Opportunistic Infections and Associated Factors among HIV/AIDS Patients taking Ante-Retroviral Therapy at Selected Hospitals in Sidama Zone, Southern Ethiopia: A facility-based cross-sectional study

Background Opportunistic infections are late complications of HIV infection is the depletion of the immune system. It is a major public health problem and high morbidity AIDS patients die of AIDS-related infections in developing countries like Ethiopia. Identi�cation of opportunistic infections (OIs) is important to develop a speci�c intervention. Therefore, this study aimed to assess the burden and associated factors of opportunistic infections. Method A facility-based cross-sectional study was conducted on 420 randomly selected HIV/AIDS patients taking anti-retroviral therapy. Data was collected from selected hospitals in Sidama Zone based on population proportion to size. Data was collected by a pre-tested questionnaire and a pre-tested checklist from the medical records of patients. Data entry and analyzed for descriptive and logistic regression models by SPSS v.23. The result declared as statistically signi�cant at p < 0.05.


Background
Human immune virus (HIV/ADIS), with which 36.7 million people were living and 2.1 million infected at the end of 2016, has been major health problem throughout the world [1].Around 36.7 million people worldwide are currently living with HIV, of which 52% reside in sub-Saharan Africa (SSA) [2].It affected 1 in every 25 Adults (4.4%) is living with the deadly virus, account for nearly 70% of the global burden of HIV [3,4].Although the natural history of HIV inclines to be similar, the patterns of OIs that mainly presented with different clinical manifestation regions to region [5,6].CDC estimates that in 2015, 15% of the people with HIV in the United States were unaware or asymptomatic of their infections [1,7].The commonly reported opportunistic diseases in sub-Saharan Africa among HIV patients are Candidasis, Pneumocystis carinii pneumonia (PCP), disseminated Mycobacterium avium complex (MAC) infection, Cryptococcus, kaposi sarcoma, herpes zoster, and tuberculosis [8,9].
The developing countries more suffer from bacterial and protozoal infections due to lack of resource [8,10], HIV diagnosis, sub-optimal HAART use, poor adherence, dug resistance, poverty, poor nutrition, and high exposure to infectious agents [11].The opportunistic infections may favour HIV replication and higher viral loads that leads to lower the quality of life of HIV infected persons, reduces patients' response to ART, increases stigma and limits one's ability to work, high medical care costs, and death [12,13].
In Ethiopia, the adult HIV prevalence of Ethiopia was estimated to be 1.1% in 2015, and second leading cause of death [14].More than 90% of HIV/AIDS deaths are attributable to opportunistic infections and malignancies [8].Even though nationally representative and comprehensive data regarding the magnitude of opportunistic infections lacks in Ethiopia, some regional studies has shown the prevalence ranging from 19.7% to 48% [13,15].The prevalence of OIs among HIV patients on ART is still high namely; oral candidiasis 11.8%, followed by chronic diarrhea, 9.9% and tuberculosis 9.7% at in DebreMarkos referral hospital in Ethiopian [16].Which associated with age, WHO stages of III and IV, chew khat, ART adherence, low level of hemoglobin, and recent weight [16].Hence, it is very important to see the magnitude of opportunistic infections and its determinant factors to to reduce the burden.This is important for researchers, clinicians, and health planners.

Methods
The source population was all HIV/AIDS patients who visited ART clinic of the selected three hospital in Sidama zone, southern Ethiopia.While all randomly selected adults from selected hospitals within Feburuary, 01 up to May, 01, 2019 preceding the study.The study was conducted on 420 calculated by a single population proportion formula by taking previously conducted prevalence of opportunistic infections in DebreMarkos Referral Hospital, Northwest Ethiopia [16] and 10% possible non-response rate.The study participants sampled according to their randomly arrivival of selected hospitals.Data was collected by face to face interview by using pre-tested questionnaire; a pre-tested checklist done to collect information regarding OIs and patients' clinical records were reviewed.The age of 18 years or older adults was included.All adults who, are unable to be interviewed, were excluded from the study.

