Knowledge, Attitude, Practice, and Adherence to Antiretroviral Therapy among People Living with HIV in Nepal

Introduction Patient's knowledge and attitude towards their treatment avert stereotypical misconceptions about the disease and its treatment, as well as aid in attaining optimal adherence. This study investigated the knowledge, attitude, practice, and adherence of antiretroviral therapy (ART) clients in Nepal. Method A cross-sectional study was conducted among 165 ART clients visiting five ART sites in the far western region and the capital city of Nepal. The convenience sampling method was employed, and the data were collected through interviews with ART clients using a validated questionnaire. Binary logistic regression was used to identify associated factors. Result Approximately 80.7% had adequate knowledge and 55% had a positive attitude towards ART. Stigmatization was associated with ARV by only 4.2%. Half of the participants (50.3%) revealed that they had surreptitiously stored their ART medication, diverging from the recommended storage guidelines. A significant proportion of respondents (33.3%) chose to repackage the medication as a strategy to prevent unintended disclosure of their HIV status. Many (59.3%) believed that ART does not prolong life. Nevertheless, they advocated the regular use of ART rather than taking it only when the health deteriorates (81.8%). The majority (97.6%) were found to be adherent to their ART. There was a significant association of age with a level of knowledge and attitude (p < 0.05). A significant association was also found between knowledge and attitude towards ART (p < 0.05). None of the variables had a significant association with adherence (p > 0.05). Conclusion Overall, adequate knowledge was demonstrated, whereas efforts are still needed to improve the attitude of ART clients towards ART. A need for counseling regarding the storage practices of ART is needed. A focus on ensuring the perfect translation of adequate knowledge and a positive attitude to the practice of ART clients is essential. Whether adequate ART knowledge and attitude scores will lead to near-perfect ART adherence needs further investigation.


Introduction
Human Immunodefciency Virus (HIV) infection and Acquired Immuno Defciency Syndrome (AIDS) have emerged as a formidable global public health crisis claiming 36.3 million lives as of year 2021 [1]. Nepal, one of the countries in South Asia, has recently confronted a meteoric inclination in HIV infection rates, with the recently reported number of people living with HIV (PLHIV) being 29,503. Antiretroviral therapy (ART) was marked as a revolutionary triumph against HIV/AIDS [2]. An antiretroviral therapy service was initiated in Nepal in 2004 by Sukraraj Tropical and Infectious Disease Hospital. To universalize access to ART, the Nepal Government has made ART freely available for all PLHIV, along with the nationwide expansion of 80 ARTsites and 20 ART dispensing centers (ADCs), covering 61 districts in Nepal. Community and home-based care (CHBC) services have been initiated to provide essential services such as prevention, counseling, nutritional support, and education on treatment for improving adherence [3]. Adherence above 95% is the benchmark for a successful ART program which otherwise might lead to a sequel of increased HIV viral load, fueling HIV transmission and the emergence of resistant strains [4][5][6][7][8][9]. Hence, curbing viral replication and achieving optimal clinical benefts contribute to a near-perfect adherence to ART.
Patients' knowledge and attitudes towards treatment play crucial roles in adherence to ART. Understanding the medication regimen and the disease itself empowers individuals to address misconceptions and overcome barriers to adherence [10,11]. Understanding one's medication regimen and disease tends to give the individual cues to identify and revoke misconceptions about the disease and its treatment which are the principal threats to adherence [12][13][14][15]. Improving knowledge of disease and treatment regimens as well as the patient's attitude towards the regimen should be targeted to address the inconsistencies of adherence [16]. Despite the importance of knowledge and attitudes in ART adherence, limited study has been conducted in Nepal specifcally addressing the knowledge, attitude, and practice of PLHIV towards HIV/AIDS only [2]. Tis research gap underscores the need to explore and understand the unique challenges faced by PLHIV in Nepal, shedding light on their knowledge levels, attitudes towards ART, and adherence practices.
In line with this rationale, this study aimed to assess the knowledge, attitude, practice, and adherence of PLHIV towards ART in Nepal. By examining these key factors, we aim to identify areas for improvement and develop targeted interventions to enhance adherence and optimize treatment outcomes.

