Prevalence, Perception and Predictors of Concomitant Herbal Medicine Use among HIV/AIDS and Tuberculosis Patients in Metekel Zone, Northwest Ethiopia: A Cross-Sectional Study

Background The use of herbal medicine is common in Ethiopia. However, evidence on the extent and predictors of concomitant use of herbal medicine with conventional treatment among HIV/AIDS and tuberculosis patients is limited. Objective To assess the extent of concomitant use of herbal medicine with conventional therapy and associated factors among HIV/AIDS and tuberculosis patients in Metekel Zone, Northwest Ethiopia. Method A cross-sectional study was conducted from January to March 2020. HIV/AIDS and tuberculosis patients who visited the health facilities during the study were interviewed face-to-face using a structured and pretested questionnaire. The descriptive statistics and univariate and multivariate logistic regression analyses were conducted using SPSS version 25. A P-value of <0.05 was considered significant. Results 412 patients on conventional treatment were included in this study; 355 (86.2%) were HIV patients, and 57 (13.8%) were TB patients. More than half, 217 (52.7%) participants reported using herbal medicine while on conventional therapy. Among those who claimed to have used herbal medicines, 32 (14.7%) received herbal medicine from traditional healers. About four of five herbal users did not disclose their use to their healthcare providers. The type of health facility on follow-up (P=0.03), disease status (P=0.01), occupation (P=0.02), discontinuing ART (P=0.03), and encountering side (P=0.04) were the determinant factors for the use of herbal medicine among our study participants. Conclusion In the Metekel Zone, concomitant consumption of herbal medication is common among HIV/AIDS and tuberculosis patients. Furthermore, most patients did not disclose the healthcare practitioners about their herbal use. Therefore, healthcare practitioners must assess and counsel patients regarding the potential adverse effects and herb-drug interaction to optimize therapy.


Introduction
Te human immunodefciency virus (HIV) remains a global challenge, particularly in sub-Saharan Africa, as it afects the young and economically productive population [1,2]. An estimated 38.4 million people were living with HIV, with 1.5 million new infections in 2021. Te Eastern and Southern Africa region carries more than half (54%) of the global HIV burden [1]. Ethiopia is among the most highly afected countries, with a 0.9% national HIV prevalence. Also, HIV/ AIDS is among Ethiopia's top ten killer diseases [1,3].
Tere is a widespread use of traditional medicine among PLWHA, although early initiation of antiretroviral therapy (ART) has reduced mortality and morbidity and improved their quality of life [7]. Several comorbid physical and psychosocial issues such as pain, opportunistic infections, side efects of ART, depression, and anxiety encountered by PLWHA contribute to the greater use of traditional medicine [8]. Te chronic nature and incurability of HIV led patients to practice both conventional and traditional therapies to improve their quality of life and longevity. In Ethiopia, herbal medicine is the most commonly used traditional medicine [9].
Many independent factors predict herbal medicines use among PLWHA. Several studies reported that higher herbal medicine use is associated with shorter duration since diagnosis (<5 years), shorter duration on ART (<4 years), experiencing opportunistic infections (OIs), the occurrence of ART side efects, living in a rural province, female gender, older age, being unmarried, employed, and limited education among HIV patients on ART [14,15,19,20].
Even though herbal medicine use is common among PLWHA on ART, it is difcult to accurately determine the prevalence of concomitant use since patients rarely inform herbal use health care providers [15,21]. According to studies, more than half of patients who used herbal medicine did not reveal their usage to healthcare [10,18]. Similarly, Onifade et al. [22] reported that 73.4% of herbal medicine users denied use when asked by a medical practitioner.
Many patients perceive herbal remedies as efective and safe for managing HIV. A study revealed that 67.2% of the patients believe that herbal therapy is efective, and 64.1% use herbal therapy as complementary therapy [22]. Tis contributed to the continued use of herbal remedies concurrently with ART.
In Ethiopia, herbal medicine is widely used by HIV/ AIDS patients [9]. However, there is limited evidence on the extent and predictors of herbal medicine use among PLWHA while on ART. Two studies conducted in Gondar Teaching Hospital, Northwest Ethiopia reported that 43.7% and 70.8% of patients use traditional medicines while on ART [10,23]. A study in four referral hospitals revealed 28.5% concomitant herbal use among PLWHA [24]. Te most common herbal preparations used by PLWHA were Allium sativum, Moringa stenopetala, and Zingiber ofcinale [10,24].
Few studies assessed the Prevalence of herbal medicine use among TB patients. A study in Peru reported 63% of herbal use among TB patients [25]. However, herbal medicines are used by TB patients for symptomatic treatment [26], managing hepatotoxicity due to anti-TB drugs [27], prevention of TB resistance [28], and for their antimycobacterial activity [29].
Te potential of herbal medicines to interfere with ART or anti-TB treatment efectiveness is a pressing concern due to little evidence supporting their safety and efcacy [30]. Indeed, using certain types of herbs may compromise the efcacy of ART due to an unanticipated drug interaction or side efects from herbs [31]. Te potential for adverse outcomes may be amplifed when patients do not disclose herbal medicine use to their healthcare providers and when the patient preference for herbs interferes with the uptake of conventional ART [10]. Hence, research determining the extent and the determinant factors for using herbal medicine is paramount to recognizing the impact of herbal use on HIV/AIDS and TB care. It also signals health care providers to consider herbal use during patient assessment and care and identify patients who need counseling on herbal use. In Ethiopia, no study has determined the extent of herbal medicine use among PLWHA receiving ART in primary healthcare facilities such as health centers. Terefore, this study aimed to assess the prevalence and contributing factors for use of herbal medicine among PLWHA and TB patients attending treatment in the health facilities of Metekel Zone, Northwest Ethiopia.