Data collection method and processing
A pre-tested structured questionnaire was utilized to collect socio-demographic characteristics, clinical information and other risk factors.The questionnaires were pretested and validated before two weeks in the study time in Dore Bafana primary hospital on 5% of HIV positive patients who attend ART clinic which was outside of the study area and necessary modi cations were done based on the ndings.Data collectors were ve clinical nurses supervised by one BSC nurse supervisor and investigators.Training and practical demonstrations on interview techniques and document extraction procedures based on check list were given to data collectors for two consecutive days assessed for competency.

Quality control and data analysis
Data collectors were trained and the questioners were pretested before the study time.After data collection process, the data were checked for completeness and any incomplete or mis led questionnaires led again.Data entry, cleaning, and analysis were done by SPSS V. 23.All factors with a p-value <0.2 in the bivariate logistic regression analysis were a candidate to the multivariable model to control confounding effects.The Hosmer -Lemeshow goodness-of-t statistic was used to assess whether the necessary assumptions for the application of multiple logistic regression are ful lled.Odds ratios (OR) with 95% con dence intervals (CI) were calculated.Finally, p-value <0.05 declared a signi cant association.
Ethical clearance was obtained from Hawassa university college of medicine and health sciences ethical review committee, support letter was also requested from the Sidama zone health bureau.All participants informed well about purpose, risk and bene t, and con dentiality.Participation was fully voluntary and written informed consent (verbal consent for who cannot read and write respondent) was obtained from each participant.The patients' medical records were reviewed anonymously, and all information obtained from medical records was kept con dential.

Terms and de nitions
Opportunistic infection-If the study participant diagnosed atleast were one or more opportunistic infections; any infections of bacteria, viruses, fungi, Parasitic or protozoa or multiple infections reported on their medical record [7].
Adverse effectan unwanted effect caused by the administration of drugs.On set may be sudden or developed over time.
Highly active antiretroviral therapy (HAART)the name given to treatment regimens meant to aggressively suppress viral replication and progress of HIV disease the usual HAART regimen combines three or more different drugs.
Cigarette smokers: who had used cigarette smokers form of tobacco in the last 30 days [17].

Environmental and Behavioral related characteristics
The majority of 273 (65.9%) were live in cemented oor house.Most of 401 (96.9%) had latrine, among this 395 (95.4%) were shared with their family and neighbors.More than half of 287 (69.8%) used Garbage can or sac to disposer refuse.Main source of drinking water was 398 (96.1%) pipe water.

Health care system and Clinical Setting related factors
Out of the respondents, 263 (63.5%) were had doubts on ARV and health care provider.Majority of 376 (90.8%) were know the importance of adherence on ART and 352 (85.0%) were believe it improve life.

Associated Factors for Opportunistic Infections
In the multivariate analysis age of respondent, household monthly income, initial CD4 count, WHO clinical staging, education, had no extra medicine additional to ART (prophylaxis), taking ART medicines properly, and Khat chewing were remains as determinant of opportunistic infections.This study result shows that the advancing in the age had about 2. were more exposed to OIs when compared to their counterparts (Table 3).

