Factors Influencing Adherence to HAART among Patients Living with HIV Infection in Southwest Nigeria: A Cross-Sectional Analysis

Background: Nigeria has 10% of the global burden of HIV/AIDS and had HIV prevalence rate of 3.0% in 2014. Adherence to ART is a determinant of viral suppression and risk of transmission, disease progression but suboptimal adherence has been a major challenge associated with a diversity of patientand programme-related challenges. This study was done to find factors that influence adherence to HAART among HIV/AIDS Patients in Southwest Nigeria. Methods: Structured interviewer-administered questionnaires were used to collect information from the 225 participants. Findings: There were more female (80.4%) than male (19.6%) living with HIV infection. About 96% of the respondents were literate with 2.7% illiteracy rate. Employment rate was also more than half (59%). Over 90% were of the Christianity faith. None of these and other factors had any significant influence on ability of the study participants to adhere to HAART (P>0.05). Excellent or optimal HAART adherence level (≥ 95%) was found among 42% of the respondents. Another 49% had fair adherence level of between 85% and 94% while 8.4% had poor level of adherence of <85%. The five commonest reasons given for failure to adhere were forgetfulness, Stigma, seeing someone with HIV doing well on HAART, fear of discrimination and the fact that HIV has no known cure. Conclusion: In conclusion, demographic factors such as gender, religion, finance, education, marital status do not have any significant associations with adherence to HAART. In addition, less than half of the study participants living with HIV infection had excellent adherence level needed to ensure treatment success and good health. These findings showed that there is still a huge gap in PLHIV achieving optimal adherence on HAART and therefore health workers and HIV control programme implementers need to continually emphasize and support optimal adherence.


Introduction Epidemiology
Globally in 2015 there were about 36.7 million (34.0 million-39.8 million) people living with HIV, out of which 2.1 million were new HIV infections [1]. This gives a global HIV prevalence of 0.8%.
About 71% of the global burden of HIV infection is borne by the Sub-Saharan region, which account for about 11% of the world population [2]. In 2015, there were 2.1 million (1.8 million-2.4 million) new HIV infections and 1.5 million deaths due to HIV/ AIDS. In addition, although the prevalence has stabilized, the absolute number of people infected with HIV continues to grow steadily as the number of new infections outnumbers the number of AIDS-related deaths and access to HAART improves in the developing world [3].
In the world's most affected region, eastern and southern Africa, the number of people on treatment has more than doubled since 2010, reaching nearly 10.3 million people in 2015 AIDS related deaths in the region have also decreased by 36% since 2010.
Global coverage of antiretroviral therapy reached 46% (43-50%) at the end of 2015. Gains were greatest in the world's most affected region, eastern and southern Africa. Coverage increased from 24% (22-26%) in 2010 to 54% (50-58%) in 2015, reaching a regional total of 10.3 million people. South Africa alone had nearly 3.4 million people on treatment, more than any other country in the world. Next to South Africa is Kenya, which has the largest treatment programme in Africa, with nearly 900000 people on treatment at the end of 2015. Botswana, Eritrea, Kenya, Malawi, Mozambique, Rwanda, South Africa, Swaziland, Uganda, the United Republic of Tanzania, Zambia and Zimbabwe all increased treatment coverage by more than 25 percentage points between 2010 and 2015. Western and central Africa and the Middle East and North Africa also made important gains but achieved lower levels of coverage in 2015, 28% (23-34%) and 17% (12-24%), respectively. Treatment coverage in other regions of the world like the Latin American, the Caribbean, the Asia and Pacific region were also more than doubled, in 2015 [3].
The gains in treatment are largely responsible for a 26% decline in AIDS-related deaths globally since 2010, from an estimated 1.5 million (1.3 million-1.7 million) in 2010 to 1.1 million (940,000-1.3 million) in 2015. The reduction in deaths since 2010 has been greater among adult women (33% decrease) compared with adult men (15% decrease), reflecting higher treatment coverage among women than men, 52% (48-57%) and 41% (33-49%), respectively. This gender gap in HIV treatment among adults highlights the impact of gender norms on delay initiation of treatment among men, reduced treatment adherence among men, thus leading to men accounting for 58% of adult AIDS related deaths.
This expansion in HIV treatment globally is responsible for the declines in new HIV infections among adults which have slowed alarmingly in recent years, with the estimated annual number of new infections among adults remaining nearly static at about 1.9 million (1.7 million-2.2 million) in 2015. However, marked disparities in HIV incidence still exists across regions, within countries, between men and women and young and old and among specific key populations [4]. Ignorance and misunderstanding leading to discriminatory attitudes and behavior continue to undermine efforts to end AIDS. This is particularly seen with the key populations. The People Living with HIV Stigma Index measures stigma and discrimination reported by people living with HIV. Stigma Index surveys has been conducted in more than 65 countries. In 22 of these countries, more than 10% of people living with HIV reported they had been denied health care and more than 1 in 10 people living with HIV reported they had been refused employment or a work opportunity because of their HIV status in the 12 months before the survey [5]. In 30 countries where surveys were conducted, 1 in 10 people living with HIV reported they had lost a job or another source of income because of their HIV status [6].
A collection of effective HIV prevention strategies is available, including condoms, harm reduction, voluntary medical male circumcision, pre-exposure prophylaxis, cash transfers for girls and structural approaches that promote gender equality and access to secondary education. Community and peer-based approaches to sharing prevention tools have also proven effective. The key is to combine these tools into combination HIV prevention packages that address the specific needs of key populations, and to establish enabling environments that allow these populations to access HIV, health and social services without fear of violence, arrest or persecution.
Though much progress has been made in reaching people with HIV treatment and in reducing AIDS related deaths, approximately 54% (50-57%) of people living with HIV are still in need of treatment, many of whom do not know their HIV status.

