Survey of antiretroviral therapy adherence and predictors of poor adherence among HIV patients in a tertiary institution in Nigeria

Introduction Adherence is vital to effective antiretroviral therapy (ART) for reducing viral load and HIV/AIDS-related morbidity and mortality. This study was aimed at evaluating the adherence of HIV seropositive patients to ART in a tertiary institution in Nigeria. Methods A cross sectional observational study was conducted among 400 HIV seropositive patients. The study was carried out between December 2016 and February 2017 at the HIV clinic of the Ekiti State University Teaching Hospital, Ado-Ekiti, Nigeria. Results The mean age of the HIV patients was 42.2±9.5 years with a predominant female gender (Male:Female = 1:2.8). The median CD4 counts increased from 302.1±15.0cells/mm3 at diagnosis to 430.8±13.3cells/mm3 at the time of the study. Majority of participants were unaware of their spouses' HIV status (59.3%) while 32.5% of participants had a serodiscordant spouse. Poverty was a major challenge as 73.3% earned less than 140 dollars per month. Depressive symptoms, anxiety disorder and insomnia were also reported in 40.7%, 33.2% and 47.2% respectively. Poor adherence to ART was observed in almost 20% of the patients. Logistic regression indicated that predictors of poor adherence were depression, anxiety and low CD4 counts. Conclusion Adherence to anti-retroviral therapy was good amongst the majority of HIV seropositive patients. Depression, anxiety disorder and low CD4 count were however associated with poor adherence. This emphasizes the role of the psychology units as integral part of the HIV clinic to assist patients' adherence to anti-retroviral regimens.


Introduction
HIV remains a major pandemic that has claimed more than 35 million lives over the last three decades [1]. In 2017, approximately a million HIV related death and 1.8 million newly infected were reported by the World Health Organization with a major burden in sub-Saharan Africa [2]. Globally, nearly 40 million people are living with the disease, with a decline in the annual death from AIDS-related causes by nearly half in the past ten years, but this is still higher than the proposed UN target of 500,000 deaths in 2020 [3]. Since the first two AIDS cases were diagnosed in Nigeria in 1985, there has been an increase in the number of new cases with 9% of the global HIV burden coming from this region [4]. Antiretroviral therapy (ART) transformed this potentially incurable disease to a manageable chronic illness by suppressing the viral load and reducing the risk of transmission of the disease [5,6]. Nevertheless, the continued success of ART is highly dependent on early initiation of therapy, continuity in care and high treatment adherence [7]. Drug adherence is the key factor in disease control, as ART adherence of ≥95.0% can achieve suppression of viral load to undetectable levels, improve immune system function and reduce AIDS-related morbidity and mortality [8,9]. In addition, achieving the UNAIDS 90-90-90 targets (90% of all people living with HIV will know their HIV status, 90% of those people will be on ART and 90% of them will be virally suppressed) issues of adherence to ART and viral suppression need to be given more attention [10]. An observational study indicated that just 62% of HIV infected patients take at least 90% of their prescribed ART doses [11]. Therefore, drug adherence is a major challenge to effective ART patient management and the development of ART adherence intervention research is crucial for effective HIV management with the aim of achieving the 90-90-90 goal of the UNAIDS/WHO [7]. This study was aimed at evaluating the adherence of HIV seropositive patients to ART treatment regimens in a tertiary institution in Nigeria. Sampling and sample size: Raosoft incorporation software was used to calculate the sample size of 327 using a 95% confidence level [13]. Furthermore, this was increased to 400 for absolute precision of 5% points to have sufficient variation in the population characteristics (age and sex) that may influence adherence as well as power of the study. The list of 1,128 adult HIV patients from HIV clinic register was used to select 400 patients by simple random sampling method. Patients who were aged 18 years or older and had been on anti-retroviral therapy for a minimum period of 6 months were recruited for the study. Patients below 18 years, drug addicts, patients on chronic use of other medications aside anti-retroviral drugs or patients whose treatments were interrupted due to adverse effects were excluded from the study.