Study Area.
Tis research was carried out in the Metekel Zone, a rural area in the Benishangul Gumuz regional state, about 650 kilometers northwest of Addis Ababa. Recently, the Metekel zone has been a hot spot for spreading HIV and TB infections as small towns are booming due to signifcant government projects, including the Ethiopian great renaissance dam in the zone. Moreover, communities of the Metekel Zone are known for their culture of using herbal medicine for the management of diferent illnesses [32,33].
Tis study was conducted in fve health facilities in fve diferent districts in Metekel Zone. Te selected health facilities were Pawi General Hospital in the Pawi district, Gilgel Beles Heath Center in the Mandura district, Dibate Health Center in the Dibate district, Bullen Health Center in the Bullen district, and Debrezeit Health Center in the Wonbera district. Health facilities were selected purposively for this study based on the availability of both HIV/AIDS and TB care and treatment services in these facilities. Approximately 2000 HIV/AIDS patients were on active ART follow-up during the study period in the selected facilities. As an ambulatory care service, HIV/AIDS prevention, care, and treatment are provided in dedicated HIV clinics in each health facility. Similarly, the TB clinics ofer care for patients in the intensive phase with directly observed therapy and continuation phase TB treatment as ambulatory care in each facility.
Since, the total this population is <10,000, Cochran's sample size correction formula for fnite population size was applied.
where nf is the fnal corrected sample size, n 0 is the sample size for an infnite population, and N is the population size. Considering the 10% contingency for nonresponse, a total sample of 355 HIV/AIDS patients was included in the study. Te samples were distributed proportionally to each study facility based on the total number of patients. Accordingly, 210 participants in Pawi Hospital and about 50 patients in each health center (Bullen, Dibate, Wonbera, and Mandura Health centers) were included in this study.
Te total number of TB patients treated in the selected health facilities was small; therefore, all TB patients on follow-up during the study period were included. A convenient sampling technique was used where participants who voluntarily gave verbal consent were interviewed until the fnal sample size was reached for PLWHA.

Study Variables.
Te dependent variable was the concomitant use of herbal medicine and conventional treatment, whereas independent variables include sociodemographic characteristics of participants such as age, gender, religion, marital status, educational status, and occupation; and clinical characteristics of participants such as duration since diagnosis, duration on treatment, ART regimen, phase of treatment for TB, recent CD4 count, the experience of opportunistic infection, presence of comorbidity, and occurrence of ART side efects.