Antiretroviral therapy (ART)
This refers to the use of antiretroviral drugs in the management of HIV/AIDS conditions in humans. ART should be offered to all persons who are eligible in a comprehensive manner, which means that the persons should have access to ongoing HIV Counseling for adherence, baseline and routine periodic laboratory investigation, concurrent management of OIs and routine treatment monitoring and follow-up. When properly administered ART should achieve the following goals: 1) Reduce morbidity (includes morbidity from OIs) 2) Prolong life of HIV infected individuals: Prior to the advent of ARVs mortality rates due to advanced HIV disease was unacceptably high nearing 100% in most cases. However, following the introduction of HAART many people on HAART live long and productive lives.
3) Improve quality of life of infected persons: The absence of symptomatic HIV and HIV-related illness means that persons infected with HIV are able to go about their normal existence and fend for themselves and their families unlike in the past when they were largely bedridden and dependent on others for support 4) Achieve rapid and sustained suppression of viral load: Under optimal conditions of excellent adherence should lead to rapid and sustained suppression of viral load. Usually by the 24 weeks following initiation of treatment patient's viral load should be undetectable. 8) Prophylaxis (Pre-exposure/Post-exposure): HIV negative individuals can take ARV to reduce their chances of contracting the HIV prior to or after their being exposed to high risk behaviors.

ART adherence
Adherence to ART is an essential component of individual and programmatic treatment success. Higher levels of drug adherence are associated with improved virological, immunological and clinical outcomes. Adherence rates exceeding 95% are necessary in order to maximize the benefits of ART. Adherence is crucial for delaying or avoiding the development of drug resistance and ensuring maximum durability of the first-line ARV regimen. The measures to ensure optimal adherence should be taken before commencement of therapy, at initiation and should continue during therapy.

Measurement of adherence
Adherence in many studies is measured by expressing the number of doses taken as a percentage of the number of doses prescribed. For example if 20 doses are prescribed and 19 doses are taken adherence is 95%. This translates to missing one dose in ten days on a twice daily regimen. Other measurement methods include the patient self-report, pharmacy drug pick-up and electronic method (e.g. the MEMS cap) The gold standard for assessing adherence is the ARV level in the blood. Viral load could also serve as a surrogate for assessing adherence because medication adherence will lead to low viral load, but self-reported data is reliable and easier to obtain. Studies show that self-reported data correlates with viral load [10], so self-reporting using interviewer-administered questionnaire was used in this study.