Discussion
This facility-based cross-sectional study revealed that, the maginitude of opportunistic infections was 39.6%, [95% CI: 35.0 -44.4] were found to be infected by one or more opportunistic infections among HIV/AIDS Patients taking ART at Selected Hospitals in Sidama Zone, Southern Ethiopia.Major identi ed opportunistic infections were Oral candidacies 23.2%, recurrent bacterial pneumonia 21.5%, Herpes zoster 6.3%, and Pulmonary Tuberculosis 6.0%.This study result was consistent with the study ndings in Wolaita Zone, Southern Ethiopia 45.3% [8] and Uganda 43% [9].This result higher when compared eastern Ethiopia 20.2% had any form of tuberculosis, oral candidiasis, herpes zoster [13], 22.4% Nigeria [18], 19.7% Northern Ethiopia [19].While, it was slightly lower when compared with 61.7% Nigeria [18], 47.6% Taiwan [20], and 48% eastern Ethiopia [13].The discrepancy might be due to difference in geographical areas of study participants, high exposure to infectious agents, social-economic status, drug resistance, immunity and nutrition, may affect the magnitude of OIs.
This study result revealed that the advancing in the age was more exposes to OIs as compared with younger age.Similar with the United States [21], and Northwest Ethiopia [22].The possible reason may be, when they grow older the patients immune get decreased due to increased number of viral load and other factors predispose for OIs.Inaddition to that the study participants who had no formal education exposes to OIs more when compared with high and above education.This nding was also similar with DebreMarkos Referral Hospital, Northwest Ethiopia [22], and eastern Ethiopia [13].This may due to lack of health-related information about prevention, early symptoms and health bene ts.Low household monthly income was more exposed to OIs as to their counterparts.This nding is consistent with Bangladesh [23], and Lao People's Democratic Republic (PDR) [24].This might due to house hold income directly related with nutritional status and sanitation status of the individuals.Initial CD4 count less than 200 cells/mm3 was more exposed to OIs as compared with higher CD4 count.
This study nding agree with eastern Ethiopia [13], and Amhara region, Ethiopia [25].This might due to low body defense mechanism favoured the OIs.Futhermore, advancing in WHO clinical stage to II, III and IV was more exposes to OIs as compared with stage I.This study nding in line with Wolaita Zone, Southern Ethiopia [8], eastern Ethiopia [13] and Dessie hospital ART clinic, Northeast Ethiopia [26].This might due to OIs are caused when patient become late on WHO clinical staging which determine to develop AIDS.
The study prticipants who interrupt ART medicines and who had no extra medicine additional to ART (prophylaxis) had high odds of to develop OIs.This study nding consistent with eastern Ethiopia [13], and Dessie hospital ART clinic, Northeast Ethiopia [26].This might due to OIs could be prevented by using extra drugs additional to ART drugs or prophylaxis.
This study result showed that Khat chewing were more exposed to OIs.Similarly reported in Northwest Ethiopia [22], and eastern Ethiopia [13].The possible reason may be, chewing Khat cause malnutrition due to poor appitiet and it affect health seeking behavior by temporary relief.This study result shows there was high prevalence of OIs.This may due to there are endemic intestinal parasite in the area which expose the patient on daily activities or this could be a sign of resistance/ treatment failure that needs to be further investigated.Which related to occurred irrespective of the income status, chewing Khat, interrupt ART medicines and who had no extra medicine additional to ART (prophylaxis), low educational status and due to poor level of health seeking behaviour of the study participants.This study ndings recommend for more consideration on different strategies to address early detection for better prevention, evaluation, and management.Future research should explore more by triangulating with qualitative study for factors with OIs to design taregeted interventions.
This study has potential limitations as the study is cross-sectional in design; it neither represents seasonal variation of nutritional outcomes nor establishes causal relationship.

Conclusions
This study result shows there was high prevalence of opportunistic infection among HIV/AIDS patients taking anti-retroviral therapy.This indicates that the threatening burden of opportunistic infections couldn't be averted by only provision of ante-retroviral therapy.The most common opportunistic infections were of oral candidiasis, herpes zoster and tuberculosis (pulmonary and extra pulmonary).Older age of respondent, household monthly income, initial CD4 count, advancing WHO clinical staging, had no formal education, had no extra medicine additional to ART (prophylaxis), prticipants who interrupt ART medicines, and Khat chewing were found determinant factors for opportunistic infections when compared to their counterparts.

Table 2 :
Environmental and Behavioral related characteristics among HIV/AIDS Patients taking ART at Selected Hospitals in Sidama Zone, Southern Ethiopia, 2019.