{'fraction_non_alphanumeric': 0.03695479777954005, 'fraction_numerical': 0.026381178958498546, 'mean_word_length': 5.234673698088332, 'pattern_counts': {'":': 0, '<': 1, '<?xml version=': 0, '>': 0, 'https://': 0, 'lorem ipsum': 0, 'www.': 0, 'xml': 0}, 'pii_count': 0, 'substrings_counts': 0, 'word_list_counts': {'cursed_substrings.json': 0, 'profanity_word_list.json': 0, 'sexual_word_list.json': 0, 'zh_pornsignals.json': 0}}
MEDICINAL HERBS USED BY HIV-POSITIVE PEOPLE IN LESOTHO

Background: The use of medicinal herbs whose efficacy and toxicities are not known by HIV-positive people in Lesotho is a threat to the effectiveness of antiretroviral treatment. This study explored some medicinal herbs used by HIV-positive people in Lesotho and the reasons for their use. Methods: This was a cross sectional study based on a questionnaire distributed to purposively-sampled HIV-positive people in Leribe and Maseru districts of Lesotho. The participants’ socio-demographic and clinical variables were summarized using frequency tables in Stata version 13 statistical software. Data variables for medicinal herbs used, frequency of use, uses by the participants and in the literature, parts of plants used and the method of preparation were also explored. Results: Out of 400 questionnaires distributed to the participants, 389 were returned with data acceptable for analysis. Ages of the participants ranged from 18 to 75 years (Mean=43 + 11.6). Out of the 272 (69.9%) participants who conceded that they had used medicinal herbs at least once, 30 (7.7%) participants used medicinal herbs frequently while 242 (62.2 %) rarely used the herbs. At least 20 plant species belonging to 16 families were reportedly used by the participants. Asteraceae was the most common plant family reportedly used by the participants. Allium sativum and Dicoma anomala, reportedly used by 21.0% and 14.3% respectively, were the most commonly used medicinal herbs in this population. In addition, boosting the immune system and treating gastrointestinal ailments, apparently cited by 32% and 28% participants respectively, were the most commonly reported reasons for using medicinal herbs. Conclusion: A considerable proportion (69.9%) of HIV-positive people use medicinal herbs in this population, and 7.7% use them frequently. At least 20 plant species belonging to 16 families were reportedly used by the participants. HIV counselling protocols in Lesotho should emphasize the dangers of using medicinal herbs whose safety and compatibility with antiretroviral drugs is not known. The efficacy and toxicity profiles of the medicinal plants identified in this study need to be investigated. Furthermore, the effects of these plants on antiretroviral treatment outcomes including herb-drug interactions need to be explored.


Introduction Background to the Research Problem
Available statistics shows that Lesotho, which has an estimated adult HIV prevalence rate of 23%, has the third highest HIV prevalence worldwide (WHO, 2014). The use of medicinal herbs to treat Human immunodeficiency virus (HIV) and Acquired immunodeficiency syndrome (AIDS) in developing countries, including Lesotho, remains a contentious issue due to their unknown safety profiles. Medicinal herbs are often preferred because they are affordable and are purported to have less side effects compared to pharmaceutical drugs (Rafieian-Kopaei, 2011). The HIV/AIDS burden and cultural norms in African countries have continued to promote the use of medicinal herbs as complementary and alternative medicines to clinical antiretroviral drugs (Puoane, Hughes, Uwimana, Johnson, & Folk, 2012).
In the context of the African traditional religion, the worshiping of a Supreme Being connects Africans with their ancestors and is at the core of how they treat diseases (Dilger, Burchardt, & van Dijk, 2010). The African traditional religion surmises that HIV/AIDS partly results from punishment by the Supreme Being (Wasti, Randall, Simkhada, & van Teijlingen, 2011). The religion therefore encourages that herbalists, traditional healers and diviners be consulted as part of the treatment of disease conditions. Many Basotho in Lesotho who believe in the African traditional religion observe this cultural norm (African Technology Policy Studies, 2013). Hussain (2011) notes that medicinal herb dosages are often not evaluated in clinical trials. Resultantly, their dosages and safety are not known (Petzer & Mngqundaniso, 2008). In some cases, there are concerns about deliberate adulteration of herbs with clinical drugs by some herbalists and contamination by microbial organisms when herbs are prepared in unhygienic conditions (Hussain, 2011). interactions are either pharmacokinetic or pharmacodynamic in nature. Pharmacokinetic interaction is the effect of a medicinal herb on the absorption, distribution, metabolism, or excretion of a therapeutic drug, while pharmacodynamic interactions are often attributed to pharmacological activity of herbs, which results in the potentiated or decreased action of drugs (Chen et al., 2012;Hussain, 2011). Enzyme induction and inhibition particularly in the intestines, liver and kidneys is thought to play an important role in the pharmacokinetic and pharmacodynamic herb-drug interactions (Chen et al., 2012).
Pharmacokinetic and pharmacodynamic interactions may alter the concentration of a therapeutic drug in the blood. The most common interactions include the interaction with the hepatic cytochrome P450 enzymes, the P-glycoprotein drug transporters and the organic anion transporters (Hussain, 2011). For example, Allium sativum (garlic) is known to pharmacokinetically reduce the serum concentration of protease inhibitors (PIs) such as saquinavir and indinavir (Langlois-Klassen, Kipp, Jhangri, & Rubaale, 2007; Nagata et al., 2011). Hypericum perforatum (St John's wort) is also known to significantly reduce blood concentrations of several drugs, including amitriptyline, warfarin and indinavir (Chen et al., 2012).