Study design
Questionnaire based cross sectional study.

Study population
Persons living with HIV/AIDS infection.

Study areas
Public hospitals in Ondo and Ekiti states.

Sample and sampling technique
Convenient sampling.

Sample size
225 persons were recruited for this study. The sample size was calculated online using raosoft statistical package online formula: Sample size n=N x/((N-1)E2 + x)) (17).

Sampling method
Non-probability convenient sampling was used to select the sample size of into 225 HIV infected persons.

Study instrument design
Structured questionnaire was used to gather the needed information and data needed in this research. The reliability and validity of the questionnaire was tested in a pilot study and subjected to review by experts in the field. drug cocktail 46%, stigma 68%, inaccessible treatment 20%, believe that HIV is a hoax 18%, to avoid discrimination 57% and believe that HIV has no treatment (23%) ( Table 3).

Discussion
All the 225 questionnaires were administered to the respondents and were completely filled, cleaned and retrieved for analysis. This represents 100% response rate. A higher proportion of the respondents, were female, married and had secondary school as the highest levels of education attained. These findings are similar to results from other works done on adherence in the region [13].
Other African studies among adult HIV patients in clinic settings also had higher proportions of female respondents [14,15]. More than half of the respondents were employed and most were of the Christianity faith. This is contrary to national demographic survey which showed almost equal proportions of Christian and Muslims in the country and lower proportions of Nigerians with secondary and tertiary education [16]. However, it is a reflection of the demographic distribution in the southwestern part of the country where a greater proportion of the populace is of the Christian faith and the level of literacy is very high compared to the other parts. The adherence levels among the respondents were classified into three categories with adherence level of above 95% being excellent or optimal, while adherence level of between 85% and 94% was classified as being Fair and Adherence level of less than 85% being Poor Adherence. This classification was based on the PEPFAR adherence assessment tool used in all PEPFAR supported facilities in Nigeria. Less than half (42%) of the respondents had excellent adherence. This translates to missing only one dose in ten days on a twice daily regimen. Whereas about half (49%) had fair adherence level, very small proportion (8.4%) had poor level of adherence. This low level of optimal adherence has been corroborated by almost all the adherence studies conducted in other regions of Nigeria [12,13,17]. It is however lower than 87.9% reported in a tertiary facility in Jos, north-central Nigeria [18]. Excellent adherence to antiretroviral therapy is essential to reaching and maintaining an undetectable viral load and avoiding emergence of resistant HIV,

Ethical consideration
Ethical approval with protocol number (ERC/2016/03/02/10B) was obtained from the IRB committee of the Federal Teaching hospital, Ado ekiti, Ekiti state, Southwest Nigeria.
The proportions of those adherent and those not adherent were also the same across the two genders (Male-80%, Female-82%) and (Male-20%, Female-18%) respectively. Equal number of respondents believed that having more money (77%, 81) and not having more money (71, 86%) will improve adherence. Respondents who having more time dedicated to ARV treatment (79%, 131) and those who do not have enough time (91%, 20) were ART adherent. 80% (110) of the respondents who had psychosocial support from others and 90% (35)of those who did not have the social support were HAART adherent. 82% (138) of the respondents who had access to ARV and 85% (11) of those who had difficulty access to ARV were adherent to HAART. About 80% of the respondents believed that the presence or absence of ethical practice at the care centers will make them adhere to HAART. Equal number of respondents who believed that there was confidentiality of information (80%; 142) and those who believed there was none (71%; 5) had good adherence.