Study Design, Study Site, and Population Characteristics.
Multicentric cross-sectional study was conducted at fve ART centers: Teku Hospital, Kathmandu; Bhaktapur Hospital, Bhaktapur; Mahakali Hospital, Mahendranagar; Dadeldhura Hospital; and Doti District Hospital. All the patients visiting the ART were receiving the ART during the study period.
Te study population consisted of PLHIV who visited the selected ART sites during the study period of 6 months from August 9, 2021 to February 10, 2022. ART clients, who were 18 years old, had been on the ART for at least three months, and agreed to provide written consent to participate in the study were included in the study. ART clients with the coexisting condition of pregnancy, pediatrics, and the patients admitted to the hospital were excluded. (2) Table 1 shows the sample size stratifcation in diferent districts/hospitals. their KAP of ART, and their adherence. Te knowledge section includes 11 multiple-choice questions on ART. Te attitude section has 8 Likert-like questions with strongly agree, agree, undecided, disagree, and strongly disagree choices. Te score for each question ranges from +2 to −2 (+2, +1, 0, −1, and −2) for the correct statements. For incorrect statements, reverse scoring was done where the score ranged from −2 to +2 (−2, −1, 0, +1, and +2). Practice section contains 7 questions related to the users' practice of ART. Each correct answer scored 1 point, whereas the incorrect answer scored 0 points. For question number 1, the respondents scored 1 point only if they could name all three components of the fxed-dose regimen. Similarly, for question number 6, the respondents achieved 1 point only if they could mention suppressing the power of HIV and not curing the disease as the primary purpose of ART. Anyone selecting only one of the the correct options was given a 0.5 score. Te total scores were 0-11 for knowledge and between −16 and +16 for attitude. Knowledge and attitude scores were converted to a percentage by dividing the total score of each respondent in each section by the maximum score of the same section. Te practice of the interviewees was expressed in terms of frequency and percentage. Te respondents scoring ≤50% were said to have inadequate knowledge, and those scoring >50% were said to have adequate knowledge on ART [19]. Similarly, the respondents scoring ≤50% were said to have a negative attitude, and those scoring >50% were said to have a positive attitude [19]. Te development of the data collection tool was followed by validation of the tool. For content validation, the content validity ratio (CVR = (ne − N/2)/(N/2)), relevance content validity index (R-CVI), clarity content validity index (C-CVI), and simplicity content validity index (S-CVI) were calculated. Eight experts were asked to score the questionnaire items for necessity, relevance, clarity, and simplicity. As per Lawshe's Table, the signifcance level was considered 0.75. All the items had a CVR ≥0.75 and a CVI average was 0.96. None of the items required any modifcations. Cronbach alpha value was 0.72, indicating good reliability. Tis was followed by translation validation, where the questionnaire was initially translated into Nepali language and then back-translated into English. Te fnal version was compared with the original version of the questionnaire. Te fnal version of the questionnaire was tested among 18 PLHIV in Mahakali Hospital.

Sampling
Adherence was assessed based on patients' self-report, one of the simplest and most extensively used methods. It was calculated using the formula from the National HIV Testing and Treatment Guidelines, 2017. Adherence percentage � [number of pills taken during the specifc period (1 month)/number of pills to be taken during that particular period (1 month)] × 100. Patients were categorized as ART adherent if adherence was ≥95% and nonadherent if adherence was <95% [8,20].

Data Collection Process. PLHIV in Bagmati Province
(Teku Hospital, Kathmandu and Bhaktapur Hospital, Bhaktapur) and Far West Province (Mahakali Hospital, Dadeldhura Hospital, and Doti District Hospital) were approached by the researcher, and the objectives of the study were explained. Written informed consent was obtained from each respondent, and assurance was conveyed regarding their voluntary participation and maintenance of their confdentiality. Te interviewer administered the questionnaire to each PLHIV who agreed to participate in the study. All the PLHIV visiting the ART sites were receiving ART.

Statistical Analysis.
Te collected data were entered and analyzed using Statistical Package for Social Sciences (SPSS) version 26 (SPSS Inc., Chicago, IL, USA). Descriptive analyses were performed using frequencies and percentages. Pearson chi-square test (χ 2 ) for independence was used to determine the association of adherence with patients' knowledge and attitude towards ART and to determine the association of patients' attitude towards ART with their corresponding knowledge level. A binary logistic regression analysis was done to identify determinant variables associated with knowledge, attitudes, and adherence. A p value <0.05 was considered statistically signifcant.