Medicinal Herbs Believed to Have Antiviral Properties and Their Effects
According to Peltzer et al. (2011) and Langlois-Klassen et al. (2007), Hypoxis hemerocallidea (African potato), Hypericum perforatum (St. John's wort), Sutherlandia frutescens (Sutherlandia) and Allium sativum (garlic) are some of the most commonly used herbs by HIV-positive people in sub-Saharan Africa.
African potato is commonly used as an immune booster (Mills, Cooper, Seely, & Kanfer, 2005). The active ingredients in the African potato which are thought to have anti-HIV activity include phytosterols, hypoxide, aglycone and rooperol (Wink & Van Wyk, 2004). However, according to Müller and Kanfer (2011), African potato may interfere with antiretroviral drugs such as efavirenz through inhibition of cytochrome P450 and P-glycoprotein, which are important liver enzymes that metabolise and eliminate antiretroviral drugs.
Hypericum perforatum (St. John's wort), is a small shrub which contains hyperforin, hypericin, pseudohypericin, flavonoids and oligomeric procyanidines (Nathan, 2001;Wink & Van Wyk, 2004). Petijová, Skyba, and Cellárová (2012), note that biologically active metabolites such as hypericins and phloroglucinols in this plant may have anti-cancer, antiviral and antiinflammatory properties. However, Hussain (2011) notes that St. John's wort has potential toxic effects through substrate-mediated inhibition or inducement of cytochrome liver enzymes, including an intestinal and a hepatic cytochrome known as CYP3A4.
Allium sativum (Garlic) is a perennial herb which contains sulphur-containing biologically active compounds, including Sallyl-l-cysteine, diallyl disulfide, diallyl trisulfide, ajoene, and allicin, which gives it its antimicrobial, antioxidative, antiviral, anticancer and lipid lowering effects Sutherlandia frutescens (Sutherlandia) is another perennial shrub believed to have anti-HIV activity. The herb contains triterpenoids glycosides, flavonoids, amino-acids, including L-canavine which is a non-protein amino-acid and pinitol, which is a cyclitol (Wink & Van Wyk, 2004). Canavine has been demonstrated to have the capacity to disturb protein biosynthesis, a property which is thought to contribute to its anticancer and antiviral activity (Wink & Van Wyk, 2004). Sutherlandia has been used to treat HIV symptoms and opportunistic infections, including tuberculosis, chronic fatigue, influenza, indigestion, peptic ulcers, and diarrhoea (Mills et al., 2005). However, like African potato, sutherlandia inhibits cytochrome P450 and P-glycoprotein, which implies that the herb may interfere with antiretroviral treatment (Müller & Kanfer, 2011).
To improve antiretroviral treatment outcomes in Lesotho, more data on the medicinal herbs used by HIV-positive people and the reasons for their use is required. This study therefore explored some medicinal herbs used by HIV-positive people in Lesotho and the reasons for their use.