Common reasons for non-adherence to HAART
Among the list of reasons given for non-adherent to HAART, bitter taste accounted for 20%, forgetfulness 54%, cumbersome relatively well at taking their drugs compared to people with other chronic conditions. For example, people with diabetes have around a 67.5% adherence rate, while the adherence rate in those with HIV is closer to 88%, according to some studies People living with HIV relatively adherent, are also usually honest about skipping doses or stopping treatment, hence self-reported data is fairly reliable.
For patients having problem with adherence, options to consider include switching the patient to medication with a longer half-life, moving to medication that will reduce any side effects the patient is experiencing or reducing the patent's pill burden, treatment counseling which could include SMS text-message reminders, leveraging on a patient's existing social relationships (treatment partner) as an extra support system for medication adherence could also help [11,19,20]. But offering small payments to patients in exchange for adherence has been proven not to make much of a difference in adherence rates [21].
All the factors studied in this research which include religion, monthly income, highest educational level attained, marital status, gender, finance, having enough more time for HAART, having psychosocial support from others, accessibility to ARV medication, assurance of ethical standards in the health care system and confidentiality of information do not have any significant associations with adherence level among the respondents (P>0.05). Other studies have however suggested a mixed outcome in the association between adherence and sociodemographic characteristics; while some studies found associations, others did not [22,23]. Among factors that have been known to promote adherence include lower pill burden such as the use of fixed dose combination (FDC) and patient adherence counseling [24].
Some of the common reasons for failure to adhere to HAART among the PLHIV respondents include forgetfulness(54%; P=0.00), Stigma(68%, P=0.001),seeing someone with HIV doing well on HAART (71%, P=0.041), fear of discrimination (57%, P=0.001) and the fact that HIV has no known cure (69%, P=0.00).These findings are similar to what has been highlighted in other studies [13,15]. For instance, the WHO 2015 guideline on when to start ART and PrEP which stipulate that adherence to ART is a primary determinant of viral suppression and risk of transmission, disease progression and death also acknowledged that suboptimal adherence is a major challenge in all regions, at all stages of HIV disease, and is associated with diversity of patient and programme-related challenges. According to this guideline some individual factors responsible for failure to adhere may include forgetting doses; being away from home; changes in daily routines; depression or other illness; limited understanding of treatment benefits; a lack of interest or desire to take the medicines; and substance or alcohol use. Adherence to ART may also be challenging in the absence of supportive environments for people living with HIV and because of HIVrelated stigma and discrimination.  A limitation to this study was that it depended mainly on selfreport to assess adherence level, which could be influenced by patient ability to recall and patient's desire to provide socially desirable answers.

Strengths and weaknesses (advantages and limitations) of the method used
The study is limited to Nigeria residents, a heterogeneous population. Conclusions on the random sample will be representative of those who complete the survey and not the Nigeria resident as a whole. The respondents are likely to give the socially acceptable answers and incomplete responses, considering the sensitive questionnaire and perceived socioeconomic position.
As a cross-sectional analysis, the study is short of temporal sequence; incapable of estimating any causal association. Additionally, the findings may be subject to potential selection bias as women and men who failed to participate in the survey may have differed from respondents with respect to Adherence to HAART. The accuracy of the study depends on the authenticity of the responses given by the participants. Information and selective bias are potential limitations of this study.
In spite of these limitations, this research had strength, including (a) the use of accurate point estimate (prevalence odds ratio) to examine the association between the independent and dependent variables which does not inflate the effect size compared with odds ratio, and (b) the ability to identify Adherence to HAART risk determinants/factors in Nigerian resident sample, which have neither been studied nor documented as far as we know.

Conclusion
In conclusion less than half of the study participants living with HIV infection had excellent adherence level needed to ensure treatment success and good health.
There were more female than male living with HIV infection among the respondents. Over 90% of the respondents were literate with less than 3% illiteracy rate.
Employment rate was also more than half (59%) while the unemployed rate was about 31.6%. Most were of the Christianity faith None of the factors studied had any significant association with HAART adherence.
The five commonest reasons for failure to adhere were forgetfulness, Stigma, seeing someone with HIV doing well on HAART, fear of discrimination and the fact that HIV has no known cure.
These findings showed that there is still a huge gap in PLHIV achieving optimal adherence on HAART and therefore health workers and HIV control programme implementers need to continually emphasize and support optimal adherence.