mouth, genital and (n=11/55) TB co-infections with herpes zoster and chronic diarrhea. This finding has disagreed with a report from Gondar, Ethiopia, which reported 50% TB and oral candidacies co-infections [22]. A higher proportion of oral candidacies with mouth ulcers, genital co-infections in the current study might be explained by a higher prevalence of these two OIs among the study participants.
More than two OIs were also reported from studies conducted in Debre Markos, Ethiopia and Nigeria [16,23]. Oral candidacies were the most prevalent species isolated from both HIV seropositive subjects on ART 17 (76.19%) and that not on ART 8 (88.89%) [24]. The present study also revealed that oral candidacies infection is the predominant OI identified, with a prevalence of 11% (44/400). This was comparable with a study conducted in Abakaliki in which the prevalence of oral candidacies related OIs was found to be 12.5% [24], but, it was greater than the prevalence reported from East Ethiopia 7.5% and Nigeria (7.7%), which also reported TB as a major OI [23,25]. This might possibly be explained by methodological differences in selecting study subjects and the prevalence of oral candidacies in the total population. Next oral candidacies, herpes zoster, and TB were the second and the third most prevalent OIs in the present study, at 10.7% (43/400) and 9.5% (38/400), consequently. The prevalence of candidacies was higher compared with a report from Debre Markos, Ethiopia and a report from Nigeria in which prevalence rates of 11.8% and 8.6% were noted, respectively [16,23]. The prevalence of herpes zoster is in agreement with the study carried out in India, which revealed the prevalence of 14.7%. Eighteen, this rate was higher than the study reported in Nigeria [16] similarly, higher (30.7%) prevalence of HZ was reported in ART-naïve, HIV/AIDS-infected patients in Bahir Dar, Ethiopia [14]. This difference might be due to methodological differences in selecting study participants and the prevalence of HZ in the general population. The hospital where this study was conducted initiates ART when the CD4 level of a patient falls below 200 cells/mm 3 of blood, which is far lower than the suggested by WHO, which increases the risk of HIV-infected individuals to OIs. In the current study, the HIV-infected patient with CD4 counts of 200 cells/mm 3 was more similar to develop OIs compared to those with CD4 counts of $200 cells/mm 3 [21,[24][25][26]].

Conclusion
In this study, a high rate (55.3%) of OIs was reported. This suggests that OIs remain a challenge in patients receiving and taking ART in Ethiopia. Oral candidacies followed by herpes zoster and TB were the major OIs encountered by HIV-infected patients taking ART. Illiterate, WHO clinical stages III and IV were found to be strongly associated with the prevalence of OIs. That is why interventions need to be

What is known about this topic
• OIs were the cause of death in HIV infected individuals; • WHO clinical stage develop when the immunity system of patients decreases and viral load increases; • Proper prevention of mother-to-child transmission (PMTCT) service prevents HIV transmission from mother to child.

What this study adds
• A high rate of OIs was reported. This suggests that OIs remain a challenge in patients receiving and taking ART;

Competing interests
The authors declare no competing interests.  Table 1: socio-demographic and clinical characteristics of the study participants (n=400) among HIV/AIDS patients on ART clinic at general hospital southern zone Tigray, Northern Ethiopia, 2017