Data collection tools: the modified 8-item Morisky Medication
Adherence Scale (MMAS-8), a validated self-reported questionnaire, was used to assess the adherence of patients to medication [14]. It had eight questions to assess the knowledge and motivation levels of participants regarding adherence. Each question was used in determining a specific type of adherence behaviour. In order for a participant to achieve an optimum result, seven of the questions must have had a negative response while one of them must have had a positive response. One of the questions was answered using a scale of five options: never; almost never; sometimes; often and always.
A closed ended self-assessment questionnaire was employed in the collection of data regarding number of medications which have been taken, number of doses missed by each of the participants, sociodemographic information, information regarding family support and reasons for not taking medications as directed by their doctor. In addition, the Hospital Anxiety Depression Scale (HADS) was also used to assess the prevalence of anxiety and depression among the respondents [15]. Insomnia among the patients was assessed with insomnia severity index scale. The questionnaires were administered to consenting patients who met the inclusion criteria [16]. All recruited patients were on same antiretroviral therapy combination (Atripla-Efavirenz 600mg/Emtricitabine 200mg/Tenofovir 300mg) for at least six months. The lymphocyte CD4 cell counts were measured for eligible patients who had been on ART for the stipulated time period using flow cytometer (Cyflow Partec Counter 2) likewise the viral load was determined using polymerase chain reaction.
Data analysis: data collected were analyzed using SPSS 20.
Categorical variables were expressed in proportions and compared using chi-square while continuous variable were expressed in means and compared using T-test. In order to explore the factors associated with lower adherences scores, a logistic regression analysis was employed. P-value <0.05 will be considered as statistically significant.
For ease of analysis, the adherence categories comprising of low, medium and high adherence were merged into two groups. The medium and high adherences were merged together as "good adherence" while low adherence remained as "poor adherence".

Ethical approval: approval was obtained from the Ethical and
Research committee of Ekiti State University Teaching Hospital, Ado-Ekiti. Informed consent was obtained from all participants and confidentiality was ensured in the obtained information.

Results
Socio-demographic characteristics of HIV patients: four hundred HIV seropositive patients were randomly selected for the study. The socio-demographics of the patients presented in Table 1, indicated that their mean age was 42.18±9.5 years with almost three quarter of the respondents being females (74%). A large proportion of the participants were married (76%) and self-employed (60.7%).
Most of the patients had formal education as a negligible percentage of 1% of the participants had no formal education. It was observed from the study that a large proportion of the patients were low income earners with monthly pay below 140 dollars (less than 5 dollars per day). The majority of the HIV infected patients were unaware of their partners HIV status (59.3%) while 32.5% had serodiscordant spouse.
Clinical characteristics: the mean CD4 count of the HIV seropositive patients at diagnosis was an average of 302.06±15.82cells/mm 3 (mean ± SEM). It also showed that about half of the HIV infected patients (44.8%) had an initial CD4 count below 200cells/mm 3 . An increase in the CD4 count of the patients to an average of 430.8±13.30 cells/mm 3 (mean ± SEM) was observed, with a high proportion of the seropositive patients (34.9%) having a CD4 count above 500 cells/mm 3 at the time of the study and also the viral load of half of the patients (51.3%) was undetectable (<50 copies).
About forty percent of the patients were clinically depressed, 47.2% had insomnia and 33.2% had anxiety disorder while 81% had good adherence to their medications as shown in Table 2.
ART adherence and associated factors: multivariate analysis on the association of ART adherence against predictors such as; gender, age, CD4 count, viral load, insomnia index, depression score and anxiety score were carried out using binary logistic regression. Table 3 shows that the predictors of poor adherence were depression, anxiety and CD4 count below 200 cells/mm 3 . As presented in Table 3, the odds of depressed patients adhering to ART regimens were 0.2 times lower than patients who were not depressed (0.001). The result also indicates that seropositive patients suffering from anxiety are less adherent to ART (0.25 times, p=0.006). The current CD4 count of the patients was also a predicator of non-adherence as seropositive patients with CD4 below 200 were 15 times less adherent to ART regimens in comparison to patients whose CD4 count was between 200-350 cells/m 2 (p=0.0005). As indicated by the results presented in the table, patients with CD4 below 200 cells/m 2 also had ART adherence levels that were 3.75 times lower than those of patients with CD4 above 500 cells/m 2 (p=0.001).

Discussion
In this study, majority of the HIV seropositive patients were young Limitation of the study: a multi-center study and community based study would have been more representative compared to our study which was hospital based. Also, the data on adherence was based on responses from patients which may have some level of bias.

Conclusion
This study indicates a good adherence in majority of the patients but a small proportion with predictors of poor adherence to anti-retroviral therapy which were depression, anxiety disorder and low CD4 count.
An integration of a psychology unit in the HIV programme with regular and active monitoring of patients will be crucial for improved adherence.

What is known about this topic
• Adherence to antiretroviral medication is crucial to medication effectiveness;

Competing interests
The authors declare no competing interests.  Table 1: socio-demographics of the HIV patients