Study Setting
The study was conducted at antiretroviral therapy (ART) centres of Motebang Government Hospital in Leribe District and St. Joseph's District Hospital in Maseru District. Maseru District has an HIV prevalence rate of about 27%, while that of Leribe is estimated at 25%. In 2009, about 80,190 people in Maseru and 68,850 people in Leribe were HIV-positive (GoL, 2009). Lesotho is a small landlocked independent country which is completely surrounded by its only neighbour, South Africa.

Study Design
The study was based on a cross sectional descriptive and qualitative questionnaire, which was distributed to HIV-positive people at two district hospitals in Lesotho.

Study Population and Sample Size
The target population was 80,190 and 68,850 HIV-positive people in Maseru and Leribe districts of Lesotho, respectively. The sample size was calculated according to the survey guidelines recommended by the WHO (Raosoft, 2004). Assuming a target population of 80,190 and 68,850 HIV-positive people in Maseru and Leribe districts of Lesotho, an error of margin of 5% at 95% confidence interval and a minimum response rate of 50%, the minimum sample size required was 377 (Raosoft, 2004).

Data Collection
Data were collected between the 6 th of March and 20 th of May 2015 using a semi-structured questionnaire designed by the researchers and pilot-tested with 10 participants who were not included in the final data collection. The questionnaire was translated and each participant completed it in vernacular language (Sotho). Out of 400 questionnaires distributed to HIV positive patients who attended their ART appointments during the time of data collection at the two hospitals included in the study, 389 questionnaires were returned with data acceptable for analysis.

Statistical Analysis
Data was cleaned and checked for completeness. The participants' socio-demographic and clinical variables were summarized using frequency tables in Stata version 13 statistical software. Data variables for medicinal herbs used, frequency of use, uses by the participants, parts of plants used and the method of preparation were also tabulated. In addition, uses of the medicinal herbs as recorded in literature were also compiled.

Ethical Consideration Related to Data Collection
The research proposal was submitted and approved by the institutional ethical review board of the Faculty of Health Sciences at the National University of Lesotho and the Ethics Committee at the Ministry of Health of Lesotho. Permission to conduct the study was also sought and granted by the relevant authorities at St Joseph's and Motebang hospitals. The participants were provided with information on the background of the study. The participants were also informed that their participation was voluntary and that they could decline to answer certain questions, including that they could withdraw their participation at any time. In addition, confidentiality of their information was also assured. Subsequently, each respondent signed a written consent form before data collection.

Socio-Demographic and Clinical Characteristics of the Participants
A total of 389 participants were interviewed. Their ages ranged between 18 and 75 years, (Mean=43 years+11.6). Figure 1 presents the socio-demographic characteristics of the participants. Concerning the marital statuses of the participants; 201 (51.7%, n=389) participants were married, while 96 (24.7%) were widowed. Notably, 54 (13.9%) participants were never married, 27 (6.9%) participants were separated, 7 (1.8%) participants were divorced and 4 (1.0%) had cohabitation With regard to gender, there were more female (60.4%) than male (39.6%) HIV-positive participants. Out of the 389 participants, 169 (43.4%) had primary education as their highest level of education, while 16 (4.1%) had no formal education. Only 23 (5.9%) participants had tertiary education. Regarding work status, 201 (51.7%) participants were unemployed, while 44 (11.3%) were selfemployed.  Figure 2 presents clinical variables of the participants. In total, 377 (96.9%, n=389) were on antiretroviral drugs while 10 (2.6%) were not on treatment. The most common first-line regimen was tenofovir/lamivudine/efavirenz which had 241 (61.9%) participants. Only three (0.8%) participants were on second line regimens. In total, 21 (5.4%) reported that they had experienced some side effects from antiretroviral drugs. When median CD4 counts were considered, 36 (9.9%, n=389) participants had CD4<200 cells/mmᵌ while 48 (13.3%) had CD4 levels between 200 and 350 cells/mmᵌ. Figure 3 presents medicinal herb usage by the participants. Out of 389 participants, 242 (62.2%) conceded that they used medicinal herbs rarely while 30 (7.7%) participants reported that they used medicinal herbs frequently. In total, 69.9% had used medicinal herbs at least once. 117 (30.1%) reported that they had never used medicinal herbs. Out of the 272 who reported that they had used medicinal herbs at least once, only 210 (77.2%) disclosed the identity of herbs they had used. Table 1 presents the medicinal herbs used by the participants and the associated information, including the proportion of the participants using the herbs, parts of plants used and the methods of preparation. Out of the 210 participants who disclosed the identity of the medicinal herbs they used, 44 (21.0%) reported that they had used Allium sativum (Garlic) while 30 (14.3%) had used Dicoma anomala (Hloenya). Twenty (9.5%) participants reported that they had used Aloe striatula (Seholobe) while 18 (8.6%) had used Xysmalobium undulatum (Poho tšehla). Notably, 33 (15.7%) participants reported that they had used unidentified herbal concoctions.   Figure 4 presents the frequency of the reasons cited for using medicinal herbs by the participants. Of all the reasons cited for using medicinal herbs by the participants, boosting the immune system and treating gastrointestinal (GIT) problems had the highest frequencies of 32.0% and 28%, respectively. Treating opportunistic infections had the least frequency (5%). However, 8.0% used the herbs for unspecified conditions while 1.0% did not indicate any reason for using the herbs.