Attitude of PLHIV to ART.
Approximately 54.5% had a positive attitude towards ART. Te majority believed that ART is currently the most efective available therapy to combat HIV (99.3%) and were convinced that they have HIV and need to be concerned about taking ART (95.1%). Te majority (90.9%) was assured of the positive efect of ART on health and was persuaded by the fact that ART does more benefts than harm (79.3%). Very few (5.4%) felt that taking ART for one's lifetime is tiring and felt stigmatized by being on ARV therapy (4.2%). A maximal percentage (59.3%) presumed that ARV drugs have no role in prolonging the life of PLHIV and seemed to favor the regular use of ART (81.8%) ( Table 4).

Practice of PLHIV towards Use of ART.
A slight majority (50.3%) reportedly stored their ART "hidden and out of sight." Most participants (n = 110, 66.7%) chose to store ART by transferring it to other plastic packaging, contrary to its storage in its original container (n = 55, 33.3%). When asked about the action to be taken in case of missed doses, (n � 34, 20.6%) rightly mentioned taking the missed doses only if it was not near the time of the next dose, whereas (n � 124, 75.2%) opted for skipping the dose of ART medication that was missed. In the case of running out of prescription for ARV medication, (n � 132, 80%) defned their practice of borrowing from friends, whereas only one patient preferred to call and ask for a refll. Concerning the source of information about ART, (n � 145, 87.9%) seemed to have received information on ART from the ART dispensing staf, followed by referring physicians (n � 107, 64.8%). None of the patients had ever increased or decreased the dose of their ART on their own. Out of 165 participants, a considerable majority (n � 151, 91.5%) practiced selfmedications, including the intake of antibiotics (n � 27, 16.4%), and very few reported taking herbal and ayurvedic drugs (n � 4, 2.4%) ( Table 5).

Association of Demographic Characteristics and ART
Knowledge and Attitude. Binary logistic regression was used to determine the association between sociodemographic characteristics and ART knowledge (Table 6). Tere was a signifcant association of age with a level of knowledge and attitude (p < 0.05). PLHIV in the age group 18-38 years were found to be 5.5 times more knowledgeable than those in the age group 38-58 years concerning ART (11.63 vs. 2.10). PLHIV in the age group 18-38 years were found to have 1.2 times more positive attitude than people in the age group 38-58 years (3.29 vs. 2.66). Te other sociodemographic variables were not signifcantly associated with ART knowledge and attitude towards ART (p > 0.05) (Tables 6  and 7).
A signifcant association was found between ART knowledge and attitude (p < 0.05) ( Table 8).

Discussion
Te present study reported an adequate level of knowledge on ARTamong most of the participating PLHIV; this fnding is in congruence to the previous fndings [18,19,[21][22][23][24]. Still, it contradicted a report where a sizeable proportion of PLHIV in Brazil was unaware of the crucial information on the prescribed ART [7]. All the respondents were aware of their once-daily regimen to be taken at a fxed time. However, none were able to name their ART or mention the components of the combination, which agrees with the earlier reports where only 5.8% and 13.7% could correctly quote the brand name or the ART regimen constituent [18,25]. Nevertheless, this contradicts the fndings of Potchoo et al., where 44.4% could ideally name the ARVs in the fxed-dose regimen [23]. A misconception was observed among the majority of the PLHIV who were ignorant of the fexibility of the dolutegravir-(DTG-) based regimen regarding food intake. All the ART clients in this study had been kept on the frst-line ART regimen that consisted of 2 NRTIs (nucleoside reverse transcriptase inhibitors) and an INSTI (integrase strand transfer inhibitor), namely, TDF + 3TC + DTG (tenofovir, lamivudine, and dolutegravir; TLD). All the respondents perfectly knew their dosage regimen, including the number of tablets to be taken per dose, the frequency of daily intakes, and the times of drug intake. Contrary to the present study, most ART clients are reported to be using a treatment regimen comprising 2 NRTIs plus 1 nonnucleoside reverse transcriptase inhibitor (NNRTI), as reported by Yao et al. As of today, a DTG-based regimen where DTG is combined with 2 NRTIs, TLD is the preferred frst-line regimen for PLHIV in Nepal. Tis switchover from the efavirenz-based regimen to the new regimen is backed by the fndings of the HIV Drug Resistance study conducted by the Ministry of Health and Population (MoHP) that has identifed the emergence of resistant strains to the earlier used ARV regimen. Tis transition, as recommended by the new National HIV Testing and Treatment Guidelines, 2020, is also primarily based on the WHO guidelines published in 2018. Te guideline iterates that a DTG-based regimen in combination with two NRTIs results in greater and faster viral suppression, a lesser incidence of adverse efects, a higher retention rate on treatment, fewer drug interactions, and a lower risk of developing resistance to ART as compared to efavirenz-(EFV-) based regimens [26,27]. A patient's medication knowledge has been defned as "the awareness of the drug name, purpose, administration schedule, adverse efects or side efects, or special administration instructions," and knowledge about medications is one of the most prominent patient-related factors afecting their drug-taking behavior, especially in chronic diseases [28]. Te majority of the PLHIV in the present study were unaware of the names of their ART regimen, which refects the gap in the information provided by the physicians, pharmacists, or ART counselors [29]. Some respondents were ignorant of the duration for which ART should be taken. A few also believed that ART needs to be taken only for some years, in consistency with other literature [18,30]. However, our result mirrors a percentage lower than that of Almeida and Vieira [7]. Regular interaction is required between healthcare professionals and PLHIV, where they must be reminded that HIV/AIDS is an incurable, chronic disease that demands strict adherence and persistent treatment [25]. Te majority believed that ART decreases the viral load, increases the CD4 count, and acts by suppressing the power of HIV, but does not cure the disease.