Data Collection
Methods. Data were collected by six data collectors (2 data collectors in Pawi General Hospital and 1 data collector in each health center) selected among healthcare providers working in the same facilities as health ofcers or nurses. Data collectors were trained for a day by the research team on how to approach participants, interview them, and adequately fll in the required data.
Data were collected using a structured and pretested questionnaire, which was frst prepared in English and then translated into the Amharic language (the ofcial language of the study area). Te survey questionnaire contained three sections; the sociodemographic characteristics (age, gender, marital status, occupation, and educational level); clinical characteristics (duration since diagnosis and ART initiation, current use of ART, CD4 count, and symptoms experienced and any side efect encountered during treatment); and the practice of herbal medicine use (commonly used herbs, reasons for use, and disclosure to healthcare providers). To maintain the quality of data, the questionnaire was pretested, and ambiguous statements were rephrased to improve clarity. Te research team checked the completeness and accuracy of the data collected throughout the data collection process.

Data Analysis.
Te data were entered and analyzed using SPSS version 25. Descriptive statistics such as frequency distribution and percentages were determined. Te independent association between herbal medicine use and sociodemographic and clinical characteristics was analyzed using univariate logistic regression. Te variables with P < 0.25 in this model were kept for multivariate logistic regression to identify independent predictors for the concomitant use of herbal medicine adjusted for other factors. Te P-value of <0.05 was considered signifcant.

Glossary of Terms
(i) Traditional medicine is the total of the knowledge, skill, and practices based on the theories, beliefs, and experiences indigenous to diferent cultures, whether explicable or not, used in the maintenance of health as well as in the prevention, diagnosis, improvement, or treatment of physical and mental illness (ii) Herbal medicines include herbs, herbal materials, herbal preparations, and fnished herbal products that contain active ingredients, parts of plants, other plant materials, or combinations. (iii) Traditional medical practitioner or traditional healer (TH) is a person who is recognized by the community where he lives as competent to provide health care by using vegetable, animal, mineral substances, and certain other methods. (iv) Concomitant herbal use: using herbal medicine for self-medication or using herbal therapies obtained from traditional medical practitioners while on conventional treatment.

Evidence-Based Complementary and Alternative Medicine
(v) Self-medication is the selection and use of medicines (herbal and traditional products) by individuals to treat self-recognized illnesses or symptoms without consulting health care providers.

Sociodemographic Characteristics of Study Participants.
In this study, a total of 412 participants were included. About half of the participants were from Pawi General Hospital 210 (51%) and in the age group between 30

Prevalence of Herbal Medicine Use, Reasons for Use, and
Source of Information. A total of 217 (52.7%) study participants used herbal medicine concomitantly with conventional therapy. Te concomitant use of herbal medicine is signifcantly higher among the PLWHA than among TB patients (54.9% vs. 38.6%, OR � 1.94, P � 0.012). Te primary reasons for the use of herbal medicine by respondents were to improve general well-being 112 (52.1%), the belief that herbal medicine is natural and safe 72 (33.2%) and to improve appetite 63 (29.0%) ( Figure 1). As shown in Table 4, the most common herbal medicines used by HIV and TB patients were garlic (Allium sativum) 124 (57.4%) followed by Ginger (Zingiber ofcinale) 108 (50%), rue (Ruta chalapensis) 40 (18.5%), and moringa (Moringa stenopetala) 34 (15.3%). Regarding ethnopharmaceutical processing for herbal products, participants mostly prepared herbal remedies as decoctions and drank while hot as tea, chewed and swallowed, and infusions in hot tea/cofee. Study participants used herbal medicine for several indications, mostly for managing the common cold, sore throat, rash, herpes zoster, hepatitis, arthritis, poor appetite, and improving general well-being.

Reasons for Not Using Herbal Medicine.
A total of 195 (47.6%) study participants said they did not use herbal medicine while on their conventional therapy ART or TB treatment. Te reasons given by participants for not using herbal medicine were counseling of health care providers against the concomitant use of herbal medicine 88 (43.9%), being satisfed with conventional therapy 67 (33.7%), and fear of side efects of herbal remedies 38 (19.4%) (Figure 2).

Perception of Concomitant Use of Herbal Medicine.
Most participants believe that herbal remedies efectively manage HIV/AIDS-related illnesses 376 (91.3%) but only 34 (8.3%) believe that herbal medicine can cure HIV/AIDS and/or TB. Furthermore, most participants believed herbal medicines were natural and safe 336 (81.6%) and did not interact with ARTor anti-TB medications 365 (88.6%). Following an HIV or tuberculosis diagnosis, the majority of patients 369 (89.6%) sought frst medical care from biomedical healthcare facilities. As the frst action for the treatment of HIV/AIDS or TB, only 8 (1.9%) of the patients used herbal medicine while 39 (9.5%) used a religious practice like "Tsebel" (Table 5).