Discussion
About 69.9% of HIV-positive people in this population have used medicinal herbs concurrently with antiretroviral drugs at least once in their lives. Out of the 69.9%, 7.7% conceded that they frequently used medicinal herbs concurrently with antiretroviral treatment. It is important to note that some participants may not have disclosed their use of medicinal herbs. According to Petzer and Mngqundaniso (2008), up to 70% of people living with HIV do not disclose to the health professionals when they use complementary and alternative therapies. Therefore, this study highlights the level of popularity of medicinal herbs among HIV positive people in Lesotho.
The study identified 20 plant species belonging to 16 families that were reportedly used by the participants. Asteraceae was the most common plant family used by the participants. However, the effects of most of these plants on antiretroviral drugs are not known.
In terms of plant species, Allium sativum and Dicoma anomala were cited as the most common (21.0% and 14.3%, respectively) medicinal herbs used in this population. A study in Kenya which reported similar results found that more than 25% of HIV-positive people used Allium sativum (Nagata et al., 2011). The current study also concurs with Langlois-Klassen et al.   (Bhat, Kumar, & Bussmann, 2013). There is need to increase the awareness about the conservation of these plants, particularly among the people who are responsible for harvesting the plants. With respect to the reasons for use of medicinal herbs, 32% of the participants in this study cited boosting the immune system as the main reason for using medicinal herbs. It is possible that some traditional healers and dealers in the medicinal herbs may take advantage of the demand for the herbs and sell unsafe herbs to unsuspecting clients. Therefore, users of medicinal herbs in this population need to be made aware about toxicity of some of the plants and their interaction with antiretroviral drugs.
It is important to note that most of the medicinal plants used by HIV-positive people in this study were found to be used to treat other conditions in the literature. However, in some cases, the uses cited by the participants did not concur with the literature. On one hand, this may indicate the diversity of uses of medicinal plants in different societies. On the other hand, it may imply that herbalists may be selling fraudulent medicinal herbs or wrongly prescribing them to unsuspecting clients. The efficacy and safety of most of the medicinal plants used by HIV-positive people was not known. This highlights the need to incorporate information on the possible dangers of using medicinal herbs whose safety is not known into the counselling protocols of HIV positive patients in Lesotho and other countries. Several limitations might have affected this study, including reluctance by some participants to disclose the medicinal herbs they used. The other limitation is that this study could not establish the effect of medicinal herbs on antiretroviral treatment outcomes. However, the plants identified in this study can be a useful resource to researchers who may want to study the effects of these medicinal herbs on antiretroviral treatment outcomes.

Conclusion
A considerable proportion (69.9%) of HIV-positive people use medicinal herbs in this population and 7.7% use them frequently. Of the 20 plant species belonging to 16 families reportedly used in this study, Asteraceae was the most common family. Allium sativum and Dicoma anomala were the most commonly used medicinal herbs in this population. Boosting the immune system and treating gastrointestinal ailments were the most commonly reported reasons for using medicinal herbs.
HIV counselling protocols in Lesotho should emphasize the dangers of using medicinal herbs whose safety and compatibility with antiretroviral drugs is not known. The efficacy and toxicity profiles of the medicinal plants identified in this study need to be investigated. Furthermore, the effects of these plants on antiretroviral treatment outcomes including herb-drug interactions need to be explored.