AIDS Research and Treatment
Nevertheless, a noticeable percentage remained unaware of the facts mentioned above. Tis echoes the fndings of the antecedent studies [18,22,25,31] and refects a reportedly lower percentage than presented by Almeida and Vieira [7]. Te users must obviate ART's unrealistic benefts, such as curing an incurable disease that otherwise might negatively impact their treatment adherence [32]. Most respondents opined that ART has a role in preventing MTCT. In contrast, nearly one-third lacked comprehension in this regard,  [18,33]. MTCT has been stated as one of the most prevalent routes of transmission of HIV infection among children [34]. UNAIDS has spearheaded a comprehensive and accelerated approach towards eliminating MTCT by implementing various interventions. As WHO guidelines recommend, one such intervention is initiating and maintaining the HIV-infected pregnant or breastfeeding women on ART [35]. Lack of information on  ART's efectiveness in preventing vertical transmission, especially among HIV-positive women, might undermine the eforts to end MTCT globally. Te majority were aware of the 95-100% adherence requirement for ART efciency, whereas a small percentage remained ignorant on this which is in line with previous literature [22]. Nearly half the respondents perceived that treatment efciency can be maintained despite missing ART doses, a percentage higher than that reported by preceding studies [18,22,30,33]. It is incumbent on us to bridge such knowledge gaps, as interruptions in treatment can fuel the emergence of ARV resistance [2]. Te majority had a positive attitude towards the use of ART, which corroborates the fndings of Raberahona et al. Almost all the respondents denied the existence of therapies more efective than ART to battle HIV (99.3%), contradicting what is reported in Madagascar and India, where a handful of respondents were not completely persuaded of the efectiveness of ART. As mentioned earlier, some of the study respondents opined that traditional healers are more reliant on ART for the treatment of HIV [18,21]. In contrast, such a misconception was not expressed in our study. Delayed access to HIV testing and ART initiation among PLHIV has been documented as a sequel of medical pluralism resulting from diversion to traditional healing, causing a serious impediment to the HIV care cascade [36]. In low-resource settings like Nepal, where traditional healing receives high patronage, initiatives in education are an absolute necessity to avert such defections of PLHIV. Paradoxically, some opined that ART does not prolong life; this fgure is higher than the studies conducted in Nigeria [19,22,32]. Te majority were convinced of being infected with HIV and agreed that ART does more beneft than the harm which translated into their favoring attitude towards the positive efect of ART on health. Tis is in line with other studies [18,22]. Most did not perceive taking ARV drugs for a lifetime as exhausting and were against the idea that ART should be taken only when sick. Tis outcome may be accounted to the various support programs that the government was running at the time of the study that provided care and support to the PLHIV, facilitated them in viral load sampling, and helped the client with their medication counseling and usage of ART. A minority were ashamed to be on ARV therapy. Te stigma and discrimination PLHIV confront is a considerable setback for disclosing their HIV status and willingness to initiate or retain ART therapy. Sociocultural factors may have constituted a massive impediment that made them apprehensive about taking ART at home or at work [37]. Stigma and discrimination are the recognized barriers to testing, treating, and retaining patients in care and a bottleneck in achieving the 90-90-90 target by 2021. Acknowledging the criticality of such sociocultural issues can pose, Nepal's National HIV/AIDS Strategy 2016-2021 has undertaken the reduction of stigma and discrimination as one of its commitments [38].
Although the majority of respondents claimed to be open about their ART, this was not seen to have translated into practice, as nearly 50% of the users acknowledged keeping their ART hidden and out of sight. Only less than half of the study population followed the storage