Communication with Health Care Providers about Herbal
Medicine Use. Among claimed herbal medicine users, only  Table 6 shows the factors associated with herbal medicine use among the study participants.

Discussion
Despite the improved accessibility and early initiation of ART, there is still widespread use of herbal medicine among HIV patients. In this study, over half of the participants, 52.7% (54.9% PLWHA and 38.6% TB patients) used herbal medicine while on conventional treatment. Our fnding on the herbal medicine use among PLWHA is comparable with reports from other African countries that reported a prevalence between 53.7% and 58% [11,14,34]. However, it is lower than the fndings reported by Haile et al. [10] in northwest Ethiopia (70.8%) and another study in Lesotho (69.9%) [35] but higher than the prevalence of herbal medicine use reports by two studies in Uganda [15,36]. Te fndings between studies might be due to diferences in study populations, unstandardized defnitions for herbal medicine, and inclusion/exclusion criteria for specifc types of therapies in these studies.    Similarly, among TB patients included in the present study, 38.6% reported concomitant herbal medicine use. Generally, studies on the prevalence of herbal use among TB patients are limited. However, a study in Peru showed a higher rate than what was found in our study [25]. Besides, ethnobotanical studies indicated herbal medicines are used for the symptomatic treatment of TB [26], management of hepatotoxicity due to anti-TB drugs [27], prevention of TB resistance [28], and their antimycobacterial activity [29].

Evidence-Based Complementary and Alternative Medicine
Improving general well-being, the perception that herbal medicines are natural and safe and improving appetite were the major reasons for using herbal medicine among our study participants. Similarly, a study by Littlewood and Vanable [37] reported alleviating HIV symptoms and ART side-efects and improving the quality of life as reasons for herbal medicine use. According to Lubinga et al. [36], the main reason for using herbal medicine is to treat symptoms related to OIs. In contrast, dissatisfaction with conventional therapy, 39.6% and belief in the advantages of herbal medicines was cited as primary reasons for use in another study done in Northwest Ethiopia [10]. Te diferences in perception, culture, and belief of the study population towards herbal medicines and ART would determine the reason for using herbal medicine by HIV/AIDS patients.
Te most commonly used herbal remedies by our study participants were A. Sativum, 57.1% and Z. ofcinale, 49.7%. Similar to our fnding, Z. ofcinale, and A. sativum have been reported as the most commonly used herbal remedies [10,38]. Another study, however, stated N. sativa and M. oleifera as frequently used herbal products along with ART [23]. Despite the notion that herbal remedies are safe concurrent use with ARV drugs may lead to herb-drug interactions that may interfere with the efectiveness of ART, causing either potentially dangerous side efects and/ or reduced benefts [15,39]. Even the likelihood of herb-drug interactions could be higher than drug-drug interactions since herbs contain mixtures of pharmacologically active constituents [40][41][42]. Tere are proven adverse interactions between herbal medications and ARV drugs, African potato (Hypoxis hemerocallidea) can potentially inhibit ARV drug metabolism and transport, and garlic supplements have detrimental efects on the plasma concentrations of saquinavir [11]. Also, Cordova et al. [43] reported 2 cases of virologic breakthrough failure due to possible herb-drug interaction between horsetail (Equisetum arvense) and antiretroviral therapy.
Disclosing the HCPs about herbal therapies can help reduce the risk of harmful interactions by improving effective management, counseling, and treatment monitoring [16]. However, the disclosure of herbal medicine among patients in the present study is very low; only one out of fve patients informed their HCPs that they use herbs. Tis fnding is in line with the 15% disclosure rate by Issa et al. [24], but it is higher than the 7.7% disclosure rate in Uganda  Evidence-Based Complementary and Alternative Medicine 7 [36] and lower than 38.8% in Gondar, Ethiopia [10]. Patients preferred not to disclose herbal medicine use to HCPs due to fear of lack of support and understanding by HCPs [44]. Most patients think HCPs have a dismissive attitude toward traditional medicine because of the lack of credible evidence [45]. However, our study revealed that most HCPs (77%) are supportive and encourage patients who disclose their concomitant herbal use. However, considering the potential adverse herb-drug interaction and lack of evidence on the safety of herbal therapy, it is not appropriate to encourage patients to continue the use of herbal therapy. Terefore, HCPs need to inform patients of the potential for adverse herb-drug interaction and adverse outcomes. Many patients believe herbal medicines are natural, safe, and culturally acceptable remedies to treat several illnesses. In the present study, 91.3% of participants believe herbal remedies are efective and 81.6% think herbal medicines are natural and safe with no adverse efects. Besides, only 11.4% of participants were aware of the potential interaction with conventional medicine. Tis fnding is consistent with the study in Nigeria, where 34.7% of HIV patients believed that herbal remedies are natural [34]. Using relatively small quantities of herbs and spices as part of a regular diet is not likely to cause adverse herb-drug interactions, but using a higher amount for medicinal purposes might increase the likelihood of adverse interaction with conventional therapy [46]. For instance, adverse interactions are documented with the medicinal use of garlic with anticoagulants, antihypertensives, antiviral, anticancer, antidiabetic, and antitubercular drugs [46][47][48]. Te interactions between garlic and antiretroviral protease inhibitors may lead to a decreased concentration of protease inhibitors and increased resistance to ART [31].
Most HIV/AIDS and TB patients in our study practiced self-medication of herbal medicine as a homemade remedy for self-care. Te patients used information from families, friends, and diverse sources to choose herbal medicine. Among our participants, 14.7% received herbal medicine prescribed by healers. Tis is consistent with a report where 18.8% of PLWHA used herbs prescribed by traditional healers in Gondar, Ethiopia [23]. Despite having little evidence about their role, many traditional healers are involved in treating HIV/AIDS in Africa [49]. However, the role of traditional healers in managing HIV/AIDS remained unexplored in Ethiopia.
Several factors independently predict the use of herbal medicine among patients. In the present study, signifcant predictors of herbal medicine use were the type of healthcare facility on follow-up (P ≤ 0.03), disease state [HIV vs. TB] (P � 0.02), occupation (P � 0.01), encountering side efects from ART (P � 0.04), and history of discontinuing ART (P � 0.03). Our fnding is similar to the reports that independent predictors of herbal medicine use among HIV/ AIDS patients are a history of experiencing side efects from ART [15,20,36], nonadherence to ART (15), and occupation [14]. Despite our fndings, several other factors such as older  [20], the occurrence of OIs [20,37], educational level [10,11], duration on ART, self-perceived health status [36], and perceptions towards herbal therapy [12] are found to be independent predictors for herbal medicine among HIV patients.