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AIDS Research and Treatment recommendation given by the manufacturers, and the majority reported the practice of self-repackaging. PLHIV are involved in self-repackaging of ART, where they transfer the medication from the original repository to other containers in an attempt to camoufage it out of an apprehension of unwanted disclosure of their HIV status and getting stigmatized. Such self-repackaging obviates the protection provided by the original packaging against external conditions such as light and moisture. Furthermore, patients fail to familiarize themselves with the essential drug-related instructions (expiration dates, maintenance of the fxed dosing time, and taking the drug concerning food intake) printed on the packaging [39]. Te majority opted to skip the missed ART dose, one of the drivers for antiretroviral resistance [7]. Most were engaged in self-medication practices; some reported taking acid suppressants and herbal or ayurvedic medications concurrently with ART. Te other reviews were divided mainly between antibiotics, antipyretics, and analgesics.
Self-medication has been common among PLHIV, mainly due to the adverse efects of ARV, their willingness to get better, and for alleviating mild symptoms. Less aware are the patients that potential interactions with the self-medicated products may compromise the efcacy or lead to toxicity of ARVs. Around 50 to 80% of PLHIV did not confde in their self-medication practice to their physicians. Tis calls for integrating self-medication practice questions in medication history taking by physicians and pharmacists and ruling out the chances of potential interactions [39].
Most respondents were found to adhere to their ART regimen in congruence to previous studies in Nepal [8,17]. A greater percentage of PLHIV has been found to adhere to their ART regimen compared to other studies [4,23,40,41]. Tis refects increased awareness of PLHIV on ART, possibly accounting for CHBC services initiated in Nepal and additional support programs [8]. Regarding probable reasons for missing ART doses, most respondents stated remaining too busy with other works, staying away from home, forgetting and feeling better, and hence, missing out on some of the doses. Tis is similar to previous fndings [15,22,23]. Te PLHIV might carry fewer reserves of their ART tablets and possibly miss the refll appointments due to being away from their homes and their working allegiance [42]. Some PLHIV patients may also overestimate the improvement in their health and miss some of the doses of ART. Hence, physicians or ART counselors should not overestimate their patients' adherence and should understand that continuous patient education and counseling are essential to ensure optimal adherence to ART and retention in treatment [19].

Strengths, Limitations, and Recommendations.
Tis study represents a novel inquiry into the understanding, disposition, and behavior of people living with HIV (PLHIV) concerning their antiretroviral therapy (ART). Specifcally, it includes participants from the far western regions of Nepal, which have been identifed as high-risk areas for HIV transmission in accordance with the National HIV Strategic Plan 2016-2021, primarily due to heightened male labor migration to India. Te constraints imposed by the limited timeframe of the study necessitated the utilization of a convenience sampling method. Subsequent stages of research can entail the development of educational interventions targeting specifc population subsets, including pediatric patients and pregnant women with HIV.

Conclusion
An adequate knowledge of PLHIV on ART was observed. However, improving their attitude towards ART requires attention. Education to the concerned individuals should incorporate elements such as ART names, their mechanism of action, the harms of missed doses, and its' role in prolonging life. Te fndings of this study indicate that despite possessing good knowledge and a positive attitude towards ART, the majority of ART clients reported hiding their medication and not following the manufacturer's recommended storage guidelines to prevent the inadvertent disclosure of their HIV status. Although adherence to ART was high among the clients, it is necessary to conduct further investigations to determine if sufcient knowledge and positive attitudes towards ART can result in nearly perfect adherence.