Strengths and Limitations of the Study.
Te strength of this study involves multiple health facilities such as a hospital and health centers; hence, the fnding can well represent the extent of herbal medicine use among HIV and TB patients in the Metekel zone. Furthermore, the selected study site is an unexplored rural area where a majority of the community rely on traditional medicine for primary health care. However, this fnding cannot be extrapolated to general concomitant herbal use among PLWHA and TB while on conventional therapy. Tis study was based on a crosssectional design; hence, causal inference between independent factors and herbal medicine use cannot be made. Moreover, as the participants were asked about their past use of herbal medicine, recall bias may contribute to underreporting of the use.

Conclusion and Recommendations
Te concomitant use of herbal medicines with conventional ART and anti-TB drugs is high among PLWHA and TB patients in the Metekel zone. Te most commonly consumed herbal remedies were A. sativum and Z. ofcinale as homemade remedies. Te main reasons for utilizing herbal medicine were the improvement of general well-being and the belief that herbal therapy is natural and safe. Besides, the majority of participants who utilized herbal medicine did not inform their healthcare providers. Terefore, healthcare providers must proactively assess and advise patients' concomitant use of herbal medicine. On the other hand, most HCPs in the Metekel zone encouraged the use of herbal medicine for those who disclosed their use despite a lack of supporting evidence. Te counseling on herbal medicine should address the benefts, potential adverse herb-drug interaction, and toxicities of concomitant use with ART or anti-TB drugs. Training is required for HCPs to appropriately counsel patients on herbal medicine use. Terefore, the Federal Ministry of Health should develop a guideline for HCPs to assess and counsel patients on herbal medicine use efectively. In addition, training health care providers on herbal medicine are also paramount to improve the safe use of herbal medicine.